ISSN 2531-1379 VOLUME 46, ISSUE 1, JANUARY-MARCH, 2024 HEMATOLOGY TRANSFUSION AND CELL THERAPY
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TaggedH1Hematology, Transfusion and Cell Therapy TaggedP ISSN 2531-1379 print version ISSN 2531-1387 online versionTaggedEnd EDITOR INCHIEF Eduardo Magalh~aes Rego, Ribeir~ao Preto, Brazil DEPUTYEDITOR Erich Vinicius de Paula, Campinas, Brazil ASSOCIATE EDITORS Alfredo Mendrone Junior S~ao Paulo, Brazil Belinda Pinto Sim~oes Ribeir~ao Preto, Brazil Behnaz Bayat Giessen, Germany Carla Luana Dinardo S~ao Paulo, Brazil CarlosS ergio Chiattone S~ao Paulo, Brazil C armino Antonio de Souza Campinas, Brazil DanteM ario Langhi Junior S~ao Paulo, Brazil Dimas Tadeu Covas Ribeir~ao Preto, Brazil Elvira Deolinda Rodrigues Pereira Velloso S~ao Paulo, Brazil Fabiola Traina Ribeir~ao Preto, Brazil Helio Moraes de Souza Uberaba, Brazil Irene Lorand-Metze Campinas, Brazil Jos e Orlando Bordin S~ao Paulo, Brazil Luis Fernando S. Bouzas Rio de Janeiro, Brazil Marcelo Pasquini Wisconsin, USA M arcio Nucci Rio de Janeiro, Brazil Marcos Borato Viana Belo Horizonte, Brazil Marcos de Lima Cleveland, USA Margareth Castro Ozelo Campinas, Brazil Maria Helena Pitombeira Fortaleza, Brazil Maria Stella Figueiredo S~ao Paulo, Brazil Marilda de Souza Gon¸calves Salvador, Brazil Nelson Hamerschlak S~ao Paulo, Brazil Nelson Spector Rio de Janeiro, Brazil Nicola Conran Campinas, Brazil PauloS ergio da Silva Santos S~ao Paulo, Brazil Roberto Passetto Falc~ao Ribeir~ao Preto, Brazil Rodrigo Tocantins Calado Ribeir~ao Preto, Brazil Sara Teresinha Olalla Saad Campinas, Brazil Silvia Maria Meira Magalh~aes Fortaleza, Brazil Valder Arruda Philadelphia, USA Vanderson Rocha S~ao Paulo, Brazil Vania Tietsche de Moraes Hungria S~ao Paulo, Brazil Editorial Board Alois Gratw€ohl Basel, Switzerland Alvaro Urbano-Ispizua Barcelona, Spain Andrea Bacigalupo Genoa, Italy ^Angelo Maiolino Rio de Janeiro, Brazil Antonio Fabron J unior Marilia, Brazil Christian Gisselbrecht Paris, France Corrado Tarella Turin, Italy Daniel Tabak Rio de Janeiro, Brazil DavidG omez Almaguer Mexico City, Mexico Elbio A. DAmico S~ao Paulo, Brazil Enric Carreras Barcelona, Spain Eugenia Maria Amorim Ubiali - Ribeir~ao Preto, Brazil Fernando Ferreira Costa, Campinas, Brazil Frederico Luiz Dulley S~ao Paulo, Brazil Gino Santini Genoa, Italy Guillermo Dighiero Montevideo, Uruguay Guillermo Ruiz-Arguelles Puebla, Mexico Jesus Fernando San Miguel Salamanca, Spain Jo~ao Carlos Pina Saraiva Bel em, Brazil La ercio de Melo Belo Horizonte, Brazil L ılian Maria Castilho Campinas, Brazil Linamara Rizzo Batistella S~ao Paulo, Brazil Lucia Mariano da Rocha Silla Porto Alegre, Brazil Marcos Antonio Zago Ribeir~ao Preto, Brazil Maria de Lourdes L. F. Chauffaile S~ao Paulo, Brazil Maria do Socorro P. de Oliveira Rio de Janeiro, Brazil Mario Cazolla Pavia, Italy Mary Evelyn Flowers Seattle, USA Nelson Abrahin Fraiji Manaus, Brazil Nelson J. Chao Durham, USA Paul M. Ness Baltimore, USA PauloC esar Naoum S~ao Jos e do Rio Preto, Brazil Raul C. Ribeiro Memphis, USA Raul Gabus Montevideo, Uruguay Ricardo Pasquini Curitiba, Brazil Richard K. Burt Chicago, USA Sergio Giralt New York, USA V^ania Tietsche Hungria S~ao Paulo, Brazil Vicente Odone Filho S~ao Paulo, Brazil PAST EDITORS Antonio P. Capanema 1973-1981; Milton A. Ruiz 1981-1990; Carlos S. Chiattone 1991-1994; Milton A. Ruiz 1995-2014; Fernando Ferreira Costa 2015-2022. The Hematology, Blood Transfusion and Cell Therapy succeeded the Revista Brasileira de Hematologia e Hemoterapia (Brazilian Journal of Hematology and Hemotherapy) , ISSN 1516-8484, which succeeded the Boletim da Sociedade Brasileira de Hematologia e Hemoterapia (Bulletin of the Brazilian Society of Hematology and Hemotherapy) ISSN 0102-7662, which was published from 1973 to 1998 with 179 issues in 20 volumes. ABHH Rua Diogo de Faria, 775/conjunto 133 04037-002 Vila Clementino - S~ao Paulo/SP - Brazil (11) 2369-7767 / (11) 2338-6764 (WhatsApp) E-mail: abhh@abhh.org.br www.abhh.org.br HTCT Internal Editorial Committee Executive Secretary: Luciana de Souza secretaria@rbhh.org | www.htct.com.br The Hematology, Transfusion and Cell Therapy is the offi cial publication of the Associa¸c~ao Brasileira de Hematologia, Hemoterapia e Terapia Celular (ABHH), the Associazione Italo-Brasiliana di Ematologia (AIBE), Eurasian Hematology Oncology Group (EHOG), and the Sociedade Brasileira de Oncologia Pedi atrica (SOBOPE), published by Elsevier Editora Ltda. The journal is indexed to the Literatura Latino-Americana e do Caribe em Ci^encias da Sa ude (Lilacs), SciELO Brazil, PubMed/PMC, Web of Science (ESCI), Extramed and Scopus. It is distributed for free to regional libraries and Medical, Pharmacy and Biochemistry Schools in Brazil and sister societies in South, Central and North America and Europe. 2023 Associa¸c~ao Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda. All rights reserved. All rights reserved and protected by law 9.610 - 19/02/98. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording or any information storage and retrieval system, without permission in writing from ABHH and the Publisher. 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Board Of Directors 2022-2023 President Angelo Maiolino Vice-President Eduardo Magalh~aesRego Administrative Director Glaciano Nogueira Ribeiro Vice Administrative Director Silvia Maria Meira Magalh~aes Scientific Director Carmino Antonio de Souza Vice-Scientific Director Dimas Tadeu Covas Financial Diretor Celso Arrais Rodrigues da Silva Vice Financial Director Leny Nascimento da Motta Passos Director of Communications Renato Sampaio Tavares Vice-Director of CommunicationsVania T. de Moraes Hungria Director of Institutional RelationsCarlosS ergio Chiattone Vice-Director of Institutional RelationsDante Langhi Junior Director of Professional PracticeEdvan de Queiroz Cruso e Vice-Director of Professional PracticeJos e Francisco Comenalli Marques Jr Director Social Action BoardJorge Vaz Pinto Neto Vice-Director Social Action BoardViolete Petitto Laforga Emeritus Scientific Director Roberto Passetto Falc~ao General Manager AlineAch^e Deliberative Committee Elected 2022-2025 Thiago Xavier Carneiro Aderson