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1. Age, successive waves, immunization, and mortality in elderly COVID-19 hematological patients: EPICOVIDEHA findings

Author

Giuseppe Rossi, Jon Salmanton-García, Chiara Cattaneo, Francesco Marchesi, Julio Dávila-Valls, Sonia Martín-Pérez, Federico Itri, Alberto López-García, Andreas Glenthøj, Maria Gomes da Silva, Caroline Besson, Monia Marchetti, Barbora Weinbergerová, Ozren Jaksic, Moraima Jiménez, Yavuz M. Bilgin, Jaap Van Doesum, Francesca Farina, Pavel Žák, Luisa Verga, Graham P. Collins, Valentina Bonuomo, Jens Van Praet, Marcio Nucci, Stef Meers, Ildefonso Espigado, Nicola S. Fracchiolla, Toni Valković, Christian Bjørn Poulsen, Natasha Čolović, Giulia Dragonetti, Marie-Pierre Ledoux, Carlo Tascini, Caterina Buquicchio, Ola Blennow, Francesco Passamonti, Marina Machado, Jorge Labrador, Rafael F. Duarte, Martin Schönlein, Lucia Prezioso, Iker Falces-Romero, Austin Kulasekararaj, Carolina Garcia-Vidal, Noemí Fernández, Ghaith Abu-Zeinah, Irati Ormazabal-Vélez, Tatjana Adžić-Vukičević, Klára Piukovics, Igor Stoma, Annarosa Cuccaro, Gabriele Magliano, Tomáš Szotkowski, Tomás-José González-López, Shaimaa El-Ashwah, Rui Bergantim, Uluhan Sili, Johan Maertens, Fatih Demirkan, Cristina De Ramón, Verena Petzer, Maria Ilaria Del Principe, Milan Navrátil, Michelina Dargenio, Guldane Cengiz Seval, Michail Samarkos, Zdeněk Ráčil, László Imre Pinczés, Tobias Lahmer, Alessandro Busca, Gustavo-Adolfo Méndez, Antonio Vena, Monika M. Biernat, Maria Merelli, Maria Calbacho, Aleksandra Barać, Martina Bavastro, Alessandro Limongelli, Osman Ilhan, Dominik Wolf, Gökçe Melis Çolak, Ramón García-Sanz, Ziad Emarah, Bojana Mišković, Stefanie K. Gräfe, Miloš Mladenović, Tommaso Francesco Aiello, Lucía Núñez-Martín-Buitrago, Anna Nordlander, Elena Arellano, Giovanni Paolo Maria Zambrotta, Emanuele Ammatuna, Alba Cabirta, Maria Vittoria Sacchi, Raquel Nunes Rodrigues, Ditte Stampe Hersby, Michaela Hanakova, Laman Rahimli, Raul Cordoba, Oliver A. Cornely, Livio Pagano, Joyce MARQUES DE ALMEIDA, José-Ángel HERNÁNDEZ-RIVAS, Anna GUIDETTI, Olimpia FINIZIO, Zlate STOJANOSKI, Milche CVETANOSKI, Joseph MELETIADIS, Nick DE JONGE, Darko ANTIĆ, Natasha ALI, Maria Chiara TISI, Laura SERRANO, Gaëtan PLANTEFEVE, Nina KHANNA, Martin HOENIGL, Martin ČERŇAN, Carolina MIRANDA-CASTILLO, María FERNÁNDEZ-GALÁN, Alexandra SERRIS, Nurettin ERBEN, Rémy DULÉRY, Avinash AUJAYEB, Mario Virgilio PAPA, Jan NOVÁK, Mario DELIA, Giuseppe SAPIENZA, Florian REIZINE, Ali S. OMRANI, Roberta DI BLASI, Sylvain LAMURE, Ľuboš DRGOŇA, Nicola COPPOLA, Josip BATINIĆ, Murtadha AL-KHABORI, José-María RIBERA-SANTA SUSANA, Monica PIEDIMONTE, Jorge LOUREIRO-AMIGO, Guillemette FOUQUET, Rita FAZZI, François DANION, Jörg SCHUBERT, Baerbel HOELL-NEUGEBAUER, Nathan C. BAHR, Ayel Omar YAHIA, Ana TORRES-ATIENZA, Ikhwan RINALDI, Marina POPOVA, Hans-Beier OMMEN, Maria Enza MITRA, Malgorzata MIKULSKA, Ira LACEJ, Sofya KHOSTELIDI, Sein WIN, Donald VINH, Modar SALEH, Juergen PRATTES, Pavel JINDRA, Fabio GUOLO, Roberta DELLA PEPA, Ekaterina CHELYSHEVA, Przemyslaw ZDZIARSKI, Vivien WAI-MAN, Andrés SOTO-SILVA, Hans Martin ORTH, Sandra MALAK, Lisset LORENZO DE LA PEÑA, Martin KOLDITZ, Chi Shan KHO, Christopher H. HEATH, Ana GROH, Eleni GAVRIILAKI, Monica FUNG, Matthias EGGER, Elizabeth DE KORT, Erik DE CABO, Tania CUSHION, Fazle Rabbi CHOWDHURY, M. Mansour CEESAY, Mathias BREHON, Gina VARRICCHIO, Agostino TAFURI, María-Josefa JIMÉNEZ-LORENZO, Nikolai KLIMKO, Panagiotis TSIRIGOTIS, Anastasia ANTONIADOU, and Maria VEHRESCHILD

Subjects
Elderly, SARS-CoV-2, Hematological malignancy, High-risk patient, COVID-19, Infectious and parasitic diseases, RC109-216
Abstract

Objectives: Elderly patients with hematologic malignancies face the highest risk of severe COVID-19 outcomes. The infection's impact on different age groups remains unstudied in detail. Methods: We analyzed elderly patients (age groups: 65-70, 71-75, 76-80, and >80 years old) with hematologic malignancies included in the EPICOVIDEHA registry between January 2020 and July 2022. Univariable and multivariable Cox regression models were conducted to identify factors influencing death in COVID-19 patients with hematological malignancy. Results: The study included data from 3,603 elderly patients (aged 65 or older) with hematological malignancy, with a majority being male (58.1%) and a significant proportion having comorbidities. The patients were divided into four age groups, and the analysis assessed COVID-19 outcomes, vaccination status, and other variables in relation to age and pandemic waves. The 90-day survival rate for patients with COVID-19 was 71.2%, with significant differences between groups. The pandemic waves had varying impacts, with the first wave affecting patients over 80 years old, the second being more severe in 65-70, and the third being the least severe in all age groups. Factors contributing to 90-day mortality included age, comorbidities, lymphopenia, active malignancy, acute leukemia, less than three vaccine doses, severe COVID-19, and using only corticosteroids as treatment. Conclusion: These data underscore the heterogeneity of elderly hematological patients, highlight the different impacts of COVID-19 waves and the pivotal importance of vaccination, and may help in planning future healthcare efforts.

