JOURNAL OF BONE MARROW TRANSPLANTATION AND CELLULAR THERAPY
The Journal of Bone Marrow Transplantation and Cellular Therapy (JBMTCT) was established in 2020 as the official vehicle for disseminating scientific information from the Brazilian Society of Bone Marrow Transplantation (Sociedade Brasileira de Terapia Celular e Transplante de Medula Óssea - SBTMO). The target audience is researchers, teachers, professionals and students with an interest in the medicine field, especially bone marrow transplantation, cell therapy and related sciences. Aiming to facilitate the immediate dissemination of articles, the Journal of Bone Marrow Transplantation and Cellular Therapy adopts a continuous publication model, with articles made available as soon as they are approved and are compiled into a single annual volume. The journal's abbreviated title is J Bone Marrow Transplant Cell Ther and should be used in bibliographies, footnotes, references and bibliographic captions. Focus and Scope The Journal of Bone Marrow Transplantation and Cellular Therapy publishes the results of basic and applied research that promotes scientific development in Hematology, Bone Marrow Transplantation, Cellular Therapy and related áreas. Open Access The Journal of Bone Marrow Transplantation and Cellular Therapy follows the Diamond Open Access model and authors or readers are not charged for any fees. The Journal of Bone Marrow Transplantation and Cellular Therapy offers immediate open access to its content, adhering to the principles of free access and the democratization of scientific knowledge. To maximize the dissemination and use of published material, the Journal of Bone Marrow Transplantation and Cellular Therapy adopts the Creative Commons license with CC BY 4.0 attribution. Thus, the copyright belongs to the authors, granting free and immediate access to the work and allowing any user to read, download, copy, distribute, print, search the full texts of the articles, or create links to them, crawl the articles for indexing, use them as data for software, or use them for any other lawful purpose, including commercial purposes, provided that proper credit is given. Authors are allowed to deposit all versions of their work [Preprint (submitted version), Accepted Manuscript (version of the manuscript that received acceptance), Published Article (version of record)] in an institutional or thematic repository without embargo. Ethics in Publication The publication involves the authors, the editors, the reviewers, and the Brazilian Society of Bone Marrow Transplantation who have responsibilities that affect all process stages, from submission to publication. The Journal of Bone Marrow Transplantation and Cellular Therapy is committed to high standards of ethical behavior in management and editorial practices, with an emphasis on relationships with authors and, mainly, in the evaluation of their manuscripts, under procedures established by international institutions such as the Committee on Publication Ethics (COPE) Principles of Transparency and Best Practice in Scholarly Publishing), Directory of Open Access Journals (DOAJ) (Transparency & Best Practice), Open Access Scholarly Publishing Association (OASPA) (Principles of Transparency and Best Practice in Scholarly Publishing), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (Code of Good Scientific Practices) e Scientific Electronic Library Online (SciELO) Guidelines on Best Practices for Strengthening Ethics in Scientific Publication). The Editorial Board ensure the quality of the material they publish, prohibiting any form of plagiarism and/or fraudulent data to maintain the integrity of the academic record and ensure intellectual standards. They are always ready to publish corrections, clarifications and retractions, when necessary, thus following the Guidelines for Good Practices in Scientific Publishing. The Journal of Bone Marrow Transplantation and Cellular Therapy adheres to international guidelines for good practice, recommended principles for investigating cases of research misconduct, and texts suggested by the World Science Forum and the Council of Scientific Editors when conducting investigations into international misconduct. Digital Preservation The Journal of Bone Marrow Transplantation and Cellular Therapy utilizes the PKP PN system to establish a distributed archiving system among participating libraries, enabling them to create permanent journal archives for preservation and future access. Archiving The Journal of Bone Marrow Transplantation and Cellular Therapy also uses the system LOCKSS for the preservation and archiving of the issues.
Sociedade Brasileira de Transplante de Medula Óssea
Hematopoietic cell transplantation in inborn errors of immunity Part I: severe combined immunodeficiency
Severe Combined Immunodeficiencies (SCID) are rare diseases characterized by a blockage in T-lymphocyte development. Hematopoietic Cell Transplantation (HCT) is the primary curative therapy, with the highest survival rates correlated to early diagnosis and the absence of active infections at transplant. The gold standard is a matched related sibling donor (MSD), but alternative donors like haploidentical family donors are increasingly used. Conditioning regimens vary, with reduced intensity busulfan and fludarabine often indicated. Early diagnosis via newborn screening and referral to experienced HCT centers are crucial for improving outcomes. Long-term follow-up is essential, as the cumulative incidence of late effects, such as neurologic and neurodevelopmental issues, increases over time.
Copyright (c) 2025 Rafaella Muratori, Juliana Folloni Fernandes, Gisele Loth, Ana Karine Vieira, Paulo Klinger, Simone Franco, Carmem Bonfim https://creativecommons.org/licenses/by/4.0
Inborn errors of metabolism and osteopetrosis
Allogeneic hematopoietic cell transplantation (HCT) remains the standard and potentially curative therapy for certain inborn errors of metabolism (IEM) and for osteopetrosis. This paper updates the Brazilian consensus guidelines for HCT indications in pediatric patients with IEM, specifically focusing on mucopolysaccharidosis, X-linked adrenoleukodystrophy, Krabbe disease, metachromatic leukodystrophy, and osteopetrosis. We emphasize the importance of early diagnosis, timely referral, and multidisciplinary follow-up to optimize patient outcomes. Additionally, we discuss the evolving landscape of conditioning regimens and donor selection criteria, underscoring the critical need for genetic testing to guide therapy. Future directions in research, including gene therapy and novel therapeutic strategies, are also highlighted.