da Silva Araujo Silvia Maria Meira Magalh~aes Renato Sampaio Tavares Karina Correia Barcelos Jo~ao Paulo de Oliveira Guimar~aes Angelo Maiolino Carla Luana Dinardo Eduardo Magalh~aesRego Monika Conchon Renato Luiz Guerino Cunha Rodolfo Delfini Can¸cado Talita Maira Bueno da Silveira Vanderson Rocha Vaneuza Araujo Moreira Funke Elected 2024-2027 Leny Nascimento da Motta Passos Edvan de Queiroz Cruso e Jorge Vaz Pinto Neto Gustavo Henrique Silveira Marcos Daniel de Deus Santos Amanda Pifano Soares Ferreira Glaciano Nogueira Ribeiro Adriana Alves Scheliga Clarisse Lopes de Casto Lobo Roberto Jos e Pessoa de Magalh~aes Celso Arrais Rodrigues da Silva Jos e Eduardo Bernardes Jos e Francisco Comenalli Marques J unior V^ania Tietsche de Moraes Hungria Violete Petitto Laforga Lifelong Deliberative Committee Carlos Sergio Chiattone Carmino Antonio de Souza DanteM ario Langhi J unior Dimas Tadeu Covas Eur ıpedes Ferreira Fernando Ferreira Costa H elio Moraes de Souza H elioRamos Jo~ao Carlos Pina Saraiva Jos e Orlando Bordin Jos eKerbauy Marco Antonio Zago Milton Artur Ruiz Nelson Ibrahim Fraiji Nelson Hamerschlak Nelson Spector Orion de Bastos Ricardo Pasquini Roberto Passetto Falc~ao Romeu Ibrahim de Carvalho Sara Teresinha Olalla Saad Therezinha Verrastro de Almeida Ubiratan Ouvinha Peres Past Presidents of Sociedade Brasileira de Hematologia e Hemoterapia 1950 Walter Oswaldo Cruz 1951 Michel Abujamra 1954 Darcy Lima 1955 Jos e Candido C. Villela 1957 Joaquim M. Barreto 1959 Oswaldo Kessler Ludwing 1961 Walter Hupsel 1963 Rui Faria 1965 Orion Bastos 1967 Ubiratan Ouvinha Peres 1970 Oswaldo Mellone 1973 Pedro Cl ovis Junqueira 1975 Pedro Cl ovis Junqueira 1977 Maria Nazareth Petrucelli 1979 Celso Carlos de C. Guerra 1981 Jacob Rosenblit 1983 Luiz Gast~ao M. Rosenfeld 1985 Augusto Luiz Gonzaga 1987 Helio Ramos 1988 Milton Artur Ruiz 1990 Nelson Hamerschlak 1992Eur ıpedes Ferreira 1994 Jo~ao Carlos Pina Saraiva 1996 Jo~ao Pedro E. M. Pereira 1998 Celso Carlos de C. Guerra 2000 Dante M ario Langhi Junior 2002 Dante M ario Langhi Junior 2004 Carlos S ergio Chiattone 2006 Carlos S ergio Chiattone 2008 Carlos S ergio Chiattone Past Presidents of Col egio Brasileiro de Hematologia 1965 Hildebrando M. Marinho 1967 Michel Abujamra 1969 Romeu Ibrahim de Carvalho 1971 Paulo Barbosa da Costa 1973 Romildo Lins 1975 Renato Rego Failance 1977 Dilson Jos e Fernandes 1981 Jos eKerbauy 1985 Eurico Coelho 1989 Romeu Ibrahim de Carvalho 1993 Jos eKerbauy 1997 Roberto Passetto Falc~ao 2005 Jos e Orlando Bordin Past Presidents of Associa¸c~ao Brasileira de Hematologia, Hemoterapia e Terapia Celular 2009 Carlos S ergio Chiattone Jos e Orlando Bordin 2010-2013: Carmino Antonio deSouza 2014-2017: Dimas Tadeu Covas 2018-2021: Dante Langhi J unior Associa¸c~ao Brasileira de Hematologia, Hemoterapia e Terapia Celular
Associazione Italo-Brasiliana di Ematologia Board of Directors President Carlos S. Chiattone (Brazil) Vice-President Stefano Luminari Scientific Director −Brazil Carmino Antonio de Souza Treasurer −Brazil Natalia Zing Honorary PresidentsGino Santini and Angelo Maiolino and Ricardo Pasquini Scientific Director −ItalyMaurizio Martelli Treasurer −ItalyLuca Arcaini Board of Advisors - Brazil Eduardo Magalh~aes Rego, Eliana C. M. Miranda, Guilherme Duffl es, Irene de Almeida Biasoli, Marcia Torresan Delamain, Milton Artur Ruiz, Sergio A.B. Brasil, Thais Fischer Board of Advisors - Italy Angelo Michelle Carella, Gian Luca Gaidano, Ignazio Majolino, Maurizio Martelli, Robin Fo a, Teodoro Chisesi Associazione Italo-Brasiliana di Ematologia Viale Benedetto XV 16100 - Genoa GE Italy Eurasian Hematology Oncology Group Board of Directors President Giuseppe Saglio Vice-President Birol Guvenc General Secretaryehmus Ertop Member Ahmad Ibrahim, Lebanonn Member Burhan Ferhanoglu, Turkiye Member Carmino de Souza, Brazil Member Claudio Cerchione, Italy Member Jean FranO´ ois Rossi, France Member Moshe Mittelman, Israel Member Tariq Mughal, USA Member Vera Donnenberg, USA Eurasian Hematology Oncology Group www.ehog.net - sekreterlik@hematoloji.org.tr Yurt Mahallesi Kurttepe Cad. 71517 Sokak No.2 Sabahattin Akg€un Apt. Kat.1 Daire.1 ¸Cukurova - Adana Phone: 00 90 555 881 01 99 Sociedade Brasileira de Oncologia Pedi atrica Board of Directors - 2023-2024 President Nevi¸colino Pereira de Carvalho Filho 1st Vice-President Flavia Delgado Martins 1st SecretaryMaristela Francisco dos Reis 1st Treasurer Carolina Madalena Souza Pinto Alvares 2nd Vice-President Mario Jos e Aguiar de Paula 2nd SecretaryAnnemeri Livinalli 2nd Treasurer Patrick Rezende Godinho Members of Advisory Board Andrea Maria Capellano, Elione Soares de Albuquerque, Elvis Terci Valera, Simone dos Santos Aguiar, Val eria Pereira Paiva Sociedade Brasileira de Oncologia Pedi atrica www.sobope.org.br - sobope@uol.com.br / sobope@sobope.org.br 94/53 04077-020 S~ao Paulo-SP Phone: 55 11 5052-7537
Instituições Programa de Apoio em Residência Médica em Hematologia, Hemoterapia e Terapia Celular. Estudantes Residentes CATEGORIA DE Especialistas Médicos ou outros profissionais da saúde. Programa Sangue Jovem, estudandes de graduação, participantes de Ligas Acadêmicas. Organização na área da saúde que desenvolva atividades na área da hematologia, hemoterapia e terapia celular. www.abhh.org.br ASSOCIADOS