Published
2023
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2. Decoding the historical tale: COVID-19 impact on haematological malignancy patients—EPICOVIDEHA insights from 2020 to 2022Research in context

Author

Jon Salmanton-García, Francesco Marchesi, Francesca Farina, Barbora Weinbergerová, Federico Itri, Julio Dávila-Valls, Sonia Martín-Pérez, Andreas Glenthøj, Ditte Stampe Hersby, Maria Gomes da Silva, Raquel Nunes Rodrigues, Alberto López-García, Raúl Córdoba, Yavuz M. Bilgin, Iker Falces-Romero, Shaimaa El-Ashwah, Ziad Emarah, Caroline Besson, Milena Kohn, Jaap Van Doesum, Emanuele Ammatuna, Monia Marchetti, Jorge Labrador, Giovanni Paolo Maria Zambrotta, Luisa Verga, Ozren Jaksic, Marcio Nucci, Klára Piukovics, Alba Cabirta-Touzón, Moraima Jiménez, Elena Arellano, Ildefonso Espigado, Ola Blennow, Anna Nordlander, Stef Meers, Jens van Praet, Tommaso Francesco Aiello, Carolina Garcia-Vidal, Nicola Fracchiolla, Mariarita Sciumè, Guldane Cengiz Seval, Pavel Žák, Caterina Buquicchio, Carlo Tascini, Stefanie K. Gräfe, Martin Schönlein, Tatjana Adžić-Vukičević, Valentina Bonuomo, Chiara Cattaneo, Summiya Nizamuddin, Martin Čerňan, Gaëtan Plantefeve, Romane Prin, Tomas Szotkovski, Graham P. Collins, Michelina Dargenio, Verena Petzer, Dominik Wolf, Natasha Čolović, Lucia Prezioso, Toni Valković, Francesco Passamonti, Gustavo-Adolfo Méndez, Uluhan Sili, Antonio Vena, Martina Bavastro, Alessandro Limongelli, Rafael F. Duarte, Marie-Pierre Ledoux, Milche Cvetanoski, Zlate Stojanoski, Marina Machado, Josip Batinić, Gabriele Magliano, Monika M. Biernat, Nikola Pantić, Christian Bjørn Poulsen, Annarosa Cuccaro, Maria Ilaria Del Principe, Austin Kulasekararaj, Irati Ormazabal-Vélez, Alessandro Busca, Fatih Demirkan, Marriyam Ijaz, Nikolai Klimko, Igor Stoma, Sofya Khostelidi, Noemí Fernández, Ali S. Omrani, Rui Bergantim, Nick De Jonge, Guillemette Fouquet, Milan Navrátil, Ghaith Abu-Zeinah, Michail Samarkos, Johan Maertens, Cristina De Ramón, Anna Guidetti, Ferenc Magyari, Tomás José González-López, Tobias Lahmer, Olimpia Finizio, Natasha Ali, László Imre Pinczés, Esperanza Lavilla-Rubira, Alessandra Romano, Maria Merelli, Mario Delia, Maria Calbacho, Joseph Meletiadis, Darko Antić, José-Ángel Hernández-Rivas, Joyce Marques de Almeida, Murtadha Al-Khabori, Martin Hoenigl, Maria Chiara Tisi, Nina Khanna, Aleksandra Barać, Noha Eisa, Roberta Di Blasi, Raphaël Liévin, Carolina Miranda-Castillo, Nathan C. Bahr, Sylvain Lamure, Mario Virgilio Papa, Ayel Yahya, Avinash Aujayeb, Jan Novák, Nurettin Erben, María Fernández-Galán, José-María Ribera-Santa Susana, Ikhwan Rinaldi, Rita Fazzi, Monica Piedimonte, Rémy Duléry, Yung Gonzaga, Andrés Soto-Silva, Giuseppe Sapienza, Alexandra Serris, Ľuboš Drgoňa, Ana Groh, Laura Serrano, Eleni Gavriilaki, Athanasios Tragiannidis, Juergen Prattes, Nicola Coppola, Vladimir Otašević, Miloš Mladenović, Mirjana Mitrović, Bojana Mišković, Pavel Jindra, Sofia Zompi, Maria Vittoria Sacchi, Carolin Krekeler, Maria Stefania Infante, Daniel García-Bordallo, Gökçe Melis Çolak, Jiří Mayer, Marietta Nygaard, Michaela Hanáková, Zdeněk Ráčil, Matteo Bonanni, Philipp Koehler, Laman Rahimli, Oliver A. Cornely, Livio Pagano, Francisco Javier Martín-Vallejo, Przemyslaw Zdziarski, Hossein Zarrinfer, Jana Wittig, Sein Win, Vivien Wai-Man, Benjamín Víšek, Donald C. Vinh, Maria Vehreschild, Gina Varricchio, Panagiotis Tsirigotis, Ana Torres-Tienza, Alina Daniela Tanase, Agostino Tafuri, Maria Stamouli, Jiří Sramek, Carole Soussain, Ayten Shirinova, Jörg Schubert, Enrico Schalk, Mohammad Reza Salehi, Modar Saleh, Giorgio Rosati, Elisa Roldán, Florian Reizine, Mayara Rêgo, Isabel Regalado-Artamendi, Marina Popova, Fernando Pinto, Laure Philippe, Hans Martin Orth, Hans-Beier Ommen, Aleš Obr, Lucía Núñez-Martín-Buitrago, Nicolas Noël, Julia Neuhann, Gianpaolo Nadali, Julia A. Nacov, Ana M. Munhoz Alburquerque, Maria Enza Mitra, Malgorzata Mikulska, Sibylle Mellinghoff, Ben Mechtel, Juan-Alberto Martín-González, Sandra Malak, Jorge Loureiro-Amigo, Lisset Lorenzo De La Peña, Giulia Liberti, Marianne Landau, Ira Lacej, Martin Kolditz, Chi Shan Kho, Reham Abdelaziz Khedr, Meinolf Karthaus, Linda Katharina Karlsson, María-Josefa Jiménez-Lorenzo, Macarena Izuzquiza, Baerbel Hoell-Neugebauer, Raoul Herbrecht, Christopher H. Heath, Fabio Guolo, Jan Grothe, Antonio Giordano, Sergey Gerasymchuk, Ramón García-Sanz, Nicole García-Poutón, Vaneuza Araújo Moreira Funke, Monica Fung, Charlotte Flasshove, Luana Fianchi, Jenna Essame, Matthias Egger, Bernard Drenou, Giulia Dragonetti, Maximilian Desole, Roberta Della Pepa, Bénédicte Deau Fischer, Elizabeth De Kort, Erik De Cabo, François Danion, Etienne Daguindau, Tania Cushion, Louise Cremer, Marianna Criscuolo, Gregorio Cordini, Antonella Cingolani, Fabio Ciceri, Fazle Rabbi Chowdhury, Ekaterina Chelysheva, Adrien Chauchet, Louis Yi Ann Chai, M. Mansour Ceesay, Elena Busch, Mathias Brehon, Davimar M.M. Borducchi, Stephen Booth, Serge Bologna, Caroline Berg Venemyr, Rebeca Bailén-Almorox, Anastasia Antoniadou, Amalia N. Anastasopoulou, and Fevzi Altuntaş

Subjects
Vaccination, ICU, COVID-19, Haematological malignancy, Immunosuppression, Medicine (General), R5-920
Abstract

Summary: Background: The COVID-19 pandemic heightened risks for individuals with hematological malignancies due to compromised immune systems, leading to more severe outcomes and increased mortality. While interventions like vaccines, targeted antivirals, and monoclonal antibodies have been effective for the general population, their benefits for these patients may not be as pronounced. Methods: The EPICOVIDEHA registry (National Clinical Trials Identifier, NCT04733729) gathers COVID-19 data from hematological malignancy patients since the pandemic's start worldwide. It spans various global locations, allowing comprehensive analysis over the first three years (2020–2022). Findings: The EPICOVIDEHA registry collected data from January 2020 to December 2022, involving 8767 COVID-19 cases in hematological malignancy patients from 152 centers across 41 countries, with 42% being female. Over this period, there was a significant reduction in critical infections and an overall decrease in mortality from 29% to 4%. However, hospitalization, particularly in the ICU, remained associated with higher mortality rates. Factors contributing to increased mortality included age, multiple comorbidities, active malignancy at COVID-19 onset, pulmonary symptoms, and hospitalization. On the positive side, vaccination with one to two doses or three or more doses, as well as encountering COVID-19 in 2022, were associated with improved survival. Interpretation: Patients with hematological malignancies still face elevated risks, despite reductions in critical infections and overall mortality rates over time. Hospitalization, especially in ICUs, remains a significant concern. The study underscores the importance of vaccination and the timing of COVID-19 exposure in 2022 for enhanced survival in this patient group. Ongoing monitoring and targeted interventions are essential to support this vulnerable population, emphasizing the critical role of timely diagnosis and prompt treatment in preventing severe COVID-19 cases. Funding: Not applicable.