Copyright (c) 2025 Juliana Folloni Fernandes, Adriana Melo Rodrigues, Liane Esteves Daudt, Paulo Klinger, Carmem Bonfim https://creativecommons.org/licenses/by/4.0
Hematopoietic stem cell transplantation for extracranial germ cell tumors
Malignant extracranial germ cell tumors (GCT) are uncommon in the pediatric population. Most affected children can achieve cure using conventional chemotherapy combined with appropriate local control. The role of high-dose chemotherapy with autologous stem cell transplantation (HDCT/ASCT) in GCT has been studied mainly in adult cohorts. In this article, we reviewed the current evidence and indications for HDCT/ASCT in the management of pediatric GCT.
Copyright (c) 2025 Neysimelia Costa Villela, Patricia Shimoda Ikeuti, Paulo Henrique dos Santos Klinger, Antonella Zanette, Cláudio Galvão de Castro Junior, Luiz Fernando Lopes https://creativecommons.org/licenses/by/4.0
HEMATOPOIETIC CELL TRANSPLANTATION FOR JUVENILE MYELOMONOCYTIC LEUKEMIA AND OTHER MYELOPROLIFERATIVE NEOPLASMS
Juvenile myelomonocytic leukemia (JMML) is a rare and distinctive hematologic neoplasm affecting infants and younger children. Hyperactivation of the RAS signaling pathway is a central initiating event in JMML, which also delineates its various genetic and clinical subtypes. While a small percentage of children may achieve spontaneous clinical remission, allogeneic hematopoietic cell transplantation (HCT) remains the only possible cure for most JMML patients. In this article, we reviewed the indications of HCT in JMML. Other myeloproliferative diseases, such as polycythemia vera, essential thrombocythemia, and primary myelofibrosis, are extremely rare in pediatrics and are briefly discussed.
Copyright (c) 2025 Neysimelia Costa Villela, Anita Frisanco Oliveira, Rafaela de Souza Ferreira, Gustavo Zamperlini, Andréia Cristina Fortes Bassani, Mariana Bohns Michalowski, Maria Lúcia de Martino Lee https://creativecommons.org/licenses/by/4.0
Acquired severe aplastic anemia is a rare, life-threatening condition characterized by pancytopenia and hypocellularity of the bone marrow. It shows a bimodal age distribution, with approximately 70–80% of cases classified as idiopathic. Recent advances in hematopoietic cell transplantation, immunosuppressive therapy, biological agents, and supportive care have greatly improved survival rates, reaching a 95% cure rate. Differential diagnoses include refractory cytopenia of childhood, inherited bone marrow failure syndromes, and other blood disorders. The aim of this article was to update the Brazilian consensus previously published by the Brazilian Society of Cellular Therapy and Bone Marrow Transplantation in 2021, highlighting the latest developments in the treatment and monitoring of severe aplastic anemia patients undergoing hematopoietic cell transplantation.
Virginio Climaco de Araujo Fernandes Junior
Copyright (c) 2025 Luiz Guilherme Darrigo Junior, Gisele Loth, Virginio Climaco de Araujo Fernandes Junior, Alexandre de Albuquerque Antunes, Gabriela Gaspar Filgueiras Landi, Carmem Bonfim https://creativecommons.org/licenses/by/4.0
Management of pediatric acute leukemias relapse after hematopoietic cell transplantation
Prevention is the best way to avoid relapse after hematopoietic cell transplantation (HCT). Immunomodulation can enhance graft-versus-leukemia effect and, if graft-versus-host disease (GVHD) is absent, prophylactic donor lymphocyte infusion (DLI) may be indicated for high-risk patients. Maintenance strategies with blinatumomab, inotuzumab, tyrosine kinase inhibitors, hypomethylating agents or venetoclax can be effective in reducing relapse rates. However, maintenance therapy response depends on individual toxicity and physician’s experience in handle with dose adjustments, undesirable drug interactions and complications. Preemptive approach guided by minimal residual disease (MRD) or mixed chimerism is fundamental to prevent hematologic relapse. Target agent or immunotherapy followed by DLI can be used, and if no response, low-dose chemotherapy can be added to reach disease control. After relapse, antigen-directed therapies with blinatumumab for CD19 ALL and inotuzumab for CD22 ALL are good options to induce MRD negativity and bridge to second HCT. Emerging therapies like daratumumab, immune checkpoint or menin inhibitors are promising but require validation. CAR-T cell therapy can provide a better chance of long-term survival if low leukemia burden and absence of GVHD. It is also effective in extramedullary disease, mainly in central nervous system relapse. Patients with B-cell aplasia loss after CAR T-cell therapy are second transplant candidates, as well as those with acute myeloid leukemia who respond to salvage therapy. Second HCT outcomes are better if relapse occurred ≥ 12 months after the first HCT. Strategies for expanding access to immunotherapy and target agents are crucial to improve long-term survival in these children.
Copyright (c) 2025 Rita de Cássia Barbosa Tavares, Polliany Roberta Dorini Pelegrina, Carla Nolasco Monteiro Breviglieri, Ana Luiza de Mello Rodrigues, Gustavo Zamperlini, Adriana Martins de Sousa, Patricia Regina Cavalcanti Barbosa Horn, Luiz Guilherme Darrigo Jr, Liane Daudt https://creativecommons.org/licenses/by/4.0
Non-infectious complications after hematopoietic cell transplantation
Hematopoietic cell transplantation (HCT) is a curative treatment for children with malignant and non-malignant diseases. In recent years, we have observed a significant increase in the survival of these patients, due to improved resources. In this article, we discuss non-infectious complications related to HCT, including their management, prevention, and best options of treatment.
