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101. Development of acute myeloid leukemia with NPM1 mutation, in Ph-negative clone, during treatment of CML with imatinib

Author

Georgiou, G, primary, Efthymiou, A, additional, Vardounioti, I, additional, Boutsikas, G, additional, Angelopoulou, M K, additional, Vassilakopoulos, T P, additional, Kyrtsonis, M-C, additional, Plata, E, additional, Tofas, P, additional, Bitsani, A, additional, Bartzi, V, additional, Pessach, I, additional, Dimou, M, additional, and Panayiotidis, P, additional

Published
2011
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102. 294 Prognostic significance of beta 2 microglobulin in survival and transformation to acute myelogenous leukemia in patients with myelodysplastic syndrome

Author

Galanopoulos, A., primary, Aggelidis, A., additional, Gogos, D., additional, Megalakaki, A., additional, Kotsianidis, I., additional, Dimou, M., additional, Panagiotidis, P., additional, Zoumbos, N., additional, Anagnostopoulos, N.I., additional, Voulgarelis, M., additional, Papadaki, H., additional, and Symeonidis, A., additional

Published
2011
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103. 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

Anargyrou, K., primary, Vassilakopoulos, T.P., additional, Tsionos, K., additional, Kokkoris, P., additional, Boutsikas, G., additional, Angelopoulou, M.K., additional, Christoulas, D., additional, Masouridou, S., additional, Gkotzamanidou, M., additional, Dimou, M., additional, Papatheodorou, A., additional, Chatzifotiadis, D.N., additional, Panayiotidis, P., additional, Pangalis, G.A., additional, Meletis, J., additional, and Terpos, E., additional

Published
2011
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106. A433 Comparison of Serum Cytokines with Prognostic Impact in MM

Author

Maltezas, D, primary, Tzenou, T, additional, Vassilakopoulos, TP, additional, Repousis, P, additional, Papanikolaou, X, additional, Dimou, M, additional, Stavropoulos, N, additional, Pouli, A, additional, Panayiotidis, P, additional, Pangalis, GA, additional, and Kyrtsonis, MC, additional

Published
2009
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107. A436 Role of Soluble Syndecan-1 in FLC Hypersecretion in MM

Author

Maltezas, D, primary, Repousis, P, additional, Tzenou, T, additional, Kafasi, N, additional, Dimou, M, additional, Papanikolaou, X, additional, Vassilakopoulos, TP, additional, Stavropoulos, N, additional, Pouli, A, additional, Panayiotidis, P, additional, Pangalis, GA, additional, and Kyrtsonis, MC, additional

Published
2009
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111. Gene transcript accumulation and in situ mRNA hybridization of two putative glutamate dehydrogenase genes in etiolated Glycine max seedlings.

Author

Dimou, M, Tsaniklidis, G, Aivalakis, G, and Katinakis, P

Subjects
*MESSENGER RNA, *IN situ hybridization, *GLUTAMATE dehydrogenase, *SEEDS, *SOYBEAN, *ANTISENSE DNA
Abstract

Glutamate dehydrogenase (EC 1.4.1.2) is a multimeric enzyme that catalyzes the reversible amination of α-ketoglutarate to form glutamate. We characterized cDNA clones of two Glycine max sequences, GmGDH1 and GmGDH2, that code for putative α- and β-subunits, respectively, of the NADH dependent enzyme. Temporal and spatial gene transcript accumulation studies using semiquantitative RT-PCR and in situ hybridization have shown an overlapping gene transcript accumulation pattern with differences in relative gene transcript accumulation in the organs examined. Detection of NADH-dependent glutamate dehydrogenase activity in situ using a histochemical method showed concordance with the spatial gene transcript accumulation patterns. Our findings suggest that although the two gene transcripts are co-localized in roots of etiolated soybean seedlings, the ratio of the two subunits of the active holoenzyme may vary among tissues. [ABSTRACT FROM AUTHOR]

Published
2015
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118. Pharmaceutical ethics and moral imagination in the modern Hellenic society.

Author

DIMA, E., DIMOU, M., and TZAVELLA, F.

Subjects
*DRUG administration, *PHARMACIST malpractice, *MEDICAL ethics, *NEUROLOGICAL disorders, *PSYCHIATRIC clinics
Abstract

In the area of health care and particularly pharmaceutical care moral judgments are directly related to socio-economic and demographic factors. Health care professionals are obliged to work in an extremely complex environment and their decisions will be shaped not only by their Code of Ethics, but also by other parameters such as their individual culture and their "moral imagination". Cultivation of the moral aspect is required and the subsequent drawing upon the so-called "moral imagination" will allow health professionals to distance themselves from the "typical" standards and grow closer to more substantial moral considerations; otherwise they are in serious danger of adopting preconceived models of thinking and unrealistic standards. Society today is facing a series of challenges, including the recent economic crisis that has led to a decrease in income, an increase in unemployment, especially for women and young people, and a rise in the overall costs in the health area. Especially concerning pharmaceutical care, many patients find it difficult to cover the cost of their medication, which may result in the deterioration of their health, with frequent visits to the emergency services, symptoms of anxiety and sleep disorders and even hospitalization in psychiatric clinics. The public health sector is having difficulty coping with the demands of society, which leads to poorer access of a large sector of the population to less than satisfactory health care, due to socio-economic difficulties, and to false promises of social justice from the state. [ABSTRACT FROM AUTHOR]

Published
2013

120. Response to Bortezomib in Refractory/Relapsed Multiple Myeloma Patients: A Single Center Experience with Discussion on Specific Issues.

Author

Kyrtsonis, M-C, Mattezas, D, Koutieris, E, Zaroutis, C, Tzenou, T, Sachanas, S, Bartzis, V, Georgiou, G, Dimou, M, Siakavellas, S, Vassitakopouios, TP, Angeiopouiou, MK, Koutra, E, Mauzaki, A, Pangalis, GA, and Panayiatidis, P

Subjects
MULTIPLE myeloma treatment, THERAPEUTICS, DEXAMETHASONE, MULTIVARIATE analysis, LACTATE dehydrogenase, THROMBOCYTOPENIA
Abstract

Prognostic fsctors of response to bortezomib, event-free (EFS) snd oversil survivsl (OS), snd pstients' course, were evaluated in s series of relapsed/refractory multiple myeloma (MM) patients with long follow-up. Eighty relapsed and five refractory patients were treated with bortezomib at standard doses and schedule, while intermediate-dose dexamethasone was added if at least MR was not observed. The median time from diagnosis to bortezomib administration was 25.3 months. Seventy-one patients responded (including 42% complete remission (CR) and near CR (nCR)). Median time to response was 1.4 months. The i-year EFS was 34% and the 2-year OS was 6i%. Median survival after bortezomib was 26.4 months. In multivariate analysis, elevated lactate dehydrogenase (LDH) and anemia were independent factors for EFS, and increased LDH, thrombocytopenis, and performance status (PS) for OS (P=o.000i, 0.0006, and 0.043 respectively). The depth of response affected both EFS and OS. Patients' i-year EFS and 2-year OS was ii months and not reached for CR/nCR, respectively, vs 9.5 and 27 months for partial remission (PR), vs 3.5 and iS months for minimal response (MR)/progressive disease (PD) (P=o.0006 and 0.002 respectively). The main side-effect was peripheral neuropathy that was mainly of sxonsl type and affected sensory nerves of distal extremities, had peak manifestations after three or four cycles, and usually regressed after 3 months. In conclusion, bortezomib produced impressive response rates in this observational study. The depth of response influenced both EFS and OS, the main other prognostic factors were LDH, PS, and thrombocytopenis, while the significance of staging and serum-free light chains was overcome. [ABSTRACT FROM AUTHOR]

Published
2010

121. What is the current state of the artificial pancreas in diabetes care?

Author

Dimou, M., Laimer, M., Stettler, C., and Bally, L.

