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1. Management of secondary immunodeficiency in hematological malignancies: a Delphi consensus from the Middle East

Author

Maria Dimou, Mohamed Abuzakouk, Mona Al Ahmad, Khalil Al Farsi, Ahmad Alhuraiji, Fayhan Al Roqi, Ahmed Alsaeed, Mohsen Alzahrani, Ali Bazarbachi, Honar Cherif, Riad El Fakih, Carla Irani, Faraz Khan, Iman Nasr, Hani Yousif Osman, and Mustaqeem Siddiqui

Subjects
secondary immunodeficiency, Middle East, Delphi consensus, immunoglobulin replacement therapy, acquired hypogammaglobinemia, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Secondary immunodeficiency (SID), acquired hypogammaglobinemia, is an immunodeficiency caused by different factors like diseases, medications, and/or nutrition disorders. Most patients with hematological malignancies (HM), namely chronic lymphocytic leukemia (CLL) and multiple myeloma (MM), experience such SID. These patients have a consistently high risk of infection throughout the disease course. Traditional chemotherapy and novel agents used to treat HM may further increase infection susceptibility. Immunoglobulin replacement therapy (IgRT) is an effective management option for SID. The prevalence of SID in the Middle East needs better documentation. Healthcare providers should consider and evaluate SID in patients at risk, monitor for infection occurrence, and treat accordingly (including initiating IgRT when indicated). A Delphi initiative was conducted by a consensus panel of 15 experts from the Middle East who have over 20 years of experience in actively managing patients with SID. The modified Delphi process was used, and 16 questions reached a consensus on managing SID patients with IgRT. In addition, the consensus panel of Middle East experts recommended real-world practice recommendations regarding initiating, dosing, and discontinuing IgRT in managing SID. This consensus recommendation aims to assist healthcare practitioners in the Middle East in evidence-based clinical decision-making for better management of SID.

Published
2024
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2. The Role of Methylation in Chronic Lymphocytic Leukemia and Its Prognostic and Therapeutic Impacts in the Disease: A Systematic Review

Author

Sevastianos Chatzidavid, Christina-Nefeli Kontandreopoulou, Nefeli Giannakopoulou, Panagiotis T. Diamantopoulos, Christos Stafylidis, Marie-Christine Kyrtsonis, Maria Dimou, Panayiotis Panayiotidis, and Nora-Athina Viniou

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Epigenetic regulation has been thoroughly investigated in recent years and has emerged as an important aspect of chronic lymphocytic leukemia (CLL) biology. Characteristic aberrant features such as methylation patterns and global DNA hypomethylation were the early findings of the research during the last decades. The investigation in this field led to the identification of a large number of genes where methylation features correlated with important clinical and laboratory parameters. Gene-specific analyses investigated methylation in the gene body enhancer regions as well as promoter regions. The findings included genes and proteins involved in key pathways that play central roles in the pathophysiology of the disease. Τhe application of these findings beyond the theoretical understanding can not only lead to the creation of prognostic and predictive models and scores but also to the design of novel therapeutic agents. The following is a review focusing on the present knowledge about single gene/gene promoter methylation or mRNA expression in CLL cases as well as records of older data that have been published in past papers.

Published
2024
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3. A Nationwide Study of the Delayed Diagnosis and the Clinical Manifestations of Predominantly Antibody Deficiencies and CTLA4-Mediated Immune Dysregulation Syndrome in Greece

Author

Androniki Kapousouzi, Fani Kalala, Styliani Sarrou, Evangelia Farmaki, Nikolaos Antonakos, Ioannis Kakkas, Alexandra Kourakli, Vassiliki Labropoulou, Charikleia Kelaidi, Georgia Tsiouma, Maria Dimou, Theodoros P. Vassilakopoulos, Michael Voulgarelis, Ilias Onoufriadis, Eleni Papadimitriou, Sophia Polychronopoulou, Evangelos J. Giamarellos-Bourboulis, Argiris Symeonidis, Christos Hadjichristodoulou, Anastasios E. Germenis, and Matthaios Speletas

Subjects
predominantly antibody deficiencies, common variable immunodeficiency, IgA deficiency, IgG subclass deficiency, CTLA4, diagnosis, Medicine (General), R5-920
Abstract

Background and Objectives: Predominantly antibody deficiencies (PAD) represent the most common type of primary immunodeficiencies in humans, characterized by a wide variation in disease onset, clinical manifestations, and outcome. Considering that the prevalence of PAD in Greece is unknown, and there is limited knowledge on the clinical and laboratory characteristics of affected patients, we conducted a nationwide study. Materials and Methods: 153 patients (male/female: 66/87; median age: 43.0 years; range: 7.0–77.0) diagnosed, and followed-up between August 1979 to September 2023. Furthermore, we classified our cohort into five groups according to their medical history, immunoglobulin levels, and CTLA4-mutational status: 123 had common variable immunodeficiency (CVID), 12 patients with “secondary” hypogammaglobulinemia due to a previous B-cell depletion immunotherapy for autoimmune or malignant disease several years ago (median: 9 years, range 6–14) displaying a typical CVID phenotype, 7 with combined IgA and IgG subclass deficiencies, 5 patients with CVID-like disease due to CTLA4-mediated immune dysregulation syndrome, and 6 patients with unclassified hypogammaglobulinemia. Results: We demonstrated a remarkable delay in PAD diagnosis, several years after the onset of related symptoms (median: 9.0 years, range: 0–43.0). A family history of PAD was only present in 11.8%, with the majority of patients considered sporadic cases. Most patients were diagnosed in the context of a diagnostic work-up for recurrent infections, or recurrent/resistant autoimmune cytopenias. Interestingly, 10 patients (5.6%) had no history of infection, diagnosed due to either recurrent/resistant autoimmunity, or during a work-up of their medical/family history. Remarkable findings included an increased prevalence of lymphoproliferation (60.1%), while 39 patients (25.5%) developed bronchiectasis, and 16 (10.5%) granulomatous disease. Cancer was a common complication in our cohort (25 patients, 16.3%), with B-cell malignancies representing the most common neoplasms (56.7%). Conclusion: Our findings indicate the necessity of awareness about PAD and their complications, aiming for early diagnosis and the appropriate management of affected patients.

Published
2024
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4. The Total Phenolic Content and Antioxidant Activity of Nine Monofloral Honey Types

Author

Chrysoula Tananaki, Maria-Anna Rodopoulou, Maria Dimou, Dimitrios Kanelis, and Vasilios Liolios

Subjects
monofloral honeys, total phenolic content, total antioxidant activity, electrical conductivity, color, Technology, Engineering (General). Civil engineering (General), TA1-2040, Biology (General), QH301-705.5, Physics, QC1-999, Chemistry, QD1-999
Abstract

Honey is well known for its antioxidant and antimicrobial properties, which significantly contribute to its high demand among consumers. While there is plenty of information available about the antioxidant potential of honey, there is still a lack of research specifically focused on monofloral honeys, as most studies have been based on market samples. To address this issue, in the present study we analyzed the total phenolic content and antioxidant activity of nine monofloral honey types produced in Greece: fir, chestnut, citrus, erica, cotton, Jerusalem thorn, pine, oak and thyme, in comparison with manuka honey. The samples were collected from beekeepers applying the appropriate beekeeping practices. In total, ninety-six representative monofloral honey samples meeting the microscopic, physicochemical, and sensory characteristics were analyzed. Oak honey stood out as the darkest type (L* = 33.67) with the highest total phenolic content (203.75 mg GAE/100 g) and antioxidant activity (106.2 mg AAE/100 g). Chestnut honey closely followed, having also the highest electrical conductivity (1.679 mS/cm). Although manuka honey had a high total phenolic content, its total antioxidant activity was found to be medium-low compared to fir, pine, and erica honeys. Citrus honey, being the lightest in color (L* = 37.2), exhibited the lowest total antioxidant activity (6.36 mg AAE/100 g). Statistical analysis revealed significant positive correlation between total antioxidant activity and electrical conductivity (ra-e = 0.587, pa-e = 0.000), and negative correlation between total antioxidant activity and L* parameter (ra-L = −0.424, pa-L = 0.000). Similar correlations were also observed regarding total phenolic content (rp-e = 0.457, pp-e = 0.000, rp-L = −0.455, pp-L = 0.000). In conclusion, oak and chestnut honeys seem to have a high antioxidant potential, that should be further explored, to highlight their value and help promote them worldwide.

Published
2024
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5. Other malignancies in the history of CLL: an international multicenter study conducted by ERIC, the European Research Initiative on CLL, in HARMONYResearch in context

Author

Thomas Chatzikonstantinou, Lydia Scarfò, Georgios Karakatsoulis, Eva Minga, Dimitra Chamou, Gloria Iacoboni, Jana Kotaskova, Christos Demosthenous, Lukas Smolej, Stephen Mulligan, Miguel Alcoceba, Salem Al-Shemari, Thérèse Aurran-Schleinitz, Francesca Bacchiarri, Mar Bellido, Fontanet Bijou, Anne Calleja, Angeles Medina, Mehreen Ali Khan, Ramona Cassin, Sofia Chatzileontiadou, Rosa Collado, Amy Christian, Zadie Davis, Maria Dimou, David Donaldson, Gimena Dos Santos, Barbara Dreta, Maria Efstathopoulou, Shaimaa El-Ashwah, Alicia Enrico, Alberto Fresa, Sara Galimberti, Andrea Galitzia, Rocío García-Serra, Eva Gimeno, Isabel González-Gascón-y-Marín, Alessandro Gozzetti, Valerio Guarente, Romain Guieze, Ajay Gogia, Ritu Gupta, Sean Harrop, Eleftheria Hatzimichael, Yair Herishanu, José-Ángel Hernández-Rivas, Luca Inchiappa, Ozren Jaksic, Susanne Janssen, Elżbieta Kalicińska, Laribi Kamel, Volkan Karakus, Arnon P. Kater, Bonnie Kho, Maria Kislova, Eliana Konstantinou, Maya Koren-Michowitz, Ioannis Kotsianidis, Robert J. Kreitman, Jorge Labrador, Deepesh Lad, Mark-David Levin, Ilana Levy, Thomas Longval, Alberto Lopez-Garcia, Juan Marquet, Lucia Martin-Rodríguez, Marc Maynadié, Stanislava Maslejova, Carlota Mayor-Bastida, Biljana Mihaljevic, Ivana Milosevic, Fatima Miras, Riccardo Moia, Marta Morawska, Roberta Murru, Uttam Kumar Nath, Almudena Navarro-Bailón, Ana C. Oliveira, Jacopo Olivieri, David Oscier, Irina Panovska-Stavridis, Maria Papaioannou, Tomas Papajík, Zuzana Kubova, Punyarat Phumphukhieo, Cheyenne Pierie, Anna Puiggros, Lata Rani, Gianluigi Reda, Gian Matteo Rigolin, Rosa Ruchlemer, Marcos Daniel de Deus Santos, Mattia Schipani, Annett Schiwitza, Yandong Shen, Martin Simkovic, Svetlana Smirnova, Dina Sameh Abdelrahman Soliman, Martin Spacek, Tamar Tadmor, Kristina Tomic, Eric Tse, Theodoros Vassilakopoulos, Andrea Visentin, Candida Vitale, Julia von Tresckow, George Vrachiolias, Vojin Vukovic, Renata Walewska, Ewa Wasik-Szczepanek, Zhenshu Xu, Munci Yagci, Lucrecia Yañez, Mohamed Yassin, Jana Zuchnicka, Maria Angelopoulou, Darko Antic, Bella Biderman, Mark Catherwood, Rainer Claus, Marta Coscia, Antonio Cuneo, Fatih Demirkan, Blanca Espinet, Gianluca Gaidano, Olga B. Kalashnikova, Luca Laurenti, Eugene Nikitin, Gerassimos A. Pangalis, Panagiotis Panagiotidis, Viola Maria Popov, Sarka Pospisilova, Paolo Sportoletti, Niki Stavroyianni, Constantine Tam, Livio Trentin, Anastasia Chatzidimitriou, Francesc Bosch, Michael Doubek, Paolo Ghia, and Kostas Stamatopoulos

Subjects
Chronic lymphocytic leukemia, Other malignancies, Other cancers, Second primary malignancies, Medicine (General), R5-920
Abstract

Summary: Background: Patients with chronic lymphocytic leukemia (CLL) have a higher risk of developing other malignancies (OMs) compared to the general population. However, the impact of CLL-related risk factors and CLL-directed treatment is still unclear and represents the focus of this work. Methods: We conducted a retrospective international multicenter study to assess the incidence of OMs and detect potential risk factors in 19,705 patients with CLL, small lymphocytic lymphoma, or high-count CLL-like monoclonal B-cell lymphocytosis, diagnosed between 2000 and 2016. Data collection took place between October 2020 and March 2022. Findings: In 129,254 years of follow-up after CLL diagnosis, 3513 OMs were diagnosed (27.2 OMs/1000 person-years). The most common hematological OMs were Richter transformation, myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Non-melanoma skin (NMSC) and prostate cancers were the most common solid tumors (STs).The only predictor for MDS and AML development was treatment with fludarabine and cyclophosphamide with/without rituximab (FC ± R) (OR = 3.7; 95% CI = 2.79–4.91; p

Published
2023
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6. Prognostic Impact of Serum β2-Microglobulin Levels in Hodgkin Lymphoma Treated with ABVD or Equivalent Regimens: A Comprehensive Analysis of 915 Patients

Author

Theodoros P. Vassilakopoulos, Maria Arapaki, Panagiotis T. Diamantopoulos, Athanasios Liaskas, Fotios Panitsas, Marina P. Siakantaris, Maria Dimou, Styliani I. Kokoris, Sotirios Sachanas, Marina Belia, Chrysovalantou Chatzidimitriou, Elianna A. Konstantinou, John V. Asimakopoulos, Kyriaki Petevi, George Boutsikas, Alexandros Kanellopoulos, Alexia Piperidou, Maria-Ekaterini Lefaki, Angeliki Georgopoulou, Anastasia Kopsaftopoulou, Kalliopi Zerzi, Ioannis Drandakis, Maria N. Dimopoulou, Marie-Christine Kyrtsonis, Panayiotis Tsaftaridis, Eleni Plata, Eleni Variamis, Gerassimos Tsourouflis, Flora N. Kontopidou, Kostas Konstantopoulos, Gerassimos A. Pangalis, Panayiotis Panayiotidis, and Maria K. Angelopoulou

Subjects
Hodgkin’s lymphoma, β2-microglobulin, prognostic factors, chemotherapy, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

The significance of serum beta-2 microglobulin (sβ2m) in Hodgkin lymphoma (HL) is controversial. We analyzed 915 patients with HL, who were treated with ABVD or equivalent regimens with or without radiotherapy. Sβ2m levels were measured by a radioimmunoassay (upper normal limit 2.4 mg/L). Sequential cutoffs (1.8–3.0 by 0.1 mg/L increments, 3.5 and 4.0 mg/L) were tested along with ROC analysis. The median sβ2m levels were 2.20 mg/L and were elevated (>2.4 mg/L) in 383/915 patients (41.9%). Higher sβ2m was associated with inferior freedom from progression (FFP) at all tested cutoffs. The best cutoff was 2.0 mg/L (10-year FFP 83% vs. 70%, p = 0.001), which performed better than the 2.4 mg/L cutoff (“normal versus high”). In multivariate analysis, sβ2m > 2.0 mg/L was an independent adverse prognostic factor in the whole patient population. In multivariate overall survival analysis, sβ2m levels were predictive at 2.0 mg/L cutoff in the whole patient population and in advanced stages. Similarly, sβ2m > 2.0 mg/L independently predicted inferior HL-specific survival in the whole patient population. Our data suggest that higher sβ2m is an independent predictor of outcome in HL but the optimal cutoff lies within the normal limits (i.e., at 2.0 mg/L) in this predominantly young patient population, performing much better than a “normal versus high” cutoff set at 2.4 mg/L.

Published
2024
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7. S149: OTHER MALIGNANCIES IN THE HISTORY OF CLL: THE FINAL ANALYSIS OF THE INTERNATIONAL MULTICENTER STUDY CONDUCTED BY ERIC, IN HARMONY.

Author

Thomas Chatzikonstantinou, Lydia Scarfò, Georgios Karakatsoulis, Eva Minga, Dimitra Chamou, Gloria Iacoboni, Jana Kotaskova, Christos Demosthenous, Miguel Alcoceba, Salem Al-Shemari, Thérèse Aurran-Schleinitz, Francesca Bacchiarri, Mar Bellido, Fontanet Bijou, Anne Calleja, Angeles Medina, Mehreen Ali Khan, Ramona Cassin, Sofia Chatzileontiadou, Rosa Collado, Zadie Davis, Maria Dimou, David Donaldson, Gimena Dos Santos, Barbara Dreta, Maria Efstathopoulou, Shaimaa El-Ashwah, Alicia Enrico, Alberto Fresa, Sara Galimberti, Andrea Galitzia, Rocío García-Serra, Eva Gimeno, Isabel González-Gascón-Y-Marín, Alessandro Gozzetti, Valerio Guarente, Romain Guieze, Ajay Gogia, Ritu Gupta, Sean Harrop, Eleftheria Hatzimichael, Yair Herishanu, José-Ángel Hernández-Rivas, Luca Inchiappa, Ozren Jaksic, Susanne Janssen, Elżbieta Kalicińska, Laribi Kamel, Volkan Karakus, Arnon P Kater, Bonnie Kho, Maria Kislova, Εliana Konstantinou, Maya Koren-Michowitz, Ioannis Kotsianidis, Robert J Kreitman, Jorge Labrador, Deepesh Lad, Mark-David Levin, Ilana Levy, Thomas Longval, Alberto Lopez-Garcia, Juan Marquet, Marc Maynadié, Stanislava Maslejova, Carlota Mayor-Bastida, Biljana Mihaljevic, Ivana Milosevic, Fatima Miras, Riccardo Moia, Marta Morawska, Roberta Murru, Uttam Kumar Nath, Almudena Navarro-Bailón, Ana C. Oliveira, Jacopo Olivieri, David Oscier, Irina Panovska-Stavridis, Maria Papaioannou, Tomas Papajík, Punyarat Phumphukhieo, Cheyenne Pierie, Anna Puiggros, Lata Rani, Gianluigi Reda, Gian Matteo Rigolin, Aharon Ronson, Rosa Ruchlemer, Marcos Daniel de Deus Santos, Mattia Schipani, Annett Schiwitza, Yandong Shen, Martin Simkovic, Svetlana Smirnova, Dina Sameh Abdelrahman Soliman, Martin Spacek, Tamar Tadmor, Kristina Tomic, Eric Tse, Theodoros Vassilakopoulos, Andrea Visentin, Candida Vitale, Julia von Tresckow, George Vrachiolias, Vojin Vukovic, Renata Walewska, Ewa Wasik-Szczepanek, Zhenshu Xu, Munci Yagci, Lucrecia Yañez, Mohamed Yassin, Jana Zuchnicka, Maria Angelopoulou, Darko Antic, Bella Biderman, Mark Catherwood, Rainer Claus, Marta Coscia, Antonio Cuneo, Fatih Demirkan, Blanca Espinet, Gianluca Gaidano, Olga Kalashnikova, Luca Laurenti, Eugene Nikitin, Gerassimos A. Pangalis, Panagiotis Panagiotidis, Stephen Mulligan, Viola Maria Popov, Sarka Pospisilova, Lukas Smolej, Paolo Sportoletti, Niki Stavroyianni, Constantine Tam, Livio Trentin, Anastasia Chatzidimitriou, Francesc Bosch, Michael Doubek, Paolo Ghia, and Kostas Stamatopoulos

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2023
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8. P1606: PRIMARY AND SECONDARY IMMUNE THROMBOCYTOPENIA (ITP) IN ADULTS: REAL WORLD COMPARATIVE RETROSPECTIVE STUDY FROM THE ITP REGISTRY OF THE HELLENIC SOCIETY OF HEMATOLOGY

Author

Emily Stavroulaki, Charalampos Pontikoglou, Theodora Chatzilygeroudi, Alexandra Kouraklis-Symeonidis, Argiris Symeonidis, Maria Dimou, Panayiotis Panayiotidis, Giorgos Drakos, Aspasia Koudouna, Athanasios Galanopoulos, Vasileia Kaliafentaki, Angelos Matheakakis, Christina Lekarakou, Peggy Kanellou, Eleni Gavriilaki, Syrigou Antonia, Ioanna Sakellari, Dimitra Liapi, Georgios Tsirakis, Anna Kolovou, Sofia Chatzileontiadou, Maria Papaioannou, Aikaterini Souravla, Maria Dellatola, Maria Pagoni, Maria Bobola, Panagiotis Diamantopoulos, Marina Mantzourani, Nora-Athina Viniou, Aikaterini Megalakaki, Ioanna Christodoulou, Efthymia Vlachaki, Stavroula Giannouli, Vasiliki Gkalea, Charis Matsouka, Ioannis Kotsianidis, George Vassilopoulos, Maria Protopappa, Eleftheria Hatzimichael, Panagiotis Zikos, Marianna Politou, George N Chalkiadakis, and Helen Papadaki