Thábata Cristina Paradas Moreira da Silva
Copyright (c) 2025 Gustavo Zamperlini, Aline Ferrari Martins, Barbara da Cunha Arantes e Silva, Maite Freire Cardoso, Analiz Marchini Rodrigues, Thábata Cristina Paradas Moreira da Silva, Ana Carolina Ferreira Castro Salum, Adriana Seber, Natalia Borges, Alessandra Araujo Gomes https://creativecommons.org/licenses/by/4.0
Hematopoietic cell transplantation for pediatric myelodysplastic syndromes
Myelodysplastic syndromes (MDS) are uncommon in children and present distinct features compared to adults. Allogeneic hematopoietic cell transplantation (HCT) is considered the standard curative treatment for many children with MDS, including all patients with MDS with excess of blasts and those with refractory cytopenia of childhood associated with unfavorable karyotype, severe neutropenia or transfusion dependence. In this article, we reviewed the indications of HCT in pediatric MDS.
Copyright (c) 2025 Neysimelia Costa Villela, Anita Frisanco Oliveira, Roseane Vasconcelos Gouveia, Mariane Farherr Caleff, Gabriela Gaspar Filgueiras Landi, Maria Lúcia de Martino Lee https://creativecommons.org/licenses/by/4.0
Hematopoietic stem cell transplantation in children with thalassemia: Brazilian Society of Bone Marrow Transplantation Consensus
Allogeneic hematopoietic cell transplantation (HCT) represents a critical therapeutic option for patients with transfusiondependent thalassemia (TDT), with thalassemia-free survival rates exceeding 90% in cases involving HLA-matched sibling donors. Due to the limited availability of matched donors, alternative sources such as HLA-matched unrelated donors, haploidentical donors, and umbilical cord blood have broadened HCT eligibility. Despite its potential for cure, HCT involves risks like graft-versus-host disease, graft rejection, and transplant-related mortality. Recent improvements in conditioning regimens have enhanced patient outcomes and quality of life. Factors affecting HCT success in TDT include recipient age, disease complications, effective chelation therapy, Pesaro score, and donor compatibility. This article aimed to update the Brazilian consensus established by the Brazilian Society of Cellular Therapy and Bone Marrow Transplantation in 2021, incorporating the latest advances in treating and managing TDT patients undergoing transplantation.
Copyright (c) 2025 Luiz Guilherme Darrigo Junior, Ana Karine Vieira, Cilmara Kuwahara, Roseane Vasconcelos Gouveia, Paulo Klinger, Alexandre de Albuquerque Antunes, Julia Lopes Garcia https://creativecommons.org/licenses/by/4.0
Sickle cell disease (SCD) is known as the most common hemoglobin disorder, with severe forms of thalassemia syndromes following closely. Current standard treatments, including transfusions, hydroxyurea, and L-glutamine, still do not significantly improve life expectancy and quality of life for patients. Allogeneic hematopoietic cell transplantation (HCT) remains the only curative option, showing overall survival and event-free survival rates over 90%, especially in patients under 16 years old. However, only 15% of SCD patients have access to an unaffected family donor. To increase donor availability, alternative sources such as matched unrelated donors, unrelated umbilical cord blood, and haploidentical donors have become viable options for patients without a matched related donor. The aim of this article was to update the Brazilian consensus previously published by the Brazilian Society of Cellular Therapy and Bone Marrow Transplantation in 2021, highlighting the latest developments in the treatment and monitoring of patients with SCD undergoing HCT.
Copyright (c) 2025 Luiz Guilherme Darrigo Junior, Roseane Vasconcelos Gouveia, Cilmara Kuwahara, Alexandre de Albuquerque Antunes, Adriana Martins de Sousa , Ana Karine Vieira, Ainá Henriques Melgaço, Juliana Folloni Fernandes, Adriana Seber https://creativecommons.org/licenses/by/4.0
Hematopoietic cell transplantation in inherited bone marrow failure syndromes
Inherited bone marrow failure syndromes (IBMFS) comprise a heterogeneous group of rare genetic disorders characterized by defective hematopoiesis, congenital anomalies, and a predisposition to clonal evolution and malignancies. Hematopoietic cell transplantation remains the only curative option for the hematologic manifestations of these disorders, although it does not correct congenital malformations or eliminate the long-term risk of non-hematopoietic cancers. This review summarized current evidence and transplantation strategies for major IBMFS, including Fanconi anemia, dyskeratosis congenita/telomere biology disorders, Diamond-Blackfan anemia, Shwachman-Diamond syndrome, congenital neutropenia, congenital amegakaryocytic thrombocytopenia, and other inherited thrombocytopenias. We discussed disease-specific transplant indications, donor selection, conditioning regimens, graft source preferences, and outcomes across different patient populations. Advances in reduced-intensity conditioning and post-transplant cyclophosphamide have expanded donor availability, improving survival even with alternative donors. Nevertheless, long-term challenges persist, such as increased risks of solid tumors, endocrine dysfunction, and organ toxicity, emphasizing the need for multidisciplinary care and lifelong surveillance. Optimal outcomes depend on timely referral to specialized centers, meticulous donor screening, and individualized transplant strategies tailored to the unique biology of each disorder.
Copyright (c) 2025 Gisele Loth, Luiz Guilherme Darrigo, Adriana Martins, Alexandre de Albuquerque Antunes, Ana Karine Vieira https://creativecommons.org/licenses/by/4.0
Long-term follow-up after pediatric hematopoietic stem cell transplantation
This article, part of the Pediatric Group consensus of the Brazilian Society of Bone Marrow Transplantation, addresses lifelong follow-up in pediatric hematopoietic stem cell transplant survivors. With the growing number of long-term survivors, specialized monitoring is essential, especially for high-risk groups such as infants, recipients of total body irradiation, and those with inherited bone marrow failure syndromes. The consensus outlines surveillance strategies for detecting and managing late complications, including chronic graft-versus-host disease and secondary effects. Multidisciplinary recommendations aim to optimize early intervention and quality of life, establishing a standardized follow-up framework for pediatric transplant care in Brazil.