Published
2024
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3. S292: NIRMATRELVIR/RITONAVIR IN COVID-19 PATIENTS WITH HAEMATOLOGICAL MALIGNANCIES: A REPORT FROMTHE EPICOVIDEHA REGISTRY

Author

Jon Salmanton-García, Francesco Marchesi, Maria Gomes Da Silva, Francesca Farina, Julio Dávila-Valls, Yavuz M. Bilgin, Andreas Glenthøj, Iker Falces-Romero, Jaap Van Doesum, Jorge Labrador, Caterina Buquicchio, Shaimaa EL-Ashwah, Verena Petzer, Jens VAN Praet, Martin Schönlein, Michelina Dargenio, Gustavo-Adolfo Méndez, Stef Meers, Federico Itri, Antonio Giordano, Laszlo Imre Pinczes, Ildefonso Espigado, Zlate Stojanoski, Alberto Lopez-Garcia, Lucia Prezioso, Ozren Jaksic, Antonio Vena, Nicola Stefano Fracchiolla, Tomas Jose Gonzalez-Lopez, Natasa Čolović, Mario Delia, Barbora Weinbergerová, Monia Marchetti, Joyce Marques DE Almeida, Olimpia Finizio, Caroline Besson, Monika M. Biernat, Toni Valkovic, Tobias Lahmer, Annarosa Cuccaro, Irati Ormazabal Velez, Josip Batinic, Noemí Fernández, Nick de Jonge, Carlo Tascini, Amalia N. Anastasopoulou, Rémy Duléry, Maria Ilaria DEL Principe, Gaëtan Plantefeve, Mario Virgilio Papa, Marcio Nucci, Moraima Carmen Jimenez Balarezo, Avinash Aujayeb, Jose Angel Hernandez Rivas, Maria Merelli, Chiara Cattaneo, Ola Blennow, Anna Nordlander, Alba Cabirta, Gina Varricchio, Maria Vittoria Sacchi, Raul Cordoba, Elena Arellano, Stefanie Gräfe, Dominik Wolf, Ziad Emarah, Emanuele Ammatuna, Ditte Stampe Hersby, Sonia Martín-Pérez, Raquel Nunes Rodrigues, Laman Rahimli, Livio Pagano, and Oliver A. Cornely

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2023
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4. P1521: IMPROVED CLINICAL OUTCOME OF COVID-19 IN HAEMATOLOGIC MALIGNANCY PATIENTS RECEIVING A FOURTH DOSE OF ANTI-SARS-COV-2 VACCINE: AN EPICOVIDEHA REPORT

Author

Jon Salmanton-García, Francesco Marchesi, Andreas Glenthøj, Yavuz M. Bilgin, Jens VAN Praet, Julio Dávila-Valls, Sonia Martín-Pérez, Jorge Labrador, Jaap Van Doesum, Iker Falces-Romero, Francesca Farina, Martin Schönlein, Caroline Besson, Verena Petzer, Ildefonso Espigado, Michelina Dargenio, Avinash Aujayeb, Uluhan Sili, Laura Serrano, Laszlo Imre Pinczes, Nick de Jonge, Andrés Soto-Silva, Caterina Buquicchio, Lucia Prezioso, Monia Marchetti, Stef Meers, Alessandro Busca, Paolo Corradini, Martin Hoenigl, Philipp Koehler, Laman Rahimli, Gökçe Melis Çolak, Elena Arellano, Dominik Wolf, Stefanie Gräfe, Emanuele Ammatuna, Caroline Berg Venemyr, Oliver A. Cornely, and Livio Pagano

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2023
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6. Nirmatrelvir/ritonavir in COVID-19 patients with haematological malignancies: a report from the EPICOVIDEHA registryResearch in context

Author

Jon Salmanton-García, Francesco Marchesi, Maria Gomes da Silva, Francesca Farina, Julio Dávila-Valls, Yavuz M. Bilgin, Andreas Glenthøj, Iker Falces-Romero, Jaap Van Doesum, Jorge Labrador, Caterina Buquicchio, Shaimaa El-Ashwah, Verena Petzer, Jens Van Praet, Martin Schönlein, Michelina Dargenio, Gustavo-Adolfo Méndez, Stef Meers, Federico Itri, Antonio Giordano, László Imre Pinczés, Ildefonso Espigado, Zlate Stojanoski, Alberto López-García, Lucia Prezioso, Ozren Jaksic, Antonio Vena, Nicola S. Fracchiolla, Tomás José González-López, Natasa Colović, Mario Delia, Barbora Weinbergerová, Monia Marchetti, Joyce Marques de Almeida, Olimpia Finizio, Caroline Besson, Monika M. Biernat, Toni Valković, Tobias Lahmer, Annarosa Cuccaro, Irati Ormazabal-Vélez, Josip Batinić, Noemí Fernández, Nick De Jonge, Carlo Tascini, Amalia N. Anastasopoulou, Rémy Duléry, Maria Ilaria Del Principe, Gaëtan Plantefeve, Mario Virgilio Papa, Marcio Nucci, Moraima Jiménez, Avinash Aujayeb, José-Ángel Hernández-Rivas, Maria Merelli, Chiara Cattaneo, Ola Blennow, Anna Nordlander, Alba Cabirta, Gina Varricchio, Maria Vittoria Sacchi, Raul Cordoba, Elena Arellano, Stefanie K. Gräfe, Dominik Wolf, Ziad Emarah, Emanuele Ammatuna, Ditte Stampe Hersby, Sonia Martín-Pérez, Raquel Nunes Rodrigues, Laman Rahimli, Livio Pagano, Oliver A. Cornely, Klára Piukovics, Cristina De Ramón, François Danion, Ayel Yahya, Anna Guidetti, Carolina Garcia-Vidal, Uluhan Sili, Joseph Meletiadis, Elizabeth De Kort, Luisa Verga, Laura Serrano, Nurettin Erben, Roberta Di Blasi, Athanasios Tragiannidis, José-María Ribera-Santa Susana, Hans-Beier Ommen, Alessandro Busca, Nicola Coppola, Rui Bergantim, Giulia Dragonetti, Marianna Criscuolo, Luana Fianchi, Matteo Bonanni, Andrés Soto-Silva, Malgorzata Mikulska, Marina Machado, Chi Shan Kho, Nazia Hassan, Eleni Gavriilaki, Gregorio Cordini, Louis Yi Ann Chi, Matthias Eggerer, Martin Hoenigl, Juergen Prattes, María-Josefa Jiménez-Lorenzo, Sofia Zompi, Giovanni Paolo Maria Zambrotta, Gökçe Melis Çolak, Nicole García-Poutón, Tommaso Francesco Aiello, Romane Prin, Maria Stamouli, and Michail Samarkos