Editorial Therapeutic plasma exchange and HLA desensitization Eduardo Magalh~aesRego a,b,c aInstituto do C^ancer do Estado de S~ao Paulo (ICESP), S~ao Paulo, SP, Brazil bInstituto D Or de Pesquisa e Ensino (IDOR), S~ao Paulo, SP, Brazil c Laborat orio de Investiga¸c~oes M edicas 31, Faculdade de Medicina da Universidade de S~ao Paulo (LIM 31 FM USP), S~ao Paulo, SP, Brazil ARTICLE INFO Article history: Received 6 February 2024 Accepted 6 February 2024 Available online 16 February 2024 HLA sensitization remains a significant hurdle in renal transplantation, affecting approximately one-third of the patient population on the waiting list.1 Despite considerable advancements over the past two decades, effective desensitization strategies are still urgently needed in clinical practice. A range of therapies, including therapeutic plasma exchange, immunotherapies targeting CD20 or CD38, proteasome inhibitors, complement inhibitors, and interleukin-6 blockade, have emerged as potential desensitization interventions.2 However, the outcomes from these therapies vary considerably, with each having different cost implications andprofiles of adverse events.2 In this issue of HTCT, Dr. Chowdry et al.3 have provided valuable comparative insights. Their study evaluated graft survival rates in 106 patients who underwent a desensitization regimen combining therapeutic plasma exchange with intravenous immunoglobulin against a control group that received HLA-compatible transplants. The desensitized cohort exhibited improved graft survival rates, with antibodymediated graft rejection occurring in only 6.6 % of cases. Yet, the mortality rate stood at 4.7 %, attributed to anaphylaxis, cardiogenic shock, and multiorgan failure. The risk associated with transplanting a kidney in the presence of high donor-specific antibody (DSA) levels is well established. A positive cytotoxic crossmatch and DSA mean fluorescence intensity (MFI) above 10,000, as determined by flow cytometry, are considered high-risk factors for hyperacute rejection, often leading to immediate graft loss.4 Consequently, these high-risk factors generally contraindicate transplantation. Chowdry et al.’s protocol highlights the possibility of safely proceeding with transplants in sensitized patients through meticulous desensitization and monitoring of DSA levels.3 While the study did not offer a direct cost analysis compared to other therapies, it indicates that such a desensitization protocol might be economically feasible, especially in resource-limited settings. Importantly, the principles established in this research may have broader implications, potentially guiding the development of desensitization strategies across various forms of solid organ transplantation. This could significantly improve organ transplant success rates and patient outcomes across diverse health care environments. E-mail address: eduardo.rego@fm.usp.br https://doi.org/10.1016/j.htct.2024.02.001 2531-1379/ 2024 Published by Elsevier España, S.L.U. on behalf of Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). hematol transfus cell ther. 2024;46(1):1−2 Hematology, Transfusion and Cell Therapy www.htct.com.br
Conflicts of interest The author declare no conflicts of interest. references 1. Montgomery RA, Lonze BE, King KE, Kraus ES, Kucirka LM, Locke JE, et al. Desensitization in HLA-incompatible kidney recipients and survival. N Engl J Med. 2011;365(4):318–26. 2. Schinstock C, Tambur A, Stegall M. Current approaches to desensitization in solid organ transplantation. Front Immunol. 2021;12:686271. https://doi.org/10.3389/fimmu. 2021.686271. 3. Chowdhry M, Yadav A, Sharma V, Agrawal S. Role of therapeutic plasma exchange as a desensitization therapy in human leukocyte antigen incompatible renal transplant patients: a single-center experience. Hematol Transfus Cell Ther. 2022:S2531-1379(22)01469-9. https://doi.org/10.1016/j. htct.2022.11.009. (atualizar a refer^encia com a edi¸c~ao da revista). 4. Stegall MD, Gloor J, Winters JL, Moore SB, Degoey S. A comparison of plasmapheresis versus high-dose IVIG desensitization in renal allograft recipients with high levels of donor specific alloantibody. Am J Transplant. 2006;6:346–51. https://doi.org/ 10.1111/j.1600-6143.2005.01178.x. 2 hematol transfus cell ther. 2024;46(1):1−2
Original article TaggedH1The course of COVID-19 in patients with hematological malignancies and risk factors affecting mortality: A cross-sectional studyTaggedEnd TaggedPEsma Eryilmaz-Eren a,*, Zeynep Ture b,Ay¸sinKilin¸c-Toker a, Serdal Korkmaz a, _Ilhami ¸Celik a TaggedEnd TaggedP aKayseri City Education and Research Hospital, Kayseri, Turkey bErciyes University, Faculty of Medicine, Kayseri, Turkey TaggedEnd TAGGEDPARTICLE INFO Article history: Received 25 January 2022 Accepted 25 October 2022 Available online 2 December 2022TaggedEnd Objective: This study aimed to determine the clinical outcomes and risk factors affecting mortality in patients with COVID-19 following hematological malignancy (HM). Methods: Patients diagnosed with HM and hospitalized for COVID-19 were included in this retrospective study. The age, demographic and clinical characteristics, prognosis and treatment of surviving and non-surviving patients were compared. Results: A total of 49 patients were included in this study, 17 (34.6%) of whom died within 28 days of being diagnosed with COVID-19. Olderage (p= 0.001), diabetes (p= 0.001), chronic obstructive pulmonary disease (p = 0.002), secondary infection (p < 0.001) and secondary bacterial infection (p = 0.005) were statistically significantly higher in non-survivors. The remission status of HM was higher in surviving patients (p <0.001). In multivariate regression analysis, age (OR: 1.102, p = 0.035) and secondary infection (OR: 16.677, p = 0.024) were risk factors increasing mortality, the remission status of HM (OR: 0.093, p= 0.047) was a protective factor from mortality. Conclusion: The older age, the remission status of HM and secondary infection due to COVID-19 were determined as prognostic factors predicting mortality in HM patients with following COVID-19. 2022 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier España, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). TaggedEndTaggedPKeywords: Hematological malignancy COVID-19 Olderage RemissionTaggedEnd TaggedH1IntroductionTaggedEnd TaggedPHematological malignancies (HMs) are one of the leading causes of mortality and morbidity worldwide.1 The patient TaggedEndTaggedPwith HM usually has long-term immunodeficiency due to the malignancy, anti-cancer treatments or procedures, such as hematopoietic stem cell transplantation (HSCT).2 These people are very concerned about the high risk of morbidity and mortality from COVID-19. According to the literature, the overall mortality associated with COVID-19 among hematologic patients ranges from 32% to 40%.3 TaggedEnd TaggedPRecent studies have demonstrated that COVID-19 has a two-phase illness process. The classic upper respiratory tract infection symptoms are observed during thefirst phase. If the disease does not improve, it progresses to the second phase TaggedEnd * Corresponding author at: Kayseri City Education and Research Hospital, Department of Infectious Diseases and Clinical Microbiology, Kayseri, Turkey. E-mail address: esmaereneryilmaz@gmail.com (E. Eryilmaz-Eren). https://doi.org/10.1016/j.htct.2022.10.001 2531-1379/ 2022 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier España, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). TaggedEndhematol transfus cell ther. 2024;46(1):3−7 TaggedFigure TaggedEnd Hematology, Transfusion and Cell Therapy www.htct.com.br TaggedFigure TaggedEnd