Copyright (c) 2025 Polliany Roberta Dorini Pelegrina, Roseane Vasconcelos Gouveia , Antonio Vaz de Macedo, Ana Karine Vieira, Gabriela Gaspar Filgueiras Landi, Julia Lopes, Osvaldo Alves de Menezes Neto, Rafaela de Souza Ferreira, Adriana Aparecida Siviero Miachon, Rita de Cássia Barbosa da Silva Tavares , Carmem Bonfim https://creativecommons.org/licenses/by/4.0
Central nervous system (CNS) tumors represent one of the most prevalent groups of neoplasms in the pediatric population. Recent advances in molecular biology and neuro-oncology have led to continuous updates in the classification of these tumors, which poses significant diagnostic challenges, particularly in low- and middle-income countries, with limited access to advanced diagnostic tools. The therapeutic approach varies according to tumor subtype, often requiring complex and resource-intensive protocols. One such strategy involves the use of high-dose chemotherapy followed by autologous stem cell rescue, which has shown promise in improving outcomes for select pediatric patients with CNS tumors. However, implementation of this therapy in countries like Brazil faces logistical, financial, and clinical practice challenges. This article aimed to provide a brief overview and suggestions to use high-dose chemotherapy with autologous stem cell transplantation in the treatment of pediatric CNS tumors. We discussed practical considerations for patient selection, and conditioning regimens. Our objectives were to optimize and guide current practices by proposing strategies that maybe feasible in the Brazilian public and private healthcare systems.
Copyright (c) 2025 Gustavo Zamperlini, Paulo Henrique dos Santos Klinger, Antonella Zanette, Cilmara Kuwahara, Sidnei Epelman, Adriana Seber, Cláudio Galvão de Castro Junior https://creativecommons.org/licenses/by/4.0
Outcomes in acute myeloid leukemia among older adults: a five-year retrospective cohort from a Brazilian public hospital
Acute myeloid leukemia (AML) remains a significant public health issue in the Brazilian public healthcare system. A retrospective chart review was conducted for patients diagnosed with AML between 2019 and 2024 at a university hospital in northeastern Brazil. Six patients underwent intensive chemotherapy with daunorubicin and cytarabine. Fourteen patients received low-intensity therapy (venetoclax combined with low-dose cytarabine, venetoclax and azacitidine, and azacitidine monotherapy). The overall one-year survival rate in this age group was 28.9%, with a median overall survival of 8.3 months. When stratified by treatment intensity, patients receiving low-intensity therapy had a median overall survival of 10.9 months, compared to 1.1 month for those receiving intensive chemotherapy and 1.5 month for those receiving supportive care alone. The incorporation of low intensity therapies may reduce toxicity and improve survival among elderly patients in low- and middle-income countries.
Copyright (c) 2025 Hercules Amorim Mota Segundo, Fernando Barroso Duarte https://creativecommons.org/licenses/by/4.0
Development of a data manager support manual for hematopoietic cell transplantation and cellular therapy for Latin America: an innovative approach to data reporting to the Center for International Blood & Marrow Transplant Research
The Brazilian Hematopoietic Cell Transplantation and Cellular Therapy (HCT-CT/BR) Registry depends on data manager (DM) training to ensure sustainability, for which it is essential to standardize processes. The objectives of this study were to describe the development of a support manual for Brazilian DMs reporting to the Center for International Blood and Marrow Transplant Research and to present quality assessment results. The descriptive study (Feb–Aug 2024) included structuring, content creation, and dissemination of the manual. Survey assessed satisfaction. The manual was launched at the XXVIII Brazilian Society of Cellular Therapy and Bone Marrow Transplantation Congress. Thirty-nine professionals rated it 9.3/10 for satisfaction and 9.4/10 for recommendation. A manual is crucial for standardizing processes and ensuring data quality, offering clear and up-to-date guidance.
Copyright (c) 2025 Flavia Ferreira da Costa, Paula Moreira da Silva Sabaini, Cinthya Muniz Corrêa Rocha da Silva, Anderson João Simeone, Heliz Regina Alves das Neves, Monique Ammi, Rosana Rocha Batista Concilio, Afonso Celso Vigorito, Eliana Cristina Martins Miranda, Leonardo Jun Otuyama, Joaquim Gasparini dos Santos, Mariza Toledo, Adriana Mendes de Quadros Cavilha, Jessica Di Chiara Salgado, Eudoxiana Melo, Simone Ojima Ferreira, Antonio Vaz Macedo, Adriana Seber, Carmem Maria Sales Bonfim, Vaneuza Araújo Moreira Funke, Marcelo Pasquini, Mary Flowers, Nelson Hamerschlak, Fernando Barroso Duarte https://creativecommons.org/licenses/by/4.0
Hematopoietic cell transplantation for all: report from the 2025 Congress of the Brazilian Bone Marrow Transplantation and Cellular Therapy Society
This article provides an analysis of the current landscape of hematopoietic cell transplantation (HCT) in Brazil, highlighting current data, challenges, and ongoing initiatives, as presented at the Brazilian Society of Cellular Therapy and Bone Marrow Transplantation (SBTMO) 2025 meeting. Brazil has seen a significant increase in the number of HCT procedures in recent years, being the country with the highest number of transplants, HCT centers, and transplant teams in Latin America. However, important challenges remain, including regional disparities in access, limited local availability of HCT, and insufficient hospital beds. These topics were discussed alongside partial updates of the new National Transplant System (SNT) regulations with representatives from SBTMO, SNT, Brazilian Health Regulatory Agency, Brazilian National Cancer Institute, Brazilian Association of Lymphoma and Leukemia, and Brazilian Association of Hematology, Hemotherapy, and Cellular Therapy, to improve equity, safety, and outcomes of hematopoietic stem cell transplants across Brazil.
