ISSN 2531-1379 VOLUME 46, ISSUE 4, OCTOBER-DECEMBER, 2024 HEMATOLOGY TRANSFUSION AND CELL THERAPY
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. 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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
TaggedH1CONTENTSTaggedEnd Editorial The challenge of timely diagnosis and management of acute leukemias and associated infections in Latin America Eduardo Magalh~aes Rego ................................................................................................ ............................ 325 Original Articles The association of HLA-DRB1 alleles and MBL2 gene variant in pediatric acute lymphoblastic leukemia patients Rustu Oguz, Hayriye Senturk Ciftci, Muge Gokce, Yeliz Ogret, Sedat Karadeniz, Sacide Pehlivan, Kursat Ozdilli, Zeynep Karakas, Serap Karaman and Filiz Ayd{n .............................................................. 327 Retrospective comparison of two different cell separators for autologous peripheral blood stem cell collection: Single center experience Muzaffer Keklik ................................................................................................ ............................................ 335 Tumor lysis syndrome in hematological inpatients, experience from a university hospital in Brazil: A retrospective cohort study Ebellins Tabares Calvache, Allison Dessiret Tabares Calvache and Cristiane Seganfredo Weber ............. 340 Dyslipidemia and atherogenic indexes in children with transfusion-dependent thalassemia Sanghamitra Ray, Diganta Saikia, Yachika Vashisht, Shikha Sharma, Rajesh Kumar Meena and Manish Kumar ................................................................................................ ............................................. 345 IL-4Ra(rs1801275) A>G polymorphism in Egyptian immune thrombocytopenia (ITP) patients: a single center experience Mohamed Abdelkader Morad, Noha A. Doudar, Nehad Tawfeek, Maha Yacoub, Taha Azoz and Doaa El Demerdash ................................................................................................ ...................................... 352 Human leukocyte antigen immunization in transfusion-dependent Moroccan patients with beta-thalassemia major: prevalence and risk factors Sanae Ouadghiri, Kaoutar El Morabit, Naoual Elansari, Ouafae Atouf, Maria Elkababri, Laila Hessissen and Malika Essakalli ................................................................................................ .......... 360 Are delays in diagnosis and treatment of acute leukemia in a middle-income country associated with poor outcomes? A retrospective cohort study Yadith Karina Lopez-Garcia, Mayra Valdez-Carrizales, Jorge Adri anNu~nez-Zuno, Elia Apodaca-Ch avez, Juan Rangel-Pati~no and Roberta Demichelis-G omez .............................................. 366 IL-8 in bone marrow and peripheral blood of patients with B-cell acute lymphoblastic leukemia is associated with high regulatory T cell counts, degree of tumor infiltration and expression of CXCR1 in blasts Diana Anaya, Sandra Paola Santander Gonz alez, Natalia Murillo, Ricardo Ballesteros-Ramírez, Iliana De los Reyes, María V. Herrera, Julio Solano, Susana Fiorentino and Sandra Quijano .................... 374 TaggedFigure TaggedEnd Hematology, Transfusion and Cell Therapy www.htct.com.br TaggedFigure TaggedEnd Volume46•Number 4•October/December 2024
Blood components requirement in Brazilian dengue outbreaks: A retrospective analysis between 2008 to 2019 Deivide de Sousa Oliveira, Daniel Gir~ao Britto, Gabriella Fidelis de S a, Ana Carolina Nogueira Rocha Lima, Jo~ao Victor Ara ujo Silva, Antonio Vinícius Barros de Ara ujo, Rejane Cavalcante Rebelo, Larissa Ciarlini Varandas Sales, Marcus F abio Tavares de Abreu and Ednardo Ramos de Meneses ......................................................................................................................... 381 Impact of Imatinib on reducing the painful crisis in patients with sickle cell disease Mojtaba Karimi, Mohammad Bahadoram, Ladan Mafakher and Mohammadhossein Rastegar .............. 387 Evaluation of erythrocytapheresis compared to phlebotomy in polycythaemia vera patients Sergio Cabibbo, Giovanna Oriella Manenti, Agostino Antolino, Massimo Poidomani, Raffaele Elia, Giuseppe A. Palumbo and Francesco Di Raimondo ..................................................................................... 393 Toxicity and outcome of adults with acute myeloid leukemia receiving consolidation with high-dose cytarabine Lais Moreira Lopes, Marcio Nucci and Rodrigo Doyle Portugal ................................................................... 397 ABO blood group discrepancies in blood donor and patient samples at a tertiary care oncology centre: analysis and serological resolution Priti Desai, Anisha Navkudkar and Sunil Rajadhyaksha ........................................................................... 402 Dental tissues of sickle cell anemia and its impact on the quality of life related to oral health Danny Kanyana Makolo, Alphonse Mutombo Mutombo, Fidele Nyimi Bushabu, Grace Paka Lubamba, Baruch Kabungu Yemweni, Ediz Ekofo Inganya, Patrick Sekele Marob, Em Kalala Kazadi, Jean Marie Kayembe Bukama and Augustin Mantshumba Milolo ............................................................. 408 Indigenous antithymocyte globulin-equine to treat aplastic anaemia in adults: a case series from two centres in northeast India Asif Iqbal, Abhijit Phukan and Chandana Sharma ..................................................................................... 