TaggedEndTaggedPand a ’cytokine storm’ develops, in which increased cytokine levels characterize an enhanced immune response. There are dyspnea and hypoxia, with infiltrates in the lung.4-6 TaggedEnd TaggedPIt was determined that activated and depleted CD8+ T cells were associated with the severity of the disease in COVID-19.7 In the early stages of the pandemic, the cytokine storm seen in the course of COVID-19 was identified. It was thought that the existing immunodeficiency in patients with HM would not allow for the development of a cytokine storm and would limit the progression to severe/critical COVID-19. However, real-life data indicate that morbidity and mortality rates are variable. The subtype and activation status of HM, age and comorbidities were identified as factors influencing mortality.8, 9 TaggedEnd TaggedPThis study aimed to determine the factors that affect the clinical development and prognosis of HM patients treated for COVID-19.TaggedEnd TaggedH1MethodsTaggedEnd TaggedPThis retrospective study was conducted in a tertiary hospital with a total of 1,600 beds and a hematology unit with a capacity for 24 patients.TaggedEnd TaggedH2Patients and definitionsTaggedEnd TaggedPPatients with a diagnosis of HM and COVID-19 who were hospitalized in the Kayseri City Training and Research Hospital between April 2020 and October 2021 were included in this retrospective study. Demographic characteristics, HM diagnoses and clinical conditions (new diagnosis, remission and recurrence) of the patients and the clinical course and treatments for COVID-19 were recorded. During the COVID-19 process, 28-day mortality cases were evaluated. The patients were divided into two groups: survivors and non-survivors and the factors predicting mortality were determined.TaggedEnd TaggedPPatients with PCR-positive SARS-CoV-2 were diagnosed with COVID-19. According to the clinical severity classification of COVID-19, patients with fever and cough, but with normal O2 saturation and no change in X-rays and/or CT scans, were classified as mild COVID-19; patients with ground glass opacities, lung consolidation and O2 saturation < 94%, as moderate COVID-19, and; patients with PaO2/FiO2 < 300 mmHg and respiratory frequency > 30 breaths/min., as severe/critical COVID-19.6 TaggedEnd TaggedPDiagnosis and treatment strategies for HM were determined according to the National Comprehensive Cancer Network (NCCN).10 The COVID-19 treatment was carried out in accordance with the COVID-19 treatment management guidelines of the Ministry of Health. 11 Favipiravir is given as an antiviral drug to patients who have received treatment for COVID-19. The IL-6 inhibitor tocilizumab, steroids and highdose steroids were used in accordance with the guidelines for patients with increased inflammatory markers. 12 TaggedEnd TaggedPSecondary bacterial infections were defined as bacterial infections occurring during the COVID-19 disease course or hospital stay (> 48 - 72 h after hospitalization).13 Secondary fungal infections were defined according to the CDC.14 TaggedEnd TaggedH2Statistical analysisTaggedEnd TaggedPThe statistical analysis was performed using the SPSS 22.0 (IBM Corp., Armonk, NY, USA) package program. The ShapiroWilk test was performed to check the normality assumption of the data. Categorical variables were expressed as numbers and percentages and Chi-square or Fisher’s Exact Test analysis was used for comparisons. Variables with a p-value ≤0.05 were included in the multivariate logistic regression analysis. Ap-value ≤0.05 was considered statistically significant in all analyses.TaggedEnd TaggedH2Ethical approvalTaggedEnd TaggedPThis study was approved by the Kayseri City Hospital, Clinical Research Ethics Committee (Date: 24.12.2020 and Approval Number: 251) and was conducted in accordance with the Principles of the Declaration of Helsinki. As it was performed retrospectively by the file scanning method, an ’informed voluntary consent form’ was not obtained from the patients.TaggedEnd TaggedH1ResultsTaggedEnd TaggedPA total of 49 patients were included in the study. The clinical and demographic data of the patients are presented in Table 1. Twenty-eight (57.1%) patients were male and the mean age was57.90§16.43 years. Of the patients, 17 (34.6%) died within 28 days of being diagnosed with COVID-19 and 32 (65.3%) of them recovered. The mean age of the non-survivor group was 67.23 (§13.33) and of the survivor group, 48.68 (§15.95), this difference is statistically significant (p <0.001). At the time of admission, complaints of fever, cough and shortness of breath were similar in both groups (p = 1.000, p = 0.20,2 and p = 0.096, respectively). The prevalence of diabetes was 76.5% in the survivor group and 25.0% in the non-survivor group and this difference was statistically significant (p = 0.001). When the frequency of diagnosis of HM was evaluated, it was observed that 22 (44.9%) patients were followed up for lymphoma, 18 (36.7%) patients, for leukemia, and 9 (18.4%) patients, for multiple myeloma. No statistically significant difference was found between the survivor and non-survivor groups in the type of HM (p>0.05). The HM was evaluated for disease activation status and 81.3% of the survivors and 23.5% of the non-survivors were in remission (p < 0.001). A total of 12 (24.5%) patients were HSCT recipients. Allogeneic HSCT was performed in three patients (9.1%) and autologous SCT was performed in six patients (18.8%). The frequency of patients receiving HSCT and the frequency of performing allogeneic and autologous HSCT were found to be statistically similar between survivor and non-survivor patients (p=0.175, p= 0.646, andp= 0.397, respectively).TaggedEnd TaggedPAccording to the clinical severity of COVID-19, a total of 14 (28.6%) patients were mild, 15 (30.6%) patients were moderate, and 15 (40.8%) patients severe/critical COVID-19. There was no difference between the two groups in the classification according to the clinical severity of COVID-19 (p = 0.323, p=0.526andp= 0.075, respectively).TaggedEnd TaggedEnd4 hematol transfus cell ther. 2024;46(1):3−7