Subjects
Nirmatrelvir, SARS-CoV-2, Haematology, Malignancy, COVID-19, Medicine (General), R5-920
Abstract

Summary: Background: Nirmatrelvir/ritonavir treatment decreases the hospitalisation rate in immunocompetent patients with COVID-19, but data on efficacy in patients with haematological malignancy are scarce. Here, we describe the outcome of nirmatrelvir/ritonavir treatment in a large cohort of the latter patients. Methods: This is a retrospective cohort study from the multicentre EPICOVIDEHA registry (NCT04733729) on patients with haematological malignancy, who were diagnosed with COVID-19 between January and September 2022. Patients receiving nirmatrelvir/ritonavir were compared to those who did not. A logistic regression was run to determine factors associated with nirmatrelvir/ritonavir administration in our sample. Mortality between treatment groups was assessed with Kaplan–Meier survival plots after matching all the patients with a propensity score. Additionally, a Cox regression was modelled to detect factors associated with mortality in patients receiving nirmatrelvir/ritonavir. Findings: A total of 1859 patients were analysed, 117 (6%) were treated with nirmatrelvir/ritonavir, 1742 (94%) were treated otherwise. Of 117 patients receiving nirmatrelvir/ritonavir, 80% had received ≥1 anti-SARS-CoV-2 vaccine dose before COVID-19 onset, 13% of which received a 2nd vaccine booster. 5% were admitted to ICU. Nirmatrelvir/ritonavir treatment was associated with the presence of extrapulmonary symptoms at COVID-19 onset, for example anosmia, fever, rhinitis, or sinusitis (aOR 2.509, 95%CI 1.448–4.347) and 2nd vaccine booster (aOR 3.624, 95%CI 1.619–8.109). Chronic pulmonary disease (aOR 0.261, 95%CI 0.093–0.732) and obesity (aOR 0.105, 95%CI 0.014–0.776) were not associated with nirmatrelvir/ritonavir use. After propensity score matching, day-30 mortality rate in patients treated with nirmatrelvir/ritonavir was 2%, significantly lower than in patients with SARS-CoV-2 directed treatment other than nirmatrelvir/ritonavir (11%, p = 0.036). No factor was observed explaining the mortality difference in patients after nirmatrelvir/ritonavir administration. Interpretation: Haematological malignancy patients were more likely to receive nirmatrelvir/ritonavir when reporting extrapulmonary symptoms or 2nd vaccine booster at COVID-19 onset, as opposed to chronic pulmonary disease and obesity. The mortality rate in patients treated with nirmatrelvir/ritonavir was lower than in patients with targeted drugs other than nirmatrelvir/ritonavir. Funding: EPICOVIDEHA has received funds from Optics COMMIT (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223).

Published
2023
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7. Outcome of COVID-19 in allogeneic stem cell transplant recipients: Results from the EPICOVIDEHA registry

Author

Alessandro Busca, Jon Salmanton-García, Francesco Marchesi, Francesca Farina, Guldane Cengiz Seval, Jaap Van Doesum, Nick De Jonge, Nathan C. Bahr, Johan Maertens, Joseph Meletiadis, Nicola S. Fracchiolla, Barbora Weinbergerová, Luisa Verga, Zdeněk Ráčil, Moraima Jiménez, Andreas Glenthøj, Ola Blennow, Alina Daniela Tanase, Martin Schönlein, Lucia Prezioso, Nina Khanna, Rafael F. Duarte, Pavel Žák, Marcio Nucci, Marina Machado, Austin Kulasekararaj, Ildefonso Espigado, Elizabeth De Kort, José-María Ribera-Santa Susana, Monia Marchetti, Gabriele Magliano, Iker Falces-Romero, Osman Ilhan, Emanuele Ammatuna, Sofia Zompi, Panagiotis Tsirigotis, Anastasia Antoniadou, Giovanni Paolo Maria Zambrotta, Anna Nordlander, Linda Katharina Karlsson, Michaela Hanakova, Giulia Dragonetti, Alba Cabirta, Caroline Berg Venemyr, Stefanie Gräfe, Jens Van Praet, Athanasios Tragiannidis, Verena Petzer, Alberto López-García, Federico Itri, Ana Groh, Eleni Gavriilaki, Michelina Dargenio, Laman Rahimli, Oliver A. Cornely, Livio Pagano, EPICOVIDEHA Consortium, Juergen Prattes, Malgorzata Mikulska, Gustavo-Adolfo Méndez, Tobias Lahmer, Pavel Jindra, Anna Guidetti, Rita Fazzi, Maria Ilaria Del Principe, Cristina De Ramón, Maria Calbacho, Zlate Stojanoski, Andrés Soto, Alexandra Serris, Irati Ormazabal-Vélez, Ali S. Omrani, Milan Navrátil, Sonia Martín-Pérez, Joyce Marques De Almeida, Sylvain Lamure, Martin Kolditz, Ozren Jaksic, Martin Hoenigl, Carolina Garcia-Vidal, Noemí Fernández, Shaimaa El-Ashwah, Natasha Čolović, Martin Čerňan, Caterina Buquicchio, Valentina Bonuomo, Josip Batinić, Murtadha Al-Khabori, Tatjana Adžić-Vukičević, Juan-Alberto Martín-González, Maria Vittoria Sacchi, María-Josefa Jiménez-Lorenzo, Dominik Wolf, Maria Vehreschild, Raul Cordoba, Ramón García-Sanz, Toni Valković, Miloš Mladenović, Nicole García-Poutón, Ziad Emarah, and Julio Dávila-Valls

Subjects
allogeneic HSCT, COVID-19 infection, immunocompromised patients, SARS-CoV-2, hematological malignances, Immunologic diseases. Allergy, RC581-607
Abstract

BackgroundThe outcome of COVID-19 in allogeneic hematopoietic stem cell transplantation (HSCT) recipients is almost uniformely considered poor. The aim of present study was to retrospectively analyse the outcome and risk factors for mortality in a large series of patients who developed COVID-19 infection after an allogeneic HSCT.MethodsThis multicenter retrospective study promoted by the European Hematology Association – Infections in Hematology Study Working Group, included 326 adult HSCT patients who had COVID-19 between January 2020 and March 2022.ResultsThe median time from HSCT to the diagnosis of COVID-19 was 268 days (IQR 86-713; range 0-185 days). COVID-19 severity was mild in 21% of the patients, severe in 39% and critical in 16% of the patients. In multivariable analysis factors associated with a higher risk of mortality were, age above 50 years, presence of 3 or more comorbidities, active hematologic disease at time of COVID-19 infection, development of COVID-19 within 12 months of HSCT, and severe/critical infections. Overall mortality rate was 21% (n=68): COVID-19 was the main or secondary cause of death in 16% of the patients (n=53).ConclusionsMortality in HSCT recipients who develop COVID-19 is high and largely dependent on age, comorbidities, active hematologic disease, timing from transplant and severity of the infection.