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2023
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9. Real world data on the prognostic significance of monocytopenia in myelodysplastic syndrome

Author

Panagiotis T. Diamantopoulos, Emmanouil Charakopoulos, Argiris Symeonidis, Ioannis Kotsianidis, Nora-Athina Viniou, Vassiliki Pappa, Charalampos Pontikoglou, Dimitrios Tsokanas, Georgios Drakos, Alexandra Kourakli, Elena Solomou, Eleftheria Hatzimichael, Anastasia Pouli, Maria Kotsopoulou, Evangelos Asmanis, Maria Dimou, Panayiotis Panayiotidis, Sotirios Papageorgiou, Georgios Vassilopoulos, Achilles Anagnostopoulos, Theodoros Vassilakopoulos, Helen Papadaki, and Athanasios Galanopoulos

Subjects
Medicine, Science
Abstract

Abstract Monocytopenia is a common finding in patients with myelodysplastic syndrome (MDS), but although monocytes may exhibit prognostic significance in MDS due to their role in innate immunity, they have not been incorporated in any prognostic scoring system for MDS. In this study, we analyzed national registry data from 1719 adults with MDS. Monocytopenia was present in 29.5% of the patients and was correlated with the presence of excess blasts and higher revised international prognostic scoring system categories. Univariate analysis showed that monocytopenia was prognostic of a lower overall survival [(OS), 32.0 versus 65.0 months, p

Published
2022
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10. Thrombotic and bleeding complications in patients with chronic lymphocytic leukemia and severe COVID-19: a study of ERIC, the European Research Initiative on CLL

Author

Darko Antic, Natasa Milic, Thomas Chatzikonstantinou, Lydia Scarfò, Vladimir Otasevic, Nina Rajovic, David Allsup, Alejandro Alonso Cabrero, Martin Andres, Monica Baile Gonzales, Antonella Capasso, Rosa Collado, Raul Cordoba, Carolina Cuéllar-García, Juan Gonzalo Correa, Lorenzo De Paoli, Maria Rosaria De Paolis, Giovanni Del Poeta, Maria Dimou, Michael Doubek, Maria Efstathopoulou, Shaimaa El-Ashwah, Alicia Enrico, Blanca Espinet, Lucia Farina, Angela Ferrari, Myriam Foglietta, Alberto Lopez-Garcia, José A. García-Marco, Rocío García-Serra, Massimo Gentile, Eva Gimeno, Maria Gomes da Silva, Odit Gutwein, Yervand K. Hakobyan, Yair Herishanu, José Ángel Hernández-Rivas, Tobias Herold, Gilad Itchaki, Ozren Jaksic, Ann Janssens, Olga B. Kalashnikova, Elżbieta Kalicińska, Arnon P. Kater, Sabina Kersting, Maya Koren-Michowitz, Jorge Labrador, Deepesh Lad, Luca Laurenti, Alberto Fresa, Mark-David Levin, Carlota Mayor Bastida, Lara Malerba, Roberto Marasca, Monia Marchetti, Juan Marquet, Biljana Mihaljevic, Ivana Milosevic, Fatima Mirás, Marta Morawska, Marina Motta, Talha Munir, Roberta Murru, Raquel Nunes, Jacopo Olivieri, Miguel Arturo Pavlovsky, Inga Piskunova, Viola Maria Popov, Francesca Maria Quaglia, Giulia Quaresmini, Gianluigi Reda, Gian Matteo Rigolin, Amit Shrestha, Martin Šimkovič, Svetlana Smirnova, Martin Špaček, Paolo Sportoletti, Oana Stanca, Niki Stavroyianni, Doreen Te Raa, Kristina Tomic, Sanne Tonino, Livio Trentin, Ellen Van Der Spek, Michel van Gelder, Marzia Varettoni, Andrea Visentin, Candida Vitale, Vojin Vukovic, Ewa Wasik-Szczepanek, Tomasz Wróbel, Lucrecia Yáñez San Segundo, Mohamed Yassin, Marta Coscia, Alessandro Rambaldi, Emili Montserrat, Robin Foà, Antonio Cuneo, Marc Carrier, Paolo Ghia, and Kostas Stamatopoulos

Subjects
CLL, COVID-19, Thrombosis, Bleeding, D-dimer, Anticoagulation therapy, Diseases of the blood and blood-forming organs, RC633-647.5, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to COVID-19 related poor outcomes, including thrombosis and death, due to the advanced age, the presence of comorbidities, and the disease and treatment-related immune deficiency. The aim of this study was to assess the risk of thrombosis and bleeding in patients with CLL affected by severe COVID-19. Methods This is a retrospective multicenter study conducted by ERIC, the European Research Initiative on CLL, including patients from 79 centers across 22 countries. Data collection was conducted between April and May 2021. The COVID-19 diagnosis was confirmed by the real-time polymerase chain reaction (RT-PCR) assay for SARS-CoV-2 on nasal or pharyngeal swabs. Severe cases of COVID-19 were defined by hospitalization and the need of oxygen or admission into ICU. Development and type of thrombotic events, presence and severity of bleeding complications were reported during treatment for COVID-19. Bleeding events were classified using ISTH definition. STROBE recommendations were used in order to enhance reporting. Results A total of 793 patients from 79 centers were included in the study with 593 being hospitalized (74.8%). Among these, 511 were defined as having severe COVID: 162 were admitted to the ICU while 349 received oxygen supplementation outside the ICU. Most patients (90.5%) were receiving thromboprophylaxis. During COVID-19 treatment, 11.1% developed a thromboembolic event, while 5.0% experienced bleeding. Thrombosis developed in 21.6% of patients who were not receiving thromboprophylaxis, in contrast to 10.6% of patients who were on thromboprophylaxis. Bleeding episodes were more frequent in patients receiving intermediate/therapeutic versus prophylactic doses of low-molecular-weight heparin (LWMH) (8.1% vs. 3.8%, respectively) and in elderly. In multivariate analysis, peak D-dimer level and C-reactive protein to albumin ratio were poor prognostic factors for thrombosis occurrence (OR = 1.022, 95%CI 1.007‒1.038 and OR = 1.025, 95%CI 1.001‒1.051, respectively), while thromboprophylaxis use was protective (OR = 0.199, 95%CI 0.061‒0.645). Age and LMWH intermediate/therapeutic dose administration were prognostic factors in multivariate model for bleeding (OR = 1.062, 95%CI 1.017–1.109 and OR = 2.438, 95%CI 1.023–5.813, respectively). Conclusions Patients with CLL affected by severe COVID-19 are at a high risk of thrombosis if thromboprophylaxis is not used, but also at increased risk of bleeding under the LMWH intermediate/therapeutic dose administration.

Published
2022
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11. Very late relapses in Hodgkin lymphoma treated with chemotherapy with or without radiotherapy: linear pattern and distinct prognostic factors

Author

Theodoros P. Vassilakopoulos, Evrydiki Kravvariti, Fotios Panitsas, Maria K. Angelopoulou, Athanasios Liaskas, Flora N. Kontopidou, Xanthoula Yiakoumis, Eleni Variami, Maria N. Dimopoulou, Marina P. Siakantaris, John V. Asimakopoulos, Maria Arapaki, Maria Dimou, Panagiotis Diamantopoulos, Sotirios Sachanas, Chrysovalantou Chatzidimitriou, Marina Belia, Elianna Konstantinou, George Boutsikas, Kyriaki Petevi, Alexandros Kanellopoulos, Styliani Kokoris, Marie-Christine Kyrtsonis, Nora-Athina Viniou, Eleftheria Lakiotaki, Gerasimos Tsourouflis, Penelope Korkolopoulou, Kostas Konstantopoulos, Panayiotis Panayiotidis, and Gerassimos A. Pangalis

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published
2022
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12. Insights into Facilitated Subcutaneous Immunoglobulin Use in Patients with Secondary Immunodeficiency Diseases: A FIGARO Subgroup Analysis

Author

Maria Dimou, Matthaios Speletas, Cinzia Milito, Aleksandra Pyzik, Dörte Huscher, Marta Kamieniak, David Pittrow, and Michael Borte

Subjects
facilitated subcutaneous immunoglobulin, immunoglobulin replacement therapy, secondary immunodeficiency diseases, real-world study, self-administration, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

The Facilitated Immunoglobulin Administration Registry And Outcomes (FIGARO) Study was a European, multicenter, prospective, observational study conducted across Europe designed to provide insights on the clinical use and tolerability of facilitated subcutaneous immunoglobulin (fSCIG). Data herein are reported for the cohort of patients with secondary immunodeficiency (SID), with a subgroup analysis by age. The SID cohort included 31 patients: 1 pediatric, 15 adult, and 15 older adult patients. Over the 36-month observation period, the median monthly dose of fSCIG (30 g) and median monthly infusion volume per patient (300 mL) remained constant in both adult-age cohorts. Serum trough levels tended to increase over time. Most patients required only one infusion site and could receive the full dose every 3–4 weeks. There was a trend toward self-administration at home. In the adult group, infusion site inflammation and headache were reported at the inclusion visit (n = 1 each), with no adverse drug reactions reported at any of the follow-up visits. No acute severe bacterial infections were reported during the study follow-up. These results demonstrate the feasibility and tolerability of fSCIG use in patients with SID and the flexibility of administration settings including self-administration at home in patients aged ≥65 years.

Published
2023
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13. The Role of mTOR in B Cell Lymphoid Malignancies: Biologic and Therapeutic Aspects

Author

Eleni A. Karatrasoglou, Maria Dimou, Alexia Piperidou, Eleftheria Lakiotaki, Penelope Korkolopoulou, and Theodoros P. Vassilakopoulos

Subjects
mTOR, DLBCL, MCL, mTOR inhibitors, temsirolimus, everolimus, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

Non-Hodgkin lymphoma’s (NHL) incidence is rising over time, and B cell lymphomas comprise the majority of lymphomas. The phosphoinositide 3-kinase (PI3K)/v-akt murine thymoma viral oncogene homologue 1 (Akt)/mammalian target of the rapamycin (mTOR) signaling pathway plays a critical role in a variety of cellular processes, such as cell proliferation and survival. Its role in lymphomagenesis is confirmed in many different types of B cell lymphomas. This review is mainly focused on the PI3K/v-akt/mTOR pathway-related oncogenic mechanisms in B cell NHLs with an emphasis on common B cell lymphoma types [diffuse large B cell lymphoma (DLBCL) and mantle cell lymphoma (MCL)]. Furthermore, it summarizes the literature regarding the clinical applications of the mTOR inhibitors temsirolimus and everolimus in B cell NHLs, which have been tested in a range of clinical trials enrolling patients with B cell malignancies, either as monotherapy or in combination with other agents or regimens.

Published
2023
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14. New Functionalities and Regional/National Use Cases of the Anomaly Hotspots of Agricultural Production (ASAP) Platform

Author

Felix Rembold, Michele Meroni, Viola Otieno, Oliver Kipkogei, Kenneth Mwangi, João Maria de Sousa Afonso, Isidro Metódio Tuleni Johannes Ihadua, Amílcar Ernesto A. José, Louis Evence Zoungrana, Amjed Hadj Taieb, Ferdinando Urbano, Maria Dimou, Hervé Kerdiles, Petar Vojnovic, Matteo Zampieri, and Andrea Toreti

Subjects
agriculture, early warning, drought, decision support system, food security, earth observation, Science
Abstract

The Anomaly hotSpots of Agricultural Production (ASAP) Decision Support System was launched operationally in 2017 for providing timely early warning information on agricultural production based on Earth Observation and agro-climatic data in an open and easy to use online platform. Over the last three years, the system has seen several methodological improvements related to the input indicators and to system functionalities. These include: an improved dataset of rainfall estimates for Africa; a new satellite indicator of biomass optimised for near-real-time monitoring; an indicator of crop and rangeland water stress derived from a water balance accounting scheme; the inclusion of seasonal precipitation forecasts; national and sub-national crop calendars adapted to ASAP phenology; and a new interface for the visualisation and analysis of high spatial resolution Sentinel and Landsat data. In parallel to these technical improvements, stakeholders and users uptake was consolidated through the set up of regionally adapted versions of the ASAP system for Eastern Africa in partnership with the Intergovernmental Authority on Development (IGAD) Climate Prediction and Applications Centre (ICPAC), for North Africa with the Observatoire du Sahara et du Sahel (OSS), and through the collaboration with the Angolan National Institute of Meteorology and Geophysics (INAMET), that used the ASAP system to inform about agricultural drought. Finally, ASAP indicators have been used as inputs for quantitative crop yield forecasting with machine learning at the province level for Algeria’s 2021 and 2022 winter crop seasons that were affected by drought.

Published
2023
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15. Richter's transformation as leptomeningeal infiltration in a chronic lymphocytic leukemia patient receiving venetoclax. Could blood‐brain barrier be a disease 'sanctuary' during venetoclax treatment?

Author

Maria Dimou, Aikaterini Bitsani, Maria Roumelioti, Aglaia Dimitrakopoulou, Theodore Iliakis, Vasileios Pardalis, Ioannis Grafakos, Sotiria Kalyva, Athanasios Markopoulos, Marie‐Christine Kyrtsonis, and Panayiotis Panayiotidis

Subjects
blood‐brain barrier, chronic lymphocytic leukemia, leptomeningeal infiltration, Richter's transformation, venetoclax, Medicine, Medicine (General), R5-920
Abstract

Abstract Our unique case of Richter's Transformation presenting as leptomeningial infiltration in a CLL patient receiving venetoclax raises questions on whether the drug penetrates the blood‐brain barrier and at what extend, especially in reduced doses given for drug‐drug interactions.

Published
2021
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16. Refinement of prognosis and the effect of azacitidine in intermediate-risk myelodysplastic syndromes

Author

Konstantinos Liapis, Vasileios Papadopoulos, George Vrachiolias, Athanasios G. Galanopoulos, Menelaos Papoutselis, Sotirios G. Papageorgiou, Panagiotis T. Diamantopoulos, Vassiliki Pappa, Nora-Athina Viniou, Alexandra Kourakli, Dimitris Τsokanas, Theodoros P. Vassilakopoulos, Eleftheria Hatzimichael, Eleni Bouronikou, Maria Ximeri, Charalambos Pontikoglou, Aekaterini Megalakaki, Panagiotis Zikos, Panayiotis Panayiotidis, Maria Dimou, Stamatis Karakatsanis, Maria Papaioannou, Anna Vardi, Flora Kontopidou, Nikolaos Harchalakis, Ioannis Adamopoulos, Argiris Symeonidis, and Ioannis Kotsianidis

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published
2021
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17. The Free-Living Nematodes as Indicators of the Soil Quality in Relation to the Clay Content, When Coffee Waste Is Applied

Author

Panagiotis Kekelis, Efimia M. Papatheodorou, Eleni Terpsidou, Maria Dimou, Vassilis Aschonitis, and Nikolaos Monokrousos

Subjects
coffee waste, organic matter, soil free-living nematode community, enrichment, depletion, Panagrolaimus, Agriculture
Abstract

Coffee waste is an organic material that can potentially be used in agricultural systems as an organic amendment. This study investigated the effects of the application of three concentrations of coffee waste (1%, 2%, and 4% w/v), used as an organic amendment, on soil free-living nematode communities, and in two different soil types (clay and sandy loam). Coffee waste incorporation did not appear to be toxic to the soil’s free-living nematodes; on the contrary, it favored the nematode populations; this increase was greater in the sandy loam soil type. Our results show that the abundance of the cp-1 bacteria-feeding nematodes can be used as an indicator of the soil’s enrichment or depletion phase. Panagrolaimus was the most promising genus to describe quality differentiations that occur in the soil system. Three months after coffee waste application, Panagrolaimus was found to be dominant in all coffee waste applications, indicating that the soil was in a phase of enrichment. Six months after the application, nematode community structure indices (enrichment and structure) showed that coffee waste was decomposed in the 1 and 2% treatments and that these systems were in a stage of nutrient depletion. In terms of agricultural practices, when a coffee waste dose is lesser than 4%, a second application is recommended before 6 months to avoid soil degradation.

Published
2022
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18. P051: Serum procalcitonin levels in newly diagnosed classical Hodgkin Lymphoma (cHL): Correlation with other inflammatory biomarkers

Author

Alexia Piperidou, Eleftherios Zografos, Theodoros P. Vassilakopoulos, Maria K. Angelopoulou, Georgios Hlias, Vassiliki Pappis, George Boutsikas, Maria Dimou, Kyriaki Petevi, Alexandros Kanellopoulos, Marie-Christine Kyrtsonis, and Panayiotis Panayiotidis

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2022
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19. P114: Very late relapses in patients with Hodgkin Lymphoma occuring ≥5 years after initial treament with chemotherapy ± radiotherapy: Treatment strategies and prognostic factors for the outcome

Author

Theodoros P. Vassilakopoulos, Athanasios Liaskas, Giuliana Rizzuto, Argyrios Symeonidis, Marzia Palma, Maria K. Angelopoulou, Chara Giatra, Flora Kondopidou, Maria Dimou, Alberto Musseti, Ioanna Xagoraris, Marina Siakantaris, Evgenia Verigou, Fotios Panitsas, John Asimakopoulos, Maria Arapaki, Chrysovalantou Chatzidimitriou, Marina Belia, Sotirios Sachanas, Penelope Korkolopoulou, Antonello Cabras, Eleni Variamis, Panayiotis Panayiotidis, Maria Bakiri, Themistoklis Karmiris, Georgios Z. Rassidakis, Paolo Corradini, Gerassimos Pangalis, and Simonetta Viviani

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2022
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20. Complete eradication of chronic lymphocytic leukemia with unusual skin involvement of high mitotic index after time‐limited venetoclax/obinutuzumab treatment

Author

Maria Dimou, Theodoros Iliakis, Vasileios Paradalis, Aikaterini Bitsani, Marie‐Christine Kyrtsonis, and Panayiotis Panayiotidis

Subjects
CLL/SLL, MRD negativity, skin nodules, time‐limited treatment, venetoclax, Medicine, Medicine (General), R5-920
Abstract

Abstract The novel time‐limited combinations with the bcl‐2 inhibitor venetoclax can induce deep responses even in CLL cases with unusual and biologically aggressive presentations, like the skin masses of our patient.

Published
2021
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21. Serum Procalcitonin Levels in Newly Diagnosed Hodgkin Lymphoma: Correlation with Other Inflammatory Biomarkers

Author

Alexia Piperidou, Eleftherios Zografos, Theodoros J. Vassilakopoulos, Maria K. Angelopoulou, Georgios Hillas, Vassiliki Pappis, George Boutsikas, Maria Dimou, Kyriaki Petevi, Alexandros Kanellopoulos, Marie-Christine Kyrtsonis, Panayiotis Panayiotidis, and Theodoros P. Vassilakopoulos

Subjects
procalcitonin, C-reactive protein, Hodgkin lymphoma, inflammation, Medicine (General), R5-920
Abstract

Background and Objectives: Procalcitonin (PCT) is a useful biomarker for the diagnosis of sepsis. Inflammatory markers are elevated in patients with Hodgkin lymphoma (HL), and yet ongoing infection rarely coexists at diagnosis. PCT levels might be helpful in differentiating bacterial from disease-related inflammation. Materials and Methods: We evaluated serum PCT levels and other inflammation markers in newly diagnosed HL patients. Values < 0.50 ng/mL were considered normal (0.10–0.50 ng/mL: detectable, Results: Among 137 patients, 55 had B symptoms (40%), 77/130 (59%) had elevated Erythrocyte Sedimentation Rate (ESR) and 116 (85%) had elevated C-Reactive Protein (CRP) (median 38.1 mg/L (range; 2.97–328)). PCT levels were normal in most patients (undetectable 94/137 (68.5%) and detectable 41/137(30%)) with median value < 0.10 ng/mL (range; Conclusions: This is the first study showing that the inflammation characterizing HL is not associated with PCT elevations, although CRP levels are elevated in 85% of the patients. Normal PCT levels may rule out the possibility of occult infection, thus preventing extensive evaluation, which may delay treatment initiation.