415 Outcomes and challenges treating pediatric acute myeloid leukemia: a retrospective analysis of patients treated at the Fundaci on Valle del Lili between 2011 and 2020 Alexis A. Franco, Viviana Lotero, Pamela Rodríguez, Estefania Beltran, Eliana Manzi, Angela Devia-Zapata and Diego Medina-Valencia ..................................................................................... 420 Evaluation of efficacy and safety in the use of cytarabine for mobilization of hematopoietic stem cells in a reference hospital in northeastern Brazil Kaio Jos e Santos de Andrade, Luís F abio Barbosa Botelho, Rodolfo Froes Calixto, Manuela Gomes de Oliveira, Leina Yukari Etto and Luiz Victor Maia Loureiro .......................................... 428 Epidemiology and risk factors for the development of infectious complications in newly diagnosed multiple myeloma: a multicenter prospective cohort study in Uruguay Eloísa Riva, David Garrido, Fiorella Villano and Virginia Bove ................................................................... 434 Therapeutic role of plasma exchange in the management of stiff person syndrome: experience from a tertiary care centre Vijay Kumawat, Parmatma Prasad Tripathi, Netravathi M, Anita Mahadevan and Anchan Vidyashree Vittal ................................................................................................ ............................ 443 Direct antiglobulin test in the differential diagnosis of ABO hemolytic disease of the newborn: an important tool with high negative predictive value Samira Ali Abbas, Carla Luana Dinardo, C arlei Heckert Godinho, Karen Ziza, Bruno Cruz, Juliana Oliveira Martins, Elyse Moritz, Dante M. Langui and Jos e O. Bordin ............................................. 450 Prevalence of anti-HLA antibodies in COVID-19 convalescent plasma donors: an Indian experience Ram Mohan Jaiswal, Aseem Kumar Tiwari, Ashina Singla, Ashish Jain, Rajaat Vohra, Munish Kakkar and Prashanth Suravajhala ............................................................................................... 455
Case Reports Detection of ABL1 deletion without BCR-ABL rearrangement in ETP-ALL Ahmed Makboul, Walaa T. El-Mahdy and Doaa F. Temerik ...................................................................... 462 Sudden painless loss of vision as the initial manifestation of acute myeloid leukemia: a case report Vishal Mangal, Harshit Khurana, Deepti Mutreja, Navin Kumar Yadav and Phani Kumar Chakilam ........ 465 Immune thrombocytopenia in a patient with essential thrombocythemia after SARS-CoV-2 infection: A case report Barbora Bacova, Maria Maco, Lucie Geislerova, Ivana Zubata, Tomas Kozak and Jan Novak .................. 469 Multiple mononeuritis as a manifestation of graft versus host disease Agustín Matías Mu~noz, Alberto Daniel Gim enez Conca, Ariel Alejandro Luzzi, Pablo Sebasti anSosa, Federico Sberna, Florencia Bel en Comacchio, Natalia Paola Schutz and Georgina Emilia Bendek ............. 473 Intravascular large B-cell lymphoma with primary bone marrow involvement −Report of a rare disease Samikshya Thapa, Anchal Tandon, Subhajit Hajra, Sonali Mishra, Kavya UR, Aishwarya Chandra and Arvind Gupta ................................................................................................ ............................................... 477 Long-term follow-up of patients with LPS-responsive beige-like anchor protein deficiency after reduced-intensity conditioning for allogeneic hematopoietic stem cell transplantation: report of two cases Leila Jafari, Rashin Mohseni, Dima Barhoom, Faihaa Hakima Abou fakher, Maryam Behfar and Amir Ali Hamidieh ................................................................................................................................ ....... 481 Severe Relapsed Autoimmune Hemolytic Anemia after Booster with mRNA-1273 COVID-19 vaccine Flordeluna Z. Mesina ................................................................................................ ................................... 485 Coincidental or causal? A case report of acquired thrombotic thrombocytopenic purpura following mRNA-1273 Covid-19 vaccination Erinie M Mekheal, Christopher Millet, Nader Mekheal, Moutaz Ghrewati, Ashesha Mechineni and Michael Maroules ................................................................................................ ......................................... 489 Thrombotic thrombocytopenic purpura and mushroom-shaped red blood cells secondary to COVID-19: A case report Tarcísio Silva Borborema, Joziele de Souza Lima, J ulioC esar Moreira Brito, Mitiko Murao and Rodrigo Siqueira-Batista ................................................................................................ .............................. 494 Myeloid/lymphoid neoplasms withfibroblast growth factor receptor-1 (FGFR1) rearrangement in Vietnam: a case report and literature review Tan-Huy Chu, Thien-Ngon Huynh, Kim-Son Nguyen and Chi-Dung Phu .................................................. 498 Application of Monocyte Monolayer Assay technique to predict hyperhemolysis in patients with sickle cell disease Dahra Teles Cruz, Marina C.V. Conrado, Alfredo Mendrone and Carla L. Dinardo ................................... 503 Spontaneous remission without treatment of acute myelomonocytic leukemia associated with COVID-19 infection Rafael Pe~nuela, Indira Hernandez, M onica Fernandes-Pineda, L azaro Cortina, Diana Zapata, Olga Urrego, Juan Herrera, Isabel Saenz, Recio Orduz, Fabi an Mejia, Liliana Moreno and Margarita Velazco ................................................................................................................................ ....... 506 Thrombocytopenic thrombotic purpura related to COVID-19 vaccine: apropos of 4 cases C elia Dos Santos, Santiago Castera, Jos e Fernandez, Julieta Soledad Rosales, Franco Crescitelli, Santiago Boughen, Marcelo Iastrebner, Osvaldo Guerrero, Carlos Amell Menco, Mariela Gomez, Jacqueline Gonzalez, Maria Fabiana Alberto and Analía Sanchez-Luceros ................................................ 511