TaggedEnd Table1 – Demographic and clinical characteristics of patients Survivor Non-survivor Total p n=32 (%) n=17 (%) n=49 (%) Age (mean§SD) 48.6 (§15.9) 67.2 (§13.3) 56.4 (§16.9) 0.001 Age (median, min-max) 54.5 (18.0-78.0) 71.0 (41.0-87.0) 58.0 (18.0-87.0) 0.001 Male gender 18 (56.3) 10 (58.8) 28 (57.1) 1.000 COVID-19 symptoms Fever 16 (50.0) 9 (52.9) 25 (51.0) 1.000 Cough 20 (62.5) 14 (82.4) 34 (69.4) 0.202 Shortness of breath 20 (62.5) 15 (88.2) 35 (71.4) 0.096 Comorbidities Diabetes Mellitus 8 (25.0) 13 (76.5) 21 (42.9) 0.001 Hypertension 7 (21.9) 8 (47.1) 15 (30.6) 0.104 Chronic Obstructive Pulmonary Disease - 6 (35.3) 6 (12.2) 0.002 Coronary arter disease 5 (15.6) 6 (35.3) 11 (22.4) 0.156 Hematological malignancy diagnosis Leukemia 12 (37.5) 6 (35.3) 18 (36.7) 1.000 Acute Myeloid Leukemia 4 (12.5) 3 (17.6) 7 (14.3) 0.681 Acute Lymphoblastic Leukemia 4 (12.5) 1 (5.9) 5 (10.2) 0.646 Hairy-Cell Leukemia 2 (6.3) - 2 (4.1) 0.537 Chronic Lymphocytic Leukemia 2 (6.3) 2 (11.8) 4 (8.2) 0.273 Lymphoma 12 (37.5) 10 (58.8) 22 (44.9) 0.228 Diffuse Large B Cell Lymphoma 4 (12.5) 6 (35.3) 10 (20.4) 0.075 Non- Hodgkin Lymphoma, Nos 4 (12.5) 1 (5.9) 5 (10.2) 0.646 Hodgkin Lymphoma 2 (6.3) 2 (11.8) 4 (8.2) 0.602 Marginal Zone Lymphoma 1 (3.1) 1 (2.0) 1.000 Mantle Cell Lymphoma 1 (3.1) 1 (5.9) 2 (4.1) 1.000 Multiple Myeloma 8 (25.0) 1 (5.9) 9 (18.4) 0.136 Hematological malignancy condition Remission 26 (81.3) 4 (23.5) 30 (61.2) <0.001 New diagnosis 4 (12.5) 6 (35.3) 10 (20.4) 0.075 Refractory disease - 3 (17.6) 3 (6.1) 0.037 Recurrence 2 (6.3) 4 (23.5) 6 (12.2) 0.164 Hematopoietic Stem Cell Transplantation 10 (31.3) 2 (11.8) 12 (24.5) 0.175 Allogeneic 4 (12.5) 1 (5.9) 5 (10.2) 0.646 Autolog 6 (18.8) 1 (5.9) 7 (14.3) 0.397 Vaccination Inactivated vaccine 2 (6.2) 1 (5.9) 3 (6.1) 0.380 m-RNA Vaccine 4 (12.5) - 4 (8.2) - COVID-19 severity Mild COVID-19 11 (34.4) 3 (17.6) 14 (28.6) 0.323 Moderate COVID-19 11 (34.4) 4 (23.5) 15 (30.6) 0.526 Severe/critical COVID-19 10 (31.3) 10 (58.8) 20 (40.8) 0.075 COVID-19 treatment Favipiravir 32 (100) 17 (100) 49 (100) 1.000 Corticosteroid 27 (84.4) 16 (94.1) 43 (87.8) 0.650 Duration of corticosteroid, day 8.5§3.5 7.7§3.3 8.2§3.4 0.439 Metilprednisolone 24 (75.0) 13 (76.5) 37 (75.5) 1.000 Daily dose, mean (§sd) (mg) 55.8§19.5 69.2§13.2 60.5§18.5 0.058 Total dose, mean (§sd) (mg) 362.5§301.3 410.5§326.4 379.1§307.7 0.542 Dexametasone 3 (9.4) 3 (9.4) 6 (12.2) 0.405 Daily dose, mean (§sd) (mg) 13.3§4.6 10.6§4.6 12.0§4.3 0.519 Total dose, mean (§sd) (mg) 34.4§9.7 47.9§83.5 39.2§12.2 0.900 Pulse- steroid 10 (31.3) 9 (52.9) 19 (38.8) 0.218 Intravenous immunoglobulin 2 (6.3) - 2 (4.1) 0.537 Tocilizumab 7 (21.9) 3 (17.6) 10 (20.4) 1.000 Outcomes Secondary Infection 4 (12.5) 11 (64.7) 15 (24.5) <0.001 Bacterial Infection 1 (3.1) 6 (35.3) 7 (14.3) 0.005 Bacterial pnemonia - 3 (17.7) 3 (6.1) Isolates Acinetobacter baumannii 1 (5.9) Klebsiella pneumonie 1 (5.9) Klebsiella oxytoca 1 (5.9) Bacteremia 1 (3.1) 3 (17.7) 4 (8.2) Enterococcus gallinarum 1 (3.1) Staphylococcus aureus 1 (5.9) hematol transfus cell ther. 2024;46(1):3−7 5
TaggedPThe rate of corticosteroid and tocilizumab used for the treatment of COVID-19 was similar in the survivor and nonsurvivor groups (p=0.650andp= 1.000, respectively).TaggedEnd TaggedPIn a total of 15 patients (24.5%), secondary infection developed while being followed up for COVID-19. Seven (14.3%) of these were bacterial infections, while four (8.2%) were invasive fungal infections. Secondary bacterial infection was seen in 6 (35.3%) in non-survivors and in one (3.1%) patient from the survivors (p = 0.005). Bacterial pneumonia was observed in three patients and bacteremia was observed in four patients as the secondary bacterial infection. AnAcinetobacter baumannii strain causing bacterial pneumonia and a Klebsiella pneumoniae strain had carbapenem resistance. In addition, the Klebsiella pneumoniae strain, isolated as a bacteremia agent, was resistant to carbapenem and the Staphylococcus aureus strain was resistant to methicillin.TaggedEnd TaggedPThe frequency of invasive fungal infections was similar in both groups (11.8%vs. 12.5%, p = 1.000). Rhinocerebral mucormycosis was seen in three patients. The only patient with candidemia died.TaggedEnd TaggedPIn multivariate regression analysis (Table 2), older age (OR: 1.150, p= 0.024) and secondary infection (OR: 16.677, p=0.024) were evaluated as factors predicting mortality in patients with HM. Being in remission of the HM was found to be a factor reducing mortality (OR: 0.093, p=0.047).TaggedEnd TaggedH1DiscussionTaggedEnd TaggedPThis study evaluated the clinical features and risk factors affecting the mortality of patients with HM diagnosed and followed up for COVID-19. Older age and secondary infection have been identified as risk factors that increase mortality. Diabetes was observed more frequently in patients who died, but it was not considered a risk factor. The remission of HM was found more in surviving patients and was evaluated as a factor in reducing the risk of mortality.TaggedEnd TaggedPDuring the COVID-19 pandemic, patients with HM are a potentially high-risk population due to immunosuppressive therapies.15 The immune dysfunction of patients due to HM TaggedEndTaggedPalso affects the course of COVID-19 and there are important risk factors affecting mortality in these patients. It has been reported that older age increases mortality 1 to 13 times in COVID-19 patients without malignancy.16,17 In addition, infectious complications in patients with HM increase with age and older age is associated with a poor prognosis.18 Thereare few studies on COVID-19 patients with HM and older age has been reported as a risk factor that increases mortality and morbidity.3,9 