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1. Bone marrow stromal cells reduce low-dose cytarabine-induced differentiation of acute myeloid leukemia

Author

Tomislav Smoljo, Barbara Tomic, Hrvoje Lalic, Vilma Dembitz, Josip Batinic, Antonio Bedalov, and Dora Visnjic

Subjects
cytarabine, differentiation, acute myeloid leukemia, bone marrow stromal cells, cell cycle, Therapeutics. Pharmacology, RM1-950
Abstract

Low-dose cytarabine (LDAC) is a standard therapy for elderly acute myeloid leukemia (AML) patients unfit for intensive chemotherapy. While high doses of cytarabine induce cytotoxicity, the precise mechanism of action of LDAC in AML remains elusive. In vitro studies have demonstrated LDAC-induced differentiation; however, such differentiation is seldom observed in vivo. We hypothesize that this discrepancy may be attributed to the influence of bone marrow (BM) stromal cells on AML cells. Thus, this study aimed to investigate the impact of BM stromal cells on LDAC-induced differentiation of AML cell lines and primary samples. Our results demonstrate that the presence of MS-5 stromal cells prevented LDAC-induced cell cycle arrest, DNA damage signaling and differentiation of U937 and MOLM-13 cell lines. Although transcriptomic analysis revealed that the stroma reduces the expression of genes involved in cytokine signaling and oxidative stress, data obtained with pharmacological inhibitors and neutralizing antibodies did not support the role for CXCL12, TGF-β1 or reactive oxygen species. The presence of stromal cells reduces LDAC-induced differentiation in primary samples from AML-M4 and myelodysplastic syndrome/AML patients. In conclusion, our study demonstrates that BM stroma reduces differentiation of AML induced by LDAC. These findings provide insights into the limited occurrence of terminal differentiation observed in AML patients, and suggest a potential explanation for this observation.

Published
2023
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2. P981: DISEASE CHARACTERISTICS AND TREATMENT OUTCOMES OF MYELOMA PATIENTS

Author

Efstathios Kastritis, Meral Beksac, Sorina Badelita, Eirini Katodritou, Jelena Bila, Emmanouil Spanoudakis, Güldane Cengiz Seval, Zorica Cvetkovic, Daniel Coriu, Marko Mitrovic, Carmen Saguna, Dimitra Dalampira, Anca Bojan, Josip Batinic, Samo Zver, Margarita Guenova, Arben Ivanaj, Maria Gavriatopoulou, Evangelos Terpos, and Meletios A. Dimopoulos

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Published
2023
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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. Cytarabine-induced differentiation of AML cells depends on Chk1 activation and shares the mechanism with inhibitors of DHODH and pyrimidine synthesis

Author

Barbara Tomic, Tomislav Smoljo, Hrvoje Lalic, Vilma Dembitz, Josip Batinic, Drago Batinic, Antonio Bedalov, and Dora Visnjic

Subjects
Medicine, Science
Abstract

Abstract Acute myeloid leukemia (AML) is characterized by arrested differentiation making differentiation therapy a promising treatment strategy. Recent success of inhibitors of mutated isocitrate dehydrogenase (IDH) invigorated interest in differentiation therapy of AML so that several new drugs have been proposed, including inhibitors of dihydroorotate dehydrogenase (DHODH), an enzyme in pyrimidine synthesis. Cytarabine, a backbone of standard AML therapy, is known to induce differentiation at low doses, but the mechanism is not completely elucidated. We have previously reported that 5-aminoimidazole-4-carboxamide ribonucleoside (AICAr) and brequinar, a DHODH inhibitor, induced differentiation of myeloid leukemia by activating the ataxia telangiectasia and Rad3-related (ATR)/checkpoint kinase 1 (Chk1) via pyrimidine depletion. In this study, using immunoblotting, flow cytometry analyses, pharmacologic inhibitors and genetic inactivation of Chk1 in myeloid leukemia cell lines, we show that low dose cytarabine induces differentiation by activating Chk1. In addition, cytarabine induces differentiation ex vivo in a subset of primary AML samples that are sensitive to AICAr and DHODH inhibitor. The results of our study suggest that leukemic cell differentiation stimulated by low doses of cytarabine depends on the activation of Chk1 and thus shares the same pathway as pyrimidine synthesis inhibitors.