Review Articles Anti-PF4 antibodies and their relationship with COVID infection Chieh Yang, Irene Wang, Akshit Chitkara, Jibin Swankutty, Rushin Patel and Samir V Kubba ............... 516 The role of measuring peak systolic velocity of the middle cerebral artery bloodflow and anti-K1 titre during pregnancy to detect foetuses with severe anaemia, foetal hydrops, and the requirement of intrauterine transfusion: A systematic review and meta-analysis Mufleha Ahmed and Denise E. Jackson ....................................................................................................... 524 Epidemiology, patient journey and unmet needs related to hemophilia in Brazil: a scoping review with evidence map Nay^e Balzan Schneider, Cintia Laura Pereira de Araujo, Harryson Wings Godoy dos Santos, Simone Lima, Maicon Falavigna and Daniela Vianna Pachito .................................................................... 533 Special Article Immunophenotypic markers for the evaluation of minimal/measurable residual disease in acute megakaryoblastic leukemia Carina Maria Pinto, Camila Marques Bertolucci, Alef Rafael Severino, Juliana Fernanda dos Santos Tosi and Maura R V Ikoma-Colturato ................................................................................................ ................. 542 Should men who have ever had sex with men be allowed to donate blood in Brazil? Edson Zangiacomi Martinez, Guilherme Galdino and Miriane Lucindo Zucoloto ....................................... 549 Diagnosis and management of acute promyelocytic leukemia: Brazilian consensus guidelines 2024 on behalf of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy Lorena Lobo de Figueiredo-Pontes, Luiz Fernando Bazzo Catto, Maria de Lourdes Lopes Ferrari Chauffaille, Katia Borgia Barbosa Pagnano, Maria Isabel Ayrosa Madeira, Elenaide Coutinho Nunes, Nelson Hamerschlak, Marcela Cavalcante de Andrade Silva, Thiago Xavier Carneiro, Teresa Cristina Bortolheiro, Tiago Thalles de Freitas, Rosane Isabel Bittencourt, Evandro Maranh~ao Fagundes and Eduardo Magalh~aes Rego ............................................................... 553 Letters to the Editor Monoclonal gammopathy and myeloproliferative neoplasm molecular diagnostics Stephen E. Langabeer ................................................................................................ ................................... 570 Association between time of heparin exposure and platelets decline in patients with heparin induced thrombocytopenia Omid Moradi Moghaddam, Zohreh Heydari Ramsheh, Mohsen Sedighi, Alireza Amanollahi and Mohammad Niakan Lahiji ................................................................................................ ........................... 572 Improved overall survival of transplant eligible newly diagnosed multiple myeloma patients in a Chilean public center. How did we achieve it? CamilaPe~na, Patricia Graffigna,Mois es Russo, Esteban Forray and Pablo Bustamante ........................... 575 Images in Clinical Hematology Hungry blast and faggot neutrophils in acute myeloid leukemia with CBF::MYH11 rearrangement Ver onicaRold an Galiacho and Amaia Balerdi Malcorra ............................................................................. 577
Editorial TaggedAPTARAH1The challenge of timely diagnosis and management of acute leukemias and associated infections in Latin AmericaTaggedAPTARAEnd TaggedAPTARAPEduardo Magalh~aesRego a,b,c TaggedAPTARAEnd TaggedAPTARAP 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~oesM edicas 31, Faculdade de Medicina da Universidade de S~ao Paulo (LIM 31 FM USP), S~ao Paulo, SP, Brazil TaggedAPTARAEnd TaggedAPTARAPThe treatment of patients with acute leukemias (AL) is challenging not only because of the intrinsic aspects of the disease, such as the coexistence of multiple mechanisms of treatment resistance and the high frequency of clonal evolution, but also due to the significant resource demands placed on the health system for the prompt diagnosis, treatment, and management of adverse events related to the treatment. In this issue of our journal, two articles highlight the hurdles faced by doctors treating AL in Latin America.TaggedAPTARAEnd TaggedAPTARAPDemichelis-G omez et al. 1 analyzed the time interval from the first symptom to treatment initiation in 188 Mexican patients with AL and found that the median interval was 31 days. Patients with acute lymphoblastic leukemia had longer intervals compared to those with acute promyelocytic leukemia (APL) and acute myeloid leukemia (AML), though all three groups had a median time longer than 20 days. The complete remission (CR) rate was 76.6 %, and 39 patients (20.7 %) died within 60 days of diagnosis (early death - ED). The main cause of ED was infection (64 %). Notably, across all treatment phases, 57 patients were suspected of having a fungal infection, with 22 (12.5 %) having confirmed fungal infections.TaggedAPTARAEnd TaggedAPTARAPIn another study, Nucci et al. 2 analyzed 61 patients with AML treated at a reference university hospital in Brazil. The CR rate after the first course of intensive chemotherapy was 52.4 %. The authors detailed the adverse events observed during 67 cycles of high-dose cytarabine used as consolidation treatment for 28 patients. Febrile neutropenia occurred in 38 of these cycles (56.7 %), bacteremia in 13 cycles (34.2 %), and there were two cases of invasive fungal disease (IFD).TaggedAPTARAEnd TaggedAPTARAPThere is a paucity of studies reporting the time interval from symptom onset to diagnosis or treatment of acute leukemias. The International Consortium on Acute Leukemias reported that the interval