According to the results of our study, it was determined that the increased mean age increased mortality 1.1 times.TaggedEnd TaggedPDiabetes and impaired glucose tolerance have been associated with poor prognosis in COVID-19 disease.19 In a metaanalysis of 30 studies and 6,452 patients, it was stated that the presence of DM led to a two-fold increased mortality risk and severity of COVID-19.20 According to our study results, diabetes was found with a higher frequency in patients who died.TaggedEnd TaggedPThe remission of HM is known to be a good prognostic factor, especially in infectious complications.21 By controlling the malignancy, it is possible to regain the immune system functions. In a study conducted in Spain, in which 367 patients with HM who had COVID-19 were evaluated, uncontrolled HM was associated with an increased 45-day mortality rate.3 In another study, conducted in the early period of the COVID-19 pandemic and which evaluated 34 patients with HM, it was found that patients in remission without active malignancy had a better survival rate. In our study, the remission of HM was similarly found to be a factor in reducing mortality due to COVID-19.TaggedEnd TaggedPBacterial/fungal secondary infections contribute to the increased morbidity and mortality of viral respiratory infections.22 It has been reported that the frequency of infections caused by resistant bacteria has increased due to inappropriate antibiotic use and extended hospitalization in the intensive care unit.23 In addition, it has been reported that respiratory tract damage caused by SARS-CoV-2 and alveolar damage caused by the cytokine storm increase the risk of invasive fungal infection.24 TaggedEnd TaggedH1ConclusionTaggedEnd TaggedPOlder age, remission of HM and secondary infection were determined as prognostic factors predicting mortality in HM patients followed up with COVID-19.TaggedEnd TaggedPThere are some limitations in this study. This study was retrospectively performed at a single center. The details of chemotherapy regimens could not be fully reached. In Table1 (continued) Survivor Non-survivor Total p n=32 (%) n=17 (%) n=49 (%) Klebsiella pneumoniae 1 (5.9) Enterobacter cloacae 1 (5.9) Invasive fungal infection 2 (6.3) 2 (11.8) 4 (8.2) 0.602 Rhinocerebral mucormycosis 2 (6.3) 1 (5.9) 3 (6.1) Candidemia - 1 (5.9) 1 (2.0) TaggedEnd Table2 – Risk factors of 28-day mortality OR (95% Cl), p Age 1.102 (1.007-1.205), 0.035 Diabetes mellitus 7.893 (0.655-95.073), 0.104 Remission of hematologic malignancy 0.093 (0.009-0.973), 0.047 Secondary infection 16.677 (1.449-191.895), 0.024 TaggedEnd6 hematol transfus cell ther. 2024;46(1):3−7
TaggedEndTaggedPaddition, the small number of groups prevented sub-analysis between different hematological malignancies and thus, prospective studies with large patient groups are needed.TaggedEnd TaggedH1Ethics statementTaggedEnd TaggedPThe clinical research ethics committee of Kayseri City Hospital approved this research (Date: 12/24/2020 Number: 251).TaggedEnd TaggedH1Conflicts of interestTaggedEnd TaggedPThe authors of this manuscript have no conflicts of interest to declare.TaggedEnd taggedh1referencestaggedend TaggedP 1. Dizon DS, Krilov L, Cohen E, Gangadhar T, Ganz PA, Hensing TA, et al. Clinical cancer advances 2016: annual report on progress against cancer from the American Society of Clinical Oncology. J Clin Oncol. 2016;34(9):987–1011. https://doi.org/ 10.1200/JCO.2015.65.8427.TaggedEnd TaggedP 2. Atkins S, He F. Chemotherapy and beyond: infections in the era of old and new treatments for hematologic malignancies. Infect Dis Clin North Am. 2019;33(2):289–309. https://doi.org/ 10.1016/j.idc.2019.01.001.TaggedEnd TaggedP 3. Pi~nana JL, Martino R, García-García I, Parody R, Morales MD, Benzo G, et al. Risk factors and outcome of COVID-19 in patients with hematological malignancies. Exp Hematol Oncol. 2020;9:21. https://doi.org/10.1186/s40164-020-00177-z.TaggedEnd TaggedP 4. Siddiqi HK, Mehra MR. COVID-19 illness in native and immunosuppressed states: A clinical-therapeutic staging proposal. J Heart Lung Transplant. 2020;39(5):405–7. https://doi.org/ 10.1016/j.healun.2020.03.012.TaggedEnd TaggedP 5. Wong HYF, Lam HYS, Fong AH, Leung ST, Chin TW, Lo CSY, et al. Frequency and distribution of chest radiographic findings in patients positive for COVID-19. Radiology. 2020;296:E72–8. https://doi.org/10.1148/radiol.2020201160.TaggedEnd TaggedP 6. Baj J, Karaku»a-Juchnowicz H, Teresi nski G, Buszewicz G, Ciesielka M, Sitarz R, et al. COVID-19: specific and non-specific clinical manifestations and symptoms: the current state of knowledge. J Clin Med. 2020;9(6):1753. https://doi.org/10.3390/ jcm9061753.TaggedEnd TaggedP 7. Mathew D, Giles JR, Baxter AE, Oldridge DA, Greenplate AR, Wu JE, et al. Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications. Science. 2020;369(6508):eabc8511. https://doi.org/10.1126/science.abc8511.TaggedEnd TaggedP 8. Yigenoglu TN, Ata N, Altuntas F, Basc{ S, Dal MS, Korkmaz S, et al. The outcome of COVID-19 in patients with hematological malignancy. J Med Virol. 2021;93(2):1099–104. https://doi.org/ 10.1002/jmv.26404.TaggedEnd TaggedP 9. Passamonti F, Cattaneo C, Arcaini L, Bruna R, Cavo M, Merli F, et al. Clinical characteristics and risk factors associated with COVID-19 severity in patients with haematological malignancies in Italy: a retrospective, multicentre, cohort study. Lancet Haematol. 2020;7(10):e737–45. https://doi.org/10.1016/S23523026(20)30251-9.TaggedEnd TaggedP10. National Comprehensive Cancer Network (NCCN). Available from: https://www.nccn.org/.TaggedEnd TaggedP11. COVID-19 (SARS-CoV-2 INFECTION), Management of adult patients. Ankara, Turkey: Ministry of Health; 2020. July 31. Available from: https://www.ekmud.org.tr/files/uploads/files/ COVID-19_REHBERI_ERISKIN_HASTA_TEDAVISI.pdf.TaggedEnd TaggedP12. COVID-19 (SARS-CoV-2 INFECTION) Anticytokine-AntiInflammatory Treatments, Coagulopathy Management. Ankara, Turkey: Ministry of Health; 2020. November 7. Available from: https://covid19.saglik.gov.tr/Eklenti/39296/0/covid19rehberiantisitokin-antiinflamatuartedavilerkoagulopatiyonetimipdf.pdf.TaggedEnd TaggedP13. Russell CD, Fairfield CJ, Drake TM, Turtle L, Seaton RA, Wootton DG, et al. Co-infections, secondary infections, and antimicrobial use in patients hospitalised with COVID-19 during thefirstpandemic wave from the ISARIC WHO CCP-UK study: a multicentre, prospective cohort study. Lancet Microbe. 