Published
2022
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22. The prognostic significance of chromosome 17 abnormalities in patients with myelodysplastic syndrome treated with 5‐azacytidine: Results from the Hellenic 5‐azacytidine registry

Author

Panagiotis Diamantopoulos, Dafni Koumbi, Ioannis Kotsianidis, Vasiliki Pappa, Argiris Symeonidis, Athanasios Galanopoulos, Panagiotis Zikos, Helen A. Papadaki, Panayiotis Panayiotidis, Maria Dimou, Eleftheria Hatzimichael, George Vassilopoulos, Susan Delimpasis, Despoina Mparmparousi, Sotirios Papageorgiou, Eleni Variami, Marie‐Christine Kyrtsonis, Aekaterini Megalakaki, Maria Kotsopoulou, Panagiotis Repousis, Ioannis Adamopoulos, Flora Kontopidou, Dimitrios Christoulas, Alexandra Kourakli, Dimitrios Tsokanas, Menelaos Konstantinos Papoutselis, Georgios Kyriakakis, Nora‐Athina Viniou, and the Hellenic MDS study group

Subjects
5‐azacytidine, chromosome 17 abnormality, myelodysplastic syndrome, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract In patients with myelodysplastic syndrome (MDS), the prognostic significance of chromosome 17 abnormalities has not yet been fully elucidated, except for isochromosome 17q that has been characterized as an intermediate risk abnormality in the Revised International Prognostic Scoring System (IPSS‐R). To further characterize the prognostic significance of chromosome 17 abnormalities we analyzed the hematologic and prognostic characteristics of 548 adult patients with MDS treated with 5‐azacytidine through the Hellenic 5‐azacytidine registry and found 32 patients with a chromosome 17 abnormality (6 with i[17q], 15 with ‐17, 3 with add[17p] and the rest with other rarer abnormalities, mostly translocations). The presence of a chromosome 17 abnormality was correlated with poor prognostic features (high IPSS, IPSS‐R, and WPSS scores) and a low overall survival rate (15.7 vs 36.4 months for patients without chromosome 17 abnormalities, Kaplan–Meier, Log Rank P

Published
2019
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23. Serum ferritin and ECOG performance status predict the response and improve the prognostic value of IPSS or IPSS-R in patients with high-risk myelodysplastic syndromes and oligoblastic acute myeloid leukemia treated with 5-azacytidine: a retrospective analysis of the Hellenic national registry of myelodysplastic and hypoplastic syndromes

Author

Sotirios G. Papageorgiou, Ioannis Kotsianidis, Anthi Bouchla, Argyris Symeonidis, Athanasios Galanopoulos, Nora-Athina Viniou, Eleftheria Hatzimichael, Theodoros P. Vassilakopoulos, Dimitrios Gogos, Aikaterini Megalakaki, Panagiotis Zikos, Panagiotis Diamantopoulos, Alexandra Kourakli, Panagiota Giannoulia, Menelaos Papoutselis, Elias Poulakidas, Maria Arapaki, Anna Vardi, Achilles Anagnostopoulos, Despoina Mparmparousi, Maria Papaioannou, Eleni Bouronikou, Maria Dimou, Helen Papadaki, Panayiotis Panayiotidis, and Vasiliki Pappa

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Background: 5-azacytidine (5-AZA) improves survival of patients with higher-risk myelodysplastic syndromes (MDSs) and oligoblastic acute myeloid leukemia (AML); however, predictive factors for response and outcome have not been consistently studied. Methods: This study of the Hellenic MDS Study Group included 687 consecutive patients with higher-risk MDS and oligoblastic AML treated with 5-AZA. Results: The International Prognostic Scoring System (IPSS) revised version (IPSS-R), Eastern Cooperative Oncology Group Performance Status (ECOG PS) (0 or 1 versus ⩾2) and baseline serum ferritin (SF) levels > 520 ng/ml were shown to independently predict response to 5-AZA. In the survival analysis, the IPSS and IPSS-R risk classification systems along with the ECOG PS and SF levels > 520 ng/ml proved to be independent prognosticators for overall survival (OS), as well as for leukemia-free survival (LFS). Next, we built new multivariate models for OS and LFS, incorporating only ECOG PS and SF levels besides IPSS or IPSS-R risk classification systems. Thereby, the new modified IPSS and IPSS-R risk classification systems (H-PSS, H-PSS-R) could each discriminate a low, an intermediate and a high-risk patient group regarding OS and LFS. The H-PSS and H-PSS-R proved to be better predictors of OS than their previous counterparts as well as the French prognostic score, while the most powerful OS predictor was the new, H-PSS-R system. Conclusions: ECOG PS and SF levels > 520 ng/ml independently predict response to 5-AZA, OS and LFS. Their incorporation in the IPSS and IPSS-R scores enhances these scores’ predictive power in 5-AZA-treated higher-risk MDS and oligoblastic AML patients.

Published
2020
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24. Physicochemical Characterization and Biological Properties of Pine Honey Produced across Greece

Author

Eleni Tsavea, Fotini-Paraskevi Vardaka, Elisavet Savvidaki, Abdessamie Kellil, Dimitrios Kanelis, Marcela Bucekova, Spyros Grigorakis, Jana Godocikova, Panagiota Gotsiou, Maria Dimou, Sophia Loupassaki, Ilektra Remoundou, Christina Tsadila, Tilemachos G. Dimitriou, Juraj Majtan, Chrysoula Tananaki, Eleftherios Alissandrakis, and Dimitris Mossialos

Subjects
honeydew, pine honey, physicochemical parameters, melissopalynology, sensory evaluation, bioactivity, Chemical technology, TP1-1185
Abstract

Pine honey is a honeydew honey produced in the East Mediterranean region (Greece and Turkey) from the secretions of the plant sucking insect Marchalina hellenica (Gennadius) (Coccoidea: Marchalini-dae) feeding on living parts of Pinus species. Nowadays, honeydew honey has attracted great attention due to its biological activities. The aim of this study was to study unifloral pine honey samples produced in Greece regarding their physicochemical parameters and antioxidant and antibacterial activity against five nosocomial and foodborne pathogens. These honeys showed physicochemical and microscopic characteristics within the legal limits, except for diastase activity, a parameter known to be highly variable, depending on various factors. Substantially higher levels of H2O2 were estimated compared to other types of honeydew honey, whereas protein content was similar. The total phenolic content was 451.38 ± 120.38 mg GAE/kg and antiradical activity ranged from 42.43 to 79.33%, while FRAP values (1.87 to 9.43 mmol Fe+2/kg) were in general higher than those reported in the literature. Various correlations could be identified among these parameters. This is the first attempt to investigate in depth the antibacterial activity of pine honey from Greece and correlate it with honey quality parameters. All tested honeys exerted variable but significant antibacterial activity, expressed as MIC and MBC values, comparable or even superior to manuka honey for some tested samples. Although honey antibacterial activity is mainly attributed to hydrogen peroxide and proteins in some cases (demonstrated by elevated MICs after catalase and Proteinase K treatment, respectively), no strong correlation between the antibacterial activity and hydrogen peroxide concentration or total protein content was demonstrated in this study. However, there was a statistically significant correlation of moisture, antioxidant and antibacterial activity against Klebsiella pneuomoniae, as well as antioxidant and antibacterial activity against Salmonella ser. Typhimurium. Interestingly, a statistically significant negative correlation has been observed between diastase activity and Staphylococcus aureus antibacterial activity. Overall, our data indicate multiple mechanisms of antibacterial activity exerted by pine honey.

Published
2022
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25. Low Bone Mineral Density and High Bone Turnover in Patients With Non-Hodgkin's Lymphoma (NHL) Who Receive Frontline Therapy: Results of a Multicenter Prospective Study

Author

Konstantinos Anargyrou, Despina Fotiou, Theodoros P. Vassilakopoulos, Dimitrios Christoulas, Polyzois Makras, Maria Dimou, Ioannis Ntanasis-Stathopoulos, Stavroula Masouridou, Maria K. Angelopoulou, Athanasios Papatheodorou, Konstantinos Tsionos, Panayiotis Panayiotidis, Meletios A. Dimopoulos, and Evangelos Terpos

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Abstract. Chemotherapy associated osteoporosis is a severe problem in patients with malignant diseases as it increases the risk for fractures and deteriorates quality of life. There are very limited data in the literature for the effect of chemotherapy on bone metabolism of adult patients with Non-Hodgkin Lymphoma (NHL). We prospectively evaluated bone remodeling pre- and post-chemotherapy in 61 patients with newly diagnosed NHL. First-line chemotherapy resulted in high bone turnover, which led to increased bone loss and reduced bone mineral density (BMD) of lumbar spine (L1-L4) and femur neck (FN). The reduction of L1-L4 and FN BMD post-chemo was more profound in males and in older patients (>55 years). Patients who received 8 cycles of chemotherapy had a greater reduction of L1-L4 and FN BMD as compared to 6 cycles. The administration of chemotherapy also resulted in a dramatic increase of bone resorption markers (CTX and TRACP-5b), bone formation markers, (bALP and Osteocalcin) and of osteoblast regulator Dickkopf-1. During study period, one patient had a pathological fracture in his right FN.

Published
2019
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26. Poor Neutralizing Antibody Responses in 132 Patients with CLL, NHL and HL after Vaccination against SARS-CoV-2: A Prospective Study

Author

Evangelos Terpos, Maria Gavriatopoulou, Despina Fotiou, Chara Giatra, Ioannis Asimakopoulos, Maria Dimou, Aimilia D. Sklirou, Ioannis Ntanasis-Stathopoulos, Ismini Darmani, Alexandros Briasoulis, Efstathios Kastritis, Maria Angelopoulou, Ioannis Baltadakis, Panayiotis Panayiotidis, Ioannis P. Trougakos, Theodoros P. Vassilakopoulos, Maria Pagoni, and Meletios A. Dimopoulos

Subjects
SARS-CoV-2, COVID-19 vaccination, BNT162b2 vaccine, chronic lymphocytic leukemia, non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Emerging data suggest suboptimal antibody responses to COVID-19 vaccination in patients with hematological malignancies. We evaluated the humoral response following the BNT162b2 vaccine in patients with chronic lymphocytic leukemia (CLL), non-Hodgkin’s lymphoma (NHL), and Hodgkin’s lymphoma (HL). An FDA-approved, ELISA-based methodology was implemented to evaluate the titers of neutralizing antibodies (NAbs) against SARS-CoV-2 on day 1 of the first vaccine, and afterwards on day 22 and 50. One hundred and thirty-two patients with CLL/lymphomas and 214 healthy matched controls vaccinated during the same period, at the same center were enrolled in the study (NCT04743388). Vaccination with two doses of the BNT162b2 vaccine led to lower production of NAbs against SARS-CoV-2 in patients with CLL/lymphomas compared with controls both on day 22 and on day 50 (p < 0.001 for all comparisons). Disease-related immune dysregulation and therapy-related immunosuppression are involved in the low humoral response. Importantly, active treatment with Rituximab, Bruton’s tyrosine kinase inhibitors, or chemotherapy was an independent prognostic factor for suboptimal antibody response. Patients with HL showed superior humoral responses to the NHL/CLL subgroups. In conclusion, patients with CLL/lymphomas have low humoral response following COVID-19 vaccination, underlining the need for timely vaccination ideally during a treatment-free period and for continuous vigilance on infection control measures.

Published
2021
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27. TACI Mutations in Primary Antibody Deficiencies: A Nationwide Study in Greece

Author

Ioannis Kakkas, Gerasimina Tsinti, Fani Kalala, Evangelia Farmaki, Alexandra Kourakli, Androniki Kapousouzi, Maria Dimou, Vassiliki Kalaitzidou, Eirini Sevdali, Athanasia-Marina Peristeri, Georgia Tsiouma, Peristera Patiou, Eleni Papadimitriou, Theodoros P. Vassilakopoulos, Panayiotis Panayiotidis, Anna Kioumi, Argiris Symeonidis, and Matthaios Speletas

Subjects
TACI, CVID, autoimmune cytopenias, benign lymphoproliferation, Medicine (General), R5-920
Abstract

Background and objectives: Monoallelic (heterozygous) or biallelic (homozygous or compound heterozygous) TACI mutations have been reported as the most common genetic defects in patients with common variable immunodeficiency (CVID), which is the most common clinically significant primary immunodeficiency in humans. The aim of our study was to evaluate the prevalence and any correlations of TACI defects in Greek patients with primary antibody deficiencies. Materials and Methods: 117 patients (male/female: 53/64) with CVID (110) and a combined IgA and IgG subclass deficiency (7) with a CVID-like clinical phenotype were enrolled in the study. Genomic DNA was extracted from peripheral blood and the molecular analysis of the TACI gene was performed by PCR (Polymerase Chain Reaction) and sequencing of all 5 exons, including exon–intron boundaries. Results: Seventeen patients (14.5%) displayed TACI defects, four (23.5%) carried combined heterozygous mutations and 13 (76.5%) carried single heterozygous mutations. The most frequently detected mutation was C104R (58.8%), followed by I87N (23.5%) and A181E (11.8%), while R20C, C62Y, P151L, K188M and E236X mutations were present in only one patient each. Patients with TACI defects were more frequently male (p = 0.011) and displayed a benign lymphoproliferation (splenomegaly and lymph node enlargement, p = 0.047 and p = 0.002, respectively), had a history of tonsillectomy (p = 0.015) and adenoidectomy (p = 0.031) and more frequently exhibited autoimmune cytopenias (p = 0.046). Conclusions: Considering that accumulating evidence suggests several CVID patients have a complex rather than a monogenic inheritance, our data further support the notion that TACI mutations, particularly as monoallelic defects, should be primarily considered as susceptibility co-factors and/or modifiers of primary antibody deficiencies.

Published
2021
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28. Thymus Citriodorus (Schreb) Botanical Products as Ecofriendly Nematicides with Bio-Fertilizing Properties

Author

Nikoletta Ntalli, Athanasia Bratidou Parlapani, Kaliopi Tzani, Maria Samara, George Boutsis, Maria Dimou, Urania Menkissoglu-Spiroudi, and Nikolaos Monokrousos

Subjects
lemon thyme, meloidogyne spp., soil microbes, soil free-living nematodes, essential oil, geraniol, Botany, QK1-989
Abstract

In recent years, interest has surged in the development of plant extracts into botanical nematicides as ecofriendly plant protection products. Aromatic plants are maybe the most studied category of botanicals used in this direction and the yielding essential oils are obtained on a commodity scale by hydro distillation. Nevertheless, can the bioactivity of aromatic plants always be attributed to the terpenes content? What would it mean for soil microcosms to bear the treatment of an essential oil to cure against Meloidogyne sp.? Are there other extraction procedures to prepare more ecofriendly botanical products starting from an aromatic material? Lemon thyme is studied herein for the first time for its nematicidal potential. We compare the efficacy of lemon thyme powder, macerate, water extract and essential oil to control Meloidogyne incognita (Chitwood) and Meloidogyne javanica (Chitwood), and we additionally study the secondary effects on soil microbes and free-living nematodes, as well as on tomato plant growth. According to our results lemon thyme powder enhances tomato plants’ growth in a dose-response manner and when it is incorporated in soil at 1 g kg−1, it exhibits nematicidal activity at a 95% level on M. incognita. The water extract yielding from the same dose is nematicidal only if it is left unfiltered; otherwise only a paralysis effect is demonstrated but inside the soil the biological cycle of the pest is not arrested. The essential oil is good both in performing paralysis and biological cycle arrest, but it detrimentally lowers abundances of bacterial and fungal feeding nematodes. On the contrary, lemon thyme powder and unfiltered water extract augments the bacterial biomass, while the latter also increases the bacterivorous nematodes. Overall, the bio fertilizing lemon thyme powder and its unfiltered water extract successfully control root knot nematodes and are beneficial to soil microbes and saprophytic nematodes.

Published
2020
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29. Co-localization of Carbonic Anhydrase and Phosphoenol-pyruvate Carboxylase and Localization of Pyruvate Kinase in Roots and Hypocotyls of Etiolated Glycine max Seedlings

Author

Panagiotis Katinakis, Emmanouil Flemetakis, Anca Paunescu, Georgios Aivalakis, and Maria Dimou

Subjects
carbonic anhydrase, Glycine max, hypocotyl, in situ hybridization, phosphoenolpyruvate carboxylase, pyruvate kinase, root, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

We investigated the presence of carbonic anhydrase in root and hypocotyl of etiolated soybean using enzymatic, histochemical, immunohistochemical and in situ hybridization approaches. In parallel, we used in situ hybridization and immunolocaliza-tion to determine the expression pattern and localization of phosphoenolpyruvate carboxylase. Their co-localization in the root tip as well as in the central cylinder, suggests that a large fraction of the CO2 may be re-introduced into C4 compounds. GmPK3 expression, coding for a cytoplasmic isoform of pyruvate kinase, was detected in all different root cell types, suggesting that both phosphoenolpyruvate-utilizing enzymes are involved in phosphoenolpyruvate metabolism in etiolated soybean roots; a case indicative of the necessary flexibility plant metabolism has to adopt in order to compensate various physiological conditions.

Published
2009
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30. Ofatumumab in poor-prognosis chronic lymphocytic leukemia: a Phase IV, non-interventional, observational study from the European Research Initiative on Chronic Lymphocytic Leukemia

Author

Carol Moreno, Marco Montillo, Panayiotis Panayiotidis, Maria Dimou, Adrian Bloor, Jehan Dupuis, Anna Schuh, Stefan Norin, Christian Geisler, Peter Hillmen, Michael Doubek, Marek Trněný, Petra Obrtlikova, Luca Laurenti, Stephan Stilgenbauer, Lukas Smolej, Paolo Ghia, Florence Cymbalista, Ulrich Jaeger, Kostas Stamatopoulos, Niki Stavroyianni, Patrick Carrington, Hamadi Zouabi, Veronique Leblond, Juan C. Gomez-Garcia, Martin Rubio, Roberto Marasca, Gerardo Musuraca, Luigi Rigacci, Lucia Farina, Rossella Paolini, Sarka Pospisilova, Eva Kimby, Colm Bradley, and Emili Montserrat

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

We report the largest retrospective, phase IV non-interventional, observational study of ofatumumab therapy in heavily pre-treated patients with poor-prognosis chronic lymphocytic leukemia. Total number of patients was 103; median age was 65 years (range 39–85). Median number of prior lines of therapy was 4 (range 1–13), including, in most cases, rituximab-, fludarabine- and alemtuzumab-based regimens; 13 patients had been allografted. Of 113 adverse events, 28 (29%) were considered to be directly related to ofatumumab. Grade 3–4 toxicities included neutropenia (10%), thrombocytopenia (5%), anemia (3%), pneumonia (17%), and fever (3%). Two heavily pre-treated patients developed progressive multifocal leukoencephalopathy. On an intention-to-treat analysis, the overall response rate was 22% (3 complete response, 1 incomplete complete response). Median progression-free and overall survival times were 5 and 11 months, respectively. This study confirms in a daily-life setting the feasibility and acceptable toxicity of ofatumumab treatment in advanced chronic lymphocytic leukemia. The complete response rate, however, was low. Therefore, treatment with ofatumumab should be moved to earlier phases of the disease. Ideally, this should be done in combination with other agents, as recently approved for ofatumumab plus chlorambucil as front-line treatment for patients unfit for fludarabine. This study is registered at clinicaltrials.gov identifier:01453062.

Published
2015
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31. Induction and Spatial Organization of Polyamine Biosynthesis During Nodule Development in Lotus japonicus

Author

Emmanouil Flemetakis, Rodica C. Efrose, Guilhem Desbrosses, Maria Dimou, Costas Delis, Georgios Aivalakis, Michael K. Udvardi, and Panagiotis Katinakis

Subjects
Microbiology, QR1-502, Botany, QK1-989
Abstract

Putrescine and other polyamines are produced by two alternative pathways in plants. One pathway starts with the enzyme arginine decarboxylase (ADC; EC 4.1.1.19), the other with ornithine decarboxylase (ODC; EC 4.1.1.17). Metabolite profiling of nitrogen-fixing Lotus japonicus nodules, using gas chromatography coupled to mass spectrometry, revealed a two- to sixfold increase in putrescine levels in mature nodules compared with other organs. Genes involved in polyamine biosynthesis in L. japonicus nodules were identified by isolating cDNA clones encoding ADC (LjADC1) and ODC (LjODC) from a nodule library. Searches of the public expressed sequence tag databases revealed the presence of a second gene encoding ADC (LjADC2). Real-time reverse-transcription-polymerase chain reaction analysis showed that LjADC1 and LjADC2 were expressed throughout the plant, while LjODC transcripts were detected only in nodules and roots. Induction of LjODC and LjADC gene expression during nodule development preceded symbiotic nitrogen fixation. Transcripts accumulation was maximal at 10 days postinfection, when a 6.5-fold increase in the transcript levels of LjODC was observed in comparison with the uninfected roots, while a twofold increase in the transcript levels of LjADC1 and LjADC2 was detected. At later stages of nodule development, transcripts for ADC drastically declined, while in the case of ODC, transcript accumulation was higher than that in roots until after 21 days postinfection. The expression profile of genes involved in putrescine biosynthesis correlated well with the expression patterns of genes involved in cell division and expansion, including a L. japonicus Cyclin D3 and an α-expansin gene. Spatial localization of LjODC and LjADC1 gene transcripts in developing nodules revealed that both transcripts were expressed in nodule inner cortical cells and in the central tissue. High levels of LjADC1 transcripts were also observed in both nodule and connecting root vascular tissue, suggesting that putrescine and other polyamines may be subject to long-distance transport. Our results indicate that polyamines are primarily involved in physiological and cellular processes involved in nodule development, rather than in processes that support directly symbiotic nitrogen fixation and assimilation.