between symptom onset and diagnosis of APL exceeded 10 days in 44.7 % of 806 cases treated in Brazil, Chile, Peru, Paraguay, and Uruguay. Sekeres et al.3 analyzed 1317 patients with AML from the Cleveland Clinic and M.D. Anderson Cancer Center databases (1994−2005) and found that longer intervals between diagnosis and treatment were associated with worse CR rates and overall survival in patients younger than 60, but not in older patients. In contrast, Rollig et al.4 found no association between the diagnosis-to-treatment interval and survival in a large dataset of 2263 AML patients from the German Study Alliance Leukemia-Acute Myeloid Leukemia (SAL-AML) registry.TaggedAPTARAEnd TaggedAPTARAPThe direct comparison between the data from DemichelisG omez et al.1. and those from Europe or the US is challenging due to differences in variables and methods. However, the data suggest that AL diagnosis and treatment initiation take longer in Latin America.TaggedAPTARAEnd TaggedAPTARAPRegarding the frequency of infections during intensive chemotherapy in AL patients treated in Latin America, the results from Demichelis-G omez et al.1 and Nucci et al.2 indicate that bacterial infections, rather than IFD, are particularly concerning. The former has been reported as a primary cause of ED in various studies from the region. However, recent studies show that the frequency of IFD in Latin American centers is similar to that reported in Europe. For example, Rodríguez-Veiga et al.5 found that out of 589 intensive chemotherapy episodes in 285 AML patients at a Spanish referral center, there were 56 (10 %) IFD episodes. According to the EORTC 2008 criteria, IFD was TaggedAPTARAEnd E-mail address: eduardo.rego@fm.usp.br https://doi.org/10.1016/j.htct.2024.08.001 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 license (http://creativecommons.org/licenses/by/4.0/). TaggedAPTARAEndhematol transfus cell ther. 2024;46(4):325−326 TaggedAPTARAFigure TaggedAPTARAEnd Hematology, Transfusion and Cell Therapy www.htct.com.br TaggedAPTARAFigure TaggedAPTARAEnd
classified as possible (n = 29; 52 %), probable (n = 17; 30 %), and proven(n= 10; 18 %). The possible/probable/proven IFD rate was significantly lower during consolidation courses based on high doses of cytarabine compared to anthracycline-containing chemotherapy courses (2% vs. 11 %).TaggedAPTARAEnd TaggedAPTARAPIn summary, these two manuscripts emphasize that to improve patient outcomes in Latin America requires better access to specialized hematological care, improved diagnosis and management of infectious complications.TaggedAPTARAEnd TaggedAPTARAH1Conflicts of interestTaggedAPTARAEnd TaggedAPTARAPThe author declares no conflicts of interest.TaggedAPTARAEnd taggedaptarah1referencestaggedaptaraend TaggedAPTARAListItemTaggedAPTARAListLabel1TaggedAPTARAEnd. TaggedAPTARAListBodyLopez-Garcia YK, Valdez-Carrizales M, Nu~nez-Zuno JA, Apodaca-Ch avez E, Rangel-Pati~no J, Demichelis-G omez R. Are delays in diagnosis and treatment of acute leukemia in a middle-income country associated with poor outcomes? A retrospective cohort study. Hematol Transfus Cell Ther. 2024;46. XXXTaggedAPTARAEnd.TaggedAPTARAEnd TaggedAPTARAListItemTaggedAPTARAListLabel2TaggedAPTARAEnd. TaggedAPTARAListBodyLopes LM, Nucci M, Portugal RD. Toxicity and outcome of adults with acute myeloid leukemia receiving consolidation with high-dose cytarabine. Hematol Transfus Cell Ther. 2024;46. XXXTaggedAPTARAEnd.TaggedAPTARAEnd TaggedAPTARAListItemTaggedAPTARAListLabel3TaggedAPTARAEnd. TaggedAPTARAListBodySekeres MA, Elson P, Kalaycio ME, Advani AS, Copelan EA, Faderl S, et al. Time from diagnosis to treatment initiation predicts survival in younger, but not older, acute myeloid leukemia patients. Blood. 2009;113:28–36TaggedAPTARAEnd.TaggedAPTARAEnd TaggedAPTARAListItemTaggedAPTARAListLabel4TaggedAPTARAEnd. TaggedAPTARAListBodyR€ollig C, Kramer M, Schliemann C, Mikesch JH, Steffen B, Kr€amer A, et al. Does time from diagnosis to treatment affect the prognosis of patients with newly diagnosed acute myeloid leukemia? Blood. 2020;136:823–30TaggedAPTARAEnd.TaggedAPTARAEnd TaggedAPTARAListItemTaggedAPTARAListLabel5TaggedAPTARAEnd. TaggedAPTARAListBodyRodríguez-Veiga R, Montesinos P, Boluda B, Lorenzo I, Martínez-Cuadr on D, Salavert M, et al. Incidence and outcome of invasive fungal disease after front-line intensive chemotherapy in patients with acute myeloid leukemia: impact of antifungal prophylaxis. Ann Hematol. 2019;98: 2081–8TaggedAPTARAEnd.TaggedAPTARAEnd TaggedAPTARAEnd326 hematol transfus cell ther. 2024;46(4):325−326
TaggedAPTARADocumentOriginal article TaggedAPTARAH1The association of HLA-DRB1 alleles and MBL2 gene variant in pediatric acute lymphoblastic leukemia patientsTaggedAPTARAEnd TaggedAPTARAPRustuOguz a,*, Hayriye Senturk Ciftci b, Muge Gokce c, Yeliz Ogret b, Sedat Karadeniz d, Sacide Pehlivan b, Kursat Ozdilli e, Zeynep Karakas b, Serap Karaman f, FilizAyd{n a TaggedAPTARAEnd TaggedAPTARAP aIstanbul T.C. Demiro glu Bilim University, Faculty of Medicine, Istanbul, Turkey bIstanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey c Istanbul Yeni Yuzy{l University, Gaziosmanpasa Hospital, Istanbul, Turkey dKadir Has University, Graduate School of Science and Engineering, Istanbul, Turkey e Medipol University, Faculty of Medicine, Istanbul, Turkey f Division of Hematology and Oncology, Department of Pediatrics, Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey TaggedAPTARAEnd TAGGEDAPTARAPARTICLE INFO Article history: Received 23 August 2022 Accepted 9 February 2023 Available online 21 March 2023TaggedAPTARAEnd TAGGEDAPTARAPA B S T R A C T Introduction: Epidemiologic studies on pediatric acute lymphoblastic leukemias (ALL) have been conducted to evaluate the possible risk factors