Copyright (c) 2025 Fernando Barroso Duarte, Andresa Lima Melo, Adriano Arantes, Carmem Maria Sales Bonfim https://creativecommons.org/licenses/by/4.0
History of the Brazilian Cellular Therapy Processing Group and initial survey on cellular therapy processing, quality control, and release criteria for cryopreserved peripheral blood stem cells in autologous transplantation
There is considerable heterogeneity in peripheral blood stem cell (PBSC) cryopreservation protocols. In 2021, the Brazilian Cellular Therapy Processing Group was created to meet the need for technical specialists to exchange experiences, improve processes, and pursue international accreditation. This survey was developed to better understand national PBSC cryopreservation practices and to support the group’s technical discussions. An online questionnaire was created using Google Forms and disseminated. A total of 61 cell processing centers (CPC) responded to the survey. Most CPC showed interest in voluntary technical accreditation (n = 45; 73.8%), served one or two bone marrow transplantation units (n = 46; 75.4%) and processed bone marrow, PBSC and lymphocytes (n = 21; 34.4%). PBSCs were mainly cryopreserved within 24 hours of collection (n = 45; 73.8%), using a cryopreservation solution containing 5% DMSO and hydroxyethyl starch (n = 35; 67.3%). Most institutions froze and stored the cells at -80ÅãC until therapeutic use (n = 42; 80.8%). The maximum concentration of nucleated cells after cryopreservation varied widely across CPC. CD34+ cell quantification was most performed using the International Society for Hematotherapy and Graft Engineering dual-platform method (n = 25; 48.1%). The most frequently used post-cryopreservation quality control test was cell viability assessment using trypan blue exclusion (n = 34; 66.7%). This survey revealed considerable heterogeneity in PBSC cryopreservation practices among Brazilian CPC at the time the Cellular Therapy Processing Group was established. Since then, the group’s meetings have promoted improvements in the quality, safety, and efficacy of cell therapy products, as well as the gradual standardization of practices among its members.
Copyright (c) 2025 Karen de Lima Prata, Andrea Tieme Kondo , Brian Custer , André Rolim Belisário https://creativecommons.org/licenses/by/4.0
Two cases of clump formation after thawing of hematopoietic progenitor cell products for transplantation
While rare, clump formation has been described in the thawing of cryopreserved hematopoietic progenitor cell products intended for transplantation. When this occurs, it presents a significant challenge to the transplant team, potentially influencing the viability and safety of the product. Though the exact cause of clumping in thawed products remains unknown, studies have linked clump formation with the occurrence of adverse events. This report aimed to describe two cases of clump formation in thawed apheresis products observed in our processing laboratory, detailing the procedures followed and the outcomes achieved.
Copyright (c) 2025 JOURNAL OF BONE MARROW TRANSPLANTATION AND CELLULAR THERAPY https://creativecommons.org/licenses/by/4.0
A case-control study on cryopreserved versus non-cryopreserved strategies for autologous hematopoietic cell transplantation in multiple myeloma
Background: Autologous hematopoietic cell transplantation (aHCT) is a standard treatment for Multiple Myeloma (MM). The classic practice is with cryopreservation of the peripheral blood stem cells (PBSC) in the period from collection to infusion, but non-cryopreserved storage at 4oC has demonstrated to be feasible and safe. Methods: Here we present a retrospective, case-control study comparing the outcomes in terms of engraftment in two centers in Uruguay, one with cryopreservation (Hospital Británico-HB) and the other with 4oC storage (Hospital Maciel-HM). Results: 69 patients were included during Oct 15, 2018 and Dec 23, 2023. Median age was 60 years old (32-72). The median of collected PBSC was 9.0 x 106/kg (range 2.7 - 32.3), and the median of PBSC infused was 5.4 x 106/kg, (range 2.7 - 10.8). The time to neutrophil engraftment was 10 days (range 6-12) in HM and 9 days (range 7-12) in HB (p=0.38). The time for platelet engraftment was 20 days (range 17-25) in HM and 19 days (range 15-30) in HB (p=0.14). There were no graft failures, and no treatment-related mortality was observed at 100 days. Conclusions: Both cryopreserved and non-cryopreserved strategies appear to achieve similar outcomes in terms of engraftment and safety. Non-cryopreservation could be a way to improve affordability and accessibility to aHCT in MM, particularly in resource-limited areas.
Copyright (c) 2025 Byron Figueroa, Martin Ferrando, Sebastian Galeano, Gabriel Borelli, Eloísa Riva, Alberto Vásquez, Carolina Oliver, Rosanna De Giuda, Silvia Pierri, Leticia Martinez, Melanie Isern, Claudia Martinez, Romina Urrutia, Cristina Otero, Victoria Irigoín, Victoria Remedi, Martina Perdomo, María Mori, Regis Gai, Estefanía López, Virginia Marcalain, Camila Guidali, Laura Bello, Virginia Moraes, Lourdes Viano, Analía Olivera, Carina Lamela, Carla Ambrosini, Silvia Pisano, Juan Ferrari, Jimena Prieto, Raul Gabús, Pablo Muxí, Ana Inés Landoni https://creativecommons.org/licenses/by/4.0
Hematopoietic Cell Transplantation in Brazil: A National Benchmarking Study Focused on the Foundation for the Accreditation of Cellular Therapy (FACT) Performance Indicators
Systematic evaluation of hematopoietic cell transplantation (HCT) outcomes is essential to improve clinical practice and meet international quality standards. In Brazil, the partnership between the Brazilian Society of Cellular Therapy and Bone Marrow Transplantation (SBTMO) and the Center for International Blood and Marrow Transplant Research (CIBMTR) has advanced national data reporting and benchmarking through the Hematopoietic Cell Transplantation Brazilian Registry (HCTBR). This study reports outcomes from 11,210 first HCTs (5,984 allogeneic; 5,226 autologous) performed between 2012 and 2023 across 44 Brazilian centers. Median recipient age was 29 years for allogeneic and 53 years for autologous transplants. Acute leukemias predominated among allogeneic cases, while multiple myeloma was the most common indication for autologous HCT. Two-year overall survival was 82.0% for autologous and 59.8% for allogeneic transplants, with variation by donor type (matched related 61.8%, mismatched related 54.0%, unrelated 63.3%). Two-year non-relapse mortality was 8.0% and 21.6% for autologous and allogeneic transplants, respectively. The cumulative incidence of grade II–IV acute graft-versus-host disease (GVHD) at two years was 29.9%, with chronic GVHD incidence of 29.5%. Two-year relapse incidence was 24.1% for allogeneic and 25.8% for autologous HCT. Despite challenges within the Brazilian healthcare system, these outcomes align with international registry data. Adequate data completeness supports the robustness of these findings. Our results highlight the quality of Brazilian transplant programs and underscore the value of standardized outcome monitoring to foster continuous improvement. Strengthening center participation, follow-up, and data management remains critical to maintaining registry quality and enhancing patient care.