Subjects
610 Medicine & health
Abstract

Das künstliche Pankreas (auch Closed-loop-System genannt) bringt uns dem jahrzehntelangen Traum einer automatisierten Insulindosierung einen Schritt näher. Das System steuert die subkutane Insulinzufuhr mit einem Kontrollalgorithmus entsprechend der Glukosekonzentration. Die Studienlage zeigt, dass damit die Blutzuckerkontrolle und Lebensqualität Betroffener deutlich verbessert werden können. Vollautomatische Closed-loop-Systeme sind jedoch noch nicht erhältlich. Patienten müssen bei der Insulindosierung für Mahlzeiten und Korrekturen zusätzlich aktiv mitwirken. Die folgende Übersichtsarbeit zeigt den aktuellen Entwicklungsstand des künstlichen Pankreas in der Diabetestherapie auf., The artificial pancreas (also referred to as closed-loop system) brings us one step closer to the decade-long dream of automated insulin delivery. The closed-loop system directs subcutaneous insulin delivery corresponding to the glucose concentration using a control algorithm. Evidence shows that closed-loop systems substantially improve glucose control and quality of life; however, fully automated closed-loop systems have not yet been accomplished. Active input from patients is required for mealtime insulin dosing and corrections. This article provides an overview on the current state of development of the artificial pancreas in the treatment of diabetes.

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124. Allergic rhinitis and its impact on asthma (ARIA) in Greece: Integrated care pathways for predictive medicine across the life cycle

Author

Papadopoulos, N. G., Dimou, M. V., Vontetsianos, T., Giallouros, P., Gaga, M., Danielidis, V., Douladiris, N., Makris, M., Mikos, N., Marangoudakis, P., Xepapadaki, P., Papanikolaou, V., Pitsios, K., Prokopakis, E., Siafakas, N., Xantzi, L., Psarros, F., Aggelidis, X., Vallianatou, M., Vourdas, D., Grigoreas, C., Doulaptsi, M., Katotomichelakis, M., Kapsali, T., Kompoti, E., Kyriakakou, M., Loukidis, S., Manousakis, E., Mpakakos, P., Βotskariova, S., Paraskevopoulos, I., Piskou, K., Rovina, N., Stamataki, S., Stefanaki, E., Syrigou, E., Agache, I., Bachert, C., Bedbrook, A., Canonica, G. W., Casale, T., Cruz, A. A., Fokkens, W. J., Hellings, P. W., Samolinski, B., Jean Bousquet, Ear, Nose and Throat, and AII - Inflammatory diseases

Abstract

© Athens Medical Society. Allergic rhinitis is a serious global health problem which affects approximately 10–20% of the European population. In 1999, during a workshop of WHO, the project Allergic Rhinitis and its Impact on Asthma (ARIA) was developed. Its objective was to propose a new classification of allergic rhinitis according to the severity and the duration of the symptoms, to promote the idea of multimorbidity of allergic rhinitis and asthma, and to create guidelines for global use, with the help of local stakeholders and experts from all the countries involved. The focus of ARIA during recent years has been the use of new technologies for individualized medical care and prevention. The MASK instrument uses smartphone technology to create care pathways for controlling rhinitis, for both multidisciplinary care teams and the patients themselves. Using a mobile app (Allergy Diary), a patient can assess symptoms, control and productivity using a visual analog scale, which is connected with a clinical decision support system. The information is sent to an interoperable tablet where healthcare professionals can be informed about the patient’s rhinitis management. As the European population is ageing, the novel approach of ARIA aims to provide active and healthy ageing in order to improve the quality of life of patients with allergic rhinitis. In Greece, ARIA has been implemented since the early 2000s. In 2017 a new ARIA implementation group was established, consisting of a large number of health care professionals from both Greece and Cyprus. The MASK Allergy Diary has been translated into Greek and is currently being used in clinical practice and research protocols with great enthusiasm. In order to rectify the lack of recent studies on the epidemiology of allergic rhinitis in Greece, MASK will be the instrument which, in combination with aerobiological studies, will form the basis for reporting allergic rhinitis activity around the country. ispartof: ARCHIVES OF HELLENIC MEDICINE vol:35 issue:6 pages:824-833 status: published

127. Cathétérisme percutané de la veine humérale profonde

Author

M. Atmani, N. Drissi-Kamili, Saissy Jm, S. Berdouz, and Dimou M

Subjects
Anesthesiology and Pain Medicine, General Medicine
Abstract

Resume Une experience de 50 tentatives de catheterisme de la veine humerale profonde est rapportee. La veine satellite interne est ponctionnee, apres mise en place d'un garrot veineux, en dedans de l'artere humerale, un centimetre au-dessus du pli du coude. La veine a pu etre catheterisee dans 72 % des cas (36 malades). Le seul incident a ete a six reprises la ponction accidentelle de l'artere humerale. La duree moyenne du catheterisme a ete de 20 jours. Cette technique simple peut etre utilisee chaque fois que les veines peripheriques superficielles sont inutilisables et lorsque l'abord des gros troncs veineux centraux est dangereux ou impossible.

Published
1985

128. 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

129. 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

130. 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

131. 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

132. 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

133. Cytogenetic complexity in chronic lymphocytic leukemia: definitions, associations and clinical impact

Author

Blanca Espinet, M. Jose Calasanz, Marie Jarošová, Carolina Moreno, Julio Delgado, Andrea Visentin, Niki Stavroyianni, Rosa Collado, Florence Cymbalista, Helena Podgornik, Kostas Stamatopoulos, Zadie Davis, Michael Doubek, Claudia Haferlach, Fred Davi, Achilles Anagnostopoulos, Arnon P. Kater, Šárka Pospíšilová, Panayiotis Panayiotidis, Sabine Jeromin, David Oscier, Florence Nguyen-Khac, Maria Dimou, Neus Ruiz-Xivillé, Antonio Cuneo, Anna Puiggros, Panagiotis Baliakas, Theodoros Iliakis, Aliki Xochelli, Anastasia Athanasiadou, Alexander C. Leeksma, Paolo Ghia, Pau Abrisqueta, Karla Plevová, Virginie Eclache, George Papaioannou, Livio Trentin, Gian Matteo Rigolin, Michalis Iskas, Kristina Durechova, Evangelia Stalika, Fanny Baran-Marszak, Graduate School, CCA - Cancer biology and immunology, Clinical Haematology, Experimental Immunology, Uppsala University, MLL Münchner Leukämielabor GmbH / MLL Munich Leukemia Laboratory [Munich, Germany], General Hospital of Thessaloniki George Papanikolaou, IMIM-Hospital del Mar, Generalitat de Catalunya, Central European Institute of Technology [Brno] (CEITEC MU), Brno University of Technology [Brno] (BUT), Masaryk University [Brno] (MUNI), University Hospital Brno, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Royal Bournemouth Hospital, Università degli Studi di Ferrara = University of Ferrara (UniFE), Università degli Studi di Padova = University of Padua (Unipd), Centre for Research and Technology Hellas (CERTH), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Vall d'Hebron University Hospital [Barcelona], National and Kapodistrian University of Athens (NKUA), Consorcio Hospital General Universitario de Valencia, Universidad de Navarra [Pamplona] (UNAV), Universitat Autònoma de Barcelona (UAB), Hospital de la Santa Creu i Sant Pau, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Amsterdam institute for Infection and Immunity [Amsterdam, The Netherlands] (A3I), University Medical Centre Ljubljana [Ljubljana, Slovenia] (UMCL), Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), Lambert, Mélanie, Baliakas, P., Jeromin, S., Iskas, M., Puiggros, A., Plevova, K., Nguyen-Khac, F., Davis, Z., Matteo Rigolin, G., Visentin, A., Xochelli, A., Delgado, J., Baran-Marszak, F., Stalika, E., Abrisqueta, P., Durechova, K., Papaioannou, G., Eclache, V., Dimou, M., Iliakis, T., Collado, R., Doubek, M., Calasanz, M. J., Ruiz-Xiville, N., Moreno, C., Jarosova, M., Leeksma, A. C., Panayiotidis, P., Podgornik, H., Cymbalista, F., Anagnostopoulos, A., Trentin, L., Stavroyianni, N., Davi, F., Ghia, P., Kater, A. P., Cuneo, A., Pospisilova, S., Espinet, B., Athanasiadou, A., Oscier, D., Haferlach, C., and Stamatopoulos, K.