including genetic, infectious and environmental factors with the objective of idenfying the etiology. Mannose-binding lectin 2 (MBL2) plays an important role in first-line immune defense. HLA DRB1 alleles play a role in presentation of peptides to T cells and in activation of the adaptive immune response. Objective: In our study, we aimed to investigate both the MBL2 gene variant and HLA-DRB1 alleles in pediatric ALL patients. Materials: In this study, 86 high-risk ALL patients and 100 controls were included. Polymerase Chain Reaction (PCR)-Restriction Fragment Length Polymorphism (PCR-RFLP) and PCRsequence specific primer (SSP) methods were used for detection of polymorphism of the MBL2 and HLA-DRB1 alleles, respectively. Results: The frequency of the MBL2 AB genotype was lower in female ALL patients, compared to male ALL patients (p = 0.034). An association was found between the MBL2 BB genotype and DRB1*07 and among patients with the MBL2 BB genotype; those who also carried the DRB1*07 and *04 alleles were significantly higher than those without the DRB1*07 and *04 alleles. (p=0.048, p= 0.022, respectively). Conclusion: This is the first study suggesting that the MBL2 BB genotype in association with the DRB1*07 or co-inheritance of the HLA-DRB1*04 and HLA DRB1*07 may have an impact on the etiopathogenesis of the disease. 2023 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by TaggedAPTARAEndTaggedAPTARAPKeywords: Acute lymphoblastic leukemia Mannose-binding lectin 2 Human leukocyte antigen Polymorphism Childhood leukemiasTaggedAPTARAEnd * Corresponding author. E-mail address: rustu.oguz@florence.com.tr (R. Oguz). https://doi.org/10.1016/j.htct.2023.02.002 2531-1379/ 2023 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/). hematol transfus cell ther. 2024;46(4):327−334 TaggedAPTARAFigure Hematology, Transfusion and Cell Therapy www.htct.com.br TaggedAPTARAFigure
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/).TaggedAPTARAEnd TaggedAPTARAH1IntroductionTaggedAPTARAEnd TaggedAPTARAPAcute lymphoblastic leukemia (ALL) accounts for 75% of childhood leukemias and 25% of childhood cancers. It has been reported that preleukemic cells can usually be detected at birth in pediatric ALL. Epidemiological studies suggest that it may occur in patients with ALL as a result of an abnormal interaction between the immune system and unspecified infections.1-5 The relationship between “human leucocyte antigen (HLA) class II alleles” and pediatric leukemia has been demonstrated in different studies. This may be due to the role of the HLA allele-restricted peptide binding and T cell activation.6 The mannose-binding lectin (MBL) is involved in the lectin pathway, which is one of the pathways in the complement system. The MBL contributes to the innate immunity through opsonization and complement activation.7,8 In humans, the MBL gene is named MBL2, is located on chromosome 10q21-23 and contains 6321 base pairs, 4 exons and 3 introns.9-12 The normal “wild type” MBL2 gene is defined as allele A. There are 3 single nucleotide polymorphisms (SNPs) all identified for the MBL2 gene.12 The mutant alleles B, C and D alleles are linked to the SNP in the first exon of the MBL2 gene. The codons 54, 57 and 52 interfere with the assembly of the protein, causing decreased functional circulating MBL. In addition, the −221 X/Y promoter SNP affects the protein expression, with the −221Y variant being associated with high MBL levels in the serum.13 The functional gene variant MBL2-rs1800450 has been shown to be associated with MBL2 activity.14 Genetically determined MBL2 insufficiency is associated with increased susceptibility to both bacterial and viral infections. In individuals who are heterozygous for these alleles, the amount of protein is reduced by 10-fold, whereas the protein cannot be detected at all in individuals who are homozygous or combined heterozygous.14,15 TaggedAPTARAEnd TaggedAPTARAPThe aim of this study was to analyze the association between the MBL2 genotype and the HLA-DRB1 alleles in ALL patients who may be candidates for allogeneic hematopoietic stem cell transplantation (HSCT), and to investigate the possible role of the MBL2 genotype in the gaft versus host Disease (GvHD).TaggedAPTARAEnd TaggedAPTARAH1Materials and methodsTaggedAPTARAEnd TaggedAPTARAH2PatientsTaggedAPTARAEnd TaggedAPTARAPThis retrospective association study included 86 high-risk pediatric ALL patients and 100 healthy controls who had consecutively applied to the Istanbul Medical Faculty, Pediatric Hematology Unit and Yeni Yuzy{l Medical Faculty, Pediatric Hematology Department. As part of routine practice, leukemia patients were classifiedas ‘high-risk’ at the time of diagnosis according to the Berlin Frankfurt-Munster (BFM) study group risk factors and were HLA-typed in preparation for possible bone marrow transplantation.16 Twenty transplant patients were analyzed for MBL2 genotypes after allogeneic HSCT.TaggedAPTARAEnd TaggedAPTARAH2Molecular methodTaggedAPTARAEnd TaggedAPTARAPThe genomic DNA was isolated from the peripheral blood using the Thermo Fisher PureLink Genomic DNA Mini KitTMisolation kit (Thermo Fisher Scientific, MA, USA). The DNA concentration was measured using a Thermo Fisher Nanodrop Spectrophotometer.TaggedAPTARAEnd TaggedAPTARAH2Polymerase chain reaction (PCR)-restriction fragment length polymorphism (RLFP)TaggedAPTARAEnd TaggedAPTARAPThe SNPs for the MBL2 gene (rs:1800450) were determined by the PCR-RLFP.15 We analyzed the codon 54 A/B (gly54asp: rs rs1800450) variation in exon 1 of the MBL2 gene. In the genotyping of the MBL2 gene (gly54asp-rs1800450), the polymerase chain reaction (PCR) was performed using forward (50TAGGACAGAGGGCATGCTC-30) and reverse (50-CAGGCAGTTTCCTCTGGAAGG-30) primers. The product’s 