Published
2023
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8. COVID-19 infection in adult patients with hematological malignancies: a European Hematology Association Survey (EPICOVIDEHA)

Author

Livio Pagano, Jon Salmanton-García, Francesco Marchesi, Alessandro Busca, Paolo Corradini, Martin Hoenigl, Nikolai Klimko, Philipp Koehler, Antonio Pagliuca, Francesco Passamonti, Luisa Verga, Benjamin Víšek, Osman Ilhan, Gianpaolo Nadali, Barbora Weinbergerová, Raúl Córdoba-Mascuñano, Monia Marchetti, Graham P. Collins, Francesca Farina, Chiara Cattaneo, Alba Cabirta, Maria Gomes-Silva, Federico Itri, Jaap van Doesum, Marie-Pierre Ledoux, Martin Čerňan, Ozren Jakšić, Rafael F. Duarte, Gabriele Magliano, Ali S. Omrani, Nicola S. Fracchiolla, Austin Kulasekararaj, Toni Valković, Christian Bjørn Poulsen, Marina Machado, Andreas Glenthøj, Igor Stoma, Zdeněk Ráčil, Klára Piukovics, Milan Navrátil, Ziad Emarah, Uluhan Sili, Johan Maertens, Ola Blennow, Rui Bergantim, Carolina García-Vidal, Lucia Prezioso, Anna Guidetti, Maria Ilaria del Principe, Marina Popova, Nick de Jonge, Irati Ormazabal-Vélez, Noemí Fernández, Iker Falces-Romero, Annarosa Cuccaro, Stef Meers, Caterina Buquicchio, Darko Antić, Murtadha Al-Khabori, Ramón García-Sanz, Monika M. Biernat, Maria Chiara Tisi, Ertan Sal, Laman Rahimli, Natasa Čolović, Martin Schönlein, Maria Calbacho, Carlo Tascini, Carolina Miranda-Castillo, Nina Khanna, Gustavo-Adolfo Méndez, Verena Petzer, Jan Novák, Caroline Besson, Rémy Duléry, Sylvain Lamure, Marcio Nucci, Giovanni Zambrotta, Pavel Žák, Guldane Cengiz Seval, Valentina Bonuomo, Jiří Mayer, Alberto López-García, Maria Vittoria Sacchi, Stephen Booth, Fabio Ciceri, Margherita Oberti, Marco Salvini, Macarena Izuzquiza, Raquel Nunes-Rodrigues, Emanuele Ammatuna, Aleš Obr, Raoul Herbrecht, Lucía Núñez-Martín-Buitrago, Valentina Mancini, Hawraa Shwaylia, Mariarita Sciumè, Jenna Essame, Marietta Nygaard, Josip Batinić, Yung Gonzaga, Isabel Regalado-Artamendi, Linda Katharina Karlsson, Maryia Shapetska, Michaela Hanakova, Shaimaa El-Ashwah, Zita Borbényi, Gökçe Melis Çolak, Anna Nordlander, Giulia Dragonetti, Alessio Maria Edoardo Maraglino, Amelia Rinaldi, Cristina De Ramón-Sánchez, Oliver A. Cornely, and EPICOVIDEHA working group

Subjects
COVID-19, Pandemic, Hematological malignancies, Epidemiology, EHA, Diseases of the blood and blood-forming organs, RC633-647.5, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. Methods The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. Results The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March–May 2020) and the second wave (October–December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value

Published
2021
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9. Improved Clinical Outcome of COVID-19 in Hematologic Malignancy Patients Receiving a Fourth Dose of Anti-SARS-CoV-2 Vaccine: An EPICOVIDEHA Report

Author

Jon Salmanton-García, Francesco Marchesi, Andreas Glenthøj, Yavuz M. Bilgin, Jens van Praet, Julio Dávila-Valls, Sonia Martín-Pérez, Jorge Labrador, Jaap van Doesum, Iker Falces-Romero, Francesca Farina, Martin Schönlein, Mathilde Chanut, Verena Petzer, Ildefonso Espigado, Michelina Dargenio, Avinash Aujayeb, Uluhan Sili, Laura Serrano, László Imre Pinczés, Nick de Jonge, Andrés Soto-Silva, Caterina Buquicchio, Lucia Prezioso, Monia Marchetti, Stef Meers, Alessandro Busca, Paolo Corradini, Martin Hoenigl, Philipp Koehler, Laman Rahimli, Gökçe Melis Çolak, Elena Arellano, Dominik Wolf, Stefanie Gräfe, Emanuele Ammatuna, Caroline Berg Venemyr, Oliver A. Cornely, and Livio Pagano

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2022
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10. B-cell malignancies treated with targeted drugs and SARS-CoV-2 infection: A European Hematology Association Survey (EPICOVIDEHA)

Author

Maria Stefania Infante, Jon Salmanton-García, Ana Fernández-Cruz, Francesco Marchesi, Ozren Jaksic, Barbora Weinbergerová, Caroline Besson, Rafael F. Duarte, Federico Itri, Toni Valković, Tomáš Szotkovski, Alessandro Busca, Anna Guidetti, Andreas Glenthøj, Graham P. Collins, Valentina Bonuomo, Uluhan Sili, Guldane Cengiz Seval, Marina Machado, Raul Cordoba, Ola Blennow, Ghaith Abu-Zeinah, Sylvain Lamure, Austin Kulasekararaj, Iker Falces-Romero, Chiara Cattaneo, Jaap Van Doesum, Klára Piukovics, Ali S. Omrani, Gabriele Magliano, Marie-Pierre Ledoux, Cristina de Ramon, Alba Cabirta, Luisa Verga, Alberto López-García, Maria Gomes Da Silva, Zlate Stojanoski, Stef Meers, Tobias Lahmer, Sonia Martín-Pérez, Julio Dávila-Vals, Jens Van Praet, Michail Samarkos, Yavuz M. Bilgin, Linda Katharina Karlsson, Josip Batinić, Anna Nordlander, Martin Schönlein, Martin Hoenigl, Zdeněk Ráčil, Miloš Mladenović, Michaela Hanakova, Giovanni Paolo Maria Zambrotta, Nick De Jonge, Tatjana Adžić-Vukičević, Raquel Nunes-Rodrigues, Lucia Prezioso, Milan Navrátil, Monia Marchetti, Annarosa Cuccaro, Maria Calbacho, Antonio Giordano, Oliver A. Cornely, José-Ángel Hernández-Rivas, and Livio Pagano

Subjects
SARS-CoV-2, targeted drugs, infection risk, immune system COVID19, lymphoproliferative diseases (LPD), chronic lymphocytic leukemia (CLL), Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Patients with lymphoproliferative diseases (LPD) are vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we describe and analyze the outcome of 366 adult patients with chronic lymphocytic leukemia (CLL) or non-Hodgkin Lymphoma (NHL) treated with targeted drugs and laboratory-confirmed COVID-19 diagnosed between February 2020 and January 2022. Median follow-up was 70.5 days (IQR 0-609). Most used targeted drugs were Bruton-kinase inhibitors (BKIs) (N= 201, 55%), anti-CD20 other than rituximab (N=61, 16%), BCL2 inhibitors (N=33, 9%) and lenalidomide (N=28, 8%).Only 16.2% of the patients were vaccinated with 2 or more doses of vaccine at the onset of COVID-19. Mortality was 24% (89/366) on day 30 and 36%(134/366) on the last day of follow-up. Age >75 years (p

Published
2022
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11. COVID-19 in adult acute myeloid leukemia patients: a long-term follow-up study from the European Hematology Association survey (EPICOVIDEHA)