Subjects
Male, Chronic lymphocytic leukemia, cytogenetics, complex karyotype, prognosis, Oncology, complex karyotype, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Chronic lymphocytic leukemia, Immunology, Somatic hypermutation, Biochemistry, Somatic evolution in cancer, cytogenetics, NO, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Biomarkers, Tumor, Humans, Medicine, Survival rate, Aged, Retrospective Studies, Chromosome Aberrations, Hematology, business.industry, Cytogenetics, Cell Biology, Middle Aged, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, 3. Good health, Survival Rate, [SDV] Life Sciences [q-bio], Leukemia, 030220 oncology & carcinogenesis, Mutation, Chromosome abnormality, Female, Somatic Hypermutation, Immunoglobulin, prognosis, Tumor Suppressor Protein p53, business, Follow-Up Studies, 030215 immunology
Abstract

Recent evidence suggests that complex karyotype (CK) defined by the presence of =3 chromosomal aberrations (structural and/or numerical) identified by chromosome banding analysis (CBA) may be relevant for treatment decision-making in chronic lymphocytic leukemia (CLL). However, many challenges towards routine clinical application of CBA remain. In a retrospective study of 5290 patients with available CBA data, we explored both clinicobiological associations and the clinical impact of CK in CLL. We found that patients with =5 abnormalities, defined as high-CK, exhibit uniformly dismal clinical outcome, independently of clinical stage, TP53 aberrations (deletion of chromosome 17p and or TP53 mutations, TP53abs) and the expression of somatically hypermutated (M-CLL) or unmutated (U-CLL) immunoglobulin heavy variable genes (IGHV). Thus, they contrasted CK cases with 3 or 4 aberrations (low-CK and intermediate-CK, respectively) who followed aggressive disease courses only in the presence of TP53abs. At the other end of the spectrum, patients with CK and +12,+19 displayed an exceptionally indolent profile. Building upon CK, TP53abs and IGHV gene somatic hypermutation status, we propose a novel hierarchical model where patients with high-CK exhibit the worst prognosis, while M-CLL lacking CK or TP53abs as well as CK with +12,+19 show the longest overall survival. In conclusion, CK should not be axiomatically considered unfavorable in CLL, representing a heterogeneous group with variable clinical behavior. High-CK with =5 chromosomal aberrations emerges as prognostically adverse, independently of other biomarkers. Prospective clinical validation is warranted before finally incorporating high-CK in risk stratification of CLL.

Published
2019

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

Author

Eva Kimby, Marek Trněný, Lukas Smolej, Petra Obrtlikova, P. Panayiotidis, Michael Doubek, Ulrich Jaeger, Anna Schuh, Christian H. Geisler, Kostas Stamatopoulos, Rossella Paolini, Hamadi Zouabi, Lucia Farina, Juan C. Gomez-Garcia, Maria Dimou, Paolo Ghia, Véronique Leblond, Martin Rubio, Carol Moreno, Stefan Norin, Jehan Dupuis, Peter Hillmen, Patrick Carrington, Colm Bradley, Luigi Rigacci, Stephan Stilgenbauer, Florence Cymbalista, Emili Montserrat, Gerardo Musuraca, Šárka Pospíšilová, Marco Montillo, Adrian Bloor, Niki Stavroyianni, Roberto Marasca, Luca Laurenti, Moreno, C, Montillo, M, Panayiotidis, P, Dimou, M, Bloor, A, Dupuis, J, Schuh, A, Norin, S, Geisler, C, Hillmen, P, Doubek, M, Trněný, M, Obrtlikova, P, Laurenti, L, Stilgenbauer, S, Smolej, L, Ghia, PAOLO PROSPERO, Cymbalista, F, Jaeger, U, Stamatopoulos, K, Stavroyianni, N, Carrington, P, Zouabi, H, Leblond, V, Gomez Garcia, Jc, Rubio, M, Marasca, R, Musuraca, G, Rigacci, L, Farina, L, Paolini, R, Pospisilova, S, Kimby, E, Bradley, C, and Montserrat, E.

Subjects
Adult, Male, medicine.medical_specialty, Cyclophosphamide, Chronic lymphocytic leukemia, Antineoplastic Agents, Neutropenia, Antibodies, Monoclonal, Humanized, Ofatumumab, Drug Administration Schedule, chemistry.chemical_compound, Internal medicine, medicine, Humans, Aged, Aged, 80 and over, Chlorambucil, business.industry, Remission Induction, Antibodies, Monoclonal, Articles, Hematology, Middle Aged, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, Fludarabine, Settore MED/15 - MALATTIE DEL SANGUE, Treatment Outcome, chemistry, Retreatment, Immunology, Alemtuzumab, Female, Rituximab, business, CLL, medicine.drug
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

135. MicroRΝΑ analysis in patients with myelodysplastic neoplasms. Possible implications in risk stratification.

Author

Syriopoulou S, Kontandreopoulou CN, Diamantopoulos PT, Vlachopoulou D, Stafylidis C, Katsiampoura P, Chatzidavid S, Giannakopoulou N, Pappa V, Kotsianidis I, Hatzimichael E, Dimou M, Symeonidis A, Panayiotidis P, and Viniou NA

Abstract

MiRNAs have been identified as participants in leukemogenesis by controlling several cellular functions, such as differentiation, proliferation, and apoptosis. Their role in myelodysplastic neoplasms (MDS) pathogenesis is researched due to implementations in early identification, classification, and therapeutical options. IPSS-R, being the most widely used MDS classification, underestimates early biological events that can alter the disease's prognosis. The purpose of this study is to determine whether miRNA levels are aligned to MDS risk stratification groups and can therefore be used as diagnostic biomarkers. To evaluate miRNAs as possible biomarkers, we measured the levels of miR-181a-2-3p, miR-124-3p, miR-550a-3p, miR-155-5p, miR-151a-3p, and miR-125b-5p by a quantitative real-time PCR in bone marrow samples of 41 MDS patients. In conclusion, in myeloid malignancies, genomic characteristics may provide a wider apprehension of its clinical course and prognosis. MiRNAs constitute a possible diagnostic biomarker and therapeutic target, allowing intermediate-risk patients that express high levels of specific miRNAs to be re-classified and receive more advanced therapeutic agents. In our study, an association between high levels of miRNAs and worsening outcomes is established, supporting the need for further incorporation of molecular data into currently used classification systems.

Published
2024
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136. Therapeutic strategies and treatment sequencing in patients with chronic lymphocytic leukemia: An international study of ERIC, the European Research Initiative on CLL.

Author

Chatzikonstantinou T, Scarfò L, Minga E, Karakatsoulis G, Chamou D, Kotaskova J, Iacoboni G, Demosthenous C, Albi E, Alcoceba M, Al-Shemari S, Aurran-Schleinitz T, Bacchiarri F, Chatzileontiadou S, Collado R, Davis Z, de Deus Santos MD, Dimou M, Dmitrieva E, Donaldson D, Dos Santos G, Dreta B, Efstathopoulou M, El-Ashwah S, Enrico A, Frygier A, Galimberti S, Galitzia A, Gimeno E, Guarente V, Guieze R, Harrop S, Hatzimichael E, Herishanu Y, Hernández-Rivas JÁ, Jaksic O, Kalicińska E, Laribi K, Karakus V, Kater AP, Kho B, Kislova M, Konstantinou Ε, Koren-Michowitz M, Kotsianidis I, Kubova Z, Labrador J, Lad D, Laurenti L, Longval T, Lopez-Garcia A, Marquet J, Maslejova S, Mayor-Bastida C, Mihaljevic B, Milosevic I, Miras F, Moia R, Morawska M, Nath UK, Navarro-Bailón A, Olivieri J, Panovska-Stavridis I, Papaioannou M, Pierie C, Puiggros A, Reda G, Rigolin GM, Ruchlemer R, Schipani M, Schiwitza A, Shen Y, Shokralla T, Simkovic M, Smirnova S, Soliman DSA, Stilgenbauer S, Tadmor T, Tomic K, Tse E, Vassilakopoulos T, Visentin A, Vitale C, Vrachiolias G, Vukovic V, Walewska R, Xu Z, Yagci M, Yañez L, Yassin M, Zuchnicka J, Oscier D, Gozzetti A, Panagiotidis P, Bosch F, Sportoletti P, Espinet B, Pangalis GA, Popov VM, Mulligan S, Angelopoulou M, Demirkan F, Papajík T, Biderman B, Murru R, Coscia M, Tam C, Cuneo A, Gaidano G, Claus R, Stavroyianni N, Trentin L, Antic D, Smolej L, Kalashnikova OB, Catherwood M, Spacek M, Pospisilova S, Doubek M, Nikitin E, Chatzidimitriou A, Ghia P, and Stamatopoulos K