349 base pairs (bp) were digested with the restriction enzymeBanI (Fermentase) to identify the codon 54 polymorphism. The BanI digestion was performed at 37°C for overnight incubation. After enzyme digestion, products were visualized by electrophoresis in 3% agarose gel. The BanI restriction site is present on the wild type allele A (269 and 89 bp) and absent on the variant allele B (349 bp).15 TaggedAPTARAEnd TaggedAPTARAPAll patients and controls were typed by the sequence specific primer (PCR-SSP) typing method. All patients and controls were typed at the Tissue Typing Laboratory, Istanbul Faculty of Medicine, which is accredited to perform clinical tissue typing by the European Federation of Immunogenetics (EFI).TaggedAPTARAEnd TaggedAPTARAH2Polymerase chain reaction-sequence specific primer (PCR-SSP)TaggedAPTARAEnd TaggedAPTARAPThe HLA-DRB1 typing was performed using the PCR-SSP (Olerup SSP AB).TaggedAPTARAEnd TaggedAPTARAH2Statistical analysisTaggedAPTARAEnd TaggedAPTARAPThe data analysis was performed using the Statistical Package for the Social Sciences software version 21 (SPSS, Chicago, IL, USA). The patients and controls complied with the ‘’HardyWeinberg equilibrium’’ (p>0.05). The allele and genotype frequencies for MBL2 polymorphisms were calculated by direct counting and the associations of alleles and genotypes were compared with the chi-square test (x 2) and Fisher’s exact test using the SPSS 21. The Bonferroni correction test was analysed as well. The p-values of <0.05 were considered statistically significant.TaggedAPTARAEnd 328 hematol transfus cell ther. 2024;46(4):327−334
TaggedAPTARAH1ResultsTaggedAPTARAEnd TaggedAPTARAH2Demographics and clinical characteristicsTaggedAPTARAEnd TaggedAPTARAPEighty-six patients (62 males/24 females), aged 2−17 years, and 100 healthy controls (36 males/64 females), aged 20 −35 years, were included in this study. Twenty of the 86 patients were transplanted (23%) and 8 of these patients developed GvHD (40%).TaggedAPTARAEnd TaggedAPTARAPIn the pediatric ALL patient group, the frequency of DRB1*04 and *07 alleles (34.3% and 16.9%, respectively) was significantly higher, compared to the healthy control group (18.0% and 9.5%, respectively) (p<0.0001andp= 0.043, respectively). The frequencies of the DRB1*03 and DRB1*11 alleles (11.0% and 21.5%, respectively) were significantly lower in the pediatric ALL patients, compared to the control group (p=0.018andp= 0.008, respectively) (Table 1).TaggedAPTARAEnd TaggedAPTARAPThe frequencies of alleles/genotypes of the MBL2 variants in patients with pediatric ALL and healthy controls are shown in Table 2. The AA (73.3%), AB (18.6%) and BB (8.1%) genotypes were detected in the patients. The genotypic/allelic frequencies of MBL2 variants in the pediatric ALL patients, who had heterozygous and homozygous DRB1 alleles, and in healthy controls, are shown in Table 3. A significant difference was not found between pediatric ALL patients and healthy controls in terms of HLA-DRB1 alleles (Tables 2 and 3).TaggedAPTARAEnd TaggedAPTARAPIn pediatric ALL patients, we showed that the relationship between the MBL2 BB genotype and the DRB1*07 allele was found to be significantly frequent in those without the DRB1*07 (p = 0.048; OR = 3.933). In addition, the relationship between the MBL2 BB genotype and presence of the DRB1*07 and DRB1*04 was found to be more significantly frequent, compared to those without the DRB1*07 (p= 0.022; OR = 9.125) (Table4).TaggedAPTARAEnd TaggedAPTARAPMoreover, the association between the MBL genotypes and the HLA-DRB1*04/*07/*09 alleles separately, and with the individuals having together the HLA-DRB1*04/*07 and the DRB1*04/*09 alleles was investigated, however, no statistical significance was detected (Table 5).TaggedAPTARAEnd TaggedAPTARAPThe GvHD developed in 8 (40%) of 20 transplant patients. Among these patients, the frequency of the AA genotype was 50% in GvHD-negative patients. In patients with GVHD, the frequency of the AB genotype was 50%, the frequency of the AB genotype was 50% and the frequency of the BB genotype was 8.3% (Table 6).TaggedAPTARAEnd TaggedAPTARAH1DiscussionTaggedAPTARAEnd TaggedAPTARAPThe mannose-binding lectin deficiency has been associated with some infectious and autoimmune diseases. The fact that the MBL could affect infectious and autoimmune processes was the starting point for clinical research.7,8 TaggedAPTARAEnd TaggedAPTARAPIn the fetal immune system, the MBL2 recognizes carbohydrates in bacteria, viruses, fungi or parasites and, when bound to them, activates the MBL2 lectin pathway in the complement system.17-19 The results related to the impact of SNPs in the MBL2 gene in hematological malignancies are controversial.20 According to the hygiene hypothesis related to pediatric ALL, a lack of infection in the infant may lead to failure of normal immune system modulation, which may cause susceptibility to leukemogenic bacterial or viral infections in individuals.10,20 TaggedAPTARAEnd TaggedAPTARAPThe MBL2 gene is an important component of the innate immune system with 4 main functions, including the activation of the complement, direct promotion of opsono-phagocytosis, modulation of the inflammatory response and promotion of apoptosis.21 There are also other promoter variants that may affect gene expression.22,23 TaggedAPTARAEnd TaggedAPTARAPZerhnder et al. showed that the MBL2 serum level was not associated with the overall survival or event-free survival in a retrospective multi-center study on 372 pediatric hematologic malignancies.24 High levels of MBL-associated serine protease (MASP)-2, however, were associated with better event-free TaggedAPTARATable Table1 – TaggedAPTARACaptionHLA-DRB1 and HLA-DRB3/4/5 frequencies (%) in pediatric ALL patients and age-matched