Author

Francesco Marchesi, Jon Salmanton-García, Ziad Emarah, Klára Piukovics, Marcio Nucci, Alberto López-García, Zdeněk Ráčil, Francesca Farina, Marina Popova, Sofia Zompi, Ernesta Audisio, Marie-Pierre Ledoux, Luisa Verga, Barbora Weinbergerová, Tomas Szotkovski, Maria Gomes Da Silva, Nicola Fracchiolla, Nick De Jonge, Graham Collins, Monia Marchetti, Gabriele Magliano, Carolina García-Vidal, Monika M. Biernat, Jaap Van Doesum, Marina Machado, Fatih Demirkan, Murtadha Al-Khabori, Pavel Žák, Benjamín Víšek, Igor Stoma, Gustavo-Adolfo Méndez, Johan Maertens, Nina Khanna, Ildefonso Espigado, Giulia Dragonetti, Luana Fianchi, Maria Ilaria Del Principe, Alba Cabirta, Irati Ormazabal-Vélez, Ozren Jaksic, Caterina Buquicchio, Valentina Bonuomo, Josip Batinić, Ali S. Omrani, Sylvain Lamure, Olimpia Finizio, Noemí Fernández, Iker Falces-Romero, Ola Blennow, Rui Bergantim, Natasha Ali, Sein Win, Jens Van Praet, Maria Chiara Tisi, Ayten Shirinova, Martin Schönlein, Juergen Prattes, Monica Piedimonte, Verena Petzer, Milan Navrátil, Austin Kulasekararaj, Pavel Jindra, Jiří Sramek, Andreas Glenthøj, Rita Fazzi, Cristina De Ramón-Sánchez, Chiara Cattaneo, Maria Calbacho, Nathan C. Bahr, Shaimaa El-Ashwah, Raul Cordoba, Michaela Hanakova, Giovanni Zambrotta, Mariarita Sciumè, Stephen Booth, Raquel Nunes Rodrigues, Maria Vittoria Sacchi, Nicole García-Poutón, Juan-Alberto Martín-González, Sofya Khostelidi, Stefanie Gräfe, Laman Rahimli, Emanuele Ammatuna, Alessandro Busca, Paolo Corradini, Martin Hoenigl, Nikolai Klimko, Philipp Koehler, Antonio Pagliuca, Francesco Passamonti, Oliver A. Cornely, and Livio Pagano

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

Patients with acute myeloid leukemia (AML) are at high risk of dying from coronavirus disease 2019 (COVID-19). The optimal management of AML patients with COVID-19 has not been established. Our multicenter study included 388 adult AML patients diagnosed with COVID-19 between February 2020 and October 2021. The vast majority were receiving or had received AML treatment in the preceding 3 months. COVID-19 was severe in 41.2% and critical in 21.1% of cases. The chemotherapeutic schedule was modified in 174 patients (44.8%), delayed in 68 and permanently discontinued in 106. After a median follow-up of 325 days, 180 patients (46.4%) had died; death was attributed to COVID-19 (43.3%), AML (26.1%) or to a combination of both (26.7%), whereas in 3.9% of cases the reason was unknown. Active disease, older age, and treatment discontinuation were associated with death, whereas AML treatment delay was protective. Seventy-nine patients had a simultaneous AML and COVID-19 diagnosis, with better survival when AML treatment could be delayed (80%; P

Published
2022
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12. Clinical Impact of Polymerase Chain Reaction-Based Aspergillus and Azole Resistance Detection in Invasive Aspergillosis: A Prospective Multicenter Study

Author

Sammy Huygens, Albert Dunbar, Jochem B Buil, Corné H W Klaassen, Paul E Verweij, Karin van Dijk, Nick de Jonge, Jeroen J W M Janssen, Walter J F M van der Velden, Bart J Biemond, Aldert Bart, Anke H W Bruns, Pieter-Jan A Haas, Astrid M P Demandt, Guy Oudhuis, Peter von dem Borne, Martha T van der Beek, Saskia K Klein, Peggy Godschalk, Lambert F R Span, Douwe F Postma, Greetje A Kampinga, Johan Maertens, Katrien Lagrou, Toine Mercier, Ine Moors, Jerina Boelens, Dominik Selleslag, Marijke Reynders, Willemien Zandijk, Jeanette K Doorduijn, Jan J Cornelissen, Alexander F A D Schauwvlieghe, and Bart J A Rijnders

Subjects
Aspergillus PCR, Microbiology (medical), invasive aspergillosis, Infectious Diseases, azole resistance, clinical impact
Abstract

Background Invasive aspergillosis (IA) by a triazole-resistant Aspergillus fumigatus is associated with high mortality. Real-time resistance detection will result in earlier initiation of appropriate therapy. Methods In a prospective study, we evaluated the clinical value of the AsperGenius polymerase chain reaction (PCR) assay in hematology patients from 12 centers. This PCR assay detects the most frequent cyp51A mutations in A. fumigatus conferring azole resistance. Patients were included when a computed tomography scan showed a pulmonary infiltrate and bronchoalveolar fluid (BALf) sampling was performed. The primary end point was antifungal treatment failure in patients with azole-resistant IA. Results Of 323 patients enrolled, complete mycological and radiological information was available for 276 (94%), and probable IA was diagnosed in 99/276 (36%). Sufficient BALf for PCR testing was available for 293/323 (91%). Aspergillus DNA was detected in 116/293 (40%) and A. fumigatus DNA in 89/293 (30%). The resistance PCR was conclusive in 58/89 (65%) and resistance detected in 8/58 (14%). Two had a mixed azole-susceptible/azole-resistant infection. In the 6 remaining patients, treatment failure was observed in 1. Galactomannan positivity was associated with mortality (P = .004) while an isolated positive Aspergillus PCR was not (P = .83). Conclusions Real-time PCR-based resistance testing may help to limit the clinical impact of triazole resistance. In contrast, the clinical impact of an isolated positive Aspergillus PCR on BALf seems limited. The interpretation of the EORTC/MSGERC PCR criterion for BALf may need further specification (eg, minimum cycle threshold value and/or PCR positive on >1 BALf sample).

Published
2023

13. Outcome of infection with omicron SARS-CoV-2 variant in patients with hematological malignancies: An EPICOVIDEHA survey report