Published
2022
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5. 5-aminoimidazole-4-carboxamide ribonucleoside induces differentiation in a subset of primary acute myeloid leukemia blasts

Author

Vilma Dembitz, Hrvoje Lalic, Ivan Kodvanj, Barbara Tomic, Josip Batinic, Klara Dubravcic, Drago Batinic, Antonio Bedalov, and Dora Visnjic

Subjects
AICAr, Acute myeloid leukemia, Differentiation, Brequinar, ATRA, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background All-trans retinoic acid (ATRA)-based treatment of acute promyelocytic leukemia (APL) is the most successful pharmacological treatment of acute myeloid leukemia (AML). Recent development of inhibitors of mutated isocitrate dehydrogenase and dihydroorotate dehydrogenase (DHODH) has revived interest in differentiation therapy of non-APL AML. Our previous studies demonstrated that 5-aminoimidazole-4-carboxamide ribonucleoside (AICAr) induced differentiation of monocytic cell lines by activating the ATR/Chk1 via pyrimidine depletion. In the present study, the effects of AICAr on the viability and differentiation of primary AML blasts isolated from bone marrow of patients with non-APL AML were tested and compared with the effects of DHODH inhibitor brequinar and ATRA. Methods Bone marrow samples were obtained from 35 patients and leukemia blasts were cultured ex vivo. The cell viability was assessed by MTT assay and AML cell differentiation was determined by flow cytometry and morphological analyses. RNA sequencing and partial data analysis were conducted using ClusterProfiler package. Statistical analysis was performed using GraphPad Prism 6.0. Results AICAr is capable of triggering differentiation in samples of bone marrow blasts cultured ex vivo that were resistant to ATRA. AICAr-induced differentiation correlates with proliferation and sensitivity to DHODH inhibition. RNA-seq data obtained in primary AML blasts confirmed that AICAr treatment induced downregulation of pyrimidine metabolism pathways together with an upregulation of gene set involved in hematopoietic cell lineage. Conclusion AICAr induces differentiation in a subset of primary non-APL AML blasts, and these effects correlate with sensitivity to a well-known, potent DHODH inhibitor.

Published
2020
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9. Impact of SARS-CoV-2 vaccination and monoclonal antibodies on outcome post CD19-CAR-T: an EPICOVIDEHA survey

Author

Jaap A. van Doesum, Jon Salmanton-García, Francesco Marchesi, Roberta Di Blasi, Iker Falces-Romero, Alba Cabirta, francesca farina, caroline besson, Barbora Weinbergerová, Jens Van Praet, Martin Schönlein, Alberto Lopez-Garcia, Sylvain Lamure, Anna Guidetti, Cristina De Ramón-Sánchez, Josip Batinic, Eleni Gavriilaki, Athanasios Tragiannidis, Maria Chiara Tisi, Gaëtan Plantefeve, Verena Petzer, Irati Ormazabal-Velez, Joyce Marques de Almeida, Monia Marchetti, Johan A. Maertens, Marina Machado, Austin G Kulasekararaj, José Ángel Hernández-Rivas, Maria Gomes da Silva, Noemí Fernández, Ildefonso Espigado, Lubos Drgona, Giulia Dragonetti, Elisabetta Metafuni, Maria Calbacho, Ola Blennow, Dominik Wolf, Bjorn van Anrooij, Raquel Nunes Rodrigues, Anna Nordlander, Juan-Alberto MARTÍN-GONZÁLEZ, Raphaël Lievin, Moraima Jiménez, Stefanie K Grafe, Ramon Garcia-Sanz, Raúl Córdoba, Laman Rahimli, Tom van Meerten, Oliver A Cornely, and Livio Pagano

Subjects
Hematology
Abstract

Patients with previous CD19 directed chimeric antigen receptor T cell therapy (CAR T)-cell therapy have a prolonged vulnerability to viral infections. Coronavirus diseases 2019 (COVID-19) has a great impact and has previously been shown to cause high mortality in this population. Until now, real world data of the impact of vaccination and treatment on patients with COVID-19 after CD19 directed CAR T-cell therapy are lacking. Therefore, this multicenter retrospective study was conducted with data from the EPICOVIDEHA survey. Sixty-four patients were identified. The overall mortality caused by COVID-19 was 31%. Patients infected with the Omicron variant had a significantly lower risk of death due to COVID-19 compared to patients infected with previous variants (7% versus 58% (P=0.012)). Twenty-six patients were vaccinated at time of COVID-19 diagnosis. Two vaccinations showed marked but unsignificant reduction risk of COVID-19 caused mortality (33.3% versus 14.2% (P=0.379)).Also the course of disease appears milder with less frequent ICU admissions (39% versus 14% (P=0.054)) and shorter duration of hospitalization (7 versus 27.5 days (P=0.022)). Of the available treatment options, only monoclonal antibodies seemed to be effectively reducing mortality from 32% to zero (P=0.036). We conclude that survival rates of CAR T-cell recipients with COVID-19 improved over time and that the combination of prior vaccination and monoclonal antibody treatment significantly reduces their risk of death.