Abstract

Competing Interests: Thomas Chatzikonstantinou received honoraria from AbbVie. Lydia Scarfò received honoraria from AbbVie, AstraZeneca, BeiGene, Lilly, Janssen, Octapharma. Gloria Iacoboni received honoraria and travel support from Novartis, Kite/Gilead, Bristol‐Myers Squibb, Abbvie, Autolus, Miltenyi, and AstraZeneca. Rosa Collado received support for attending meetings from Janssen‐Cilag and S.A. Sara Galimberti received honoraria support for attending meetings from AbbVie, AstraZeneca, Jazz, Novartis, and Incyte, honoraria from Roche, Celgene, Pfizer, and Janssen, and support for attending meetings from Jazz, AstraZeneca, and Roche. Romain Guieze received honoraria, consulting fees, and support for attending meetings from AbbVie, Beigene, Roche, Janssen, and AstraZeneca. Eleftheria Hatzimichael received honoraria from AbbVie, Janssen‐Cilag, AstraZeneca, and Roche. Yair Herishanu received honoraria from Janssen, AbbVie, Roche, AstraZeneca, Medion, and Lilly. José‐Ángel Hernández‐Rivas received honoraria as a consultant from Janssen, AbbVie, AstraZeneca, Lilly, and BeiGene and support for attending meetings from Janssen, AbbVie, AstraZeneca, and BeiGene. Ozren Jaksic received honoraria from Johnson and Johnson, AstraZeneca, and Lilly, honoraria from Johnson and Johnson, AbbVie, AstraZeneca, and Lilly, and support for attending meetings from Johnson and Johnson, and AbbVie. Kamel Laribi received consulting fees from AbbVie, AstraZeneca, Janssen, Beigene, Takeda, and Novartis. Maya Koren‐Michowitz received honoraria from Novartis, Pfizer, and Gad Medical LTD. and support for attending meetings from Novartis. Arnon P. Kater received advisory board fees and research money from Janssen, AbbVie, BMS, AstraZeneca, and Roche/Genentech, and support for attending meetings from Janssen and AbbVie. Ioannis Kotsianidis received honoraria and consulting fees from AbbVie and Janssen. Ivana Milosevic received honoraria from AbbVie, Roche, Sandoz, AstraZeneca, and Janssen, and support for attending meetings from AbbVie, Roche, and Takeda. Almudena Navarro‐Bailón received honoraria, advisory board fees, and support for attending meetings from AbbVie, AstraZeneca, Takeda, Janssen, and Beigene. Jacopo Olivieri received honoraria from AbbVie, AstraZeneca, and Janssen. Gianluigi Reda received consulting fees from AbbVie, AstraZeneca, Janssen, and Beigene, and is currently employed by AstraZeneca. Gian M. Rigolin received honoraria for participation in speaker's bureau from AbbVie, Astra Zeneca, Beigene, and Janssen, and support for attending meetings from Janssen. Mattia Schipani received honoraria and support for attending meetings from AstraZeneca, AbbVie, and Janssen‐Cilag and owns shares of stock in AbbVie, AstraZeneca, Merck, Eli Lilly, Sanofi, Johnson and Johnson, Pfizer, Gilead, and GSK. Tereza Shokralla and Stephan Stilgenbauer reports research funding from, consultancy or advisory role for, honoraria from, speakers' bureau participation for, and travel support from AbbVie, Amgen, AstraZeneca, BeiGene, Bristol Myers Squibb, Celgene, Gilead, GlaxoSmithKline, Hoffmann‐La Roche, Incyte, Infinity, Janssen, Novartis, and Sunesis. Eric Tse received support for attending meetings from Takeda. Theodoros Vassilakopoulos received honoraria from Takeda, Roche, Genesis Pharma, Merck, Novartis, Gilead, Sandoz, AstraZeneca, Integris, and Servier, and support for attending meetings from Takeda, Roche, Genesis Pharma, Merck, Pfizer, and Winmedica. Candida Vitale received honoraria from AbbVie, consulting fees from AstraZeneca, and support for attending meetings from AstraZeneca, Takeda, and Janssen. Renata Walewska received honoraria from AbbVie, AstraZeneca, and Beigene, support for attending meetings from Janssen, AbbVie, and AstraZeneca, and advisory board fees from AbbVie, AstraZeneca, Janssen, Beigene, and SecuraBio. Lucrecia Yañez received honoraria from AbbVie, AstraZeneca, Novartis, Gilead, Janssen, Jazz, MSD, and Pfizer, support for attending meetings from AbbVie, AstraZeneca, Gilead, Janssen, and Pfizer, and advisory board fees from AbbVie, AstraZeneca, Jazz, Janssen, Beigene, and Celgene. Francesc Bosch received consulting fees, honoraria, and payment for expert testimony from AbbVie, Genentech, Novartis, Takeda, Janssen, Roche, Mundipharma, Celgene/BMS, AstraZeneca, Lilly, Beigene, Gilead and TG Therapeutics, Advantage Allogene, Lava Therapeutics, and Enterome. Stephen Mulligan received advisory board fees from AbbVie, AstraZeneca, Janssen, Roche, and BeiGene. Maria Angelopoulou received consulting fees from AbbVie, Takeda, Janssen, Roche, Genesis, Gilead, and Amgen and honoraria from AbbVie, Takeda, Roche, Genesis, Gilead, and Novartis. Fatih Demirkan received support for attending meetings from Janssen and AbbVie. Tomas Papajík received honoraria and advisory board fees from AbbVie, Janssen‐Cilag, and AstraZeneca, and support for attending meetings from AstraZeneca. Marta Coscia received honoraria, advisory board fees, and support for attending meetings from AbbVie, AstraZeneca, and Janssen. Constantine Tam received honoraria from AbbVie, Beigene, Janssen, and LOXO. Antonio Cuneo received honoraria, advisory board fees, and support for attending meetings from AbbVie, AstraZeneca, Beigene, Janssen, and Lilly. Gianluca Gaidano received honoraria from Abbvie, AstraZeneca, BeiGene, Hikma, Incyte, Janssen, and Lilly. Niki Stavroyianni received honoraria from Janssen, AbbVie, AstraZeneca, and Lilly, and support for attending meetings from Janssen and AstraZeneca. Lukas Smolej received consulting fees, honoraria, and support for attending meetings from AbbVie, AstraZeneca, and Janssen and advisory board fees from AbbVie and AstraZeneca. Martin Spacek received honoraria and consulting and advisory board fees, and support for attending meetings from AbbVie, AstraZeneca, and Janssen. Michael Doubek received research support and honoraria from AbbVie, AstraZeneca, and Janssen. Eugene Nikitin received honoraria from AbbVie. Kostas Stamatopoulos received research support from AbbVie, AstraZeneca, Janssen, Novartis, and Roche; honoraria from AbbVie, AstraZeneca, Bristol Myers Squibb, Lilly, and Janssen. Paolo Ghia received research support from AbbVie, AstraZeneca, BMS, Janssen and honoraria from AbbVie, AstraZeneca, BeiGene, BMS, Galapagos, Genmab, Janssen, Loxo Oncology @Lilly, MSD, Roche, and is an Editor of HemaSphere. Georgios Karakatsoulis, Eva Minga, Dimitra Chamou, Jana Kotaskova, Christos Demosthenous, Elisa Albi, Miguel Alcoceba, Salem Al‐Shemari, Thérèse Aurran‐Schleinitz, Francesca Bacchiarri, Sofia Chatzileontiadou, Zadie Davis, Marcos Daniel de Deus Santos, Maria Dimou, Elena Dmitrieva, David Donaldson, Gimena Dos Santos, Barbara Dreta, Maria Efstathopoulou, Shaimaa El‐Ashwah, Alicia Enrico, Andrzej Frygier, Andrea Galitzia, Eva Gimeno, Valerio Guarente, Sean Harrop, Elżbieta Kalicińska, Volkan Karakus, Bonnie Kho, Maria Kislova, Εliana Konstantinou, Zuzana Kubova, Jorge Labrador, Deepesh Lad, Luca Laurenti, Thomas Longval, Alberto Lopez‐Garcia, Juan Marquet, Stanislava Maslejova, Carlota Mayor‐Bastida, Biljana Mihaljevic, Fatima Miras, Riccardo Moia, Marta Morawska, Uttam K. Nath, Irina Panovska‐Stavridis, Maria Papaioannou, Cheyenne Pierie, Anna Puiggros, Rosa Ruchlemer, Annett Schiwitza, Yandong Shen, Tereza Shokralla, Martin Simkovic, Svetlana Smirnova, Dina S. A. Soliman, Tamar Tadmor, Kristina Tomic, Andrea Visentin, George Vrachiolias, Vojin Vukovic, Zhenshu Xu, Munci Yagci, Mohamed Yassin, Jana Zuchnicka, David Oscier, Alessandro Gozzetti, Panagiotis Panagiotidis, Blanca Espinet, Paolo Sportoletti, Gerassimos A. Pangalis, Viola M. Popov, Bella Biderman, Roberta Murru, Rainer Claus, Livio Trentin, Darko Antic, Olga B. Kalashnikova, Mark Catherwood, Sarka Pospisilova, and Anastasia Chatzidimitriou have no conflict of interest to disclose.