Author

Ola Blennow, Jon Salmanton‐García, Piotr Nowak, Federico Itri, Jaap Van Doesum, Alberto López‐García, Francesca Farina, Ozren Jaksic, László Imre Pinczés, Yavuz M. Bilgin, Iker Falces‐Romero, Moraima Jiménez, Irati Ormazabal‐Vélez, Barbora Weinbergerová, Rémy Duléry, Zlate Stojanoski, Tobias Lahmer, Noemí Fernández, José‐Ángel Hernández‐Rivas, Verena Petzer, Nick De Jonge, Andreas Glenthøj, Cristina De Ramón, Monika M. Biernat, Nicola Fracchiolla, Avinash Aujayeb, Jens Van Praet, Martin Schönlein, Gustavo‐Adolfo Méndez, Chiara Cattaneo, Anna Guidetti, Mariarita Sciumè, Emanuele Ammatuna, Raul Cordoba, Nicole García‐Poutón, Stefanie Gräfe, Alba Cabirta, Dominik Wolf, Anna Nordlander, Ramón García‐Sanz, Mario Delia, Caroline Berg Venemyr, Clara Brones, Roberta Di Blasi, Elizabeth De Kort, Stef Meers, Sylvain Lamure, Laura Serrano, Maria Merelli, Nicola Coppola, Rui Bergantim, Caroline Besson, Milena Kohn, Jessica Petiti, Carolina Garcia‐Vidal, Michelina Dargenio, François Danion, Marina Machado, Rebeca Bailén‐Almorox, Martin Hoenigl, Giulia Dragonetti, Louis Yi Ann Chai, Chi Shan Kho, Matteo Bonanni, Raphaël Liévin, Francesco Marchesi, Oliver A. Cornely, Livio Pagano, Institut Català de la Salut, [Blennow O, Nowak P] Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden. [Salmanton-García J] Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Excellence Center for Medical Mycology (ECMM), University of Cologne, Cologne, Germany. Faculty of Medicine and University Hospital Cologne, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany. [Itri F] Department of Clinical and Biological Sciences, San Luigi Gonzaga Hospital – Orbassano, Orbassano, Italy. [Van Doesum J] Department of Hematology, University Medical Center Groningen, Groningen, The Netherlands. [López-García A] Health Research Institute IIS-FJD, Fundacion Jimenez Diaz University Hospital, Madrid, Spain. [Jiménez M, Cabirta A] Servei d’Hematologia, Vall d'Hebron Hospital Universitari, Barcelona, Spain. Experimental Hematology, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain, Vall d'Hebron Barcelona Hospital Campus, Stem Cell Aging Leukemia and Lymphoma (SALL), Blennow, Ola, Salmanton-García, Jon, Nowak, Piotr, Itri, Federico, Van Doesum, Jaap, López-García, Alberto, Farina, Francesca, Jaksic, Ozren, Pinczés, László Imre, Bilgin, Yavuz M, Falces-Romero, Iker, Jiménez, Moraima, Ormazabal-Vélez, Irati, Weinbergerová, Barbora, Duléry, Rémy, Stojanoski, Zlate, Lahmer, Tobia, Fernández, Noemí, Hernández-Rivas, José-Ángel, Petzer, Verena, De Jonge, Nick, Glenthøj, Andrea, De Ramón, Cristina, Biernat, Monika M, Fracchiolla, Nicola, Aujayeb, Avinash, Van Praet, Jen, Schönlein, Martin, Méndez, Gustavo-Adolfo, Cattaneo, Chiara, Guidetti, Anna, Sciumè, Mariarita, Ammatuna, Emanuele, Cordoba, Raul, García-Poutón, Nicole, Gräfe, Stefanie, Cabirta, Alba, Wolf, Dominik, Nordlander, Anna, García-Sanz, Ramón, Delia, Mario, Berg Venemyr, Caroline, Brones, Clara, Di Blasi, Roberta, De Kort, Elizabeth, Meers, Stef, Lamure, Sylvain, Serrano, Laura, Merelli, Maria, Coppola, Nicola, Bergantim, Rui, Besson, Caroline, Kohn, Milena, Petiti, Jessica, Garcia-Vidal, Carolina, Dargenio, Michelina, Danion, Françoi, Machado, Marina, Bailén-Almorox, Rebeca, Hoenigl, Martin, Dragonetti, Giulia, Chai, Louis Yi Ann, Kho, Chi Shan, Bonanni, Matteo, Liévin, Raphaël, Marchesi, Francesco, Cornely, Oliver A, Pagano, Livio, and Hematology

Subjects
Science & Technology, SARS-CoV-2, COVID-19, Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES], Hematology, Neoplasms::Neoplasms by Site::Hematologic Neoplasms [DISEASES], Humans, Surveys and Questionnaires, Hematologic Neoplasms, COVID-19 (Malaltia), Cancer development and immune defence Radboud Institute for Health Sciences [Radboudumc 2], Settore MED/15 - MALATTIE DEL SANGUE, Sang - Malalties, Medicine and Health Sciences, virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES], Surveys and Questionnaire, neoplasias::neoplasias por localización::neoplasias hematológicas [ENFERMEDADES], Life Sciences & Biomedicine, Human
Abstract

SARS-CoV-2; Hematological malignancies SARS-CoV-2; Neoplasias hematológicas SARS-CoV-2; Neoplasies hematològiques Optics COMMIT (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States, Grant/Award Number: Project 2020-8223.

Published
2022
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14. Antifungal prophylaxis in adult patients with acute myeloid leukaemia treated with novel targeted therapies: a systematic review and expert consensus recommendation from the European Hematology Association

Author

Jannik Stemler, Nick de Jonge, Nicole Skoetz, János Sinkó, Roger J Brüggemann, Alessandro Busca, Ronen Ben-Ami, Zdeněk Ráčil, Vanessa Piechotta, Russell Lewis, and Oliver A Cornely

Subjects
Adult, Leukemia, Myeloid, Acute, Antifungal Agents, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Mycoses, Quality of Life, Humans, Hematology, Triazoles
Abstract

Item does not contain fulltext On the basis of improved overall survival, treatment guidelines strongly recommend antifungal prophylaxis during remission induction chemotherapy for patients with acute myeloid leukaemia. Many novel targeted agents are metabolised by cytochrome P450, but potential drug-drug interactions (DDIs) and the resulting risk-benefit ratio have not been assessed in clinical trials, leading to uncertainty in clinical management. Consequently, the European Haematology Association commissioned experts in the field of infectious diseases, haematology, oncology, clinical pharmacology, and methodology to develop up-to-date recommendations on the role of antifungal prophylaxis and management of pharmacokinetic DDIs with triazole antifungals. A systematic literature review was performed according to Cochrane methods, and recommendations were developed by use of the Grading of Recommendations Assessment, Development and Evaluation Evidence to Decision framework. We searched MEDLINE, Embase, and Cochrane Library, including Central Register of Controlled Trials, for randomised controlled trials and systematic reviews published from inception to March 10, 2020. We excluded studies that were not published in English. Evidence for any identified novel agent that is active against acute myeloid leukaemia was reviewed for the following outcomes: incidence of invasive fungal disease, prolongation of hospitalisation, days spent in intensive-care unit, mortality due to invasive fungal disease, quality of life, and potential DDIs. Recommendations and consensus statements were compiled for each targeted drug for patients with acute myeloid leukaemia and each specific setting. Evidence-based recommendations were developed for hypomethylating agents, midostaurin, and the venetoclax-hypomethylating agent combination. For all other agents, consensus statements were given for specific therapeutic settings, specifically for the management of patients with relapsed or refractory acute myeloid leukaemia, monotherapy, and combination with chemotherapy. Antifungal prophylaxis is recommended with moderate strength in most settings, and strongly recommended if the novel acute myeloid leukaemia agent is administered in combination with intensive induction chemotherapy. For ivosidenib, lestaurtinib, quizartinib, and venetoclax, we moderately recommend adjusting the dose of the antileukaemic agent during administration of triazoles. This is the first guidance supporting clinical decision making on antifungal prophylaxis in recipients of novel targeted drugs for acute myeloid leukaemia. Future studies including therapeutic drug monitoring will need to determine the role of dosage adjustment of novel antileukaemic drugs during concomitant administration of CYP3A4-inhibiting antifungals with respect to adverse effects and remission status.