Published
2023
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10. Accessing spoken language corpora: an overview of current approaches

Author

Elena Frick, Thomas C. Schmidt, and Josip Batinic

Subjects
Computer. Automation, World Wide Web, Linguistics and Language, business.industry, Computer science, Web application, Linguistics, Current (fluid), business, ComputingMethodologies_ARTIFICIALINTELLIGENCE, Language and Linguistics, Spoken language
Abstract

In this paper, we present an overview of freely available web applications providing online access to spoken language corpora. We explore and discuss various solutions with which the corpus providers and corpus platform developers address the needs of researchers who are working with spoken language. The paper aims to contribute to the long-overdue exchange and discussion of methods and best practices in the design of online access to spoken language corpora.

Published
2021
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11. All-trans retinoic acid induces differentiation in primary acute myeloid leukemia blasts carrying an inversion of chromosome 16

Author

Vilma, Dembitz, Hrvoje, Lalic, Barbara, Tomic, Tomislav, Smoljo, Josip, Batinic, Klara, Dubravcic, Drago, Batinic, Antonio, Bedalov, and Dora, Visnjic

Subjects
Gene Rearrangement, CD11b Antigen, Myosin Heavy Chains, Antineoplastic Agents, Cell Differentiation, Tretinoin, Histone-Lysine N-Methyltransferase, Core Binding Factor beta Subunit, Leukemia, Myeloid, Acute, Cell Line, Tumor, Chromosome Inversion, Humans, Gene Fusion, Blast Crisis, Chromosomes, Human, Pair 16, Myeloid-Lymphoid Leukemia Protein
Abstract

All-trans retinoic acid (ATRA)-based therapy for acute promyelocytic leukemia (APL), a subtype of acute myeloid leukemia (AML), is the most successful example of differentiation therapy. Although ATRA can induce differentiation in some non-APL AML cell lines and primary blasts, clinical results of adding ATRA to standard therapy in non-APL AML patients have been inconsistent, probably due to use of different regimens and lack of diagnostic tools for identifying which patients may be sensitive to ATRA. In this study, we exposed primary blasts obtained from non-APL AML patients to ATRA to test for differentiation potential in vitro. We observed increased expression of differentiation markers, indicating a response to ATRA, in four out of fifteen primary AML samples. Three samples in which CD11b increased in response to ATRA had an inversion of chromosome 16 as well as the CBFB-MYH11 fusion gene, and the fourth sample was from a patient with KMT2A-rearranged, therapy-related AML. In conclusion, we identified a subgroup of non-APL AML patients with inv(16) and CBFB-MYH11 as the most sensitive to ATRA-mediated differentiation in vitro, and our results can help identify patients who may benefit from ATRA treatment.

Published
2021

12. Antimicrobial Properties of Basil (Ocimum basilicum L.), Sage (Salvia officinalis L.), Lavender (Lavandula officinalis L.), Immortelle (Helichrysum italicum (Roth) G. Don), and Savory (Satureja montana L.) and Their Application in Hard Cheese Production

Author

Nevijo Zdolec, Marijana Franičević, Lucija Klanac, Ivana Kavain, Josip Batinić, Manuela Zadravec, Jelka Pleadin, Darko Čobanov, and Marta Kiš

Subjects
hard cheese, plant extracts, dried plants, safety, quality, Industrial medicine. Industrial hygiene, RC963-969, Industrial hygiene. Industrial welfare, HD7260-7780.8
Abstract

The aim of the study was to evaluate the antimicrobial activity of the extracted plants basil (Ocimum basilicum L.), sage (Salvia officinalis L.), lavender (Lavandula officinalis L.), immortelle (Helichrysum italicum (Roth) G. Don), savory (Satureja montana L.), and rosemary (Salvia rosmarinus Spenn.) against foodborne and clinical pathogens. Dried plants were used in the production of Dalmatian cow’s milk hard cheese at concentrations of 0.5, 1.0, 1.5, and 2% to evaluate the microbiological safety and sensory properties of novel cheeses. The broadest antimicrobial activity was found in rosemary and sage, inhibiting ten indicator pathogens, and the strongest antimicrobial activity was found in immortelle and sage, which showed the widest zones of inhibition. The most sensitive indicators were Staphylococcus species and Yersinia enterocolitica. The supplemented cheeses met the official microbiological criteria and were mycotoxin negative. The surface mycobiota of control and experimental cheeses consisted mainly of Penicillium sollitum, based on the sequence analysis of the beta-tubulin and calmodulin genes. The antifungal effect of the added plants was clearly demonstrated in cheeses with added basil and sage (p < 0.05).