Published
2004
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32. Lotus japonicus Gene Ljsbp Is Highly Conserved Among Plants and Animals and Encodes a Homologue to the Mammalian Selenium-Binding Proteins

Author

Emmanouil Flemetakis, Adamantia Agalou, Nektarios Kavroulakis, Maria Dimou, Anna Martsikovskaya, Andrian Slater, Herman P. Spaink, Andreas Roussis, and Panagiotis Katinakis

Subjects
Microbiology, QR1-502, Botany, QK1-989
Abstract

We have isolated and characterized a Lotus japonicus gene (Ljsbp) encoding a putative polypeptide with striking homology to the mammalian 56-kDa selenium-binding protein (SBP). cDNA clones homologous to LjSBP were also isolated from soybean, Medicago sativa, and Arabidopsis thaliana. Comparative expression studies in L. japonicus and A. thaliana showed that sbp transcripts are present in various tissues and at different levels. Especially in L. japonicus nodules and seedpods and A. thaliana siliques, sbp expression appears to be developmentally up-regulated. sbp Gene transcripts were localized by in situ hybridization in the infected cells and vascular bundles of young nodules, while in mature nodules, low levels of expression were only detected in the parenchymatous cells. Expression of sbp transcripts in young seedpods and siliques was clearly visible in vascular tissues and embryos, while in embryos, low levels of expression were detected in the root epidermis and the vascular bundles. Polyclonal antibodies raised against a truncated LjSBP recombinant protein recognized a poly-peptide of about 60 kDa in nodule extracts. Immunohistochemical experiments showed that accumulation of LjSBP occurred in root hairs, in the root epidermis above the nodule primordium, in the phloem of the vasculature, and abundantly in the infected cells of young nodules. Irrespective of the presence of rhizobia, expression of SBP was also observed in root tips, where it was confined in the root epidermis and protophloem cells. We hypothesize that LjSBP may have more than one physiological role and can be implicated in controlling the oxidation/reduction status of target proteins, in vesicular Golgi transport, or both.

Published
2002
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33. The nitrogen-fixation island insertion site is conserved in diazotrophic Pseudomonas stutzeri and Pseudomonas sp. isolated from distal and close geographical regions.

Author

Anastasia Venieraki, Maria Dimou, Eleni Vezyri, Alexandros Vamvakas, Pagona-Artemis Katinaki, Iordanis Chatzipavlidis, Anastasia Tampakaki, and Panagiotis Katinakis

Subjects
Medicine, Science
Abstract

The presence of nitrogen fixers within the genus Pseudomonas has been established and so far most isolated strains are phylogenetically affiliated to Pseudomonas stutzeri. A gene ortholog neighborhood analysis of the nitrogen fixation island (NFI) in four diazotrophic P. stutzeri strains and Pseudomonas azotifigens revealed that all are flanked by genes coding for cobalamin synthase (cobS) and glutathione peroxidise (gshP). The putative NFIs lack all the features characterizing a mobilizable genomic island. Nevertheless, bioinformatic analysis P. stutzeri DSM 4166 NFI demonstrated the presence of short inverted and/or direct repeats within both flanking regions. The other P. stutzeri strains carry only one set of repeats. The genetic diversity of eleven diazotrophic Pseudomonas isolates was also investigated. Multilocus sequence typing grouped nine isolates along with P. stutzeri and two isolates are grouped in a separate clade. A Rep-PCR fingerprinting analysis grouped the eleven isolates into four distinct genotypes. We also provided evidence that the putative NFI in our diazotrophic Pseudomonas isolates is flanked by cobS and gshP genes. Furthermore, we demonstrated that the putative NFI of Pseudomonas sp. Gr65 is flanked by inverted repeats identical to those found in P. stutzeri DSM 4166 and while the other P. stutzeri isolates harbor the repeats located in the intergenic region between cobS and glutaredoxin genes as in the case of P. stutzeri A1501. Taken together these data suggest that all putative NFIs of diazotrophic Pseudomonas isolates are anchored in an intergenic region between cobS and gshP genes and their flanking regions are designated by distinct repeats patterns. Moreover, the presence of almost identical NFIs in diazotrophic Pseudomonas strains isolated from distal geographical locations around the world suggested that this horizontal gene transfer event may have taken place early in the evolution.

Published
2014
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34. TYROSINE KINASE INHIBITORS AND INTERFERON

Author

Maria Dimou and Panagiotis Panagiotidis

Subjects
tyrosine kinase inhibitors, interferon-alpha, chronic myeloid leukemia, pegylated interferon alpha, treatment discontinuation, Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

The use of interferon-a (INF) in chronic myeloid leukemia, when it started in the 80s, was considered as a breakthrough in the therapy of this disease; INF administered alone or in combination with aracytine was the standard choice for treatment for Chronic Myeloid Leukemia (CML) patients unfit for bone marrow transplantation. With the appearance of the first Tyrosine Kinase Inhibitor (TKI) (imatinib) and based on the results of the pivotal IRIS trial, imatinib monotherapy was the new treatment of choice for CML, according to the ELN recommendations. The possibility of combining INF with imatinib, for obtaining better therapeutic responses in CML patients has been already tested and reported. The current challenge is the combined use of second generation TKIs with pegylated –IFN, in order to minimize failures to therapy and increase the number of CML patients with deep molecular responses, who may be able to discontinue lifelong treatment.

Published
2014
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35. Lotus japonicus Contains Two Distinct ENOD40 Genes That Are Expressed in Symbiotic, Nonsymbiotic, and Embryonic Tissues

Author

Emmanouil Flemetakis, Nektarios Kavroulakis, Nicolette E. M. Quaedvlieg, Herman P. Spaink, Maria Dimou, Andreas Roussis, and Panagiotis Katinakis

Subjects
nodule organogenesis, symbiosis, Microbiology, QR1-502, Botany, QK1-989
Abstract

ENOD40, an early nodulin gene, has been postulated to play a significant role in legume root nodule ontogenesis. We have isolated two distinct ENOD40 genes from Lotus japonicus. The transcribed regions of the two ENOD40 genes share 65% homology, while the two promoters showed no significant homology. Both transcripts encode a putative dodecapeptide similar to that identified in other legumes forming determinate nodules. Both ENOD40 genes are coordinately expressed following inoculation of roots with Mesorhizobium loti or treatment with purified Nod factors. In the former case, mRNA accumulation could be detected up to 10 days following inoculation while in the latter case the accumulation was transient. High levels of both ENOD40 gene transcripts were found in nonsymbiotic tissues such as stems, fully developed flowers, green seed pods, and hypocotyls. A relatively lower level of both transcripts was observed in leaves, roots, and cotyledons. In situ hybridization studies revealed that, in mature nodules, transcripts of both ENOD40 genes accumulate in the nodule vascular system; additionally, in young seed pods strong signal is observed in the ovule, particularly in the phloem and epithelium, as well as in globular stage embryos.

Published
2000
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36. Prognostic Significance of Serum Free Light Chains in Chronic Lymphocytic Leukemia

Author

Katerina Sarris, Dimitrios Maltezas, Efstathios Koulieris, Vassiliki Bartzis, Tatiana Tzenou, Sotirios Sachanas, Eftychia Nikolaou, Anna Efthymiou, Katerina Bitsani, Maria Dimou, Theodoros P. Vassilakopoulos, Marina Siakantaris, Maria K. Angelopoulou, Flora Kontopidou, Panagiotis Tsaftaridis, Nikolitsa Kafasi, Gerasimos A. Pangalis, Panayiotis P. Panayiotidis, Stephen Harding, and Marie-Christine Kyrtsonis

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Background. Serum free light chains (sFLC), the most commonly detected paraprotein in CLL, were recently proposed as useful tools for the prognostication of CLL patients. Objective. To investigate the prognostic implication of sFLC and the summated FLC-kappa plus FLC-lambda in a CLL patients’ series. Patients and Methods. We studied 143 CLL patients of which 18 were symptomatic and needed treatment, while 37 became symptomatic during follow-up. Seventy-two percent, 18%, and 10% were in Binet stage A, B and C, respectively. Median patients’ followup was 32 months (range 4–228). Results. Increased involved (restricted) sFLC (iFLC) was found in 42% of patients, while the summated FLC-kappa plus FLC-lambda was above 60 mg/dL in 14%. Increased sFLC values as well as those of summated FLC above 60 were related to shorter time to treatment (P=0.0005 and P=0.000003, resp.) and overall survival (P=0.05 and P=0.003, resp.). They also correlated with β2-microglobulin (P=0.009 and P=0.03, resp.), serum albumin (P=0.009 for summated sFLC), hemoglobin (P

Published
2013
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37. Real-world evidence on therapeutic strategies and treatment-sequencing in patients with chronic lymphocytic leukemia: an international study of ERIC, the European research initiative on CLL [Abstract]

Author

Luana Schiattone, Michel van Gelder, Jana Zuchnická, Viola Maria Popov, Rosa Collado, Candida Vitale, Marta Coscia, Gloria Iacoboni, Marta Morawska, Amy Christian, Darko Antic, Vojin Vukovic, Jorge Labrador, Elżbieta Kalicińska, Marek Trněný, Anna Puiggros, Biljana Mihaljevic, Gian Matteo Rigolin, Ioannis Kotsianidis, Dimitra Chammou, Francesca Bacchiarri, Alberto Fresa, Niki Stavroyianni, Sara Galimberti, Alicia Enrico, Lydia Scarfò, David Donaldson, Jacopo Olivieri, Cheyenne Pierie, Irina Panovska, Tamar Tadmor, Maria Papaioannou, Kostas Stamatopoulos, Christos Demosthenous, Mohamed A. Yassin, Olga Kalashnikova, Fatih Demirkan, Yair Herishanu, Livio Trentin, Theodoros P. Vassilakopoulos, Volkan Karakuş, Alessandro Gozzetti, Almudena Navarro-Bailón, Maya Koren-Michowitz, Carlota Mayor-Bastida, Eric Tse, Šárka Pospíšilová, Lucrecia Yáñez, Georgios Karakatsoulis, Roberta Murru, Martin Spacek, Rocío García-Serra, Susanne R. Janssen, Robert J. Kreitman, Michael Doubek, Valerio Guarente, Eugene Nikitin, Uttam Kumar Nath, Anastasia Chatzidimitriou, Iliana Konstantinou, Arnon P. Kater, Ivana Milosevic, Annett Schiwitza, Martin Simkovic, Romain Guièze, Zhenshu Xu, Andrea Visentin, Stanislava Maslejova, Rosa Ruchlemer, Ömür Gökmen Sevindik, Gimena Dos Santos, Alberto Lopez-Garcia, Thomas Chatzikonstantinou, Francesc Bosch Albareda, Miguel Alcoceba, E. Minga, Eleftheria Hatzimichael, Elisa Albi, Lukas Smolej, Gianluca Gaidano, Rainer Claus, Antonio Cuneo, Kamel Laribi, Ramona Cassin, Michalis Iskas, Jana Kotašková, Panayiotis Panayiotidis, Tomas Papajik, Ozren Jakšić, Fatima Miras, Paolo Ghia, Maria Efstathopoulou, Luca Inchiappa, Bonnie Kho, Marcos Daniel De Deus Santos, Barbara Dreta, Constantine S. Tam, George Vrachiolias, Münci Yağcı, Blanca Espinet, B V Biderman, Stephen P. Mulligan, Zadie Davis, Svetlana Smirnova, David Oscier, Juan Marquet Palomanes, Liat Tourjeman, Sofia Chatzileontiadou, Maria Dimou, Riccardo Moia, Isabel González-Gascón y Marín, Anne Calleja, Kristina Tomic, Ilana Levy, Mehreen Ali Khan, Gerasimos Pangalis, Sean Harrop, Thérèse Aurran, Paolo Sportoletti, Dina Sameh Soliman, Shaimaa El-Ashwah, Maria K. Angelopoulou, Gianluigi Reda, Fatiha Merabet, Yandong Shen, Mark Catherwood, Luca Laurenti, Thomas Longval, and Deepesh Lad

Subjects
Oncology, 0303 health sciences, medicine.medical_specialty, business.industry, Chronic lymphocytic leukemia, European research, Immunology, Cell Biology, Hematology, medicine.disease, Real world evidence, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, In patient, ddc:610, business, 030304 developmental biology, 030215 immunology
Abstract

The use of novel small molecule inhibitors alone or in combination with anti-CD20 monoclonal antibodies for chronic lymphocytic leukemia (CLL) has raised a number of questions on efficacy, tolerability, long-term treatment adherence in patients with heterogeneous clinical features. To fill this gap, we designed a study focusing on treatment sequencing in patients with CLL in order to (i) compare the outcome of patients treated with chemoimmunotherapy (CIT) combinations in first-line versus those receiving Bruton's tyrosine kinase inhibitors (BTKi); (ii) characterize the efficacy and tolerability of venetoclax-based regimens; (ii) understand the impact of treatment sequencing when it comes to chemo-free options including venetoclax after BTKi and vice versa. Data from consecutive sets of patients diagnosed with CLL between 2000-2020 attended at 77 institutions affiliated with ERIC were collected and analyzed. Collected variables included: demographics, clinical stage at diagnosis, IGHV gene somatic hypermutation status; cytogenetic status for chromosomes 11q, 13q 17p and 12 determined by fluorescence in situ hybridization; TP53 gene mutation status; treatment; treatment response; discontinuation; reason for discontinuation; death. We included 9173 patients with a diagnosis of CLL who received at least one line of treatment. The median age at diagnosis was 67 years with a male:female ratio of 1.9. The median follow-up was 78 months (IQR, 48-120 months). Regarding novel targeted agents, 1860/9173 (20.2%) patients had received at least one line of treatment with BTKi (ibrutinib, n=1788; acalabrutinib, n=72) over the disease course; 631/9173 (6.9%) with venetoclax; and, 447/9173 (4.9%) with the PI3K inhibitor idelalisib. Seventy-nine patients were treated with both BTKi and venetoclax (59 BTKi followed by BCL2i, 20 vice versa). At last follow-up, 5870/9173 patients (64.0%) were alive, 3229/9173 (35.2%) died and 74/9173 (0.8%) were lost to follow-up. Patients treated with BTKi in first-line were enriched for TP53 aberrations [del(17p) 27.6%, TP53 mutation 26.3%] and unmutated IGHV genes (69%) and obtained an ORR of 87.7%. Of these, 136 (26.3%) discontinued treatment after a median of 1.2 years (0.07-5.98); main reasons of discontinuation were toxicity (40.5%) and failure (26.2%). Among 631 patients treated with venetoclax at any line, 100 (15.8%) received BCL2 +/- anti-CD20 as first-line; 170 (26.9%) as second line (125 previously treated with CIT, 27 with BTKi); and, 361 as third or subsequent line. ORR ranged between 71.5% (≥3 lines) with 30.5% CR/CRi to 90.3% (first-line) with 68.1% CR/CRi. Treatment discontinuation was due to toxicity in 28.6% of patients treated in the first-line, and 17.6% and 21.8% of patients treated in second and third-or-higher-line, respectively. Disease progression led to treatment discontinuation in 14.3%, 20.6% and 33.6% in first, second and third-or-higher line, respectively. CIT was used as front-line treatment in 5465 patients (59.6%). Of these, 2070 (37.9%) and 1018 (18.6%) patients received a second and third line of treatment, respectively. The great majority (865/1086 cases, 79.7%) of patients who received a second line before 2014 were retreated with CIT, most commonly Bendamustine-Rituximab (284/1086, 26.1%) and Fludarabine-Cyclophosphamide-Rituximab (252/1086, 23.2%); alemtuzumab monotherapy was used in 55/1086 (5%) of patients. After 2014, 415/984 patients (42.1%) were retreated with BTKi; 93 (9.5%) with venetoclax; 70 (7.2%) with idelalisib; 50 (5%) with Alemtuzumab monotherapy, and 315 (32%) with CIT. Similarly, in the third-or-higher line of treatment, most patients (86.3%) were retreated with CIT before 2014, while BTKi, BCL2i, and PI3Ki were mainly used after 2014 (in 43.1%, 15.7% and 14.7% of cases, respectively). Finally, our cohort included 1075 patients with TP53 aberrations. The ORR of patients receiving BTKis (n=171) as first-line of treatment was 86.5% (22.2 CR+64.3 PR), while the ORR with venetoclax +/- anti-CD20 (n=15) was 91% (45.5% CR+45.5 PR). Patients treated with CIT (n=694) had an ORR of 68.7% (28.3% CR+40.4% PR). In conclusion, in a large international study we provide real world data regarding the selection and sequencing of treatment in CLL, charting a major shift in treatment patterns before and after the introduction of novel trargeted agents and confirming their efficacy even in high-risk CLL. Disclosures Scarfo: Janssen: Honoraria, Other: Travel grants; Astra Zeneca: Honoraria; Abbvie: Honoraria. Iacoboni: BMS/Celgene, Gilead, Novartis, Janssen, Roche: Honoraria. Collado: Abbvie,: Other: pharmaceutical Company, Research Funding; Janssen: Other: Pharmaceutical Company, Research Funding. Galimberti: AbbVie, Janssen: Honoraria, Other: Travel grants; Incyte: Speakers Bureau. García-Serra: AbbVie: Other: Educational grands; Janssen: Other: Educational grants; Novartis: Other: Educational grants. Gozzetti: Janssen: Honoraria; AbbVie: Honoraria. Hatzimichael: Amgen, Roche, Genesis, Novartis, Bristol Mayer Squibb, Celgene, Pfizer: Consultancy; Abbvie, Amgen, Bristol Mayer Squibb, MSD, Gilead, Janssen Cilag, Genesis Pharma, Roche, Takeda: Honoraria. Herishanu: AbbVie: Honoraria, Research Funding; Janssen: Honoraria; Roche: Honoraria; Medison: Honoraria. Jaksic: Roche, Oktal-Pharma/Celtrion, Sandoz: Consultancy, Honoraria. Kater: Janssen, AstraZeneca: Other: Ad Board, steering committee, Research Funding; Abbvie: Honoraria, Other: Ad Board, Research Funding; BMS, Roche/Genentech: Other: Ad Board, , Research Funding; Genmab, LAVA: Other: Ad Board, Steering Committee. Kotsianidis: Astellas: Other: NONE, Research Funding, Speakers Bureau; Genesis: Consultancy, Other: NONE; Janssen Hellas: Consultancy, Other: NONE, Speakers Bureau; Bristol Hellas: Consultancy, Other: NONE, Research Funding, Speakers Bureau; Novartis Hellas: Consultancy, Other: NONE, Research Funding, Speakers Bureau; Abbvie: Consultancy, Other: NONE, Research Funding, Speakers Bureau. Kreitman: NIH: Patents & Royalties: Moxetumomab Pasudotox; Genentech: Research Funding; Teva: Research Funding; AstraZeneca/MedImmune: Research Funding; Innate: Research Funding; GSK/Novartis: Research Funding; Array BioPharma/Pfizer: Research Funding. Laribi: BeiGene: Other: Personal Fees; Jansen: Research Funding; Novartis: Other: Personal Fees, Research Funding; Astellas Phama, Inc.: Other: Personal Fees; AstraZeneca: Other: Personal Fees; Le Mans Hospital: Research Funding; Takeda: Other: Personal Fees, Research Funding; AbbVie: Other: Personal Fees, Research Funding; IQONE: Other: Personal Fees. Lopez-Garcia: Roche: Other: Speaker Honoraria, Travel and accommodation grants; Novonordisk: Other: Speaker Honoraria; Fresenius: Other: Speaker Honoraria; Celgene: Other: Speaker Honoraria; Abbvie: Other: Speaker Honoraria, Advisor, Travel and accommodation grants; Janssen: Other: Speaker Honoraria, Advisor, Travel and accommodation grants, Research Funding. Milosevic: Roche: Honoraria; Abbvie,: Honoraria; Janssen: Honoraria; Sandoz: Honoraria. Reda: Beigene: Consultancy; Astra Zeneca: Consultancy; Abbvie: Consultancy; Janssen: Consultancy. Ruchlemer: AbbVie: Consultancy, Honoraria, Research Funding. Šimkovič: Janssen, Gilead, Roche, AstraZeneca, and AbbVie: Other: consultancy fees, advisory board participation fees, travel grants, and honoraria; University Hospital Hradec Kralove: Current Employment; AbbVie: Consultancy, Current equity holder in publicly-traded company, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses; Merck: Current equity holder in publicly-traded company; Eli Lilly: Current equity holder in publicly-traded company; J&J: Current equity holder in publicly-traded company; Gilead: Other: Travel, Accommodations, Expenses. Špaček: AbbVie, AstraZeneca, Gilead, Janssen, and Roche: Honoraria. Tadmor: Janssen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding. Visentin: Italfarmaco and Gilead: Speakers Bureau. Vassilakopoulos: AstraZeneca: Honoraria; Amgen: Honoraria, Research Funding; Pfizer: Research Funding; Dr. Reddy's: Research Funding; Novartis: Consultancy, Honoraria; GlaxoSmithKline: Honoraria, Other: Travel; Merck: Honoraria, Research Funding; Integris: Honoraria; Roche: Consultancy, Honoraria, Other: Travel; Genesis Pharma: Consultancy, Honoraria, Other: Travel; Takeda: Consultancy, Honoraria, Other: Travel, Research Funding; AbbVie: Consultancy, Honoraria; Karyopharm: Research Funding. Vitale: Janssen: Honoraria. Yáñez: Gilead-Kite, Janssen, AbbVie, AstraZeneca, Beigene, Roche, Pfizer, Jazz, BMS, and Merck: Other: Advisory board participation fees ; Janssen, AbbVie, AstraZeneca, Gilead-Kite, Roche, Pfizer, and Merck: Speakers Bureau. Antic: AbbVie, Janssen, and Roche: Honoraria. Coscia: Janssen: Honoraria, Other, Research Funding; Gilead: Honoraria; AstraZeneca: Honoraria; AbbVie: Honoraria, Other. Cuneo: AstraZeneca: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; AbbVie: Consultancy, Speakers Bureau. Gaidano: Beigene: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astrazeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Guièze: Janssen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria; Astrazeneca: Consultancy, Honoraria. Laurenti: AstraZeneca: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding; Roche: Honoraria, Research Funding; Gilead: Honoraria; Janssen: Consultancy, Honoraria; BeiGene: Honoraria. Murru: Abbvie: Consultancy, Honoraria, Other: travel and accommodation; Janssen: Consultancy, Honoraria. Sportoletti: AstraZeneca: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Tam: Beigene: Research Funding; Janssen: Research Funding; Abbvie: Research Funding; Loxo: Honoraria; Beigene: Honoraria; Janssen: Honoraria; Abbvie: Honoraria. Trněný: Amgen: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Gilead Sciences: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; MorphoSys: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Celgene: Consultancy; 1st Faculty of Medicine, Charles University, General Hospital in Prague: Current Employment; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Portola: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses. Bosch Albareda: Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria; Abbvie: Consultancy; AstraZeneca: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Kite: Honoraria; Sanofi: Honoraria; Lilly: Honoraria. Doubek: Janssen-Cilag, AbbVie, AstraZeneca, Amgen, Gilead, Novartis: Honoraria, Research Funding. Chatzidimitriou: Abbvie: Honoraria, Research Funding; Janssen: Honoraria, Research Funding. Ghia: AbbVie: Consultancy, Honoraria, Research Funding; Acerta/AstraZeneca: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding; ArQule/MSD: Consultancy, Honoraria; BeiGene: Consultancy, Honoraria; Celgene/Juno/BMS: Consultancy, Honoraria; Gilead: Consultancy, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria; Sunesis: Research Funding. Stamatopoulos: AstraZeneca: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; Gilead: Honoraria, Research Funding; Janssen: Honoraria, Research Funding.

