Dados do Registro Internacional de Transplante de Medula Óssea, International Bone Marrow Transplant Registry (IBMTR) contribuem para o progresso do transplante de medula óssea (TMO) em todo o mundo. Neste artigo relatamos a experiência brasileira em leucemia mielóide aguda e comparamos os resultados do TMO com os dados internacionais. Foi realizado um estudo retrospectivo com dados de tratamento de LMA com o TMO de 16 instituições brasileiras. A análise estatística dos transplantes da modalidade autogênica (TMO auto) e alogênica (TMO alo) foi realizada com o método de Kaplan-Meier e log-rank. Todos os valores de p foram bicaudados. Foram avaliados os dados de 731 pacientes (205 TMO auto e 526 TMO alo). A mediana de sobrevida global dos pacientes submetidos ao TMO auto foi superior à dos submetidos ao TMO alo (1.035 vs 466 dias, p=0,0012). A origem das células-tronco (OCT) no TMO alo em 73% dos pacientes foi de medula óssea (CTMO), em 23% de sangue periférico (CTSP) e em 4% de cordão umbilical. No TMO auto, a OCT foi 63% de CTSP, 22% CTMO e 15% de ambas as fontes. A OCT não teve impacto na sobrevida global (SG). Não houve diferença na SG também entre os pacientes segundo a classificação FAB no TMO alo, mas os pacientes com LMA M3 com o TMO auto tiveram SG longa. Como esperado, a principal causa de óbito entre os pacientes do TMO auto foi relacionada à recidiva de doença (60%), enquanto no TMO alo as principais causas foram a doença enxerto versus hospedeiro e infecções (38%). Em ambos os grupos foi observada SG mais longa nos pacientes tratados em primeira remissão completa (1RC) quando comparados aos de segunda remissão (2RC) e outras fases (p<0,0001), tendo sido observado SG mais longa nos pacientes com LMA de novo quando comparados aos de LMA secundária. No TMO alo a SG foi mais longa com doadores aparentados (538 versus 93 dias p=0,001). A SG foi mais curta nos pacientes que utilizaram irradiação corpórea total no regime de condicionamento (p=0,0001). No TMO alo foram observados mais pacientes com doença avançada (60%) enquanto no grupo de TMO auto 24% eram da morfologia M3, o que pode explicar a diferença de SG entre os grupos. O resultado do estudo está em concordância com os dados do IBMTR. Considerando a natureza do estudo, retrospectivo e multicêntrico, os resultados devem ser analisados com cautela.
The allogeneic hematopoietic stem cell transplant (allo-HCT) represents an important therapeutic strategy for acute leukemias, lymphomas and solid neoplasms, also used in benign diseases, such as aplastic anemia and inborn errors of immunity. This treatment requires myeloablative chemotherapy (conditioning regimen) followed by the infusion of donor-derived hematopoietic stem cells. However, this procedure carries some risks, such as infections, graft versus host disease (GVHD) and conditioning toxicity, which may result in transplant-related mortality. Over the decades, due to the increasing life expectancy and new advances in medicine, the cases of patients > 50 years with hematologic diseases that need allogeneic transplant have grown, requiring a comprehensive geriatric assessment as a mechanism for the best treatment option choice.
Objective: To apply a clinical frailty score and Karnofsky score in allogeneic hematopoietic stem cell older than 50 years old for three years in Walter Cantídio University Hospital (Fortaleza/Ceará) and in Amaral Carvalho Hospital (Jaú/São Paulo), expecting to recognize the profile of this patients and to demonstrate the relation between the clinical frailty score and overall survived, besides to estimate the contribution of GVHD prophylaxis and relapse in overall survival. Methods: Multicentric, retrospective, descriptive, analytical and quantitative study, acquiring dates by means of exams and medical record from Walter Cantídio University Hospital in Fortaleza/Ceará and Amaral Carvalho Hospital in Jaú/São Paulo. Results: The study selected 252 patients, 147 males and 105 females, sort in gender, disease, HCTCI score, CFS and KPS. In three years, the overall survival in FIT score is 2,46 years, while in FRAILTY score is 1,82 years. About the prophylaxis, the combination of cyclosporine, mycophenolate mofetil, cyclophosphamide had worse results than others prophylaxis. As expected, in case of relapse, there is shorter survival. Conclusion: The elderly population require a geriatric score in order to evaluate the profile of this patients once the allogeneic transplant must happen, then FIT patients has longer survival than FRAILTY patients.
To increase the report of Brazilian hematopoietic stem cell transplantation (HSCT) data to the Center for International Blood and Marrow Transplant Research (CIBMTR), the Data Managers Working Group (GTGD) of the Brazilian Society of Bone Marrow Transplants (SBTMO), and the Sao Paulo State Bone Marrow Association (AMEO) developed several strategies since 2016: training data managers (GDs) in national and international HSCT meetings, the development of a free online teaching course (EAD) in Portuguese on Transplant Essential Data (TED), online and presential training course for new data managers offered by AMEO, the approval by the National Committee of Ethics in Research (CONEP) of a national multicenter protocol to formalize sharing data of Brazilian transplants with the CIBMTR, and the first multicenter evaluation our HSCT results using the CIBMTR Data Back to Center. The contract between SBTMO and CIBMTR was signed in 2019 and GTGD of the SBTMO was officially created. These actions resulted in an increase from 24 to 41 transplant centers registered at the CIBMTR from 2016 to 2019. The process of increasing adherence and continuity of HSCT reports to the CIBMTR is complex and requires commitment of all professionals involved HSCT. The success of this process depends on education of the GD and the involvement of all HSCT directors.
