A multicenter feasibility study of chronic graft-versus-host disease according to the National Institute of Health criteria: efforts to establish a Brazil-Seattle consortium as a platform for future collaboration in clinical trials

BACKGROUND: New criteria for the diagnosis and classification of chronic graft-versus-host disease were developed in 2005 for the purpose of clinical trials with a consensus sponsored by the National Institute of Health. OBJECTIVES: The aim of this study is to present the results of a multicenter pilot study performed by the Brazil-Seattle chronic graft-versus-host disease consortium to determine the feasibility of using these criteria in five Brazilian centers. METHODS: The study was performed after translation of the consensus criteria into Portuguese and training. A total of 34 patients with National Institute of Health chronic graft-versus-host disease were enrolled in the pilot study between June 2006 and May 2009. RESULTS: Of the 34 patients, 26 (76 percent) met the criteria of overlap syndrome and eight (24 percent) the classic subcategory. The overall severity of disease was moderate in 21 (62 percent) and severe in 13 (38 percent) patients. The median time from transplant to onset of chronic graft-versus-host disease was 5.9 months (Range: 3 - 16 months); the median time for the overlap syndrome subcategory was 5.9 months (Range: 3 - 10 months) and for the classic subcategory, it was 7.3 months (Range: 3 - 16 months). At a median follow up of 16.5 months (Range: 4 - 39 months), overall survival was 75 percent. CONCLUSIONS: It was feasible to use the National Institute of Health consensus criteria for the diagnosis and scoring of chronic graft-versus-host disease in a Brazilian prospective multicenter study. More importantly, a collaborative hematopoietic cell transplantation network was established in Brazil offering new opportunities for future clinical trials in chronic graft-versus-host disease and in other areas of research involving hematopoietic stem cell transplantation.

Transplante de células-tronco hematopoéticas em crianças e adolescentes com leucemia aguda: experiência de duas instituições brasileiras / Hematopoietic stem cell transplantation in children and adolescents with acute leukemia: experience of two Brazilian institutions

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. ... 14/195 pacientes tiveram falha primária de pega (8 por cento). 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 por cento. Incidência cumulativa de recaída: 40 por cento (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.

Hematopoietic Stem Cell transplantation (HSCT) is the treatment of choice for patients with high-risk leukemia. In spite of this, relapse remains a major cause of death of these patients. Our objective was to analyze the outcomes of patients with acute leukemia submitted to hematopoietic stem cell transplantation in two Brazilian institutions... There were no differences in the overall survival and event free survival between patients with acute lymphocytic leukemia and acute myeloid leukemia, between sources of cells used or between those who developed acute or chronic graft-versus-host disease (GVHD). When comparing transplants from related and unrelated donors, there was no difference in the overall survival. Patients with acute lymphocytic leukemia receiving the total body irradiation (TBI) conditioning regimen had better overall survival and event free survival (p<0.001). One hundred and eighteen patients died between 0 and 1654 days after hematopoietic stem cell transplantation (M: 160 days). Transplantation-related-mortality (TRM) at D+100 was 16 percent and cumulative incidence of relapse was 40 percent (3 years). Patients with advanced disease had lower 3-year overall survival and event free survival (p<0.001). Multivariate analysis showed that disease status was the most significant factor associated with higher event free survival and overall survival . Our results show that children and adolescents transplanted with early disease can achieve considerable overall survival and also highlights the inefficacy of hematopoietic stem cell transplantation for patients with advanced disease.

Epidemiology of neglected tropical diseases in transplant recipients: review of the literature and experience of a Brazilian HSCT center / Epidemiologia das doenças tropicais negligenciadas em receptores de transplantes: revisão da literatura e experiência de um centro brasileiro

The rising success rate of solid organ (SOT) and haematopoietic stem cell transplantation (HSCT) and modern immunosuppression make transplants the first therapeutic option for many diseases affecting a considerable number of people worldwide. Consequently, developing countries have also grown their transplant programs and have started to face the impact of neglected tropical diseases (NTDs) in transplant recipients. We reviewed the literature data on the epidemiology of NTDs with greatest disease burden, which have affected transplant recipients in developing countries or may represent a threat to transplant recipients living in other regions. Tuberculosis, Leprosy, Chagas disease, Malaria, Leishmaniasis, Dengue, Yellow fever and Measles are the topics included in this review. In addition, we retrospectively revised the experience concerning the management of NTDs at the HSCT program of Amaral Carvalho Foundation, a public transplant program of the state of São Paulo, Brazil.

O sucesso crescente dos transplantes de órgãos sólidos (TOS) e de células tronco-hematopoiéticas (TCTH) e as novas drogas imunossupressoras fizeram dos transplantes a primeira opção terapêutica para muitas doenças que afetam milhares de pessoas em todo o mundo. Também os populosos países em desenvolvimento investiram no crescimento de seus programas de transplante e desde então começaram a vivenciar o impacto das doenças tropicais negligenciadas (DTNs) nestes pacientes. Revisamos os dados da literatura sobre a epidemiologia das DTNs de maior impacto clinico e social que afetam receptores de transplante de países em desenvolvimento, ou que podem representar um risco para receptores de transplante vivendo em outras regiões não afetadas por estas doenças. Tuberculose, hanseníase, doença de Chagas, malaria, leishmaniose, dengue, febre amarela e sarampo são os tópicos incluídos nesta revisão. Além disso, revisamos retrospectivamente a experiência referente ao manejo das DTNs do Serviço de Transplante de Medula Óssea da Fundação Amaral Carvalho, atualmente o maior centro de TCTH alogênico do Brasil.