2021;2(8): e354–65. https://doi.org/10.1016/S2666-5247(21)00090-2.TaggedEnd TaggedP14. Fungal Diseases and COVID-19−CDC. Available from: https:// www.cdc.gov/fungal/covid-fungal.html.TaggedEnd TaggedP15. Goldman JD, Robinson PC, Uldrick TS, Ljungman P. COVID-19 in immunocompromised populations: implications for prognosis and repurposing of immunotherapies. J Immunother Cancer. 2021;9(6):e002630. https://doi.org/10.1136/jitc-2021002630.TaggedEnd TaggedP16. Ho FK, Petermann-Rocha F, Gray SR, Jani BD, Katikireddi SV, Niedzwiedz CL, et al. Is older age associated with COVID-19 mortality in the absence of other risk factors? general population cohort study of 470,034 participants. PLoS One. 2020;15: e0241824. https://doi.org/10.1371/journal.pone.0241824.TaggedEnd TaggedP17. K{l{n¸c Toker A, Ulu K{l{¸c A, Eren E, Be¸stepe Dursun Z, Toker _I, Saat¸ci E, et al. Confronting a pandemic in early stages: a retrospective analysis from a pandemic hospital. Hamidiye Med J. 2020;1:106–18. https://doi.org/10.4274/hamidiyemedj.galenos.2021.10820.TaggedEnd TaggedP18. de Montmollin E, Tandjaoui-Lambiotte Y, Legrand M, Lambert J, Mokart D, Kouatchet A, et al. Outcomes in critically ill cancer patients with septic shock of pulmonary origin. Shock. 2013;39:250–4. https://doi.org/10.1097/SHK.0b013e3182866d32.TaggedEnd TaggedP19. Pranata R, Henrina J, Raffaello WM, Lawrensia S, Huang I. Diabetes and COVID-19: the past, the present, and the future. Metabolism. 2021;121:154814. https://doi.org/10.1016/ j.metabol.2021.154814.TaggedEnd TaggedP20. Huang I, Lim MA, Pranata R. Diabetes mellitus is associated with increased mortality and severity of disease in COVID-19 pneumonia − a systematic review, metaanalysis, and meta-regression: diabetes and COVID-19. Diabetes Metab Syndr Clin Res Rev. 2020;14:395–403. https://doi.org/10.1016/j.dsx.2020.04.018.TaggedEnd TaggedP21. Cheng LC, Yang T, Kuang HH, Yu S, Guan LX, Gu ZY, et al. Single center analysis of bloodstream infection clinical characteristics and prognosis in patients with hematological malignancies in the tropics. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2021;29(1):265–71. https://doi.org/10.19746/j.cnki.issn. 1009-2137.2021.01.044.TaggedEnd TaggedP22. Del Pozo JL. Respiratory co-and superinfections in COVID-19. Rev Esp Quimioter. 2021;34(Suppl 1):69–71. https://doi.org/ 10.37201/req/s01.20.2021.TaggedEnd TaggedP23. Rangel K, Chagas TPG, De-Simone SG. Acinetobacter baumannii infections in times of COVID-19 pandemic. Pathogens. 2021;10 (8):1006. https://doi.org/10.3390/pathogens10081006.TaggedEnd TaggedP24. Prattes J, Wauters J, Giacobbe DR, Salmanton-García J, Maertens J, Bourgeois M, et al. ECMM-CAPA Study Group. Risk factors and outcome of pulmonary aspergillosis in critically ill coronavirus disease 2019 patients-a multinational observational study by the European Confederation of Medical Mycology. Clin Microbiol Infect. 2021;28(4):580–7. https://doi.org/ 10.1016/j.cmi.2021.08.014.TaggedEnd hematol transfus cell ther. 2024;46(1):3−7 7
Original article TaggedH1Clinical outcome and prognosis of patients with acute myeloid leukemia submitted to chemotherapy with 5 years of follow-upTaggedEnd TaggedPKaira Mara Cordeiro de Albuquerque, M.Sc a,b,*, Caroline Brand~ao Joventino a, Lia Correia Moreiraa, Hermano Alexandre Lima Rocha, PhD c, Lívia Andrade Gurgel b,c, Deivide de Sousa Oliveira b,c, Carlos Ewerton Maia Rodrigues, PhD a,b,c TaggedEnd TaggedP aUniversidade de Fortaleza (Unifor), Fortaleza, CE, Brazil bFortaleza General Hospital (HGF), Fortaleza, CE, Brazil c Universidade Federal do Cear a (UFC), Fortaleza, CE, Brazil TaggedEnd TAGGEDPARTICLE INFO Article history: Received 8 March 2022 Accepted 13 November 2022 Available online 5 December 2022TaggedEnd TAGGEDPA B S T R A C T Objective: The purpose of this study was to evaluate the clinical-epidemiological profile, associated risk factors and clinical outcomes of patients with acute myeloid leukemia (AML), identifying the main causes of morbidity and mortality and overall survival rate of patients at five years of follow-up. Method: This was a retrospective cohort study evaluating the prognosis and clinical outcomes of 222 patients diagnosed with AML at three large hematology centers in Cear a (northeastern Brazil) over a period of fiveyears. Results: The mean age at diagnosis was 44.1§16 years, with a female prevalence of 1.3:1. No additional relevant risk factors associated with the development of AML were found, except for the well-established cytogenetic assessment. The overall 5-year survival rate was 39.4% (95%CI: 35.47 - 42.17). The main causes of death were disease progression (37.72%; n = 84) and sepsis (31.58%; n = 70). Conclusion: The clinical outcomes in our sample of AML patients were similar to those of other reported groups. Disease progression and infection were the main causes of death. Access to diagnostic flow cytometry and karyotyping was greater in our sample than in the TaggedEndTaggedPKeywords: Acute myeloid leukemia Prognosis Clinical outcome Leukemia Overall survival TaggedEnd TaggedEndAbbreviations: AML, acute myeloid leukemia; APL, acute promyelocytic leukemia; BMI, body mass index; BMT, bone marrow transplant; ECOG, Eastern Cooperative Oncology Group; HEPA, High-Efficiency Particulate Arrestance; MDS, myelodysplastic syndrome; SUS, Sistema UnicodeSa ude (“Unified Health System”); WHO, World Health Organization TaggedEndTaggedEndThis research received no specific grant from funding agencies in the public, commercial or not-for-profit sectors. TaggedEnd * Corresponding author at: Hospital Geral de Fortaleza (HGF), Rua Avila Goulart n umero 900, Ambulat orio de Hematologia, 1° andar, Bairro Papicu, Fortaleza, Cear a, Brazil, CEP 60.150-160. E-mail address: drakairahematologista@gmail.com (K.M.C.d. Albuquerque). https://doi.org/10.1016/j.htct.2022.11.002 2531-1379/ 2022 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier España, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). TaggedEndhematol transfus cell ther. 2024;46(1):8−13 TaggedFigure TaggedEnd Hematology, Transfusion and Cell Therapy www.htct.com.br TaggedFigure TaggedEnd