Published
2022

38. Real-life Experience With Rituximab-CHOP Every 21 or 14 Days in Primary Mediastinal Large B-cell Lymphoma

Author

STAMATIS J. KARAKATSANIS, MARIA BOUZANI, ARGYRIS SYMEONIDIS, MARIA K. ANGELOPOULOU, SOTIRIOS G. PAPAGEORGIOU, MICHAIL MICHAIL, GABRIELLA GAINARU, GEORGIA KOURTI, SOTIRIOS SACHANAS, CHRISTINA KALPADAKIS, EIRINI KATODRITOU, THEONI LEONIDOPOULOU, IOANNIS KOTSIANIDIS, ELEFTHERIA HATZIMICHAEL, MARIA KOTSOPOULOU, MARIA DIMOU, ELENI VARIAMIS, DIMITRIOS BOUTSIS, NICK KANELLIAS, MARIA N. DIMOPOULOU, EVRIDIKI MICHALI, GEORGE KARIANAKIS, PANTELIS TSIRKINIDIS, CHRYSSA VADIKOLIA, CHRISTOS POZIOPOULOS, ANNA PIGADITOU, EFFIMIA VRAKIDOU, THEOPHANIS ECONOMOPOULOS, LYDIA KYRIAZOPOULOU, MARINA P. SIAKANTARIS, MARIE-CHRISTINE KYRTSONIS, KONSTANTINOS ANARGYROU, MARIA PAPAIOANNOU, EVDOXIA HATJIHARISSI, ELISSAVET VERVESSOU, MARIA TSIROGIANNI, MARIA PALASSOPOULOU, EKATERINI STEFANOUDAKI, PANAYIOTIS ZIKOS, PANAYIOTIS TSIRIGOTIS, GERASSIMOS TSOUROUFLIS, THEODORA ASSIMAKOPOULOU, EVGENIA VERROU, HELEN PAPADAKI, POLIXENI LAMPROPOULOU, MELETIOS-ATHANASIOS DIMOPOULOS, VASSILIKI PAPPA, KOSTAS KONSTANTOPOULOS, THEMIS KARMIRIS, PARASKEVI ROUSSOU, PANAYIOTIS PANAYIOTIDIS, GERASSIMOS A. PANGALIS, and THEODOROS P. VASSILAKOPOULOS

Subjects
Pharmacology, Cancer Research, Lymphoma, B-Cell, General Biochemistry, Genetics and Molecular Biology, immune system diseases, Doxorubicin, Vincristine, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, Humans, Prednisone, Prospective Studies, Rituximab, Cyclophosphamide, Research Article, Retrospective Studies
Abstract

Background/Aim: Primary mediastinal large B-cell lymphoma (PMLBCL) is an aggressive B-cell non-Hodgkin lymphoma (NHL), whose prognosis has greatly improved since the incorporation of the anti-CD20 monoclonal antibody rituximab into current therapeutic regimens. Evidence, however, on the optimal time interval between consecutive chemoimmunotherapy (CIT) cycles is still scarce. This study aimed to evaluate the efficacy outcomes of the more commonly administered 3-weekly regimens to the biweekly ones in a PMLBCL patients’ population, who were mostly treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone every 21 days (R-CHOP-21) or R-CHOP-14. Patients and Methods: We retrospectively studied our cohort of consecutively treated PMLBCL patients, focusing on their treatment density, in order to determine possible differences in treatment outcomes. Results: CIT, in the form of both R-CHOP-21 as well as R-CHOP-14 (or similar regimens), is highly active in PMLBCL, with low rates of early treatment failure. In our cohort of patients, R-CHOP-14 did not result in a meaningful improvement of freedom from progression (FFP) or overall survival (OS). Conclusion: Both R-CHOP-14 and R-CHOP-21 are probably equally effective in PMLBCL, yet further, prospective, randomized studies are warranted to clarify whether dose-dense regimens can be associated with better disease control and long-term results.

Published
2022

39. Refinement of prognosis and the effect of azacitidine in intermediate-risk myelodysplastic syndromes

Author

Vasileios Papadopoulos, Charalambos Pontikoglou, Panagiotis Zikos, Argiris Symeonidis, Eleftheria Hatzimichael, Panayiotis Panayiotidis, Maria Papaioannou, Konstantinos Liapis, Maria Ximeri, Dimitris Τsokanas, Anna Vardi, Nora-Athina Viniou, Theodoros P. Vassilakopoulos, Flora N. Kontopidou, Stamatis Karakatsanis, Eleni Bouronikou, Nikolaos Harchalakis, Ioannis Adamopoulos, Sotirios G. Papageorgiou, Menelaos Papoutselis, Aekaterini Megalakaki, George Vrachiolias, Ioannis Kotsianidis, Alexandra Kourakli, Vassiliki Pappa, Athanasios Galanopoulos, Maria Dimou, and Panagiotis T. Diamantopoulos

Subjects
Adult, Male, Oncology, Antimetabolites, Antineoplastic, medicine.medical_specialty, Azacitidine, MEDLINE, lcsh:RC254-282, Text mining, Risk Factors, Internal medicine, Correspondence, medicine, Humans, Aged, Aged, 80 and over, business.industry, Myelodysplastic syndromes, Hematology, Translational research, Middle Aged, Prognosis, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Survival Analysis, Myelodysplastic Syndromes, Female, business, Intermediate risk, Myelodysplastic syndrome, Follow-Up Studies, medicine.drug
Published
2021

40. Outcomes of patients with chronic myelomonocytic leukaemia treated with non-curative therapies

Author

Klaus Geissler, Athina-Nora Viniou, Blanca Xicoy Cirici, Peter Valent, Alexandra Kourakli, Ulrich Germing, Jennifer Kaivers, Christoforos Roubakis, Johanna Ungerstedt, Lisa Pleyer, Guillermo Sanz, Sonja Heibl, Mikkael A. Sekeres, Maria Julia Montoro, Bhumika J. Patel, Marisa Calabuig Muñoz, Anthony M. Hunter, Eric Padron, Jaroslav Cermak, Peristera Patiou, Nicolas Bonadies, Teresa Bernal del Castillo, Jaroslaw P. Maciejewski, Antonio Almeida, Eva Hellstroem-Lindberg, Richard Greil, Andres Jerez, Alejandro Avendaño Pita, Elvira Mora, Alexander Egle, Athanasios Galanopoulos, Montserrat Arnan, Alan F. List, B. Andrade, Maria Dimou, Argiris Symeonidis, Maria-José Jimenez Lorenzo, Albert Cortés, Julian Larcher-Senn, Thomas Melchardt, and Michael Leisch

Subjects
Male, medicine.medical_specialty, Antineoplastic Agents, Disease, Time to next treatment, Kaplan-Meier Estimate, Myelomonocytic leukaemia, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, hemic and lymphatic diseases, medicine, Humans, Hydroxyurea, 610 Medicine & health, Aged, Proportional Hazards Models, Retrospective Studies, business.industry, Myelodysplastic syndromes, Hazard ratio, Retrospective cohort study, Leukemia, Myelomonocytic, Chronic, Hematology, Middle Aged, medicine.disease, Prognosis, medicine.anatomical_structure, Treatment Outcome, 030220 oncology & carcinogenesis, Azacitidine, Female, Bone marrow, Myeloid leukaemia, business, 030215 immunology
Abstract

BACKGROUND: Approval of hypomethylating agents in patients with chronic myelomonocytic leukaemia is based on trials done in patients with myelodysplastic syndromes. We aimed to investigate whether hypomethylating agents provide a benefit in subgroups of patients with chronic myelomonocytic leukaemia compared with other treatments. METHODS: For this retrospective cohort study, data were retrieved between Nov 30, 2017, and Jan 5, 2019, from 38 centres in the USA and Europe. We included non-selected, consecutive patients diagnosed with chronic myelomonocytic leukaemia, who received chronic myelomonocytic leukaemia-directed therapy. Patients with acute myeloid leukaemia according to 2016 WHO criteria at initial diagnosis (ie, =20% blasts in the bone marrow or peripheral blood) or with unavailability of treatment data were excluded. Outcomes assessed included overall survival, time to next treatment, and time to transformation to acute myeloid leukaemia. Analyses were adjusted by age, sex, platelet count, and Chronic myelomonocytic leukaemia-Specific Prognostic Scoring System (CPSS). Patients were grouped by first received treatment with either hydroxyurea, hypomethylating agents, or intensive chemotherapy, and stratified by risk according to blast count, French-American-British subtype, CPSS, WHO 2016 subtype, and the eligibility criteria of the DACOTA trial (NCT02214407). FINDINGS: 949 patients diagnosed with chronic myelomonocytic leukaemia between April 13, 1981, and Oct 26, 2018, were included. Median follow-up was 23·4 months (IQR 11·5-42·3) from diagnosis and 16·2 months (6·6-31·6) from start of first-line treatment. 412 (43%) of 949 patients received hypomethylating agents as first treatment, 391 (41%) hydroxyurea, and 83 (9%) intensive chemotherapy. Adjusted median overall survival for patients treated with hydroxyurea versus hypomethylating agents was 15·6 months (95% CI 13·1-17·3) versus 20·7 months (17·9-23·4); hazard ratio (HR) 1·39 (1·17-1·65; p=0·0002) and 14·0 months (9·8-17·2) versus 20·7 months (17·9-23·4; HR 1·55 [1·16-2·05]; p=0·0027) for those treated with intensive chemotherapy versus hypomethylating agents. In patients with myeloproliferative chronic myelomonocytic leukaemia (myeloproliferative CMML), median overall survival was 12·6 months (10·7-15·0) versus 17·6 months (14·8-21·5; HR 1·38 [1·12-1·70]; p=0·0027) for patients treated with hydroxyurea versus hypomethylating agents, and 12·3 months (8·4-16·6) versus 17·6 months (14·8-21·5; HR 1·44 [1·02-2·03]; p=0·040) for intensive chemotherapy versus hypomethylating agents. Hypomethylating agents did not confer an overall survival advantage for patients classified as having lower-risk disease (ie, myelodysplastic chronic myelomonocytic leukaemia with

Published
2021

41. COVID-19 severity and mortality in patients with CLL: an update of the international ERIC and Campus CLL study

Author

Ellen van der Spek, Emili Montserrat, Talha Munir, Paolo Ghia, Shaimaa El-Ashwah, Andreas Glenthøj, Viola Maria Popov, Sanne H. Tonino, Ann Janssens, Michel van Gelder, Lara Malerba, Rocío García-Serra, Alberto Lopez-Garcia, Juan-Gonzalo Correa, Christos Demosthenous, Idanna Innocenti, Maria Papaioannou, Lydia Scarfò, Antonio Cuneo, Francesca Romana Mauro, Sabina Kersting, Robin Foà, David Donaldson, Livio Trentin, Roberta Murru, Panagiotis Baliakas, Marina Motta, Deepesh Lad, Yervand K Hakobyan, Paolo Sportoletti, Lucrecia Yáñez San Segundo, Alicia Enrico, Elżbieta Kalicińska, Ewa Wasik-Szczepanek, Martin Spacek, Tamar Tadmor, Enrico Lista, Roel van Kampen, Lorella Orsucci, Michael Doubek, Yair Herishanu, Blanca Espinet, Jose Angel Hernandez-Rivas, Inga Piskunova, Ozren Jakšić, Georgios Karakatsoulis, Tomasz Wróbel, Oana Stanca, Luca Laurenti, Martin Andres, Roberto Marasca, Mark-David Levin, Giovanni Del Poeta, Miguel Arturo Pavlovsky, Maria Dimou, Monia Marchetti, Ivana Milosevic, Gianluigi Reda, Tobias Herold, David Allsup, Raul Cordoba, Andrea Visentin, Maria Gomes da Silva, Angela Ferrari, Antonella Capasso, Juan Marquet, Francesca Maria Quaglia, Candida Vitale, Mattias Mattsson, Marta Coscia, Moritz Fürstenau, Lucia Farina, Niki Stavroyianni, Marta Morawska, Arnon P. Kater, Mónica Baile, Gevorg Saghumyan, Carolina Cuéllar-García, Jacopo Olivieri, Darko Antic, Raquel Nunes Rodrigues, Alejandro Alonso Cabrero, Henrik Frederiksen, Alessandro Rambaldi, Marzia Varettoni, Amit Shrestha, Оlga B Kalashnikova, Thomas Chatzikonstantinou, José A. García-Marco, Martin Simkovic, Linda Katharina Karlsson, Odit Gutwein, Mohamed A. Yassin, Rosa Ruchlemer, Eva Gimeno, Kristian Qvist, Fatima Miras, Gilad Itchaki, Maria Rosaria De Paolis, Maria Efstathopoulou, Doreen te Raa, Barbara Eichhorst, Dominique Bron, Jorge Labrador, Gian Matteo Rigolin, Myriam Foglietta, Massimo Gentile, Sofia Chatzileontiadou, Carsten Utoft Niemann, Anargyros Kapetanakis, Kostas Stamatopoulos, Lorenzo De Paoli, Giulia Quaresmini, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Interne Geneeskunde, MUMC+: MA Hematologie (9), Chatzikonstantinou, T., Kapetanakis, A., Scarfo, L., Karakatsoulis, G., Allsup, D., Cabrero, A. A., Andres, M., Antic, D., Baile, M., Baliakas, P., Bron, D., Capasso, A., Chatzileontiadou, S., Cordoba, R., Correa, J. -G., Cuellar-Garcia, C., De Paoli, L., De Paolis, M. R., Del Poeta, G., Demosthenous, C., Dimou, M., Donaldson, D., Doubek, M., Efstathopoulou, M., Eichhorst, B., El-Ashwah, S., Enrico, A., Espinet, B., Farina, L., Ferrari, A., Foglietta, M., Frederiksen, H., Furstenau, M., Garcia-Marco, J. A., Garcia-Serra, R., Gentile, M., Gimeno, E., Glenthoj, A., Gomes da Silva, M., Gutwein, O., Hakobyan, Y. K., Herishanu, Y., Hernandez-Rivas, J. A., Herold, T., Innocenti, I., Itchaki, G., Jaksic, O., Janssens, A., Kalashnikova, Оb., Kalicinska, E., Karlsson, L. K., Kater, A. P., Kersting, S., Labrador, J., Lad, D., Laurenti, L., Levin, M. -D., Lista, E., Lopez-Garcia, A., Malerba, L., Marasca, R., Marchetti, M., Marquet, J., Mattsson, M., Mauro, F. R., Milosevic, I., Miras, F., Morawska, M., Motta, M., Munir, T., Murru, R., Niemann, C. U., Rodrigues, R. N., Olivieri, J., Orsucci, L., Papaioannou, M., Pavlovsky, M. A., Piskunova, I., Popov, V. M., Quaglia, F. M., Quaresmini, G., Qvist, K., Reda, G., Rigolin, G. M., Ruchlemer, R., Saghumyan, G., Shrestha, A., Simkovic, M., Spacek, M., Sportoletti, P., Stanca, O., Stavroyianni, N., Tadmor, T., Te Raa, D., Tonino, S. H., Trentin, L., Van Der Spek, E., van Gelder, M., van Kampen, R., Varettoni, M., Visentin, A., Vitale, C., Wasik-Szczepanek, E., Wrobel, T., San Segundo, L. Y., Yassin, M., Coscia, M., Rambaldi, A., Montserrat, E., Foa, R., Cuneo, A., Stamatopoulos, K., Ghia, P., Experimental Immunology, Clinical Haematology, AII - Cancer immunology, and CCA - Cancer Treatment and Quality of Life

Subjects
Chronic lymphocytic leukaemia, Cancer Research, medicine.medical_specialty, COVID-19 Vaccines, Coronavirus disease 2019 (COVID-19), Epidemiology, medicine.medical_treatment, Chronic lymphocytic leukemia, CLL, COVID-19, 610 Medicine & health, Disease, Lower risk, COVID-19 (Malaltia), Severity of Illness Index, Article, NO, law.invention, Risk Factors, law, Internal medicine, Case fatality rate, Mortalitat, medicine, Humans, Hematologi, Chronic, Mortality, Science & Technology, Leukemia, SARS-CoV-2, business.industry, Vaccination, B-Cell, Leucèmia, COVID-19, Immunosuppression, Hematology, Prognosis, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, Survival Analysis, Intensive care unit, Lymphocytic, Oncology, business, Life Sciences & Biomedicine
Abstract

Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to Coronavirus disease 2019 (COVID-19) due to age, disease, and treatment-related immunosuppression. We aimed to assess risk factors of outcome and elucidate the impact of CLL-directed treatments on the course of COVID-19. We conducted a retrospective, international study, collectively including 941 patients with CLL and confirmed COVID-19. Data from the beginning of the pandemic until March 16, 2021, were collected from 91 centers. The risk factors of case fatality rate (CFR), disease severity, and overall survival (OS) were investigated. OS analysis was restricted to patients with severe COVID-19 (definition: hospitalization with need of oxygen or admission into an intensive care unit). CFR in patients with severe COVID-19 was 38.4%. OS was inferior for patients in all treatment categories compared to untreated (p

Published
2021

42. Heterogeneity of pollen food allergy syndrome in seven Southern European countries: The @IT.2020 multicenter study

Author

Blerina Bregu, Alfred Priftanji, Ozlem Goksel, Fusun Kalpaklioglu, Elisabetta Pellegrini, Münevver Pinar, Lucia Caminiti, Dah Tay Jang, Blerta Lame, Dolores Hernandez, Paolo Maria Matricardi, Simone Pelosi, Aykut Güvensen, Fotis Psarros, Valeria Villella, Maria Dimou, Stefania Arasi, Tara Maria Hoffmann, Andrea Di Rienzo Businco, Andrea Barbalace, Antonio Nieto, Mariana Couto, Paraskevi Xepapadaki, Duygu Yazici, Javier de Andrés Suárez, Michael Makris, Ruth Llusar, Xenophon Aggelidis, Ekaterina Potapova, Eris Mesonjesi, Cansin Sackesen, Salvatore Tripodi, Nikolaos G. Papadopoulos, Mariana Pereira, Theresa Lipp, Sule Caglayan Sozmen, Aydan Acar Şahin, Alessandro Travaglini, Claire Dimier, Ifigenia Sfika, E. Caeiro, Ayşe Bilge Öztürk, Giovanni Battista Pajno, Ana Pereira, Maria Antonia Brighetti, Denis Charpin, Laurie Pahus, Valentine Verdier, Luís Delgado, Anne Bourgoin, João Fonseca, Ilenia Panasiti, Angel Mazon, Michel Thibaudon, Stephanie Dramburg, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Öztürk, Ayşe Bilge (ORCID 0000-0003-0166-424X & YÖK ID 147629), Saçkesen, Cansın (ORCID 0000-0002-1115-9805 & YÖK ID 182537), Yazıcı, Dilek, Lipp, T., Acar Şahin, A., Aggelidis, X., Arasi, S., Barbalace, A., Bourgoin, A., Bregu, B., Brighetti, M. A., Caeiro, E, Çağlayan Sözmen, S., Caminiti, L., Charpin, D., Couto, M., Delgado, L., Di Rienzo Businco, A., Dimier, C., Dimou, M. V., Fonseca, J. A., Göksel, O., Güvensen, A., Hernandez, D., Hoffmann, T. M., Jang, D. T., Kalpaklıoğlu, F., Lame, B., Llusar, R., Makris, M., Mazon, A., Mesonjesi, E., Nieto, A., Pahus, L., Pajno, G., Panasiti, I., Papadopoulos, N. G., Pellegrini, E., Pelosi, S., Pereira, A. M., Pereira, M., Pınar, N. M., Potapova, E., Priftanji, A., Psarros, F., Sfika, I., Suarez, J., Thibaudon, M., Travaglini, A., Tripodi, S., Verdier, V., Villella, V., Xepapadaki, P., Matricardi, P. M., Dramburg, S., Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), and School of Medicine