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

Author

Kapousouzi A, Kalala F, Sarrou S, Farmaki E, Antonakos N, Kakkas I, Kourakli A, Labropoulou V, Kelaidi C, Tsiouma G, Dimou M, Vassilakopoulos TP, Voulgarelis M, Onoufriadis I, Papadimitriou E, Polychronopoulou S, Giamarellos-Bourboulis EJ, Symeonidis A, Hadjichristodoulou C, Germenis AE, and Speletas M

Subjects
Humans, Greece epidemiology, Male, Female, Adult, Middle Aged, Child, Aged, Adolescent, Common Variable Immunodeficiency diagnosis, Common Variable Immunodeficiency complications, Common Variable Immunodeficiency epidemiology, Young Adult, Immunologic Deficiency Syndromes diagnosis, Immunologic Deficiency Syndromes epidemiology, Immunologic Deficiency Syndromes complications, Immunologic Deficiency Syndromes immunology, Agammaglobulinemia diagnosis, Agammaglobulinemia epidemiology, Agammaglobulinemia immunology, Agammaglobulinemia complications, CTLA-4 Antigen, Delayed Diagnosis statistics & numerical data
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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138. The Role of Methylation in Chronic Lymphocytic Leukemia and Its Prognostic and Therapeutic Impacts in the Disease: A Systematic Review.

Author

Chatzidavid S, Kontandreopoulou CN, Giannakopoulou N, Diamantopoulos PT, Stafylidis C, Kyrtsonis MC, Dimou M, Panayiotidis P, and Viniou NA

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., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Sevastianos Chatzidavid et al.)

Published
2024
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139. Prognostic Impact of Serum β 2 -Microglobulin Levels in Hodgkin Lymphoma Treated with ABVD or Equivalent Regimens: A Comprehensive Analysis of 915 Patients.

Author

Vassilakopoulos TP, Arapaki M, Diamantopoulos PT, Liaskas A, Panitsas F, Siakantaris MP, Dimou M, Kokoris SI, Sachanas S, Belia M, Chatzidimitriou C, Konstantinou EA, Asimakopoulos JV, Petevi K, Boutsikas G, Kanellopoulos A, Piperidou A, Lefaki ME, Georgopoulou A, Kopsaftopoulou A, Zerzi K, Drandakis I, Dimopoulou MN, Kyrtsonis MC, Tsaftaridis P, Plata E, Variamis E, Tsourouflis G, Kontopidou FN, Konstantopoulos K, Pangalis GA, Panayiotidis P, and Angelopoulou MK

Abstract

The significance of serum beta-2 microglobulin (sβ 2 m) in Hodgkin lymphoma (HL) is controversial. We analyzed 915 patients with HL, who were treated with ABVD or equivalent regimens with or without radiotherapy. Sβ 2 m 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 sβ 2 m levels were 2.20 mg/L and were elevated (>2.4 mg/L) in 383/915 patients (41.9%). Higher sβ 2 m 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, sβ 2 m > 2.0 mg/L was an independent adverse prognostic factor in the whole patient population. In multivariate overall survival analysis, sβ 2 m levels were predictive at 2.0 mg/L cutoff in the whole patient population and in advanced stages. Similarly, sβ 2 m > 2.0 mg/L independently predicted inferior HL-specific survival in the whole patient population. Our data suggest that higher sβ 2 m 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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140. The evolving landscape of COVID-19 and post-COVID condition in patients with chronic lymphocytic leukemia: A study by ERIC, the European research initiative on CLL.

Author

Visentin A, Chatzikonstantinou T, Scarfò L, Kapetanakis A, Demosthenous C, Karakatsoulis G, Minga E, Chamou D, Allsup D, Cabrero AA, Andres M, Antic D, Baile M, Baliakas P, Besikli-Dimou S, Bron D, Chatzileontiadou S, Cordoba R, Correa JG, Cuéllar-García C, De Paoli L, De Paolis MR, Delgado J, Dimou M, Donaldson D, Catherwood M, Doubek M, Efstathopoulou M, Eichhorst B, Elashwah S, Enrico A, Espinet B, Farina L, Ferrari A, Foglietta M, Frederiksen H, Fürstenau M, García-Marco JA, García-Serra R, Collado R, Gentile M, Gimeno E, Glenthøj A, da Silva MG, Hakobyan YK, Herishanu Y, Hernández-Rivas JÁ, Herold T, Innocenti I, Itchaki G, Jaksic O, Janssens A, Kalashnikova ОB, Kalicińska E, Kater AP, Kersting S, Labrador J, Lad D, Laurenti L, Levin MD, Lista E, Lopez-Garcia A, Malerba L, Marasca R, Marchetti M, Marquet J, Mattsson M, Mauro FR, Morawska M, Motta M, Munir T, Murru R, Niemann CU, Rodrigues RN, Olivieri J, Orsucci L, Papaioannou M, Pavlovsky MA, Piskunova I, Popov VM, Quaglia FM, Quaresmini G, Qvist K, Rigolin GM, Ruchlemer R, Šimkovič M, Špaček M, Sportoletti P, Stanca O, Tadmor T, Capasso A, Del Poeta G, Gutwein O, Karlsson LK, Milosevic I, Mirás F, Reda G, Saghumyan G, Shrestha A, Te Raa D, Tonino SH, Van Der Spek E, van Gelder M, van Kampen R, Wasik-Szczepanek E, Wróbel T, Segundo LYS, Yassin M, Pocali B, Vandenberghe E, Iyengar S, Varettoni M, Vitale C, Coscia M, Rambaldi A, Montserrat E, Cuneo A, Stavroyianni N, Trentin L, Stamatopoulos K, and Ghia P

Subjects
Humans, SARS-CoV-2, Post-Acute COVID-19 Syndrome, Retrospective Studies, COVID-19, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy
Abstract

In this retrospective international multicenter study, we describe the clinical characteristics and outcomes of patients with chronic lymphocytic leukemia (CLL) and related disorders (small lymphocytic lymphoma and high-count monoclonal B lymphocytosis) infected by SARS-CoV-2, including the development of post-COVID condition. Data from 1540 patients with CLL infected by SARS-CoV-2 from January 2020 to May 2022 were included in the analysis and assigned to four phases based on cases disposition and SARS-CoV-2 variants emergence. Post-COVID condition was defined according to the WHO criteria. Patients infected during the most recent phases of the pandemic, though carrying a higher comorbidity burden, were less often hospitalized, rarely needed intensive care unit admission, or died compared to patients infected during the initial phases. The 4-month overall survival (OS) improved through the phases, from 68% to 83%, p = .0015. Age, comorbidity, CLL-directed treatment, but not vaccination status, emerged as risk factors for mortality. Among survivors, 6.65% patients had a reinfection, usually milder than the initial one, and 16.5% developed post-COVID condition. The latter was characterized by fatigue, dyspnea, lasting cough, and impaired concentration. Infection severity was the only risk factor for developing post-COVID. The median time to resolution of the post-COVID condition was 4.7 months. OS in patients with CLL improved during the different phases of the pandemic, likely due to the improvement of prophylactic and therapeutic measures against SARS-CoV-2 as well as the emergence of milder variants. However, mortality remained relevant and a significant number of patients developed post-COVID conditions, warranting further investigations., (© 2023 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

Published
2023
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141. Other malignancies in the history of CLL: an international multicenter study conducted by ERIC, the European Research Initiative on CLL, in HARMONY.