SEROLOGICAL STATUS OF EPSTEIN-BARR VIRUS IN BONE MARROW DONOR AND RECIPIENT AND ITS IMPACT ON POST-TRANSPLANT OUTCOMES
The Epstein-Barr virus (EBV) is a highly immunogenic herpesvirus that infects more than 90% of healthy individuals and can remain latent in B lymphocytes for years. In this context, in immunocompromised patients, such as those undergoing bone marrow transplantation (BMT), viral reactivation can occur in up to 63% of cases. Among the main risk factors for viral reactivation are donor-recipient incompatibility, EBV IgG-positive donors, and conditioning regimens using lymphodepleting drugs such as anti-thymocyte immunoglobulin, high-dose cyclophosphamide, and corticosteroids. Therefore, weekly EBV monitoring is recommended during the first 100 days post-transplant to detect viremia early and enable preemptive intervention, either by reducing immunosuppression or using anti-CD20 monoclonal antibodies. These strategies aim to reduce viremia progression and the incidence of post-transplant lymphoproliferative disease (PTLD). This study seeks to estimate the serological profile of bone marrow donors and recipients and its relationship with the incidence of post-BMT viral reactivation. Additionally, it aims to evaluate monitoring and preemptive treatment strategies for managing high-risk patients at the Walter Cantídio University Hospital from 2020 to 2024, while also defining the incidence of PTLD secondary to BMT. Keywords: Bone Marrow Transplantation, Epstein Barr Virus, EBV, lymphoma
CURRENT USE AND OUTCOMES OF CELLULAR THERAPY: BRAZILIAN SUMMARY SLIDES -2025 ‎
Chimeric antigen receptor T-cells (CAR T cells) are genetically modified cellular immunotherapies approved as a standard of care treatment for patients with lymphoma and leukemia worldwide. Here, we report the initial activity in Brazilian centers through the collaboration between the Brazilian Cellular Therapy and Bone Marrow Transplant Society (SBTMO) and the Center for International Blood and Marrow Transplant Research (CIBMTR). A total of 104 patients who received commercial and academic CAR-T cells in Brazil between January 2020 and April 2025 were included. The median age was 56 years (range 4-83). Indications were Non-Hodgkin Lymphoma (NHL; 75 cases; 72%), Acute Lymphoblastic Leukemia (ALL; 23 cases; 22%), Multiple Myeloma (MM; 4 cases; 4%) and Chronic lymphoblastic leukemia (CLL; 2 cases; 2%). Anti-CD19 commercial CAR-T were 82% of the total, 68 for NHL and 17 for ALL). Most deaths were due to disease progression or relapse (n=19), followed by infections (n=8). The overall survival after a median follow-up of 200 days was 73% (95% CI: 62-86; N=63) for NHL and 79% (95% CI: 63-99; N=19) for ALL. This report demonstrates the successful initial implementation of CAR-T cells in Brazil among centers that report to the SBTMO/CIBMTR. This infrastructure will assist in further capturing the activity, assessing the outcomes, and complying with regulatory requirements.
THE CIBMTR HEMATOPOIETIC CELL TRANSPLANT RECIPIENT TRANSFER TOOL FOR FOLLOW UP MAINTENANCE: ADHERENCE ASSESSMENT OF 24 BRAZILIAN CENTERS AND ONE URUGUAYAN
Introduction: Hematopoietic Cell Transplantation (HCT) remains a curative treatment for several malignant and non-malignant hematologic diseases. Despite significant advances in the field, maintaining long-term clinical follow-up continues to be a major challenge. To enhance continuity of care, the Center for International Blood and Marrow Transplant Research (CIBMTR) developed the patient transfer tool within FormsNet3, allowing the transfer of CRID identifiers between affiliated centers. However, little is known about the extent of adherence to this tool among South American centers. Objective: To evaluate the adherence of South American centers to the CIBMTR patient transfer tool, aiming to identify gaps and opportunities to improve data completeness and patient monitoring after HCT. Methods: An electronic questionnaire was distributed to South American centers actively participating in the CIBMTR, with at least 12 consecutive months of data reporting. The survey collected information on institutional characteristics, transplant volume, and experience with the CRID transfer tool. Data were analyzed using descriptive statistics and visualized through the Power BI platform. Results: Twenty-five centers participated in the study, representing 49% of active South American centers in the CIBMTR, of which 96% were Brazilian. Most centers were located in the Southeast region (70.8%) and included a variety of institutional types: private (44%), public (36%), and mixed (20%) hospitals. Regarding experience with the transfer tool, 60% of centers reported transferring patients, accounting for 67 movements (32 sendings and 35 receivings), predominantly involving adult patients undergoing allogeneic transplants. An asymmetric transfer pattern was observed: public centers primarily received transferred patients, whereas private centers were the main origin centers. Conclusion: Although the CIBMTR CRID-patient transfer tool represents a significant advancement in promoting long-term follow-up, its adoption remains limited among South American centers. Low adherence could jeopardize continuity of care and data completeness, ultimately impairing surveillance of late complications and hindering the development of effective prevention strategies.