healthy controls. TaggedAPTARAEnd TaggedAPTARATheadTaggedAPTARATRTaggedAPTARATHHLA-DRB1TaggedAPTARAEnd TaggedAPTARATHALL (2n:172)%TaggedAPTARAEnd TaggedAPTARATHHealthy controls (2n:200)%TaggedAPTARAEnd TaggedAPTARATHp-valueTaggedAPTARAEnd TaggedAPTARATHOR (95%CI)TaggedAPTARAEndTaggedAPTARAEndTaggedAPTARAEndTaggedAPTARATbody TaggedAPTARATRTaggedAPTARATDDRB1*01TaggedAPTARAEnd TaggedAPTARATD(6) 3.5%TaggedAPTARAEnd TaggedAPTARATD(13) 6.5%TaggedAPTARAEnd TaggedAPTARATD0.239TaggedAPTARAEnd TaggedAPTARATD0.519 (0.193−1.399)TaggedAPTARAEndTaggedAPTARAEnd TaggedAPTARATRTaggedAPTARATDDRB1*03TaggedAPTARAEnd TaggedAPTARATD(7) 4.1%TaggedAPTARAEnd TaggedAPTARATD(22) 11.0%TaggedAPTARAEnd TaggedAPTARATD0.018 a TaggedAPTARAEnd TaggedAPTARATD0.343 (0.142−0.824)TaggedAPTARAEndTaggedAPTARAEnd TaggedAPTARATRTaggedAPTARATDDRB1*04TaggedAPTARAEnd TaggedAPTARATD(59) 34.3%TaggedAPTARAEnd TaggedAPTARATD(36) 18.0%TaggedAPTARAEnd TaggedAPTARATD<0.0001 a TaggedAPTARAEnd TaggedAPTARATD2.379 (1.473−3.840)TaggedAPTARAEndTaggedAPTARAEnd TaggedAPTARATRTaggedAPTARATDDRB1*07TaggedAPTARAEnd TaggedAPTARATD(29) 16.9%TaggedAPTARAEnd TaggedAPTARATD(19) 9.5%TaggedAPTARAEnd TaggedAPTARATD0.043 a TaggedAPTARAEnd TaggedAPTARATD1.932 (1.041−3.587)TaggedAPTARAEndTaggedAPTARAEnd TaggedAPTARATRTaggedAPTARATDDRB1*08TaggedAPTARAEnd TaggedAPTARATD(0) 0.0%TaggedAPTARAEnd TaggedAPTARATD(3) 1.5%TaggedAPTARAEnd TaggedAPTARATD0.252TaggedAPTARAEnd TaggedAPTARATD0.163 (0.008−3.191)TaggedAPTARAEndTaggedAPTARAEnd TaggedAPTARATRTaggedAPTARATDDRB1*09TaggedAPTARAEnd TaggedAPTARATD(3) 1.7%TaggedAPTARAEnd TaggedAPTARATD(1) 0.5%TaggedAPTARAEnd TaggedAPTARATD0.339TaggedAPTARAEnd TaggedAPTARATD3.533 (0.363−34.259)TaggedAPTARAEndTaggedAPTARAEnd TaggedAPTARATRTaggedAPTARATDDRB1*10TaggedAPTARAEnd TaggedAPTARATD(1) 0.6%TaggedAPTARAEnd TaggedAPTARATD(6) 3.0%TaggedAPTARAEnd TaggedAPTARATD0.128TaggedAPTARAEnd TaggedAPTARATD0.189 (0.022−1.587)TaggedAPTARAEndTaggedAPTARAEnd TaggedAPTARATRTaggedAPTARATDDRB1*11TaggedAPTARAEnd TaggedAPTARATD(19) 11.0%TaggedAPTARAEnd TaggedAPTARATD(43) 21.5%TaggedAPTARAEnd TaggedAPTARATD0.008 a TaggedAPTARAEnd TaggedAPTARATD0.453 (0.252−0.813)TaggedAPTARAEndTaggedAPTARAEnd TaggedAPTARATRTaggedAPTARATDDRB1*12TaggedAPTARAEnd TaggedAPTARATD(0) 0.0%TaggedAPTARAEnd TaggedAPTARATD(3) 1.5%TaggedAPTARAEnd TaggedAPTARATD0.252TaggedAPTARAEnd TaggedAPTARATD0.163 (0.008−3.191)TaggedAPTARAEndTaggedAPTARAEnd TaggedAPTARATRTaggedAPTARATDDRB1*13TaggedAPTARAEnd TaggedAPTARATD(13) 7.6%TaggedAPTARAEnd TaggedAPTARATD(22) 11.0%TaggedAPTARAEnd TaggedAPTARATD0.288TaggedAPTARAEnd TaggedAPTARATD0.661 (0.322−1.357)TaggedAPTARAEndTaggedAPTARAEnd TaggedAPTARATRTaggedAPTARATDDRB1*14TaggedAPTARAEnd TaggedAPTARATD(7) 4.1%TaggedAPTARAEnd TaggedAPTARATD(14) 7.0%TaggedAPTARAEnd TaggedAPTARATD0.264TaggedAPTARAEnd TaggedAPTARATD0.536 (0.222−1.431)TaggedAPTARAEndTaggedAPTARAEnd TaggedAPTARATRTaggedAPTARATDDRB1*15TaggedAPTARAEnd TaggedAPTARATD(16) 9.3%TaggedAPTARAEnd TaggedAPTARATD(9) 4.5%TaggedAPTARAEnd TaggedAPTARATD0.095TaggedAPTARAEnd TaggedAPTARATD2.177 (0.936−5.061)TaggedAPTARAEndTaggedAPTARAEnd TaggedAPTARATRTaggedAPTARATDDRB1*16TaggedAPTARAEnd TaggedAPTARATD(12) 6.9%TaggedAPTARAEnd TaggedAPTARATD(9) 4.5%TaggedAPTARAEnd TaggedAPTARATD0.369TaggedAPTARAEnd TaggedAPTARATD1.592 (0.653−3.875)TaggedAPTARAEndTaggedAPTARAEnd TaggedAPTARATR TaggedAPTARATD100%TaggedAPTARAEnd TaggedAPTARATD100%TaggedAPTARAEnd TaggedAPTARAEndTaggedAPTARAEnd Abbreviations: ALL: acute lymphoblastic leukemia; OR: odds ratio; CI: confidence interval; HLA: human leukocyte antigenTaggedAPTARAEnd a Statistically significant values (p<0.05) are indicated in bold. hematol transfus cell ther. 2024;46(4):327−334 329
survival in this study.24 Frakking et al. showed that MBL plasma levels increased during febrile neutropenia in “wildtype” MBL2 individuals in the first pediatric oncology cohort study.25 Allogeneic stem cell transplantation (allo-SCT) is being increasingly used worldwide for treating hematologic and nonhematologic diseases.26 The prolongation of the state of neutropenia, the presence of GvHD and steroid and/or other immunosuppressant treatments have been identified as important risk factors for the development of invasive fungal infection following allo-SCT.27 Granell et al. used 3 groups in their genotyping study for the SNPs reported in the promoter and exon 1 of the MBL2 gene. Of these groups, 102 were allo-SCT recipients, 106 were HLA-identical sibling donors, and 104 were healthy volunteer blood donors. There was no significant difference in the prevalence of MBL2 SNP in these three groups.28 Low serum MBL levels, related to promoter polymorphism and structural variants, have been associated with an increased risk of infection.29 Puente et al. showed that MBL genotypes of recipients and donors did not influence the severity of the acute graft versus host disease (aGVHD) or TaggedAPTARATable Table2 – TaggedAPTARACaptionComparison of genotype and allele frequencies of MBL2 gene variants between pediatric ALL patients and healthy controls. TaggedAPTARAEnd TaggedAPTARATheadTaggedAPTARATRTaggedAPTARATHMBL2TaggedAPTARAEnd TaggedAPTARATHALLTaggedAPTARAEnd TaggedAPTARATHHealthy controlsTaggedAPTARAEnd TaggedAPTARATHORTaggedAPTARAEnd TaggedAPTARATH95%CITaggedAPTARAEnd TaggedAPTARATHp-valueTaggedAPTARAEndTaggedAPTARAEndTaggedAPTARAEndTaggedAPTARATbody TaggedAPTARATRTaggedAPTARATDGenotypeTaggedAPTARAEnd TaggedAPTARATDn: 86 (%) a TaggedAPTARAEnd TaggedAPTARATDn: 100 (%) b TaggedAPTARAEnd TaggedAPTARAEnd TaggedAPTARATRTaggedAPTARATD AATaggedAPTARAEnd TaggedAPTARATD63 (73.3%)TaggedAPTARAEnd TaggedAPTARATD76 (76.0%)TaggedAPTARAEnd TaggedAPTARATD0.865TaggedAPTARAEnd TaggedAPTARATD0.446−1.678TaggedAPTARAEnd TaggedAPTARATD0.735TaggedAPTARAEndTaggedAPTARAEnd TaggedAPTARATRTaggedAPTARATD ABTaggedAPTARAEnd