Subjects
0301 basic medicine, Allergy, Southern Europe, Clinical immunology, [SDV]Life Sciences [q-bio], seasonal allergic rhinitis, Oral Allergy Syndrome, Panallergen, Pollen Food Allergy Syndrome, Seasonal Allergic Rhinitis, 0302 clinical medicine, Prevalence, Immunology and Allergy, Children, Profiles, ComputingMilieux_MISCELLANEOUS, food and beverages, Oral Allergy Syndrome, Panallergen, Pollen Food Allergy Syndrome, Seasonal Allergic Rhinitis, Southern Europe, Settore MED/01, panallergen, pollen food allergy syndrome, Pollen, oral allergy syndrome, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit, Food Hypersensitivity, Risk, medicine.medical_specialty, Oral allergy syndrome, Pollen food allergy syndrome, Seasonal allergic rhinitis, Population, Immunology, Settore BIO/02, Settore BIO/03, Cross Reactions, Sensitization, Pollen-food allergy, 03 medical and health sciences, otorhinolaryngologic diseases, medicine, Humans, Ige, Skin Tests, business.industry, Rhinitis, Allergic, Seasonal, Cross-Reactivity, Allergens, Peach, medicine.disease, Medicine, Cypress Pollen, 030104 developmental biology, 030228 respiratory system, Multicenter study, Family medicine, Informatics, business
Abstract

Background Pollen food allergy syndrome (PFAS) is a frequently underdiagnosed disease due to diverse triggers, clinical presentations, and test results. This is especially relevant in geographic areas with a broad spectrum of pollen sensitization, such as Southern Europe. Objectives To elucidate similarities and differences of PFAS in nine Southern European centers and identify associated characteristics and unique markers of PFAS. Methods As part of the @IT.2020 Multicenter Study, 815 patients with seasonal allergic rhinitis (SAR), aged 10-60 years, were recruited in seven countries. They completed questionnaires regarding SAR, comorbidities, family history, and PFAS, and underwent skin prick testing (SPT) and serum IgE testing. Results Of the 815 patients, 167 (20.5%) reported PFAS reactions. Most commonly, eliciting foods were kiwi (58, 34.7%), peach (43, 25.7%), and melon (26, 15.6%). Reported reactions were mostly local (216/319, 67.7%), occurring within 5 min of contact with elicitors (209/319, 65.5%). Associated characteristics included positive IgE to at least one panallergen (profilin, PR-10, or nsLTP) (p = 0.007), maternal PFAS (OR: 3.716, p = 0.026), and asthma (OR: 1.752, p = 0.073). Between centers, heterogeneity in prevalence (Marseille: 7.5% vs. Rome: 41.4%, p < 0.001) and of clinical characteristics was apparent. Cypress played a limited role, with only 1/22 SPT mono-sensitized patients reporting a food reaction (p < 0.073). Conclusions PFAS is a frequent comorbidity in Southern European SAR patients. Significant heterogeneity of clinical characteristics in PFAS patients among the centers was observed and may be related to the different pollen sensitization patterns in each geographic area. IgE to panallergen(s), maternal PFAS, and asthma could be PFAS-associated characteristics., EAACI Fellowship Award of the European Academy of Allergology and Clinical Immunology; Euroimmun [118583], SA was supported by the EAACI Fellowship Award of the European Academy of Allergology and Clinical Immunology. The study has been supported by an unrestricted grant from Euroimmun (grant number 118583). The ESEP assay has been provided by Euroimmun. The Informatics Platform AllergyCARD (TM) and the app AllergyMonitor (R) have been provided by TPS Production.

Published
2021

43. Poor Neutralizing Antibody Responses in 132 Patients with CLL, NHL and HL after Vaccination against SARS-CoV-2: A Prospective Study

Author

Alexandros Briasoulis, Panayiotis Panayiotidis, Ioannis Asimakopoulos, Ioannis Ntanasis-Stathopoulos, Meletios A. Dimopoulos, Aimilia D. Sklirou, Ismini Darmani, Efstathios Kastritis, Maria Dimou, Ioannis P. Trougakos, Maria Gavriatopoulou, Theodoros P. Vassilakopoulos, Maria K. Angelopoulou, Chara Giatra, Ioannis Baltadakis, Maria Pagoni, Despina Fotiou, and Evangelos Terpos

Subjects
Cancer Research, COVID-19 vaccination, Hodgkin’s lymphoma, Chronic lymphocytic leukemia, Article, immune system diseases, hemic and lymphatic diseases, medicine, neutralizing antibodies, Neutralizing antibody, RC254-282, BNT162b2 vaccine, biology, business.industry, SARS-CoV-2, Bruton’s tyrosine kinase inhibitors, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Hodgkin's lymphoma, non-Hodgkin’s lymphoma, humoral immune response, Non-Hodgkin's lymphoma, Lymphoma, Vaccination, Oncology, Immunology, biology.protein, chronic lymphocytic leukemia, Rituximab, Antibody, business, medicine.drug
Abstract

Emerging data suggest suboptimal antibody responses to COVID-19 vaccination in patients with hematological malignancies. We evaluated the humoral response following the BNT162b2 vaccine in patients with chronic lymphocytic leukemia (CLL), non-Hodgkin’s lymphoma (NHL), and Hodgkin’s lymphoma (HL). An FDA-approved, ELISA-based methodology was implemented to evaluate the titers of neutralizing antibodies (NAbs) against SARS-CoV-2 on day 1 of the first vaccine, and afterwards on day 22 and 50. One hundred and thirty-two patients with CLL/lymphomas and 214 healthy matched controls vaccinated during the same period, at the same center were enrolled in the study (NCT04743388). Vaccination with two doses of the BNT162b2 vaccine led to lower production of NAbs against SARS-CoV-2 in patients with CLL/lymphomas compared with controls both on day 22 and on day 50 (p &lt, 0.001 for all comparisons). Disease-related immune dysregulation and therapy-related immunosuppression are involved in the low humoral response. Importantly, active treatment with Rituximab, Bruton’s tyrosine kinase inhibitors, or chemotherapy was an independent prognostic factor for suboptimal antibody response. Patients with HL showed superior humoral responses to the NHL/CLL subgroups. In conclusion, patients with CLL/lymphomas have low humoral response following COVID-19 vaccination, underlining the need for timely vaccination ideally during a treatment-free period and for continuous vigilance on infection control measures.

Published
2021
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44. The Challenges of Open Source Software Alternatives

Author

Michal Kolodziejski, Aristofanis Chionis-Koufakos, and Maria Dimou

Subjects
Business process, business.industry, media_common.quotation_subject, Physics, QC1-999, Usability, Open source software, User requirements document, Computing and Computers, Engineering management, Presentation, Promotion (rank), Quality (business), business, media_common
Abstract

Developing an Open Source Software application is a challenge. Mainly because there are commercial alternatives that have an army of expert developers behind them, experienced supporters and wellestablished business processes in their development and promotion. Nevertheless, web-based applications, that securely handle the users’ personal data are an area of freedom and ease of use, features that make such applications very attractive. The “ease-of-use” part is very hard to achieve, for the developers and the end-users. Dependencies change often in OSS packages, so the fear that something breaks is always around the corner. If the application looks attractive, additional user requirements fall like rain. This poses a problem of continuity, maintenance and operational quality of the packages. In this paper and presentation we shall share our experience in building such a tool, using https://cern.ch/slides, as a showcase and a learning exercise. We shall describe what was available, what was missing, how it was put together, how much effort it took, and what was achieved.

Published
2021

45. Identification of Very Low-Risk Subgroups of Patients with Primary Mediastinal Large B-Cell Lymphoma Treated with R-CHOP

Author

Vassilakopoulos, Theodoros P. Michail, Michail Papageorgiou, Sotirios Kourti, Georgia Angelopoulou, Maria K. Panitsas, Fotios Sachanas, Sotirios Kalpadakis, Christina Katodritou, Eirini Leonidopoulou, Theoni Kotsianidis, Ioannis and Hatzimichael, Eleftheria Kotsopoulou, Maria Dimou, Maria and Variamis, Eleni Boutsis, Dimitrios Terpos, Evangelos and Dimopoulou, Maria N. Karakatsanis, Stamatios Michalis, Eurydiki and Karianakis, George Tsirkinidis, Pantelis Vadikolia, Chryssa and Poziopoulos, Christos Pigaditou, Anna Vrakidou, Effimia and Economopoulos, Theophanis Kyriazopoulou, Lydia Siakantaris, Marina P. Kyrtsonis, Marie-Christine Symeonidis, Argyris and Anargyrou, Konstantinos Papaioannou, Maria Hatjiharissi, Evdoxia and Vervessou, Elissavet Tsirogianni, Maria Palassopoulou, Maria and Gainaru, Gabriella Stefanoudaki, Ekaterini Zikos, Panayiotis and Tsirigotis, Panayiotis Tsourouflis, Gerasimos and Assimakopoulou, Theodora Konstantinidou, Pavlina Papadaki, Helen A. Megalakaki, Katerina Dimopoulos, Meletios-Athanasios and Pappa, Vassiliki Karmiris, Themis Roussou, Paraskevi and Panayiotidis, Panayiotis Konstantopoulos, Kostas Pangalis, Gerassimos A.

Subjects
hemic and lymphatic diseases, Health Sciences, Επιστήμες Υγείας
Abstract

Background R-CHOP can cure approximately 75% of patients with primary mediastinal large B-cell lymphoma (PMLBCL), but prognostic factors have not been sufficiently evaluated yet. R-da- EPOCH is potentially more effective but also more toxic than R-CHOP. Reliable prognostic classification is needed to guide treatment decisions. Materials and Methods We analyzed the impact of clinical prognostic factors on the outcome of 332 PMLBCL patients = 2 times upper limit of normal (model A) were significantly associated with FFP; E/IV and bulky disease (model B) were associated with LSS. Both models performed better than the International Prognostic Index (IPI) and the age-adjusted IPI by Harrel’s C rank parameter and Akaike information criterion. Both models A and B defined high-risk subgroups (13%-27% of patients [pts]) with approximately 19%-23% lymphoma-related mortality. They also defined subgroups composing approximately one-fourth or one-half of the patients, with 11% risk of failure and only 1% or 4% 5-year lymphoma-related mortality. Conclusion The combination of E/IV with either bulky disease or LDH >= 2 times upper limit of normal defined high-risk but not very-high-risk subgroups. More importantly, their absence defined subgroups comprising approximately one-fourth or one-half of the pts, with 11% risk of failure and minimal lymphoma-related mortality, who may not need more intensive treatment such as R-da-EPOCH. Implications for Practice By analyzing the impact of baseline clinical characteristics on outcomes of a large cohort of patients with primary mediastinal large B-cell lymphoma homogeneously treated with R-CHOP with or without radiotherapy, we developed novel prognostic indices which can aid in deciding which patients can be adequately treated with R-CHOP and do not need more intensive regimens such as R-da-EPOCH. The new indices consist of objectively determined characteristics (extranodal disease or stage IV, bulky disease, and markedly elevated serum lactate dehydrogenase), which are readily available from standard initial staging procedures and offer better discrimination compared with established risk scores (International Prognostic Index [IPI] and age-adjusted IPI).