CURRENT USE AND OUTCOMES OF HEMATOPOIETIC CELL TRANSPLANTATION: BRAZILIAN SUMMARY SLIDES – 2025
The development of the Brazilian Registry of Hematopoietic Cell Transplantation (HCT) in collaboration with the Center for International Blood and Marrow Transplant Research (CIBMTR) continues to provide a comprehensive assessment of the activity and general outcomes of HCT in Brazil. In this paper, we report an update of such activity. Brazilian transplant centers report their data to the CIBMTR, using the FormsNet3 platform. The data then return to the Brazilian Cellular Therapy and Bone Marrow Transplant Society (SBTMO) through the Data Back to Centers (DBtC) tool. Data from patients who received an HCT from 2012 to 2024 from Brazilian centers were extracted from the CIBMTR. A descriptive analysis was carried out using patient, disease and transplant-specific variables and overall survival analysis using the Kaplan Meier method. A total of 14,331 patients were eligible for this study (6,583 autologous and 7,748 allogeneic HCTs). The number of reporting centers increased from 40 to 45 during the period. The most common HCT indication in Brazil for allogeneic HCT was AML, with 171 HCTs per year and, for autologous HCT, multiple myeloma, with 273 HCTs per year. Among allogeneic HCT, in the last 4 years, mismatched related donor was the main source of donors. Regarding the graft source for allogeneic HCTs, bone marrow (BM) was the most frequent among pediatric HCTs, while peripheral blood (PB) was the most used in adults. Infections were the leading cause of death in the first 100 days after all types of HCTs. Patients with acute leukemia who underwent HCT at an advanced disease stage had lower survival rates compared to those at earlier stages. Despite the differences in the number of cases and follow-up time, the results in this study were similar to those presented in the United States (USA) Summary Slides.
Maria Cristina Martins de Almeida Macedo
POST-TRANSPLANT LYMPHOPROLIFERATIVE DISORDER: CLINICAL INSIGHTS AND REAL-WORLD ANALYSIS AT A SPECIALIZED CENTER IN NORTHEASTERN BRAZIL
Post-Transplant Lymphoproliferative Disorders (PTLD) comprise a heterogeneous group of lymphoid or plasmacytic neoplasms with highly variable presentations, occurring in the setting of immunosuppression following transplantation. Epstein-Barr virus (EBV)-positive PTLD accounts for 60–80% of cases. Due to the rarity of the disease, no phase 3 clinical trials have been conducted to establish standardized treatment protocols, making its management particularly challenging. Objective: to characterize the profile of patients diagnosed with PTLD following kidney, liver, or hematopoietic stem cell transplantation at a specialized center in Northeastern Brazil. Methodology: a retrospective, observational, and single-center cohort study based on medical record analysis. Results: The analysis of the frequency of PTLD by transplanted organ group showed 3.7 cases per 1000 hematopoietic stem cell transplants, 7.0 cases per 1000 kidney transplants and 7.5 cases per 1000 liver transplants. The mean survival time for all patients was 438 days. Patients who achieved complete response had a better overall survival (OS) of 87.5% at 1 year, while those who did not achieve complete response had an OS of 22.2% at 1 year (p=0.00012). Conclusion: PTLD is commonly an aggressive disease with poor OS, possibly influenced by factors such as age, transplanted organ, comorbidities, early death, and delayed diagnosis. Keywords: Post-transplant lymphoproliferative disorder, Epstein-Barr virus, solid organ transplantation, hematopoietic stem cell transplantation.
Paula Frassinetti Castelo Branco Camurça Fernandes
Updates on the management of Multiple Myeloma
Multiple Myeloma (MM) is a mature hematological neoplasm characterized by histological infiltration (bone marrow and/or extramedullary plasmacytomas) by clonal plasma cells and the presence of one or more defining events, including anemia, renal impairment, osteolytic lesions, and hypercalcemia. The management of MM has drammaticaly evolved over the past few years. However, new drugs are not available in the Brazilian public health service and treatment is still a challenge, especially in the relapsed/refractory setting. We herein summarize the updates in MM management and make recommendations for care in an optimal scenario and in the Brazilian public health service.
Beatriz Stella Gomes de Souza Pitombeira Araújo
Guidelines for the Diagnosis and Management of Paroxysmal Nocturnal Hemoglobinuria (PNH) at Hospital Universitário Walter Cantídio.
Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare and poorly understood clonal disease in our region. It is caused by somatic mutations in the PIGA gene on the X chromosome. Such mutations result in the absence of GPI production, which is an anchoring structure for proteins like CD55 and CD59 that protect red blood cells from lysis mediated by the complement system. PNH presents a diverse clinical course that includes intravascular hemolysis, thrombosis, and cytopenias. Following the advent of the humanized monoclonal antibody Eculizumab, which inhibits the C5 portion of the complement system, thereby preventing the destruction of red blood cells by the membrane attack complex, there has been a significant change in the treatment of PNH and in the lives of its patients. This study aims to present the guidelines for the diagnosis and management of patients with PNH followed at a reference public hospital in Ceará, Brazil.