TaggedAPTARATD16 (18.6%)TaggedAPTARAEnd TaggedAPTARATD16 (16.0%)TaggedAPTARAEnd TaggedAPTARATD1.200TaggedAPTARAEnd TaggedAPTARATD0.559−2.572TaggedAPTARAEnd TaggedAPTARATD0.698TaggedAPTARAEndTaggedAPTARAEnd TaggedAPTARATRTaggedAPTARATD BBTaggedAPTARAEnd TaggedAPTARATD7 (8.1%)TaggedAPTARAEnd TaggedAPTARATD8 (8.0%)TaggedAPTARAEnd TaggedAPTARATD1.019TaggedAPTARAEnd TaggedAPTARATD1.353−2.936TaggedAPTARAEnd TaggedAPTARATD0.999TaggedAPTARAEndTaggedAPTARAEnd TaggedAPTARATRTaggedAPTARATDAlleleTaggedAPTARAEnd TaggedAPTARAEnd TaggedAPTARATRTaggedAPTARATD ATaggedAPTARAEnd TaggedAPTARATD142 (82.6%)TaggedAPTARAEnd TaggedAPTARATD168 (84.0%)TaggedAPTARAEnd TaggedAPTARATD1.127TaggedAPTARAEnd TaggedAPTARATD0.667−1.902TaggedAPTARAEnd TaggedAPTARATD0.691TaggedAPTARAEndTaggedAPTARAEnd TaggedAPTARATRTaggedAPTARATD BTaggedAPTARAEnd TaggedAPTARATD30 (17.4%)TaggedAPTARAEnd TaggedAPTARATD40 (16.0%)TaggedAPTARAEnd TaggedAPTARAEnd TaggedAPTARATRTaggedAPTARATDHWEpTaggedAPTARAEnd TaggedAPTARATD0.000TaggedAPTARAEnd TaggedAPTARATD0.129TaggedAPTARAEnd TaggedAPTARAEndTaggedAPTARAEnd Abbreviations: ALL: acute lymphoblastic leukemia; MBL2: mannose-binding lectin 2; HWEp: Hardy−Weinberg equilibrium; OR: odds ratio; CI: confidence interval; HLA: human leukocyte antigen.TaggedAPTARAEnd an=86, bn= 100, *OR (95% CI) was adjusted by age, &Fisher’s exact test. TaggedAPTARAEnd TaggedAPTARATable Table 3 – TaggedAPTARACaptionComparison of MBL2 gene variants between healthy controls and pediatric ALL patients with heterozygous and homozygous HLA-DRB1 alleles. TaggedAPTARAEnd TaggedAPTARATheadTaggedAPTARATRTaggedAPTARATHMBL2TaggedAPTARAEnd TaggedAPTARATHHLA-DRB1 alleles (heterozygosity) (ALL)TaggedAPTARAEnd TaggedAPTARATHHLA-DRB1 alleles (heterozygosity) (healthy controls)TaggedAPTARAEnd TaggedAPTARATHORTaggedAPTARAEnd TaggedAPTARATH95%CITaggedAPTARAEnd TaggedAPTARATHp-valueTaggedAPTARAEndTaggedAPTARAEndTaggedAPTARAEndTaggedAPTARATbody TaggedAPTARATRTaggedAPTARATDGenotypeTaggedAPTARAEnd TaggedAPTARATD n: 57 a TaggedAPTARAEnd TaggedAPTARATDn: 86 b TaggedAPTARAEnd TaggedAPTARAEnd TaggedAPTARATRTaggedAPTARATD AATaggedAPTARAEnd TaggedAPTARATD41 (71.9%)TaggedAPTARAEnd TaggedAPTARATD66 (76.7%)TaggedAPTARAEnd TaggedAPTARATD0.776TaggedAPTARAEnd TaggedAPTARATD0.361−1.668TaggedAPTARAEnd TaggedAPTARATD0.558TaggedAPTARAEndTaggedAPTARAEnd TaggedAPTARATRTaggedAPTARATD ABTaggedAPTARAEnd TaggedAPTARATD11 (19.3%)TaggedAPTARAEnd TaggedAPTARATD12 (14.0%)TaggedAPTARAEnd TaggedAPTARATD1.475TaggedAPTARAEnd TaggedAPTARATD0.601−3.617TaggedAPTARAEnd TaggedAPTARATD0.486TaggedAPTARAEndTaggedAPTARAEnd TaggedAPTARATRTaggedAPTARATD BBTaggedAPTARAEnd TaggedAPTARATD5 (8.8%)TaggedAPTARAEnd TaggedAPTARATD8 (9.3%)TaggedAPTARAEnd TaggedAPTARATD0.937TaggedAPTARAEnd TaggedAPTARATD0.290−3.025TaggedAPTARAEnd TaggedAPTARATD1.000TaggedAPTARAEndTaggedAPTARAEnd TaggedAPTARATRTaggedAPTARATDAlleleTaggedAPTARAEnd TaggedAPTARAEnd TaggedAPTARATRTaggedAPTARATD ATaggedAPTARAEnd TaggedAPTARATD93 (81.6%)TaggedAPTARAEnd TaggedAPTARATD144 (83.7%)TaggedAPTARAEnd TaggedAPTARATD0.861TaggedAPTARAEnd TaggedAPTARATD0.461−1.606TaggedAPTARAEnd TaggedAPTARATD0.634TaggedAPTARAEndTaggedAPTARAEnd TaggedAPTARATRTaggedAPTARATD BTaggedAPTARAEnd TaggedAPTARATD21 (18.4%)TaggedAPTARAEnd TaggedAPTARATD28 (16.3%)TaggedAPTARAEnd TaggedAPTARAEnd TaggedAPTARATRTaggedAPTARATDHWEpTaggedAPTARAEnd TaggedAPTARATD0.000TaggedAPTARAEnd TaggedAPTARATD0.129TaggedAPTARAEnd TaggedAPTARAEnd TaggedAPTARATRTaggedAPTARATD an=57, bn= 86 *: OR (95%CI) was adjusted by age, &Fisher’s Exact Test. TaggedAPTARAEndTaggedAPTARAEndTaggedAPTARAEnd TaggedAPTARATheadTaggedAPTARATRTaggedAPTARATHMBL2TaggedAPTARAEnd TaggedAPTARATHHLA-DRB1 alleles (homozygosity) (ALL)TaggedAPTARAEnd TaggedAPTARATHHLA-DRB1 alleles (homozygosity) (Healthy controls)TaggedAPTARAEnd TaggedAPTARATHORTaggedAPTARAEnd TaggedAPTARATH95%CITaggedAPTARAEnd TaggedAPTARATHp-valueTaggedAPTARAEndTaggedAPTARAEndTaggedAPTARAEndTaggedAPTARATbody TaggedAPTARATRTaggedAPTARATDGenotypeTaggedAPTARAEnd TaggedAPTARATDn: 29 c TaggedAPTARAEnd TaggedAPTARATDn: 14 d TaggedAPTARAEnd TaggedAPTARAEnd TaggedAPTARATRTaggedAPTARATD AATaggedAPTARAEnd TaggedAPTARATD22 (75.9%)TaggedAPTARAEnd TaggedAPTARATD10 (71.4%)TaggedAPTARAEnd TaggedAPTARATD1.257TaggedAPTARAEnd TaggedAPTARATD0.298−5.297TaggedAPTARAEnd TaggedAPTARATD1.000TaggedAPTARAEndTaggedAPTARAEnd TaggedAPTARATRTaggedAPTARATD ABTaggedAPTARAEnd TaggedAPTARATD5 (17.2%)TaggedAPTARAEnd TaggedAPTARATD4 (28.6%)TaggedAPTARAEnd TaggedAPTARATD0.520TaggedAPTARAEnd TaggedAPTARATD0.115−2.353TaggedAPTARAEnd TaggedAPTARATD0.441TaggedAPTARAEndTaggedAPTARAEnd TaggedAPTARATRTaggedAPTARATD BBTaggedAPTARAEnd TaggedAPTARATD2 (6.9%)TaggedAPTARAEnd TaggedAPTARATD0 (%0.0)TaggedAPTARAEnd TaggedAPTARATD2.636TaggedAPTARAEnd TaggedAPTARATD0.118−58.700TaggedAPTARAEnd TaggedAPTARATD1000TaggedAPTARAEndTaggedAPTARAEnd TaggedAPTARATRTaggedAPTARATDAlleleTaggedAPTARAEnd TaggedAPTARAEnd TaggedAPTARATRTaggedAPTARATD ATaggedAPTARAEnd TaggedAPTARATD49 (84.5%)TaggedAPTARAEnd TaggedAPTARATD24 (85.7%)TaggedAPTARAEnd TaggedAPTARATD0.907TaggedAPTARAEnd TaggedAPTARATD0.253−3.248TaggedAPTARAEnd TaggedAPTARATD1.000TaggedAPTARAEndTaggedAPTARAEnd TaggedAPTARATRTaggedAPTARATD BTaggedAPTARAEnd TaggedAPTARATD9 (15.5%)TaggedAPTARAEnd TaggedAPTARATD4 (14.3%)TaggedAPTARAEnd TaggedAPTARAEnd TaggedAPTARATRTaggedAPTARATDHWEpTaggedAPTARAEnd TaggedAPTARATD0.247TaggedAPTARAEnd TaggedAPTARATD0.129TaggedAPTARAEnd TaggedAPTARAEndTaggedAPTARAEnd Abbreviations: ALL: acute lymphoblastic leukemia; MBL2: mannose-binding lectin 2; HWEp: Hardy−Weinberg equilibrium; OR: odds ratio; CI: confidence interval.TaggedAPTARAEnd cn=29, dn= 14*:OR (95%CI) was adjusted by age, &Fisher’s Exact Test. TaggedAPTARAEnd TaggedAPTARAEnd330 hematol transfus cell ther. 2024;46(4):327−334
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