Published
2022
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15. The DNA methylation inhibitor induces telomere dysfunction and apoptosis of leukemia cells that is attenuated by telomerase over-expression

Author

Dawei Xu, Bingnan Li, Xiaolu Zhang, Nick de Jonge, and Magnus Björkholm

Subjects
Adult, Male, Telomerase, DNA damage, TERT, DNA Methyltransferase Inhibitor, Apoptosis, Biology, Young Adult, AML, Cell Line, Tumor, Humans, Telomerase reverse transcriptase, neoplasms, Aged, Myeloid leukemia, Telomere, DNA Methylation, Middle Aged, Molecular biology, DNMT inhibitors, Leukemia, Myeloid, Acute, Oncology, DNA methylation, Cancer cell, Cancer research, Azacitidine, Female, Research Paper, DNA Damage
Abstract

// Xiaolu Zhang 1, * , Bingnan Li 1, * , Nick de Jonge 1 , Magnus Bjorkholm 1 , Dawei Xu 1 1 Department of Medicine, Division of Hematology and Center for Molecular Medicine, Karolinska Institutet and Karolinska University Hospital Solna, Stockholm, Sweden * These authors have contributed equally to this work Correspondence to: Dawei Xu, e-mail: Dawei.Xu@ki.se Keywords: AML, Apoptosis, DNMT inhibitors, Telomerase, Telomere, TERT Received: November 16, 2014 Accepted: December 14, 2014 Published: January 06, 2015 ABSTRACT DNA methyltransferase inhibitors (DNMTIs) such as 5-azacytidine (5-AZA) have been used for treatment of acute myeloid leukemia (AML) and other malignancies. Although inhibiting global/gene-specific DNA methylation is widely accepted as a key mechanism behind DNMTI anti-tumor activity, other mechanisms are likely involved in DNMTI's action. Because telomerase reverse transcriptase (TERT) plays key roles in cancer through telomere elongation and telomere lengthening-independent activities, and TERT has been shown to confer chemo- or radio-resistance to cancer cells, we determine whether DNMTIs affect telomere function and whether TERT/telomerase interferes with their anti-cancer efficacy. We showed that 5-AZA induced DNA damage and telomere dysfunction in AML cell lines by demonstrating the presence of 53-BP1 foci and the co-localization of 53-BP1 foci with telomere signals, respectively. Telomere dysfunction was coupled with diminished TERT expression, shorter telomere and apoptosis in 5-AZA-treated cells. However, 5-AZA treatment did not lead to changes in the methylation status of subtelomere regions. Down-regulation of TERT expression similarly occurred in primary leukemic cells derived from AML patients exposed to 5-AZA. TERT over-expression significantly attenuated 5-AZA-mediated DNA damage, telomere dysfunction and apoptosis of AML cells. Collectively, 5-AZA mediates the down-regulation of TERT expression, and induces telomere dysfunction, which consequently exerts an anti-tumor activity.

Published
2015

17. Abstract 3816: The DNA methylation inhibitor induces telomere dysfunction and apoptosis of leukemia cells that is attenuated by telomerase over-expression

Author

Dawei Xu, Nick de Jonge, Xiaolu Zhang, Bingnan Li, and Magnus Björkholm

Subjects
Cancer Research, Telomerase, Oncology, DNA damage, DNA methylation, Cancer cell, Cancer research, DNA Methyltransferase Inhibitor, Myeloid leukemia, Telomerase reverse transcriptase, Biology, Molecular biology, Telomere
Abstract

DNA methyltransferase inhibitors (DNMTIs) such as 5-azacytidine (5-AZA) have been used for the treatment of acute myeloid leukemia (AML) and other malignancies, and inhibition of global/gene-specific DNA methylation is widely accepted as a key mechanism behind their anti-tumor activity. It is currently unclear whether other mechanisms are involved in DNMTI's action. Because telomerase or telomerase reverse transcriptase (TERT) plays a key role in malignant transformation and progression through telomere elongation and other telomere lengthening-independent activities, and TERT or telomerase has been shown to confer chemo- or radio-resistance to cancer cells, we determine whether DNMTIs affect telomere function and whether TERT/telomerase interferes with their anti-cancer efficacy. We showed that 5-AZA induced DNA damage and telomere dysfunction in AML cell lines by demonstrating the presence of 53-BP1 foci and the co-localization of 53-BP1 foci with telomere signals, respectively. Telomere dysfunction was coupled with diminished TERT expression, shorter telomere and apoptosis in 5-AZA-treated cells. However, 5-AZA treatment did not lead to changes in the methylation status of subtelomere regions. Downregulation of TERT expression similarly occurred in primary leukemic cells derived from AML patients exposed to 5-AZA. TERT over-expression significantly attenuated 5-AZAmediated DNA damage, telomere dysfunction and apoptosis of AML cells. Taken together, 5-AZA mediates the down-regulation of TERT expression, and induces telomere dysfunction,which consequently exerts an anti-tumor activity. These findings may have implications in DNMTI and telomerase-based strategies for cancer therapeutics. Citation Format: Bingnan Li, Xiaolu Zhang, Nick de Jonge, Magnus Björkholm, Dawei Xu. The DNA methylation inhibitor induces telomere dysfunction and apoptosis of leukemia cells that is attenuated by telomerase over-expression. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3816. doi:10.1158/1538-7445.AM2015-3816

Published
2015
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19. Dexamethasone treatment for COVID-19 is related to increased mortality in hematologic malignancy patients: results from the EPICOVIDEHA registry.

Author

Aiello TF, Salmanton-Garcia J, Marchesi F, Weinbergerova B, Glenthoj A, Van Praet J, Farina F, Davila-Valls J, Martin-Perez S, El-Ashwah S, Schonlein M, Falces-Romero I, Labrador J, Sili U, Buquicchio C, Vena A, Plantefeve G, Petzer V, Biernat MM, Lahmer T, Espigado I, Van Doesum J, Blennow O, Piukovics K, Tascini C, Samarkos M, Bilgin YM, Fianchi L, Itri F, Valković T, Fracchiolla NS, Dargenio M, Jimenez M, Magyari F, Lopez-Garcia A, Prezioso L, Čolović N, Shumilov E, Abu-Zeinah G, Krekeler C, Lavilla-Rubira E, Papa MV, Gonzalez-Lopez TJ, Pinczes LI, Demirkan F, Ali N, Besson C, Fouquet G, Romano A, Hernandez-Rivas JA, Del Principe MI, Aujayeb A, Merelli M, Lamure S, De Almeida JM, Da Silva MG, Eisa N, Meletiadis J, Rinaldi I, Finizio O, Jaksic O, Delia M, Nizamuddin S, Marchetti M, Ijaz M, Machado M, Bailen-Almorox R, Čerňan M, Coppola N, Gavriilaki E, Cattaneo C, Groh A, Stojanoski Z, Erben N, Pantic N, Mendez GA, Di Blasi R, Meers S, De Ramon C, Bahr NC, Emarah Z, Varricchio G, Cvetanoski M, Garcia-Sanz R, Mitrovic M, Lievin R, Hanakova M, Račil Z, Vehreschild M, Tragiannidis A, Rodrigues RN, Garcia-Bordallo D, Cordoba R, Cabirta A, Nordlander A, Ammatuna E, Arellano E, Wolf D, Prin R, Limongelli A, Bavastro M, Colak GM, Grafe S, Hersby DS, Rahimli L, Cornely OA, Garcia-Vidal C, Pagano L, and Study Group E

Subjects
Humans, Male, Female, Aged, Middle Aged, Adult, Aged, 80 and over, Dexamethasone therapeutic use, Hematologic Neoplasms mortality, Hematologic Neoplasms drug therapy, Registries, COVID-19 mortality, COVID-19 complications, SARS-CoV-2 isolation & purification, COVID-19 Drug Treatment
Published
2024
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