Author

Chatzikonstantinou T, Scarfò L, Karakatsoulis G, Minga E, Chamou D, Iacoboni G, Kotaskova J, Demosthenous C, Smolej L, Mulligan S, Alcoceba M, Al-Shemari S, Aurran-Schleinitz T, Bacchiarri F, Bellido M, Bijou F, Calleja A, Medina A, Khan MA, Cassin R, Chatzileontiadou S, Collado R, Christian A, Davis Z, Dimou M, Donaldson D, Santos GD, Dreta B, Efstathopoulou M, El-Ashwah S, Enrico A, Fresa A, Galimberti S, Galitzia A, García-Serra R, Gimeno E, González-Gascón-Y-Marín I, Gozzetti A, Guarente V, Guieze R, Gogia A, Gupta R, Harrop S, Hatzimichael E, Herishanu Y, Hernández-Rivas JÁ, Inchiappa L, Jaksic O, Janssen S, Kalicińska E, Laribi K, Karakus V, Kater AP, Kho B, Kislova M, Konstantinou E, Koren-Michowitz M, Kotsianidis I, Kreitman RJ, Labrador J, Lad D, Levin MD, Levy I, Longval T, Lopez-Garcia A, Marquet J, Martin-Rodríguez L, Maynadié M, Maslejova S, Mayor-Bastida C, Mihaljevic B, Milosevic I, Miras F, Moia R, Morawska M, Murru R, Nath UK, Navarro-Bailón A, Oliveira AC, Olivieri J, Oscier D, Panovska-Stavridis I, Papaioannou M, Papajík T, Kubova Z, Phumphukhieo P, Pierie C, Puiggros A, Rani L, Reda G, Rigolin GM, Ruchlemer R, Daniel de Deus Santos M, Schipani M, Schiwitza A, Shen Y, Simkovic M, Smirnova S, Abdelrahman Soliman DS, Spacek M, Tadmor T, Tomic K, Tse E, Vassilakopoulos T, Visentin A, Vitale C, von Tresckow J, Vrachiolias G, Vukovic V, Walewska R, Wasik-Szczepanek E, Xu Z, Yagci M, Yañez L, Yassin M, Zuchnicka J, Angelopoulou M, Antic D, Biderman B, Catherwood M, Claus R, Coscia M, Cuneo A, Demirkan F, Espinet B, Gaidano G, Kalashnikova OB, Laurenti L, Nikitin E, Pangalis GA, Panagiotidis P, Popov VM, Pospisilova S, Sportoletti P, Stavroyianni N, Tam C, Trentin L, Chatzidimitriou A, Bosch F, Doubek M, Ghia P, and Stamatopoulos K

Abstract

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 < 0.001). STs were more frequent in males and patients with unmutated immunoglobulin heavy variable genes (OR = 1.77; 95% CI = 1.49-2.11; p < 0.001/OR = 1.89; 95% CI = 1.6-2.24; p < 0.001).CLL-directed treatment was associated with non-melanoma skin and prostate cancers (OR = 1.8; 95% CI = 1.36-2.41; p < 0.001/OR = 2.11; 95% CI = 1.12-3.97; p = 0.021). In contrast, breast cancers were more frequent in untreated patients (OR = 0.17; 95% CI = 0.08-0.33; p < 0.001).Patients with CLL and an OM had inferior overall survival (OS) than those without. AML and MDS conferred the worst OS (p < 0.001)., Interpretation: OMs in CLL impact on OS. Treatment for CLL increased the risk for AML/MDS, prostate cancer, and NMSC. FCR was associated with increased risk for AML/MDS., Funding: AbbVie, and EU/EFPIAInnovative Medicines Initiative Joint Undertaking HARMONY grant n° 116026., Competing Interests: TC received honoraria from AbbVie. LS received consulting fees from AbbVie, BeiGene, AstraZeneca, Lilly, and Janssen, honoraria from Janssen and Octapharma, support for attending meetings from BeiGene and Janssen and advisory board fees from Merck. SMu received advisory board fees from AbbVie, AstraZeneca, Janssen, Roche and BeiGene. JAHR received honoraria as a consultant from Janssen, AbbVie, AstraZeneca, Lilly, and BeiGene and support for attending meetings from Janssen, AbbVie, AstraZeneca, and BeiGene. LI received honoraria from AbbVie, Roche, and Janssen-Cilag. APK received advisory board fees and research money from Janssen, AbbVie, BMS, AstraZeneca, Roche/Genentech, support for attending meetings from Janssen and AbbVie. M-DL received travel expenses from Janssen and AbbVie. GMR received honoraria for participation to speaker's bureau from AbbVie, Astra Zeneca, Beigene, and Janssen, and support for attending meetings from Janssen. JVT received consulting fees from AbbVie, AstraZeneca, BeiGene, and Janssen, honoraria for scientific talks from AbbVie, AstraZeneca, BeiGene, Janssen, Lilly, and Roche, travel support from AbbVie, AstraZeneca, BeiGene, Janssen, Roche, and Lilly, and advisory boards fees for AbbVie, Amgen, AstraZeneca, BeiGene. GI received honoraria from Novartis, BMS, Sandoz, AstraZeneca, Janssen, Kite/Gilead, and Miltenyi, support for attending meetings from Kite/Gilead, AstraZeneca, and AbbVie and advisory board fees from Kite/Gilead, Novartis, BMS, and Autolus. FBi received support for attending meetings from AbbVie. RCo received support for attending meetings from Janssen-Cilag and S.A. SG received honoraria support for attending meetings from AbbVie, AstraZeneca, Jazz, Novartis, and Incyte, honoraria from Roche, Celgene, Pfizer, and Janssen, and support for attending meetings from Jazz, AstraZeneca, and Roche. RGS received support for attending meetings from AbbVie and S.L.U. RG received honoraria, consulting fees, and support for attending meetings from AbbVie, Beigene, Roche, Janssen, AstraZeneca. YH received honoraria from Janssen, AbbVie, Roche, AstraZeneca, Medion, and Lilly. OJ received honoraria from Johnson and Johnson, AstraZeneca, and Lilly, honoraria from Johnson and Johnson, AbbVie, AstraZeneca, and Lilly, and support for attending meetings from Johnson and Johnson, and AbbVie. LK received consulting fees from AbbVie, AstraZeneca, Janssen, Beigene, Takeda, and Novartis. MKM received honoraria from Novartis, Pfizer, and Gad Medical LTD and support for attending meetings from Novartis. IKo received honoraria and consulting fees from AbbVie and Janssen. IM received honoraria from AbbVie, Roche, Sandoz, AstraZeneca, and Janssen, and support for attending meetings from AbbVie, Roche, and Takeda. ANB received honoraria, advisory board fees and support for attending meetings from AbbVie, AstraZeneca, Takeda, Janssen, and Beigene. JO received honoraria from AbbVie, AstraZeneca, and Janssen. GR received consulting fees from AbbVie, AstraZeneca, Janssen, and Beigene, and is currently employed by AstraZeneca. TP received honoraria and advisory board fees from AbbVie, Janssen-Cilag, and AstraZeneca and support for attending meeting from AstraZeneca. MS received honoraria and support for attending meeting from AstraZeneca, AbbVie, and Janssen-Cilag and owns shares of stock in AbbVie, AstraZeneca, Merck, Eli Lilly, Sanofi, Johnson and Johnson, Pfizer, Gilead, and GSK. MSp received honoraria and consulting and advisory board fees, and support for attending meeting from AbbVie, AstraZeneca, and Janssen. ET received support for attending meetings from Takeda. TV received honoraria from Takeda, Roche, Genesis Pharma, Merck, Novartis, Gilead, Sandoz, AstraZeneca, Integris, and Servier and support for attending meetings from Takeda, Roche, Genesis Pharma, Merck, Pfizer, and Winmedica. CV received honoraria from AbbVie, consulting fees from AstraZeneca and support for attending meeting from AstraZeneca, Takeda, and Janssen. RW received honoraria from AbbVie, AstraZeneca, and Beigene, support for attending meetings from Janssen, AbbVie, and AstraZeneca and advisory board fees from AbbVie, AstraZeneca, Janssen, Beigene, and SecuraBio. EWS received honoraria from AbbVie, Roche, and Janssen-Cilag and support for attending meetings from AbbVie. LY received honoraria from AbbVie, AstraZeneca, Novartis, Gilead, Janssen, Jazz, MSD, and Pfizer, support for attending meetings from AbbVie, AstraZeneca, Gilead, Janssen, and Pfizer, and advisory board fees from AbbVie, AstraZeneca, Jazz, Janssen, Beigene, and Celgene. MAn received consulting fees from AbbVie, Takeda, Janssen, Roche, Genesis, Gilead, and Amgen and honoraria from AbbVie, Takeda, Roche, Genesis, Gilead, and Novartis. MC received honoraria, advisory board fees, and support for attending meetings from AbbVie, AstraZeneca, and Janssen. ACu received honoraria, advisory board fees, and support for attending meetings from AbbVie, AstraZeneca, Beigene, Janssen, and Lilly. FD support for attending meetings from Janssen and AbbVie. GG received honoraria, and advisory board fees from AbbVie, AstraZeneca, Beigene, Janssen and advisory board fees from Lilly. EN received honoraria from AbbVie. LSm received consulting fees, honoraria and support for attending meetings from AbbVie, AstraZeneca, and Janssen and advisory board fees from AbbVie and AstraZeneca. NS received honoraria from Janssen, AbbVie, AstraZeneca, and Lilly, and support for attending meetings from Janssen and AstraZeneca. CT received honoraria from AbbVie, Beigene, Janssen, and LOXO. FB received consulting fees, honoraria and payment for expert testimony from AbbVie, Genentech, Novartis, Takeda, Janssen, Roche, Mundipharma, Celgene/BMS, AstraZeneca, Lilly, Beigene, Gilead and TG Therapeutics, Advantage Allogene, Lava Therapeutics, and Enterome. MDo received honoraria and advisory board fees from AbbVie, AstraZeneca and Janssen, advisory board fees from Swixx, and support for attending meetings from Janssen. PG received honoraria and consulting fees from AbbVie, AstraZeneca, BMS, Janssen, Lilly/Loxo Oncology, MSD, and Roche; grant support from AbbVie, AstraZeneca, BMS, Janssen. KS received honoraria from Janssen, AbbVie, Lilly and AstraZeneca, consulting fees and support for attending meetings from Janssen and AstraZeneca. GK, EM, DC, JK, CD, MA, SA, TAS, FBa, MB, ACa, AM, AKM, RC, SC, ACh, ZD, MDi, DD, GDS, BD, ME, SEA, AE, AF, AG, EG, IGGM, AGo, AjG, RGu, SH, EH, SJ, EKa, VK, BK, MK, EK, RJK, JL, DL, IL, TL, ALG, JM, LMR, MMa, SM, CMB, BM, FM, RM, MMo, RMu, UKN, ACO, DO, IPS, MP, ZK, PP, CP, AP, LR, RR, MDDS, AS, YS, MSi, SS, DSAS, TT, KT, AV, GV, VV, ZX, MYa, MY, JZ, DA, BB, MCa, RCl, BE, OBK, LL, GP, PPa, VMP, SP, PS, LT, AC, have no conflict of interest to disclose., (© 2023 Published by Elsevier Ltd.)