The role of the pharmacy navigator in hematopoietic stem cell transplantation
Hematopoietic stem cell transplantation (HSCT) is a complex procedure that requires rigorous pharmacotherapeutic management. This study aimed to describe the role of the pharmacy navigator in HSCT at the Hospital das Cl.nicas of the Medical School of the Universidade de S.o Paulo. For the assessment of pharmacist activities in HSCT, a literature review was conducted, alongside direct observation of pharmaceutical activities in different HSCT phases at the service: pre-transplant, hospitalization, discharge, and outpatient follow-up. It was observed that the pharmacy navigator plays a crucial role, including medication reconciliation, dose adjustments, monitoring drug interactions and toxicities, and providing health education to patients and the multidisciplinary team. Pharmacotherapeutic follow-up contributed to reducing medication errors, improving treatment adherence, and ensuring safer administration of immunosuppressants and antimicrobials. In conclusion, the presence of a pharmacy navigator in HSCT is essential to optimize treatment, prevent complications, and enhance patients’ quality of life, consolidating this professional as a key member of the multidisciplinary healthcare team.
Copyright (c) 2025 Giovanna Fernandes Lago, Carolina Ferreira dos Santos, Andressa Pinheiro Diniz, Leonardo Jun Otuyama, Andrea Cassia Pereira Sforsin, Vanusa Barbosa Pinto https://creativecommons.org/licenses/by/4.0
Immune reconstitution inflammatory syndrome in HIV-negative patients with hematological malignancies and hematopoietic stem cell transplantation: A case series and a literature review
Immune reconstitution inflammatory syndrome (IRIS) is a potentially severe complication following the withdrawal of immunosuppressive agents, commonly studied in human immunodeficiency virus (HIV) positive patients. However, its impact on individuals with hematological malignancies and those undergoing hematopoietic stem cell transplants is less understood. This study aimed to establish diagnostic criteria for IRIS in these populations and assess its incidence and clinical progression. A cross-sectional, prospective observational study was conducted with 159 chemotherapy patients and 96 hematopoietic stem cell transplant recipients. IRIS diagnosis criteria were derived from a literature review of 70 studies, and patients were monitored for 11 months. The review identified key IRIS diagnostic criteria, including paradoxical clinical worsening, antimicrobial refractoriness, and inflammatory signs following immunosuppressive therapy. Most IRIS cases were linked to pathogens like Mycobacterium, Candida spp., and Aspergillus spp. Among our patients, three cases of IRIS were identified: one related to the Bacillus Calmette-Guérin (BCG) vaccine, another with neutrophil recovery, and the third with chronic disseminated candidiasis. Treatment with corticosteroids and antimicrobial therapy allowed continued chemotherapy without impacting the underlying disease’s outcomes. IRIS is an important complication in hematological and stem cell transplant patients. Early recognition and appropriate treatment, including corticosteroids and antimicrobial therapy, are critical for successful management and uninterrupted cancer treatment.
Haploidentical Hematopoietic Stem-cell Transplant for High-Risk Acute Myeloid Leukemia in a Kidney Transplant Recipient: Case Report
Solid organ transplantation is associated with a higher incidence of malignancies. Among them, acute myeloid leukemia has high morbidity and mortality, and its cure is only possible through allogeneic hematopoietic stem cell transplantation for high-risk disease. Case report: A 32-year-old female who underwent a kidney transplant eight years before was diagnosed with high-risk acute myeloid leukemia. She underwent induction therapy with “7+3”, achieving complete remission with measurable residual disease detectable by flow cytometry. She then underwent a myeloablative haploidentical allogeneic transplant, achieving complete remission, free of graft-versus-host disease, with a functioning renal graft.
The Effectiveness of the Multiprofessional Approach in the Pediatric Rehabilitation of Chronic GVHD: The Specific Contribution of Occupational Therapy
Este estudo relata o processo de reabilitação em terapia ocupacional de uma criança de dois anos de idade com Doença do Enxerto contra o Hospedeiro Crônica (cGVHD), afetando múltiplos órgãos e articulações, impactando seu desenvolvimento neuropsicomotor (NPMD) e funcionalidade. O método utilizado foi o relato de caso, respeitando os protocolos éticos. A avaliação incluiu a Análise Observacional dos Marcos do NPMD e a Escala de Avaliação Funcional para GVHD Crônica (NIH). Com base nos resultados, utilizamos a Classificação Internacional de Funcionalidade, Incapacidade e Saúde para Crianças e Jovens (ICF-CJ) para categorizar os objetivos das intervenções terapêuticas. A intervenção seguiu quatro etapas: avaliação inicial, definição de objetivos, aplicação do Brinquedo Terapêutico Habilitador de Funções Fisiológicas (TP) e reavaliações periódicas. Após 27 sessões, houve melhora na amplitude de movimento das articulações afetadas, aumento da resistência respiratória e avanços no NPMD, incluindo deambulação e habilidades motoras finas, como alimentação. Os resultados demonstram a eficácia da terapia ocupacional na recuperação funcional e na promoção da qualidade de vida. Conclui-se que a intervenção precoce, integrada a uma equipe multidisciplinar, é essencial para minimizar os impactos da DECHc, prevenir sequelas e favorecer o desenvolvimento infantil.
X linked- ALD: Should Loes score be the only benchmark for HSCT eligibility?
Hematopoietic stem cell transplant(HSCT) is the only modality that, if performed in the early- stages of cerebral X-linked adrenoleukodystrophy(X-ALD) can lead to good outcomes. Loes- score, calculated based on the findings of the magnetic resonance imaging(MRI) of the brain, helps in the selection of patients for HSCT. As per recommendations, the Loes-score should be <10 for a patient to be eligible for HSCT. Here we report a child of cerebral X-ALD with Loes of 12, but a good neurological function score(NFS), who was treated with HSCT, and had good outcomes. It is therefore important to utilize other parameters along with the Loes score, in selecting patients for HSCT in X-ALD.