Published
2024
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13. Outcomes of Ixazomib Treatment in Relapsed and Refractory Multiple Myeloma: Insights from Croatian Cooperative Group for Hematologic Diseases (KROHEM)

Author

Josip Batinić, Barbara Dreta, Goran Rinčić, Antonia Mrdeža, Karla Mišura Jakobac, Delfa Radić Krišto, Milan Vujčić, Mario Piršić, Željko Jonjić, Vlatka Periša, Jasminka Sinčić Petričević, Božena Coha, Hrvoje Holik, Toni Valković, Marija Stanić, Ivan Krečak, Ante Stojanović, Domagoj Sajfert, and Sandra Bašić-Kinda

Subjects
ixazomib, lenalidomide, multiple myeloma, relapsed/refractory, retrospective study, Medicine (General), R5-920
Abstract

Background and Objectives: Ixazomib, used in combination with lenalidomide and dexamethasone (IRd), has shown efficacy in clinical trials for relapsed/refractory multiple myeloma (RRMM). Materials and Methods: This study evaluates the real-world effectiveness and safety of IRd in Croatian RRMM patients. A retrospective analysis was conducted on 164 RRMM patients treated with ixazomib at nine Croatian haematology centres from November 2016 to February 2023. Data on patient demographics, treatment regimens, and outcomes were collected and analysed using Kaplan–Meier survival curves and Cox proportional hazards models in R. The median age at ixazomib initiation was 66 years (range 40–91). Results: The overall response rate (ORR) was 65.8%, with 42% of patients achieving a very good partial response (VGPR) or better. The median progression-free survival (PFS) was 15.4 months, while median overall survival (OS) was 28.2 months. Hematologic toxicities included anaemia (53%), neutropenia (50%), and thrombocytopenia (45%). Infective complications, primarily COVID-19 and pneumonia, were reported in 38% of patients. The safety profile was consistent with previous studies, indicating manageable adverse events. Ixazomib-based therapy is effective and well tolerated in a real-world Croatian RRMM population. Conclusions: The findings align with clinical trial results, demonstrating the applicability of ixazomib in routine clinical practice. Further studies are needed to optimise treatment sequencing and improve patient outcomes.

Published
2024
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14. 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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15. 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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16. Role of Plasmapheresis in the Management of Acute Kidney Injury in Patients With Multiple Myeloma: Should We Abandon It?

Author

Vedran, Premuzic, Josip, Batinic, Pavle, Roncevic, Nikolina, Basic-Jukic, Damir, Nemet, and Bojan, Jelakovic

Subjects
Male, Treatment Outcome, Humans, Female, Longitudinal Studies, Plasmapheresis, Acute Kidney Injury, Middle Aged, Multiple Myeloma, Survival Analysis, Follow-Up Studies, Retrospective Studies
Abstract

The aim of the current study was to determine whether plasmapheresis in combination with chemotherapy could significantly remove free light chains (FLC) in multiple myeloma (MM) patients with acute kidney injury (AKI) and therefore improve renal recovery and patient survival. During the study period, 29 patients with MM and AKI presented to our unit and were treated with two different therapy modalities (plasmapheresis with chemotherapy or bortezomib). At the end of treatment, a significant decrease of FLCs was present in the group treated with plasmapheresis compared to the bortezomib group. Patients treated with plasmapheresis had similar survival compared to patients treated with bortezomib. There was a significantly higher decrease of FLCs and longer survival in patients treated with three or more plasmapheresis sessions than in patients treated with two plasmapheresis sessions. Plasmapheresis therapy still remains a useful and effective method in the treatment of AKI in MM patients. Plasmapheresis significantly reduces FLCs compared to bortezomib especially with higher number of plasma exchange sessions but it must be combined with other chemotherapy agents in order to prolong renal recovery and therefore patient survival.

Published
2017

17. 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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18. 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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19. 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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20. 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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21. 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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