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

Author

Karatrasoglou EA, Dimou M, Piperidou A, Lakiotaki E, Korkolopoulou P, and Vassilakopoulos TP

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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143. Insights into Facilitated Subcutaneous Immunoglobulin Use in Patients with Secondary Immunodeficiency Diseases: A FIGARO Subgroup Analysis.

Author

Dimou M, Speletas M, Milito C, Pyzik A, Huscher D, Kamieniak M, Pittrow D, and Borte M

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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144. N-Glycosylation of the Ig Receptors Shapes the Antigen Reactivity in Chronic Lymphocytic Leukemia Subset #201.

Author

Iatrou A, Gounari M, Sofou E, Zaragoza-Infante L, Markopoulos I, Sarrigeorgiou I, Petrakis G, Pechlivanis N, Roumeliotou-Dimou M, Panayiotidis P, Stamatopoulos B, Gkanidou M, Sandaltzopoulos R, Degano M, Koletsa T, Lymberi P, Psomopoulos F, Ghia P, Agathangelidis A, Chatzidimitriou A, and Stamatopoulos K

Subjects
Humans, Receptors, Antigen, B-Cell genetics, Receptors, Antigen, B-Cell metabolism, Glycosylation, Antigens metabolism, Leukemia, Lymphocytic, Chronic, B-Cell
Abstract

Subset #201 is a clinically indolent subgroup of patients with chronic lymphocytic leukemia defined by the expression of stereotyped, mutated IGHV4-34/IGLV1-44 BCR Ig. Subset #201 is characterized by recurrent somatic hypermutations (SHMs) that frequently lead to the creation and/or disruption of N-glycosylation sites within the Ig H and L chain variable domains. To understand the relevance of this observation, using next-generation sequencing, we studied how SHM shapes the subclonal architecture of the BCR Ig repertoire in subset #201, particularly focusing on changes in N-glycosylation sites. Moreover, we profiled the Ag reactivity of the clonotypic BCR Ig expressed as rmAbs. We found that almost all analyzed cases from subset #201 carry SHMs potentially affecting N-glycosylation at the clonal and/or subclonal level and obtained evidence for N-glycan occupancy in SHM-induced novel N-glycosylation sites. These particular SHMs impact (auto)antigen recognition, as indicated by differences in Ag reactivity between the authentic rmAbs and germline revertants of SHMs introducing novel N-glycosylation sites in experiments entailing 1) flow cytometry for binding to viable cells, 2) immunohistochemistry against various human tissues, 3) ELISA against microbial Ags, and 4) protein microarrays testing reactivity against multiple autoantigens. On these grounds, N-glycosylation appears as relevant for the natural history of at least a fraction of Ig-mutated chronic lymphocytic leukemia. Moreover, subset #201 emerges as a paradigmatic case for the role of affinity maturation in the evolution of Ag reactivity of the clonotypic BCR Ig., (Copyright © 2023 by The American Association of Immunologists, Inc.)

Published
2023
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145. Facilitated Subcutaneous Immunoglobulin Treatment in Patients with Immunodeficiencies: the FIGARO Study.

Author

Borte M, Hanitsch LG, Mahlaoui N, Fasshauer M, Huscher D, Speletas M, Dimou M, Kamieniak M, Hermann C, Pittrow D, and Milito C

Subjects
Humans, Child, Aged, Prospective Studies, Immunoglobulins, Infusions, Subcutaneous, Immunoglobulins, Intravenous therapeutic use, Immunologic Deficiency Syndromes diagnosis, Immunologic Deficiency Syndromes drug therapy, Infections drug therapy
Abstract

Purpose: The FIGARO study aims to provide insights on real-world utilization and tolerability of facilitated subcutaneous immunoglobulin (fSCIG) for primary immunodeficiency disease (PID) or secondary immunodeficiency disease (SID)., Methods: This prospective, multicenter, observational study, evaluated medical records, charts, and diaries of patients who had received at least 1 fSCIG infusion for PID or SID. Data were analyzed by cohort (PID, SID) and age groups (pediatric [< 18 years], adult [18-64 years], older adult [≥ 65 years]). Patients were followed up to 36 months., Results: The study enrolled 156 patients: 15 pediatric, 120 adult, 21 older-adult. Twelve-month follow-up data were available for 128 patients. fSCIG was mainly prescribed for PID among patients aged < 65 years and for SID among older adults. At inclusion, 75.6% received their fSCIG infusion at home, and 78.7% self-administered. Adults were more likely to receive their initial infusion at home and self-administer (81.7% and 86.6%, respectively) than pediatric patients (53.3% each) and older adults (57.1% and 52.4%, respectively). At 12 months, the proportion of patients infusing at home and self-administering increased to 85.8% and 88.2%. Regardless of age, most patients self-administered the full fSCIG dose at home every 3-4 weeks and required a single infusion site. The tolerability profile was consistent with previous pivotal trials. Acute severe bacterial infections occurred in 0%-9.1% of patients during follow-up visits (full cohort)., Conclusions: FIGARO confirms the feasibility, tolerability, and good infection control of fSCIG in PID and SID patients across the age spectrum in both the home-setting and medical facility., Trial Registration Number: ClinicalTrials.gov NCT03054181., (© 2023. The Author(s).)