Published
2021

46. Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies

Author

Bousquet, Jean, Cristol, Jean-Paul, Czarlewski, Wienczyslawa, Anto, Josep M, Martineau, Adrian, Haahtela, Tari, Fonseca, Susana C, Iaccarino, Guido, Blain, Hubert, Fiocchi, Alessandro, Canonica, G Walter, Fonseca, Joao A, Vidal, Alain, Choi, Hak-Jong, Kim, Hyun Ju, Le Moing, Vincent, Reynes, Jacques, Sheikh, Aziz, Akdis, Cezmi A, Zuberbier, Torsten, Amir Hamzah Abdul Latiff, Baharudin, Abdullah, Werner, Aberer, Nancy, Abusada, Ian, Adcock, Alejandro, Afani, Ioana, Agache, Xenofon, Aggelidis, Jenifer, Agustin, Cezmi, A Akdis, Mübeccel, Akdis, Mona, Al-Ahmad, Abou Al-Zahab Bassam, Hussam, Alburdan, Oscar, Aldrey-Palacios, Emilio Alvarez Cuesta, Hiba Alwan Salman, Ashraf, Alzaabi, Salma, Amade, Gene, Ambrocio, Rosana, Angles, Isabella, Annesi-Maesano, Ignacio, J Ansotegui, Josep, M Anto, Paula Ara Bardajo, Stefania, Arasi, Margarete, Arrais, Hasan, Arshad, Maria-Cristina, Artesani, Estrella, Asayag, Francesca, Avolio, Khuzama, Azhari, Claus, Bachert, Diego, Bagnasco, Ilaria, Baiardini, Nissera, Bajrović, Petros, Bakakos, Sergio Bakeyala Mongono, Christine, Balotro-Torres, Sergio, Barba, Cristina, Barbara, Elsa, Barbosa, Bruno, Barreto, Joan, Bartra, Xavier, Basagana, Eric, D Bateman, Lkhagvaa, Battur, Anna, Bedbrook, Martín Bedolla Barajas, Bianca, Beghé, Antra, Bekere, Elizabeth, Bel, Ali Ben Kheder, Mikael, Benson, Elena-Camelia, Berghea, Karl-Christian, Bergmann, Roberto, Bernardini, David, Bernstein, Mike, Bewick, Slawomir, Bialek, Artur, Białoszewski, Thomas, Bieber, Nils, E Billo, Maria-Beatrice, Bilo, Carsten, Bindslev-Jensen, Leif, Bjermer, Hubert, Blain, Irina, Bobolea, Malgorzata Bochenska Marciniak, Christine, Bond, Attilio, Boner, Matteo, Bonini, Sergio, Bonini, Sinthia, Bosnic-Anticevich, Isabelle, Bosse, Sofia, Botskariova, Jacques, Bouchard, Louis-Philippe, Boulet, Rodolphe, Bourret, Philippe, Bousquet, Fulvio, Braido, Andrew, Briggs, Christopher, E Brightling, Jan, Brozek, Luisa, Brussino, Roland, Buhl, Roxana, Bumbacea, Rosalva, Buquicchio, María-Teresa Burguete Cabañas, Andrew, Bush, William, W Busse, Jeroen, Buters, Fernan, Caballero-Fonseca, Moïses, A Calderon, Mario, Calvo, Paulo, Camargos, Thierry, Camuzat, R Canevari, F, Antonio, Cano, G Walter Canonica, Arnaldo, Capriles-Hulett, Luis, Caraballo, Vicky, Cardona, Kai-Hakon, Carlsen, Jonas Carmona Pirez, Jorge, Caro, Warner, Carr, Pedro, Carreiro-Martins, Fredelita, Carreon-Asuncion, Ana-Maria, Carriazo, Carme Carrion, Y Ribas, Thomas, Casale, Mary-Ann, Castor, Elizabeth, Castro, G Caviglia, A, Lorenzo, Cecchi, Alfonso Cepeda Sarabia, Maciej, Chalubinski, Ramanathan, Chandrasekharan, Yoon-Seok, Chang, Victoria, Chato-Andeza, Lida, Chatzi, Christina, Chatzidaki, Niels, H Chavannes, Claudia Chaves Loureiro, Aurora-Alejandra Chavez Garcia, Marta, Chelninska, Yuzhi, Chen, Lei, Cheng, Sharon, Chinthrajah, Tomas, Chivato, Ekaterine, Chkhartishvili, George, Christoff, Henry, Chrystyn, Derek, K Chu, Antonio, Chua, Alexander, Chuchalin, Kian Fan Chung, Alberto, Cicerán, Cemal, Cingi, Giorgio, Ciprandi, Ieva, Cirule, Ana-Carla, Coelho, Enrico, Compalati, Jannis, Constantinidis, Jaime Correia de Sousa, Elisio Manuel Costa, David, Costa, María Del Carmen Costa Domínguez, André, Coste, Cottini, M, Linda, Cox, Carlos, Crisci, Maria Angiola Crivellaro, Alvaro, A Cruz, John, Cullen, Adnan, Custovic, Biljana, Cvetkovski, Wienczyslawa, Czarlewski, Gennaro, D'Amato, Jane da Silva, Ronald, Dahl, Sven-Erik, Dahlen, Vasilis, Daniilidis, Louei Darjazini Nahhas, Ulf, Darsow, Janet, Davies, Frédéric de Blay, Giulia De Feo, Eloisa De Guia, José-Ricardo De la Torre Navarrete, Chato De Los Santos, Esteban De Manuel Keenoy, Govert De Vries, Diana, Deleanu, Pascal, Demoly, Judah, Denburg, Philippe, Devillier, Alain, Didier, Sanja Dimic Janjic, Maria, Dimou, Anh Tuan Dinh-Xuan, Ratko, Djukanovic, Maria Do Ceu Texeira, Dejan, Dokic, Margarita Gabriela Domínguez Silva, Habib, Douagui, Nikolaos, Douladiris, Maria, Doulaptsi, Gérard, Dray, Ruta, Dubakiene, Eve, Dupas, Stephen, Durham, Marzia, Duse, Mark, Dykewicz, Didier, Ebo, Natalija, Edelbaher, Thomas, Eiwegger, Patrik, Eklund, Yehia, El-Gamal, Zeinab, A El-Sayed, Shereen, S El-Sayed, Magda, El-Seify, Regina, Emuzyte, Lourdes, Enecilla, Marina, Erhola, Heidilita, Espinoza, Jesús Guillermo Espinoza Contreras, John, Farrell, Lenora, Fernandez, Paola Fimbres Jimenez, Antje Fink Wagner, Alessandro, Fiocchi, Wytske, J Fokkens, Lenia, Folletti, Joao, A Fonseca, Jean-François, Fontaine, Francesco, Forastiere, Jose Miguel Fuentes Pèrez, Emily, Gaerlan-Resureccion, Mina, Gaga, José Luis Gálvez Romero, Amiran, Gamkrelidze, Alexis, Garcia, Cecilia Yvonne García Cobas, María de la Luz Hortensia García Cruz, Valeria Garcia Ortiz, Jacques, Gayraud, Matteo, Gelardi, Bilun, Gemicioglu, Dimitra, Gennimata, Sonya, Genova, José, Gereda, Roy Gerth van Wijk, Antonio, Giuliano, René-Maximiliano, Gomez, Miguel-Ange Gonzalez Ballester, Sandra González Diaz, Maia, Gotua, Christos, Grigoreas, Ineta, Grisle, Marta, Guidacci, Nick, Guldemond, Zdenek, Gutter, Antonieta, Guzmán, Tari, Haahtela, Ramsa, Halloum, David, Halpin, Eckard, Hamelmann, Suleiman, Hammadi, Richard, Harvey, Enrico, Heffler, Joachim, Heinrich, Adnan, Hejjaoui, Birthe, Hellquist-Dahl, Luiana Hernández Velázquez, Mark, Hew, Elham, Hossny, Peter, Howarth, Martin, Hrubiško, Yunuen Rocío Huerta Villalobos, Marc, Humbert, Salina, Husain, Michael, Hyland, Guido, Iaccarino, Moustafa, Ibrahim, Nataliya, Ilina, Maddalena, Illario, Cristoforo, Incorvaia, Antonio, Infantino, Carla, Irani, Zhanat, Ispayeva, Juan Carlos Ivancevich, Edgardo Ej Jares, Deborah, Jarvis, Ewa, Jassem, Klemen, Jenko, Rubén Darío Jiméneracruz Uscanga, Sebastian, L Johnston, Guy, Joos, Maja, Jošt, Kaja, Julge, Ki-Suck, Jung, Jocelyne, Just, Marek, Jutel, Igor, Kaidashev, Omer, Kalayci, Fuat, Kalyoncu, Jeni, Kapsali, Przemyslaw, Kardas, Jussi, Karjalainen, Carmela, A Kasala, Michael, Katotomichelakis, Loreta, Kavaliukaite, Kazi, S Bennoor, Thomas, Keil, Paul, Keith, Musa, Khaitov, Nikolai, Khaltaev, You-Young, Kim, Bruce, Kirenga, Jorg, Kleine-Tebbe, Ludger, Klimek, Fanny, W Ko, Bernard Koffi N'Goran, Evangelia, Kompoti, Peter, Kopač, Gerard, Koppelman, Anja Koren Jeverica, Seppo, Koskinen, Mitja, Košnik, Tomasz, Kostka, Kosta, V Kostov, Marek, L Kowalski, Tanya, Kralimarkova, Karmen Kramer Vrščaj, Helga, Kraxner, Samo, Kreft, Vicky, Kritikos, Dmitry, Kudlay, Mikael, Kuitunen, Inger, Kull, Piotr, Kuna, Maciej, Kupczyk, Violeta, Kvedariene, Marialena, Kyriakakou, Nika, Lalek, Massimo, Landi, Stephen, Lane, Désiree, E Larenas-Linnemann, Susanne, Lau, Daniel, Laune, Jorge, Lavrut, Lan, Le, Martina, Lenzenhuber, Gualtiero, Leo, Marcus, Lessa, Michael, Levin, Jing, Li, Philip, Lieberman, Giuseppe, Liotta, Brian, Lipworth, Xuandao, Liu, Rommel, Lobo, Karin, C Lodrup Carlsen, Carlo, Lombardi, Renaud, Louis, Stelios, Loukidis, Olga, Lourenço, Jorge, A Luna Pech, Bojan, Madjar, Enrico, Maggi, Antoine, Magnan, Bassam, Mahboub, Alpana, Mair, Anke-Hilse Maitland van der Zee, Mika, Makela, Michael, Makris, Hans-Jorgen, Malling, Mariana, Mandajieva, Patrick, Manning, Manolis, Manousakis, Pavlos, Maragoudakis, Gianluigi, Marseglia, Gailen, Marshall, Mohammad Reza Masjedi, Jorge, F Máspero, Juan José Matta Campos, Marcus, Maurer, Sandra, Mavale-Manuel, Cem, Meço, Erik, Melén, Giovanni, Melioli, Elisabete, Melo-Gomes, Eli, O Meltzer, Enrica, Menditto, Andrew, Menzies-Gow, Hans, Merk, Jean-Pierre, Michel, Yann, Micheli, Neven, Miculinic, Luís, Midão, Florin, Mihaltan, Nikolaos, Mikos, Manlio, Milanese, Branislava, Milenkovic, Dimitrios, Mitsias, Bassem, Moalla, Giuliana, Moda, María Dolores Mogica Martínez, Yousser, Mohammad, Frances-Montserrat, Moharra, Mostafa, Moin, Mathieu, Molimard, Isabelle, Momas, Monique, Mommers, Alessandro, Monaco, Stephen, Montefort, Lucia-Elvira, Montenegro, Riccardo, Monti, Dory, Mora, Mario, Morais-Almeida, Ralph, Mösges, Badr Eldin Mostafa, Joaquim, Mullol, Lars, Münter, Antonella, Muraro, Ruth, Murray, Antonio, Musarra, Tihomir, Mustakov, Robert, Naclerio, Kari, C Nadeau, Rachel, Nadif, Alla, Nakonechna, Leyla, Namazova-Baranova, Gretchen, Navarro-Locsin, Hugo, Neffen, Kristof, Nekam, Angelos, Neou, Eustachio, Nettis, Daniel, Neuberger, Laurent, Nicod, Stefania, Nicola, Verena, Niederberger-Leppin, Marek, Niedoszytko, Antonio, Nieto, Ettore, Novellino, Elizabete, Nunes, Dieudonné, Nyembue, Robyn, E O'Hehir, Cvetanka, Odjakova, Ken, Ohta, Yoshitaka, Okamoto, Kimi, Okubo, Brian, Oliver, Gabrielle, L Onorato, Maria Pia Orru, Solange, Ouédraogo, Kampadilemba, Ouoba, Francisco-Javier, Padilla, Pier Luigi Paggiaro, Aris, Pagkalos, Pajno, Giovanni Battista, Gianni, Pala, P Palaniappan, S, Isabella, Pali-Schöll, Susanna, Palkonen, Stephen, Palmer, Carmen Panaitescu Bunu, Petr, Panzner, Nikos, G Papadopoulos, Vasilis, Papanikolaou, Alberto, Papi, Bojidar, Paralchev, Giannis, Paraskevopoulos, Hae-Sim, Park, Giovanni, Passalacqua, Vincenzo, Patella, Ian, Pavord, Ruby, Pawankar, Soren, Pedersen, Susete, Peleve, Simona, Pellegino, Ana, Pereira, Mariana, Pereira, Tamara, Pérez, Andrea, Perna, Diego, Peroni, Oliver, Pfaar, Nhân, Pham-Thi, Bernard, Pigearias, Isabelle, Pin, Konstantina, Piskou, Constantinos, Pitsios, Davor, Plavec, Dagmar, Poethig, Wolfgang, Pohl, Antonija Poplas Susic, Todor, A Popov, Fabienne, Portejoie, Paul, Potter, Lars, Poulsen, Alexandra, Prados-Torres, Fotis, Prarros, David, Price, Emmanuel, Prokopakis, Francesca, Puggioni, Elisa, Puig-Domenech, Robert, Puy, Klaus, Rabe, Silvia, Rabotti, Filip, Raciborski, Josephine, Ramos, Cristina, Recalcati, Marysia, T Recto, Shereen, M Reda, Frederico, S Regateiro, Norbert, Reider, Sietze, Reitsma, Susana, Repka-Ramirez, Erminia, Ridolo, Janet, Rimmer, Daniela Rivero Yeverino, José Angelo Rizzo, Carlos, Robalo-Cordeiro, Graham, Roberts, Karen, Robles, Nicolas, Roche, Mónica Rodríguez González, Eréndira Rodríguez Zagal, Giovanni, Rolla, Christine, Rolland, Regina, Roller-Wirnsberger, Miguel Roman Rodriguez, Antonino, Romano, Jan, Romantowski, Philippe, Rombaux, Joel, Romualdez, Jose, Rosado-Pinto, Nelson, Rosario, Lanny, Rosenwasser, Oliviero, Rossi, Menachem, Rottem, Philip, W Rouadi, Nikoleta, Rovina, Irma Rozman Sinur, Mauricio, Ruiz, Lucy Tania Ruiz Segura, Dermot, Ryan, Hironori, Sagara, Daiki, Sakai, Daiju, Sakurai, Wafaa, Saleh, Johanna, Salimaki, Konstantinos, Samitas, Boleslaw, Samolinski, María Guadalupe Sánchez Coronel, Mario, Sanchez-Borges, Jaime, Sanchez-Lopez, Melissa, Sansonna, Codrut, Sarafoleanu, Faradiba Sarquis Serpa, Joaquin, Sastre, Eleonora, Savi, Agne, Savonyte, Bisher, Sawaf, Glenis, K Scadding, Sophie, Scheire, Peter, Schmid-Grendelmeier, Juan Francisco Schuhl, Holger, Schunemann, Maria, Schvalbová, Jorgen, Schwarze, Nicola, Scichilone, Gianenrico, Senna, Cecilia, Sepúlveda, Elie, Serrano, Sara, Shamai, Aziz, Sheikh, Mike, Shields, Vasil, Shishkov, Nikos, Siafakas, Alexander, Simeonov, Estelle Fer Simons, Juan Carlos Sisul, Brigita, Sitkauskiene, Ingelbjorg, Skrindo, Tanja Soklič Košak, Dirceu, Solé, Martin, Sondermann, Talant, Sooronbaev, Manuel, Soto-Martinez, Manuel, Soto-Quiros, Barnaro Sousa Pinto, Milan, Sova, Michael, Soyka, Krzysztof, Specjalski, Annette, Sperl, Otto, Spranger, Sofia, Stamataki, Lina, Stefanaki, Cristiana, Stellato, Rafael, Stelmach, Timo, Strandberg, Petra, Stute, Abirami, Subramaniam, Charlotte Suppli Ulrik, Michael, Sutherland, Silvia, Sylvestre, Aikaterini, Syrigou, Luis Taborda Barata, Nadejda, Takovska, Rachel, Tan, Frances, Tan, Vincent, Tan, Ing Ping Tang, Masami, Taniguchi, Line, Tannert, Pongsakorn, Tantilipikorn, Jessica, Tattersall, Filippo, Tesi, Uta, Thieme, Carel, Thijs, Mike, Thomas, Teresa, To, Ana Maria Todo-Bom, Alkis, Togias, Peter-Valentin, Tomazic, Vesna, Tomic-Spiric, Sanna, Toppila-Salmi, Maria-José Torres Jaen, Elina, Toskala, Massimo, Triggiani, Nadja, Triller, Katja, Triller, Ioanna, Tsiligianni, Uberti, M, Ruxandra, Ulmeanu, Jure, Urbancic, Marilyn Urrutia Pereira, Martina, Vachova, Felipe, Valdés, Rudolf, Valenta, Marylin Valentin Rostan, Antonio, Valero, Arunas, Valiulis, Mina, Vallianatou, Erkka, Valovirta, Michiel Van Eerd, Eric Van Ganse, Marianne van Hage, Olivier, Vandenplas, Tuula, Vasankari, Dafina, Vassileva, Cesar Velasco Munoz, Maria Teresa Ventura, Cécilia, Vera-Munoz, Frédéric, Viart, Dilyana, Vicheva, Pakit, Vichyanond, Petra, Vidgren, Giovanni, Viegi, Claus, Vogelmeier, Leena Von Hertzen, Theodoros, Vontetsianos, Dimitris, Vourdas, Vu Tran Thien Quan, Martin, Wagenmann, Samantha, Walker, Dana, Wallace, Yun De Wang, Susan, Waserman, Katrin, Wehner, Magnus, Wickman, Sian, Williams, Dennis, Williams, Nicola, Wilson, Gary, Wong, Kent, Woo, Lucyna, Wozniak, John, Wright, Piotr, Wroczynski, Paraskevi, Xepapadaki, Plamen, Yakovliev, Masao, Yamaguchi, Kwok, Yan, Yoke Yeow Yap, Mais, Yassin, Barbara, Yawn, Panayiotis, Yiallouros, Arzu, Yorgancioglu, Shigemi, Yoshihara, Ian, Young, Osman, B Yusuf, Asghar, Zaidi, Fares, Zaitoun, Petra, Zalud, Heather, Zar, T Zedda, M, Mario, E Zernotti, Luo, Zhang, Nanshan, Zhong, Mihaela, Zidarn, Torsten, Zuberbier, Celia, Zubrinich, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Humboldt University Of Berlin, Berlin Institute of Health (BIH), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), IMIM-Hospital del Mar, Generalitat de Catalunya, Universitat Pompeu Fabra [Barcelona] (UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona] (UPF)-Catalunya ministerio de salud, Barts & The London School of Medicine and Dentistry, Queen Mary University of London (QMUL), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Helsinki University Central Hospital [Finland] (HUCH), Departamento de Geociencias, Ambiente e Ordenamento do Territorio (DGAOT), Universidade do Porto = University of Porto, University of Naples Federico II = Università degli studi di Napoli Federico II, Euromov (EuroMov), Université de Montpellier (UM), IRCCS Ospedale Pediatrico Bambino Gesù [Roma], Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), Center of Research in Health Technologies and Information Systems (CINTESIS), AgroParisTech, World Institute of Kimchi [Gwangju], Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), University of Edinburgh, Universität Zürich [Zürich] = University of Zurich (UZH), Humboldt-Universität zu Berlin, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Helsinki, Universidade do Porto, University of Naples Federico II, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), MORNET, Dominique, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, UCL - (MGD) Service de pneumologie, Bousquet J., Cristol J.-P., Czarlewski W., Anto J.M., Martineau A., Haahtela T., Fonseca S.C., Iaccarino G., Blain H., Fiocchi A., Canonica G.W., Fonseca J.A., Vidal A., Choi H.-J., Kim H.J., Le Moing V., Reynes J., Sheikh A., Akdis C.A., Zuberbier T., Abdul Latiff A.H., Abdullah B., Aberer W., Abusada N., Adcock I., Afani A., Agache I., Aggelidis X., Agustin J., Akdis M., Al-Ahmad M., Al-Zahab Bassam A., Alburdan H., Aldrey-Palacios O., Alvarez Cuesta E., Alwan Salman H., Alzaabi A., Amade S., Ambrocio G., Angles R., Annesi-Maesano I., Ansotegui I.J., Ara Bardajo P., Arasi S., Arrais M., Arshad H., Artesani M.-C., Asayag E., Avolio F., Azhari K., Bachert C., Bagnasco D., Baiardini I., Bajrovic N., Bakakos P., Bakeyala Mongono S., Balotro-Torres C., Barba S., Barbara C., Barbosa E., Barreto B., Bartra J., Basagana X., Bateman E.D., Battur L., Bedbrook A., Bedolla Barajas M., Beghe B., Bekere A., Bel E., Ben Kheder A., Benson M., Berghea E.-C., Bergmann K.-C., Bernardini R., Bernstein D., Bewick M., Bialek S., Bialoszewski A., Bieber T., Billo N.E., Bilo M.-B., Bindslev-Jensen C., Bjermer L., Bobolea I., Bochenska Marciniak M., Bond C., Boner A., Bonini M., Bonini S., Bosnic-Anticevich S., Bosse I., Botskariova S., Bouchard J., Boulet L.-P., Bourret R., Bousquet P., Braido F., Briggs A., Brightling C.E., Brozek J., Brussino L., Buhl R., Bumbacea R., Buquicchio R., Burguete Cabanas M.-T., Bush A., Busse W.W., Buters J., Caballero-Fonseca F., Calderon M.A., Calvo M., Camargos P., Camuzat T., Canevari F., Cano A., Canonican G.W., Capriles-Hulett A., Caraballo L., Cardona V., Carlsen K.-H., Carmona Pirez J., Caro J., Carr W., Carreiro-Martins P., Carreon-Asuncion F., Carriazo A.-M., CarrionyRibas C., Casale T., Castor M.-A., Castro E., Caviglia A.G., Cecchi L., Cepeda Sarabia A., Chalubinski M., Chandrasekharan R., Chang Y.-S., Chato-Andeza V., Chatzi L., Chatzidaki C., Chavannes N.H., Chaves Loureiro C., Chavez Garcia A.-A., Chelninska M., Chen Y., Cheng L., Chinthrajah S., Chivato T., Chkhartishvili E., Christoff G., Chrystyn H., Chu D.K., Chua A., Chuchalin A., Chung K.F., Ciceran A., Cingi C., Ciprandi G., Cirule I., Coelho A.-C., Compalati E., Constantinidis J., Correia de Sousa J., Costa E.M., Costa D., del Carmen Costa Dominguez M., Coste A., Cottini M., Cox L., Crisci C., Crivellaro M.A., Cruz A.A., Cullen J., Custovic A., Cvetkovski B., D'Amato G., da Silva J., Dahl R., Dahlen S.-E., Daniilidis V., Darjazini Nahhas L., Darsow U., Davies J., de Blay F., De Feo G., De Guia E., De la Torre Navarrete J.-R., De los Santos C., De Manuel Keenoy E., De Vries G., Deleanu D., Demoly P., Denburg J., Devillier P., Didier A., Dimic Janjic S., Dimou M., Dinh-Xuan A.T., Djukanovic R., Do Ceu Texeira M., Dokic D., Dominguez Silva M.G., Douagui H., Douladiris N., Doulaptsi M., Dray G., Dubakiene R., Dupas E., Durham S., Duse M., Dykewicz M., Ebo D., Edelbaher N., Eiwegger T., Eklund P., El-Gamal Y., El-Sayed Z.A., El-Sayed S.S., El-Seify M., Emuzyte R., Enecilla L., Erhola M., Espinoza H., Espinoza Contreras J.G., Farrell J., Fernandez L., Fimbres Jimenez P., Fink Wagner A., Fokkens W.J., Folletti L., Fontaine J.-F., Forastiere F., Fuentes Perez J.M., Gaerlan-Resureccion E., Gaga M., Galvez Romero J.L., Gamkrelidze A., Garcia A., Garcia Cobas C.Y., de la Luz Hortensia Garcia Cruz M., Ortiz V.G., Gayraud J., Gelardi M., Gemicioglu B., Gennimata D., Genova S., Gereda J., Gerth van Wijk R., Giuliano A., Gomez R.-M., Gonzalez Ballester M.-A., Gonzalez Diaz S., Gotua M., Grigoreas C., Grisle I., Guidacci M., Guldemond N., Gutter Z., Guzman A., Halloum R., Halpin D., Hamelmann E., Hammadi S., Harvey R., Heffler E., Heinrich J., Hejjaoui A., Hellquist-Dahl B., Hernandez Velazquez L., Hew M., Hossny E., Howarth P., Hrubisko M., Huerta Villalobos Y.R., Humbert M., Husain S., Hyland M., Ibrahim M., Ilina N., Illario M., Incorvaia C., Infantino A., Irani C., Ispayeva Z., Ivancevich J.C., Jares E.E., Jarvis D., Jassem E., Jenko K., Jimeneracruz Uscanga R.D., Johnston S.L., Joos G., Jost M., Julge K., Jung K.-S., Just J., Jutel M., Kaidashev I., Kalayci O., Kalyoncu F., Kapsali J., Kardas P., Karjalainen J., Kasala C.A., Katotomichelakis M., Kavaliukaite L., Bennoor K.S., Keil T., Keith P., Khaitov M., Khaltaev N., Kim Y.-Y., Kirenga B., Kleine-Tebbe J., Klimek L., Ko F.W., Koffi N'Goran B., Kompoti E., Kopac P., Koppelman G., Koren Jeverica A., Koskinen S., Kosnik M., Kostka T., Kostov K.V., Kowalski M.L., Kralimarkova T., Kramer Vrscaj K., Kraxner H., Kreft S., Kritikos V., Kudlay D., Kuitunen M., Kull I., Kuna P., Kupczyk M., Kvedariene V., Kyriakakou M., Lalek N., Landi M., Lane S., Larenas-Linnemann D.E., Lau S., Laune D., Lavrut J., Le L., Lenzenhuber M., Leo G., Lessa M., Levin M., Li J., Lieberman P., Liotta G., Lipworth B., Liu X., Lobo R., Lodrup Carlsen K.C., Lombardi C., Louis R., Loukidis S., Lourenco O., Luna Pech J.A., Madjar B., Maggi E., Magnan A., Mahboub B., Mair A., Maitland van der Zee A.-H., Makela M., Makris M., Malling H.-J., Mandajieva M., Manning P., Manousakis M., Maragoudakis P., Marseglia G., Marshall G., Masjedi M.R., Maspero J.F., Matta Campos J.J., Maurer M., Mavale-Manuel S., Meco C., Melen E., Melioli G., Melo-Gomes E., Meltzer E.O., Menditto E., Menzies-Gow A., Merk H., Michel J.-P., Micheli Y., Miculinic N., Midao L., Mihaltan F., Mikos N., Milanese M., Milenkovic B., Mitsias D., Moalla B., Moda G., Mogica Martinez M.D., Mohammad Y., Moharra F.-M., Moin M., Molimard M., Momas I., Mommers M., Monaco A., Montefort S., Montenegro L.-E., Monti R., Mora D., Morais-Almeida M., Mosges R., Mostafa B.E., Mullol J., Munter L., Muraro A., Murray R., Musarra A., Mustakov T., Naclerio R., Nadeau K.C., Nadif R., Nakonechna A., Namazova-Baranova L., Navarro-Locsin G., Neffen H., Nekam K., Neou A., Nettis E., Neuberger D., Nicod L., Nicola S., Niederberger-Leppin V., Niedoszytko M., Nieto A., Novellino E., Nunes E., Nyembue D., O'Hehir R.E., Odjakova C., Ohta K., Okamoto Y., Okubo K., Oliver B., Onorato G.L., Orru M.P., Ouedraogo S., Ouoba K., Padilla F.-J., Paggiaro P.L., Pagkalos A., Pajno G., Pala G., Palaniappan S., Pali-Scholl I., Palkonen S., Palmer S., Panaitescu Bunu C., Panzner P., Papadopoulos N.G., Papanikolaou V., Papi A., Paralchev B., Paraskevopoulos G., Park H.-S., Passalacqua G., Patella V., Pavord I., Pawankar R., Pedersen S., Peleve S., Pellegino S., Pereira A., Pereira M., Perez T., Perna A., Peroni D., Pfaar O., Pham-Thi N., Pigearias B., Pin I., Piskou K., Pitsios C., Plavec D., Poethig D., Pohl W., Poplas Susic A., Popov T.A., Portejoie F., Potter P., Poulsen L., Prados-Torres A., Prarros F., Price D., Prokopakis E., Puggioni F., Puig-Domenech E., Puy R., Rabe K., Rabotti S., Raciborski F., Ramos J., Recalcati C., Recto M.T., Reda S.M., Regateiro F.S., Reider N., Reitsma S., Repka-Ramirez S., Ridolo E., Rimmer J., Rivero Yeverino D., Rizzo J.A., Robalo-Cordeiro C., Roberts G., Robles K., Roche N., Rodriguez Gonzalez M., Rodriguez Zagal E., Rolla G., Rolland C., Roller-Wirnsberger R., Roman Rodriguez M., Romano A., Romantowski J., Rombaux P., Romualdez J., Rosado-Pinto J., Rosario N., Rosenwasser L., Rossi O., Rottem M., Rouadi P.W., Rovina N., Rozman Sinur I., Ruiz M., Ruiz Segura L.T., Ryan D., Sagara H., Sakai D., Sakurai D., Saleh W., Salimaki J., Samitas K., Samolinski B., Sanchez Coronel M.G., Sanchez-Borges M., Sanchez-Lopez J., Sansonna M., Sarafoleanu C., Sarquis Serpa F., Sastre J., Savi E., Savonyte A., Sawaf B., Scadding G.K., Scheire S., Schmid-Grendelmeier P., Schuhl J.F., Schunemann H., Schvalbova M., Schwarze J., Scichilone N., Senna G., Sepulveda C., Serrano E., Shamai S., Shields M., Shishkov V., Siafakas N., Simeonov A., Simons E.F., Sisul J.C., Sitkauskiene B., Skrindo I., Soklic Kosak T., Sole D., Sondermann M., Sooronbaev T., Soto-Martinez M., Soto-Quiros M., Pinto B.S., Sova M., Soyka M., Specjalski K., Sperl A., Spranger O., Stamataki S., Stefanaki L., Stellato C., Stelmach R., Strandberg T., Stute P., Subramaniam A., Suppli Ulrik C., Sutherland M., Sylvestre S., Syrigou A., Taborda Barata L., Takovska N., Tan R., Tan F., Tan V., Tang I.P., Taniguchi M., Tannert L., Tantilipikorn P., Tattersall J., Tesi F., Thieme U., Thijs C., Thomas M., To T., Todo-Bom A.M., Togias A., Tomazic P.-V., Tomic-Spiric V., Toppila-Salmi S., Torres Jaen M.-J., Toskala E., Triggiani M., Triller N., Triller K., Tsiligianni I., Uberti M., Ulmeanu R., Urbancic J., Urrutia Pereira M., Vachova M., Valdes F., Valenta R., Valentin Rostan M., Valero A., Valiulis A., Vallianatou M., Valovirta E., Van Eerd M., Van Ganse E., van Hage M., Vandenplas O., Vasankari T., Vassileva D., Velasco Munoz C., Ventura M.T., Vera-Munoz C., Viart F., Vicheva D., Vichyanond P., Vidgren P., Viegi G., Vogelmeier C., Von Hertzen L., Vontetsianos T., Vourdas D., Tran Thien Quan V., Wagenmann M., Walker S., Wallace D., De Wang Y., Waserman S., Wehner K., Wickman M., Williams S., Williams D., Wilson N., Wong G., Woo K., Wozniak L., Wright J., Wroczynski P., Xepapadaki P., Yakovliev P., Yamaguchi M., Yan K., Yap Y.Y., Yassin M., Yawn B., Yiallouros P., Yorgancioglu A., Yoshihara S., Young I., Yusuf O.B., Zaidi A., Zaitoun F., Zalud P., Zar H., Zedda M.T., Zernotti M.E., Zhang L., Zhong N., and Zidarn M.