To better understand the outcomes of HSCT in Brazil, we conducted a multicenter study using the CIBMTR database. Seven participating centers extracted their own data through the Data Back to Center tool. Main indications for HSCT-auto were MM(51%), NHL(18%) and HL(17%); Allogeneic, AML(24%), ALL(23%) and SAA(15%). For acute leukemias, risk of death was higher in the 18-40 years group (HR=1.18,p=0.022), 40-60(HR=1.19,p<0.001) and 60+(HR=1.39,p=0.007), compared with 0-18 years, in ALL (HR=1.05,p <0.001, compared with AML) and with partially-matched related donor (HR=1.59,p= 0.003, compared with matched sibling), while URD was not. HSCT in CR2+(HR=1.28,p=0.01) and relapse (HR=2.44,p< 0.001) were risk factors for death. 49%(95CI:44-52)52%(95CI:43-62)45%(95CI:39-51) and 55%(95CI:49-63), somewhat poorer than the CIBMTR: 62 and 70%, respectively. Limited access to novel drugs for most centers and lack of molecular risk information are possible explanations for these differences. Further studies are necessary to better evaluate our findings and the DBtC tool enables multicenter studies.
O transplante de células-tronco hematopoéticas (TCTH) é o tratamento de escolha para leucemias agudas de alto risco. Apesar da melhora na sobrevida destes pacientes, a recidiva continua sendo a maior causa de óbito pós-transplante de células-tronco hematopoéticas. O objetivo deste trabalho foi analisar os resultados dos transplantes realizados em crianças com leucemia aguda em duas instituições brasileiras. Realizou-se estudo retrospectivo de 208 pacientes transplantados entre 1990-2007. Mediana de idade: 9 anos; 119 pacientes com leucemia linfoide aguda (LLA) e 89 com leucemia mieloide aguda (LMA). Doença precoce: CR1 e CR2. Doença avançada: >CR3, doença refratária ou recidivada. Noventa pacientes vivos entre 258-6.068 dias (M:1.438), com sobrevida global (SG) de 45% (3 anos) e a sobrevida livre de recaída (SLR) 39% (três anos). 14/195 pacientes tiveram falha primária de pega (8%). Não houve diferença na sobrevida global e sobrevida livre de recaída entre pacientes com leucemia linfoide aguda e leucemia mieloide aguda, entre transplantes aparentados e não aparentados, tampouco entre as fontes de células utilizadas. O desenvolvimento da doença do enxerto contra hospedeiro (DECH) aguda ou crônica também não influenciou a sobrevida global e sobrevida livre de recaída. Pacientes com leucemia linfoide aguda condicionados com irradiação corporal total (TBI) apresentaram melhor sobrevida global e sobrevida livre de recaída (p<0,001). Cento e dezoito pacientes morreram entre 1-1.654 dias pós-transplante de células-tronco hematopoéticas (M:160). Mortalidade relacionada a transplante (MRT) (dia+100): 16%. Incidência cumulativa de recaída: 40% (3 anos). Pacientes com doença avançada tiveram menor sobrevida global e sobrevida livre de recaída (três anos)(p<0,001). Na análise multivariada, o status da doença foi o principal fator associado ao aumento da sobrevida global e sobrevida livre de recaída. Nossos resultados mostram que é possível se atingir uma boa sobrevida para pacientes com doença precoce e também mostram a baixa eficácia naqueles com doença avançada.
The development of the Brazilian Registry of Hematopoietic Cell Transplantation in collaboration with the Center for International Blood and Marrow Transplant Research (CIBMTR) allowed for an assessment of the activity and general outcomes of transplants in Brazil. Here, we report an updated activity. Brazilian transplant centers report their data to the CIBMTR, using the FormsNet3 platform. Information returns to 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 2023 from Brazilian centers were extracted from CIBMTR. Descriptive analysis was carried out by patient-, disease- and transplant-specific variables and overall survival analysis using Kaplan Meyer. A total of 12,230 patients were eligible for this study (5,573 autologous and 6,657 allogeneic transplants). The number of reporting centers increased from 40 to 44 during the period. The most common HCT indication in Brazil is AML for allogeneic HCT with 152 transplants year and multiple myeloma for autologous HCT with 245 transplants 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 transplants, BM was the most frequent among pediatric transplants, while PBSC was the most used in adults. Infections were the leading cause of death in the first 100 days after all types of transplants. Patients with acute leukemia who underwent HCT with advanced stage disease had lower survival rates compared to those at other 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 (US) Summary Slides.
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