TaggedEndTaggedPnational average. As expected, overall survival differed significantly according to the risk, as determined by cytogenetic testing. 2022 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier España, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).TaggedEnd TaggedH1IntroductionTaggedEnd TaggedPLeukemia, a hematological neoplasm characterized by a monoclonal hyperproliferative disorder of hematopoietic cells of bone marrow origin, is the 10th most prevalent neoplasm in Brazil,1 with a worldwide incidence of 249,000 cases per year.2 The incidence increases annually and may be as high as 10% of the population over 68 years of age.2 In Brazil, estimates indicate 5.67 cases (men) and 4.56 cases (women) per 100,000 people of the population.1 The gross mortality among Brazilians with leukemia is 9,196 deaths per year. Leukemias in general is the 9th cause of death among women in Brazil, with an average case survival rate estimated at 60%.1 The median age at diagnosis of acute myeloid leukemia (AML) is 65 years, with a male-to-female incidence of 1.2 to 1.6:1.2 TaggedEnd TaggedPDespite the adoption of genetic mutations as the main prognostic factor for the clinical outcome of AML patients, it is important to investigate other non-cytogenetic factors which can make patients refractory to treatment and facilitate relapse.3 Molecular biology studies have identified genes involved in carcinogenesis, the most prevalent of which are those encoding myeloid transcription factors (RUNX1 and CBFA/CBFB) and signal transduction proteins (FLT3), for example the PML-RARA fusion gene, NPM1, CEBPA and MLL.3 Some target therapies for these mutations are gaining ground in association with the traditional induction regimen or as an option in recurrent or refractory cases.3 TaggedEnd TaggedPUnfortunately, the vast majority of Brazilian centers linked to theUnified Health Care System (SUS) do not provide access to such resources. A recent study of eleven referral centers found that only 51.2% of the services performed immunophenotyping at diagnosis and 42.7% provided access to karyotyping (though without precise molecular data).4 Patients may die before or during treatment (12% of cases)5 due to the severity of the disease itself (25%), bleeding disorders, bacterial, fungal and viral infections and treatment complications.5 The patient status at diagnosis, age, comorbidities, remission after induction and even socioeconomic and cultural profiles may impact survival rates. Based on clinical assessments, only 40% of the patients over 65 years of age are started on chemotherapy.6 TaggedEnd TaggedPThe estimated cure rate for AML is currently 40 to 60%. 7 Using the cytogenetic classification, the cure is estimated at 69% for low-risk patients, 24% for intermediate risk (including patients with normal karyotypes) and 6.5% for high risk.7 Old age also impacts cure rates: after the age of 70, the overall estimate drops drastically to 10% or less.2 TaggedEnd TaggedPThese are global estimates. Little information is available for Brazil3,4,8 especially for its northeastern region. Environmental and epigenetic factors that may interfere in the pathogenesis or prognosis of AML patients need to be further TaggedEndTaggedPinvestigated. For example, the effects of hypertension, diabetes, dyslipidemia and lifestyle on the development of AML are not fully understood.TaggedEnd TaggedPThe purpose of this study was to evaluate the clinical-epidemiological profile, associated risk factors and clinical outcomes of patients with AML, identifying the main causes of morbidity and mortality and overall survival rate of patients withfive years of follow-up.TaggedEnd TaggedH1MethodsTaggedEnd TaggedH2PatientsTaggedEnd TaggedPThis retrospective cohort study included 222 patients receiving chemotherapy treatment at three tertiary SUS hospitals (Hospital Geral de Fortaleza, n = 112; Hospital Universit ario Walter Cantídio, n = 79, and; Hospital Cesar Cals n = 31) in Cear a, a state in northeastern Brazil, between January 2013 and December 2020, with 5 years of post-diagnosis follow-up. The chemotherapy protocols were the same at the three centers. Originally, information was retrieved from 273 medical records, but 51 were excluded due to duplication (n = 3) or unavailable/incomplete archive/clinical data (n = 48). The inclusion criteria were: patients of both sexes aged 18 years or over, diagnosis of AML on bone marrow aspiration showing the presence of blasts in a count equal to or over 20% of the cells represented with characteristics of myeloblasts9 andpositive membrane surface staining for clusters of differentiation on immunophenotyping performed inflow cytometry.10 Pediatric patients and patients with other hematological diseases were excluded. Additionally, patients with acute promyelocytic leukemia with PML:RARA fusion were not excluded.TaggedEnd TaggedPThe study protocol was approved by the national clinical research platform (Plataforma Brasil, CAAE 44087220.0.1001.5052) and by the institutional review board. Following approval, the medical records were made available for analysis from May to July 2021. Data were collected by completing a questionnaire using the Google Forms platform. All patients or their legal representatives gave their written informed consent.TaggedEnd TaggedH2Clinical evaluation and outcomesTaggedEnd TaggedPThe hospitals participating in the study were requested to provide the medical records of patients diagnosed with the ICD codes C92, C92.0, C92.2, C92.4, C92.4, C92.5, C92.7 and C92.9. Information was collected on sex, date of birth, age at diagnosis and performance status at diagnosis according to the Eastern Cooperative Oncology Group (ECOG) performance scale (0 = fully active; 1 = restriction of physical activity, but able to work; 2 = able to perform self-care; 3 = limited selfcare; 4 = completely unable, and; 5 = death).11 TaggedEnd hematol transfus cell ther. 2024;46(1):8−13 9
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