Subjects
MAPK/ERK pathway, ARIA group, Allergy, [SDV]Life Sciences [q-bio], NF-KAPPA-B, debelost, Review, Pharmacology, Resveratrol, PROTECTS, chemistry.chemical_compound, 0302 clinical medicine, RESPIRATORY SYNDROME CORONAVIRUS, ENDOPLASMIC-RETICULUM STRESS, Medicine and Health Sciences, Immunology and Allergy, Medicine, OXIDATIVE STRESS, COVID-19, Foods, Insulin resistance, Nrf2, Nutrients, Obesity, TRPA1, 2. Zero hunger, 0303 health sciences, RESPIRATORY, INSULIN-RESISTANCE, Muscle cell proliferation, SULFORAPHANE, 3. Good health, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, SIGNALING PATHWAY, Signal transduction, Life Sciences & Biomedicine, Pulmonary and Respiratory Medicine, NRF2 ACTIVATORS, MUSCLE-CELL PROLIFERATION, Immunology, 610 Medicine & health, Lung injury, Settore MED/10 - Malattie Dell'Apparato Respiratorio, ACUTE LUNG INJURY, 03 medical and health sciences, COVID-19, Foods, Insulin resistance, Nrf2, Nutrients, Obesity, TRPA1, udc:616.9, odpornost proti inzulinu, SULFORAPHANE PROTECTS, Transcription factor, PI3K/AKT/mTOR pathway, 030304 developmental biology, Science & Technology, business.industry, SARS-CoV-2, food, medicine.disease, chemistry, hranila, SYNDROME CORONAVIRUS, business, hrana, GREEN TEA
Abstract

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPARγ:Peroxisome proliferator-activated receptor, NFκB: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2α:Elongation initiation factor 2α). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT1R axis (AT1R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity.

Published
2020

47. Effect of nasal irrigation on allergic rhinitis control in children; complementarity between CARAT and MASK outcomes

Author

Konstantinos Alevizopoulos, Bernardo Sousa-Pinto, John Lakoumentas, João Fonseca, Dimitrios Mitsias, Maria Dimou, Nikolaos G. Papadopoulos, Jean Bousquet, University of Athens Medical School [Athens], Universidade do Porto, Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), and University of Manchester [Manchester]

Subjects
Pulmonary and Respiratory Medicine, Sea-water solution, medicine.medical_specialty, Allergy, Children and adolescents, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Immunology, Symptomatic treatment, Spirulina platensis, CARAT questionnaire, Undaria pinnatifida, Allergic rhinitis, Treatment and control groups, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Clinical endpoint, Immunology and Allergy, Nasal irrigations, Asthma, Carat, Medication score, business.industry, Research, MASK/Allergy Diary app, RC581-607, medicine.disease, Symptom score, 3. Good health, Nasal irrigation, 030228 respiratory system, Adjunctive treatment, Immunologic diseases. Allergy, business
Abstract

International audience; Background: Nasal irrigations (NI) are increasingly used as an over-the-counter adjunctive treatment for allergic rhinitis (AR), but clinical studies on their effectiveness are limited.Methods: An open-label, controlled, non-randomized, real-life study was conducted to evaluate the effectiveness of NI with a new hypertonic solution as add-on treatment for AR. Children and adolescents with AR were prescribed symptomatic treatment. The active group also received an additional sea-water NI solution supplemented with algae extracts. The primary endpoint was symptom control, assessed by the control of allergic rhinitis and asthma test (CARAT) questionnaires. Moreover, the MASK/Allergy Diary was used to track symptoms and daily medication use that were combined in a novel total symptom/medication score (TSMS).Results: We assessed 76 patients. Overall, there was a significant improvement of CARAT results (median Z-score change of 1.1 in the active/NI group vs. 0.4 in the control group; p = 0.035). Among patients > 12 years old (n = 51), there was a significant improvement in CARAT10 results among participants receiving NI (21.0 to 25.5; p < 0.001), but not in the regular treatment group (21.5 to 24.0; p = 0.100). For children < 12 years old (n = 25), the ΝΙ group had significantly improved symptom control (CARATKids results: 5.0 to 2.0; p = 0.002), in contrast to the control group (4.0 to 2.5; p = 0.057). MASK data on allergic symptoms were comparable between groups. However, the NI group had lower TSMS, more days with < 20% symptoms and fewer days using symptomatic treatment (26.9% vs. 43.5%; p = 0.005).Conclusion: Addition of NI with a sea-water solution to regular treatment improved AR symptom control. CARAT questionnaires and MASK application can be useful outcome tools in real-life studies.

Published
2020

48. COVID-19 severity and mortality in patients with chronic lymphocytic leukemia: a joint study by ERIC, the European Research Initiative on CLL, and CLL Campus

Author

Tobias Herold, Martin Andres, Gimena Dos Santos, Livio Trentin, Monia Marchetti, Antonio Cuneo, Robin Foà, Vladimir Strugov, Sunil Iyengar, Ozren Jakšić, Mark-David Levin, Angela Ferrari, Francesca Romana Mauro, Candida Vitale, Martin Spacek, Olga Kalashnikova, Eugene Nikitin, Ann Janssens, Constantine S. Tam, Julio Delgado, Maria Papaioannou, Barbara Pocali, Davide Rossi, Marina Motta, Niki Stavroyianni, Myriam Foglietta, Alicia Enrico, Carolina Cuéllar-García, Lara Malerba, Mónica Baile, Lydia Scarfò, Ellen van der Spek, Paolo Sportoletti, Maria Rosaria De Paolis, Mihnea Zdrenghea, Macarena Ortiz Pareja, Annalisa Chiarenza, Sabina Kersting, Fatima Miras, Yair Herishanu, Emili Montserrat, Marta Coscia, Giuseppe Rossi, Jose Angel Hernandez-Rivas, Carsten Utoft Niemann, Alessandro Rambaldi, Amit Shrestha, Roberto Marasca, Rosa Ruchlemer, Marzia Varettoni, Dominique Bron, Juan Marquet, Eva Gimeno, Viola Maria Popov, Massimo Gentile, Mohamed A. Yassin, Kostas Stamatopoulos, Lorenzo De Paoli, Thomas Chatzikonstantinou, Giulia Quaresmini, Luca Laurenti, Lucia Farina, Arnon P. Kater, Nimish Shah, Elisabeth Vandenberghe, José A. García-Marco, Oana Stanca, Giovanni Del Poeta, Martin Simkovic, Yervand K Hakobyan, Enrico Lista, Michael Doubek, Gilad Itchaki, Talha Munir, Paolo Ghia, Ewa Wasik-Szczepanek, Gianluigi Reda, Francesca Maria Quaglia, Maria Dimou, Gábor Barna, Lorella Orsucci, Gian Matteo Rigolin, Scarfo', L., Chatzikonstantinou, T., Rigolin, G. M., Quaresmini, G., Motta, M., Vitale, C., Garcia-Marco, J. A., Hernandez-Rivas, J. A., Miras, F., Baile, M., Marquet, J., Niemann, C. U., Reda, G., Munir, T., Gimeno, E., Marchetti, M., Quaglia, F. M., Varettoni, M., Delgado, J., Iyengar, S., Janssens, A., Marasca, R., Ferrari, A., Cuellar-Garcia, C., Itchaki, G., Spacek, M., De Paoli, L., Laurenti, L., Levin, M. -D., Lista, E., Mauro, F. R., Simkovic, M., Van Der Spek, E., Vandenberghe, E., Trentin, L., Wasik-Szczepanek, E., Ruchlemer, R., Bron, D., De Paolis, M. R., Del Poeta, G., Farina, L., Foglietta, M., Gentile, M., Herishanu, Y., Herold, T., Jaksic, O., Kater, A. P., Kersting, S., Malerba, L., Orsucci, L., Popov, V. M., Sportoletti, P., Yassin, M., Pocali, B., Barna, G., Chiarenza, A., dos Santos, G., Nikitin, E., Andres, M., Dimou, M., Doubek, M., Enrico, A., Hakobyan, Y., Kalashnikova, O., Ortiz Pareja, M., Papaioannou, M., Rossi, D., Shah, N., Shrestha, A., Stanca, O., Stavroyianni, N., Strugov, V., Tam, C., Zdrenghea, M., Coscia, M., Stamatopoulos, K., Rossi, G., Rambaldi, A., Montserrat, E., Foa, R., Cuneo, A., Ghia, P., Experimental Immunology, Clinical Haematology, and CCA - Cancer Treatment and Quality of Life

Subjects
0301 basic medicine, Male, Chronic lymphocytic leukaemia, Cancer Research, Chronic Lymphocytic Leukemia, COVID-19, Chronic lymphocytic leukemia, Comorbidity, Severity of Illness Index, chemistry.chemical_compound, 0302 clinical medicine, Piperidines, Obinutuzumab, Surveys and Questionnaires, hemic and lymphatic diseases, 80 and over, Viral, Chronic, 610 Medicine & health, Immunodeficiency, Aged, 80 and over, Leukemia, Mortality rate, Age Factors, Hematology, Middle Aged, Prognosis, Lymphocytic, Oncology, 030220 oncology & carcinogenesis, Infectious diseases, Female, Coronavirus Infections, medicine.drug, Bendamustine, medicine.medical_specialty, Pneumonia, Viral, Antineoplastic Agents, Article, NO, 03 medical and health sciences, Betacoronavirus, Internal medicine, Severity of illness, medicine, Humans, Chronic Lymphocytic Leukemia, Pandemics, Protein Kinase Inhibitors, Aged, Retrospective Studies, SARS-CoV-2, Venetoclax, business.industry, Adenine, B-Cell, COVID-19, Odds ratio, Pneumonia, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, Settore MED/15 - MALATTIE DEL SANGUE, 030104 developmental biology, Pyrazoles, Pyrimidines, chemistry, business
Abstract

Chronic lymphocytic leukemia (CLL) is a disease of the elderly, characterized by immunodeficiency. Hence, patients with CLL might be considered more susceptible to severe complications from COVID-19. We undertook this retrospective international multicenter study to characterize the course of COVID-19 in patients with CLL and identify potential predictors of outcome. Of 190 patients with CLL and confirmed COVID-19 diagnosed between 28/03/2020 and 22/05/2020, 151 (79%) presented with severe COVID-19 (need of oxygen and/or intensive care admission). Severe COVID-19 was associated with more advanced age (≥65 years) (odds ratio 3.72 [95% CI 1.79–7.71]). Only 60 patients (39.7%) with severe COVID-19 were receiving or had recent (≤12 months) treatment for CLL at the time of COVID-19 versus 30/39 (76.9%) patients with mild disease. Hospitalization rate for severe COVID-19 was lower (p < 0.05) for patients on ibrutinib versus those on other regimens or off treatment. Of 151 patients with severe disease, 55 (36.4%) succumbed versus only 1/38 (2.6%) with mild disease; age and comorbidities did not impact on mortality. In CLL, (1) COVID-19 severity increases with age; (2) antileukemic treatment (particularly BTK inhibitors) appears to exert a protective effect; (3) age and comorbidities did not impact on mortality, alluding to a relevant role of CLL and immunodeficiency.

Published
2020

49. Cumulative Pollen Concentration Curves for Pollen Allergy Diagnosis

Author

Salvatore Tripodi, Javier de Andrés Suárez, Maria Dimou, Blerina Bregu, Fusun Kalpaklioglu, Massimo Fiorilli, Ozlem Goksel, Luís Delgado, It. study team, S Caglayan Sozmen, Nikolaos G. Papadopoulos, Valeria Villella, Angel Mazon, P M Matricardi, E Pinter, Denis Charpin, M. Pereira, Alfred Priftanji, Stefania Arasi, Stephanie Dramburg, U Ugus, Cansin Sackesen, Antonio Nieto, E. Caeiro, Michel Thibaudon, E Pellegrini, André Pereira, Ayşe Bilge Öztürk, Aydan Acar Şahin, Ifigenia Sfika, João Fonseca, Blerta Lame, Nur Münevver Pinar, Alessandro Travaglini, Tara Maria Hoffmann, Eris Mesonjesi, Giovanni Battista Pajno, and Maria Antonia Brighetti

Subjects
Adult, Male, Allergy, Seasonal allergic rhinitis, Immunology, Clinical Decision-Making, Pollen concentration, MEDLINE, Pinales, Pollen Allergy, medicine.disease_cause, Poaceae, Calendar, Allergy diagnosis, Pollen, medicine, Allergy Diagnosis, Pollen Concentration, Seasonal Allergic Rhinitis, Immunology and Allergy, Humans, business.industry, Mediterranean Region, Rhinitis, Allergic, Seasonal, Allergens, Antigens, Plant, medicine.disease, Fagales, Female, Particulate Matter, Seasons, business, Pollen allergy
Abstract

[No Abstract Available], Euroimmun [118583], This study was supported by a grant from Euroimmun (code 118583).

Published
2020

50. Frontline treatment with the combination obinutuzumab ± chlorambucil for chronic lymphocytic leukemia outside clinical trials: Results of a multinational, multicenter study by ERIC and the Israeli CLL study group

Author

Rosa Ruchlemer, Angeles Medina Perez, Ariel Aviv, Alessandra Tedeschi, Sandra Bašić-Kinda, Sarit Assouline, Marta Morawska, Mihnea Zdrenghea, Maria Papaioannou, Gilad Itchaki, Viola Maria Popov, Odit Gutwein, Rosa Collado, Michael Gregor, Horia Bumbea, Inga Mandac, Livio Trentin, Neta Goldschmidt, Paolo Sportoletti, Adir Shaulov, Marta Coscia, Gian Matteo Rigolin, Anatoly Nemets, Francesca Romana Mauro, Róbert Szász, Nagib Dali, Fatima Miras, Massimo Gentile, Shimrit Ringelstein, Martin Simkovic, Martin Spacek, Uri Greenbaum, Aaron Polliack, Lydia Scarfò, Michael Doubek, Riva Fineman, Andrei Braester, Lev Shvidel, M.R. Nijziel, Irma Slavutsky, Tamar Tadmor, Eva Gimeno Vázquez, Yair Herishanu, Juan Marquet, Ozren Jakšić, Shai Levi, Ohad Benjamini, Javier Loscertales, Oana Stanca Ciocan, Paolo Ghia, Luciano Levato, Chava Perry, Maria Dimou, Anne De Meûter, Ewa Wasik-Szczepanek, Luca Laurenti, Osnat Bairey, Herishanu, Y., Shaulov, A., Fineman, R., Basic-Kinda, S., Aviv, A., Wasik-Szczepanek, E., Jaksic, O., Zdrenghea, M., Greenbaum, U., Mandac, I., Simkovic, M., Morawska, M., Benjamini, O., Spacek, M., Nemets, A., Bairey, O., Trentin, L., Ruchlemer, R., Laurenti, L., Stanca Ciocan, O., Doubek, M., Shvidel, L., Dali, N., Miras, F., De Meuter, A., Dimou, M., Mauro, F. R., Coscia, M., Bumbea, H., Szasz, R., Tadmor, T., Gutwein, O., Gentile, M., Scarfo', L., Tedeschi, A., Sportoletti, P., Gimeno Vazquez, E., Marquet, J., Assouline, S., Papaioannou, M., Braester, A., Levato, L., Gregor, M., Rigolin, G. M., Loscertales, J., Medina Perez, A., Nijziel, M. R., Popov, V. M., Collado, R., Slavutsky, I., Itchaki, G., Ringelstein, S., Goldschmidt, N., Perry, C., Levi, S., Polliack, A., and Ghia, P.

Subjects
obinutuzumab, Oncology, Male, chemistry.chemical_compound, 0302 clinical medicine, Obinutuzumab, Monoclonal, Antineoplastic Combined Chemotherapy Protocols, 80 and over, Chronic, Humanized, chronic lymphocytic leukemia, obinutuzumab, chlorambucil, Aged, 80 and over, Leukemia, Hematology, Lymphocytic, 3. Good health, Survival Rate, 030220 oncology & carcinogenesis, Ibrutinib, Female, Aged, Antibodies, Monoclonal, Humanized, Chlorambucil, Chromosomes, Human, Pair 17, Disease-Free Survival, Humans, Retrospective Studies, Tumor Suppressor Protein p53, Chromosome Deletion, Leukemia, Lymphocytic, Chronic, B-Cell, IGHV@, medicine.drug, Human, medicine.medical_specialty, chronic lymphocytic leukemia, chlorambucil, Antibodies, Chromosomes, NO, 03 medical and health sciences, Internal medicine, medicine, Progression-free survival, Survival rate, Venetoclax, business.industry, Pair 17, B-Cell, Clinical trial, Settore MED/15 - MALATTIE DEL SANGUE, chemistry, business, 030215 immunology
Abstract

In recent years, considerable progress has been made in frontline therapy for elderly/physically unfit patients with CLL. The combination of obinutuzumab and chlorambucil (O-Clb) has been shown to prolong progression free survival (PFS, median PFS-31.5 months) and overall survival (OS) compared to chlorambucil alone. More recently, obinutuzumab given in combination with either ibrutinib or venetoclax improved PFS but not OS when compared to O-Clb. In this retrospective multinational, multicenter co-operative study, we evaluated the efficacy and safety of frontline treatment with O ± Clb in unfit patients with CLL, in a “real-world” setting. Patients with documented del (17p13.1)/TP53 mutation were excluded. A total of 437 patients (median age, 75.9 years; median CIRS score, 8; median creatinine clearance, 61.1 mL/min) were included. The clinical overall response rate was 80.3% (clinical complete and partial responses in 38.7% and 41.6% of patients, respectively). Median observation time was 14.1 months and estimated median PFS was 27.6 months (95% CI, 24.2-31.0). In a multivariate analysis, high-risk disease [del (11q22.3) and/or IGHV-unmutated], lymph nodes of diameter > 5 cm, obinutuzumab monotherapy and reduced cumulative dose of obinutuzumab, were all independently associated with shorter PFS. The median OS has not yet been reached and estimated 2-year OS is 88%. In conclusion, in a “real-world” setting, frontline treatment with O-Clb achieves PFS comparable to that reported in clinical trials. Inferior outcomes were noted in patients with del (11q22.3) and/or unmutated IGHV and those treated with obinutuzumab-monotherapy. Thus, O-Clb can be still considered as legitimate frontline therapy for unfit CLL patients with low-risk disease.

Published
2020

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