Published
2023
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146. The Clinical and Prognostic Significance of Ribonucleotide Reductase Subunits RRM1 and RRM2 mRNA Levels in Patients with Chronic Lymphocytic Leukemia.

Author

Chatzidavid S, Kontandreopoulou CN, Diamantopoulos PT, Giannakopoulou N, Katsiampoura P, Stafylidis C, Dryllis G, Kyrtsonis MC, Dimou M, Panayiotidis P, and Viniou NA

Abstract

Ribonucleotide Reductase (RNR) converts ribonucleotides to deoxyribonucleotides required for DNA replication and repair. RNR consists of subunits M1 and M2. It has been studied as a prognostic factor in several solid tumors and in chronic hematological malignancies, but not in chronic lymphocytic leukemia (CLL). Peripheral blood samples were collected from 135 CLL patients. M1/M2 gene mRNA levels were measured and expressed as a RRM1-2/GAPDH ratio. M1 gene promoter methylation was studied in a patients' subgroup. M1 mRNA expression was higher in patients without anemia (p = 0.026), without lymphadenopathy (p = 0.005) and 17p gene deletion (p = 0.031). Abnormal LDH (p = 0.022) and higher Rai stage (p = 0.019) were associated with lower M1 mRNA levels. Higher M2 mRNA levels were found in patients without lymphadenopathy (p = .048), Rai stage 0 (p = 0.025) and Trisomy 12 (p = 0.025). The correlation between RNR subunits and clinic-biological characteristics in CLL patients demonstrate RNR's potential role as a prognostic factor., (© 2023. The Author(s).)

Published
2023
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147. The prognostic significance of macrocytosis in patients with myelodysplastic neoplasms.

Author

Diamantopoulos PT, Solomou E, Symeonidis A, Pappa V, Kotsianidis I, Galanopoulos A, Pontikoglou C, Anagnostopoulos A, Vassilopoulos G, Zikos P, Hatzimichael E, Papaioannou M, Megalakaki A, Vassilakopoulos T, Dimou M, Tsokanas D, Papoutselis MK, Papageorgiou S, Kourakli A, Papadaki H, Panayiotidis P, and Viniou NA

Subjects
Humans, Prognosis, Anemia, Anemia, Macrocytic, Myelodysplastic Syndromes complications, Myelodysplastic Syndromes diagnosis, Neoplasms
Published
2023
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148. Myelodysplastic neoplasm with isolated thrombocytopenia and immune thrombocytopenic purpura in adults: insights from a comparison of two national registries.

Author

Liapis K, Papadopoulos V, Pontikoglou C, Vrachiolias G, Stavroulaki E, Kourakli A, Lazaris V, Galanopoulos AG, Papoutselis M, Papageorgiou SG, Diamantopoulos PT, Pappa V, Viniou NA, Τsokanas D, Vassilakopoulos TP, Hatzimichael E, Bouronikou E, Ximeri M, Megalakaki A, Zikos P, Panayiotidis P, Dimou M, Karakatsanis S, Papaioannou M, Papadakis S, Vardi A, Kontopidou F, Harchalakis N, Adamopoulos I, Symeonidis A, Papadaki HA, and Kotsianidis I

Subjects
Adult, Humans, Platelet Count, Registries, Myelodysplastic Syndromes complications, Neoplasms, Purpura, Thrombocytopenic, Idiopathic complications, Purpura, Thrombocytopenic, Idiopathic epidemiology, Thrombocytopenia
Published
2023
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149. Incidence and risk factors for central nervous system relapse in patients with primary mediastinal large B-cell lymphoma in the rituximab era.

Author

Vassilakopoulos TP, Panitsas F, Mellios Z, Apostolidis J, Michael M, Gurion R, Ferhanoglu B, Hatzimichael E, Karakatsanis S, Dimou M, Kalpadakis C, Katodritou E, Leonidopoulou T, Kotsianidis I, Giatra H, Kanellias N, Sayyed A, Tadmor T, Akay OM, Angelopoulou MK, Horowitz N, Bakiri M, Pangalis GA, Panayiotidis P, and Papageorgiou SG

Subjects
Humans, Rituximab therapeutic use, Incidence, Neoplasm Recurrence, Local pathology, Antineoplastic Combined Chemotherapy Protocols adverse effects, Risk Factors, Cyclophosphamide, Vincristine, Doxorubicin, Chronic Disease, Central Nervous System pathology, Central Nervous System Neoplasms drug therapy, Central Nervous System Neoplasms epidemiology, Central Nervous System Neoplasms pathology, Lymphoma, B-Cell drug therapy, Lymphoma, Large B-Cell, Diffuse pathology
Abstract

Central nervous system (CNS) involvement is rare in primary mediastinal large B-cell lymphoma (PMLBCL). We aimed to evaluate the incidence of CNS relapse as first treatment failure event and the effect of the induction chemotherapy regimen, central nervous system - international prognostic index (CNS-IPI) and other clinical and laboratory variables on the risk of CNS relapse in 564 PMLBCL patients treated with immunochemotherapy. Only 17 patients (3.0%) received CNS prophylaxis. During a 55-month median follow-up only 8 patients experienced CNS relapse as first event, always isolated. The 2-year cumulative incidence of CNS relapse (CI-CNSR) was 1.47% and remained unchanged thereafter. The CI-CNSR was not affected by the chemotherapy regimen (R-CHOP or R-da-EPOCH). None of the established International Prognostic Index factors for aggressive lymphomas predicted CNS relapse in PMLBCL. The 2-year CI-CNSR in patients with versus without kidney involvement was 13.3% versus 0.96% (p < 0.001); 14.3% versus 1.13% with versus without adrenal involvement (p < 0.001); and 10.2% versus 0.97% with versus without either kidney or adrenal involvement. CNS-IPI was also predictive (2-year CI-CNSR in high-risk vs. intermediate/low-risk: 10.37% vs. 0.84%, p < 0.001). However, this association may be driven mainly by kidney and/or adrenal involvement. In conclusion, in PMLBCL, CNS relapse is rare and appears to be strongly associated with kidney and/or adrenal involvement., (© 2022 John Wiley & Sons Ltd.)

Published
2023
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150. Real world data on the prognostic significance of monocytopenia in myelodysplastic syndrome.

Author

Diamantopoulos PT, Charakopoulos E, Symeonidis A, Kotsianidis I, Viniou NA, Pappa V, Pontikoglou C, Tsokanas D, Drakos G, Kourakli A, Solomou E, Hatzimichael E, Pouli A, Kotsopoulou M, Asmanis E, Dimou M, Panayiotidis P, Papageorgiou S, Vassilopoulos G, Anagnostopoulos A, Vassilakopoulos T, Papadaki H, and Galanopoulos A

Subjects
Adult, Humans, Prognosis, Bone Marrow, Proportional Hazards Models, Myelodysplastic Syndromes complications, Myelodysplastic Syndromes diagnosis, Thrombocytopenia complications, Neutropenia
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 < 0.001], while it retained its prognostic significance in a multivariate model comprising anemia, neutropenia and thrombocytopenia [hazard ratio (HR) for OS, 1.320, p < 0.001]. Moreover, it was prognostic of a lower leukemia free survival (LFS) both in univariate analysis and in a multivariate model comprising cytopenias, bone marrow blasts, and cytogenetic risk (HR for LFS 1.27, p = 0.031). The findings regarding OS and LFR were exclusive or more pronounced in lower risk patients, respectively. Moreover, monocytopenia could divide the low and intermediate risk groups of IPSS-R in prognostically distinct subgroups. Our results redefine the prognostic role of monocytes in MDS and set the basis for further studies to validate our results and expand our knowledge on the prognostic significance of monocytopenia in MDS., (© 2022. The Author(s).)

Published
2022
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