Marcos Augusto Mauad

Epidemiology of neglected tropical diseases in transplant recipients: review of the literature and experience of a Brazilian HSCT center

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.

Impact of pretransplant minimal residual disease after cord blood transplantation for childhood acute lymphoblastic leukemia in remission: an Eurocord, PDWP-EBMT analysis.

To address the prognostic value of minimal residual disease (MRD) before unrelated cord blood transplantation (UCBT) in children with acute lymphoblastic leukemia (ALL), we analyzed 170 ALL children transplanted in complete remission (CR) after myeloablative conditioning regimen. In all, 72 (43%) were in first CR (CR1), 77 (45%) in second CR (CR2) and 21 (12%) in third CR (CR3). The median interval from MRD quantification to UCBT was 18 days. All patients received single-unit UCBT. Median follow-up was 4 years. Cumulative incidence (CI) of day-60 neutrophil engraftment was 85%. CI of 4 years relapse was 30%, incidence being lower in patients with negative MRD before UCBT (hazard ratio (HR)=0.4, P=0.01) and for those transplanted in CR1 and CR2 (HR=0.3, P=0.002). Probability of 4 years leukemia-free survival (LFS) was 44%, (56, 44 and 14% for patients transplanted in CR1, CR2 and CR3, respectively (P=0.0001)). Patients with negative MRD before UCBT had better LFS after UCBT compared with those with positive MRD (54% vs 29%; HR=2, P=0.003). MRD assessment before UCBT for children with ALL in remission allows identifying patients at higher risk of relapse after transplantation. Approaches that may decrease relapse incidence in children given UCBT with positive MRD should be investigated to improve final outcomes.

Six cases of leprosy associated with allogeneic hematopoietic SCT.

We report here the first six cases of leprosy associated with HLA-identical allogeneic SCT in different phases and with different findings and outcomes. Skin and peripheral nerves may be sites of leprosy associated with SCT, stressing the importance of differential diagnosis between leprosy and GVHD or drug reactions. Clinical manifestations of leprosy before or after transplantation did not influence the outcome of SCT in our cases.

Survival and graft-versus-host disease in patients receiving peripheral stem cell compared to bone marrow transplantation from HLA-matched related donor: retrospective analysis of 334 consecutive patients

The objective of this study was to compare the major transplant outcomes between patients receiving hematopoietic stem cell transplantation (HSCT) from bone marrow (BM) or peripheral blood stem cells (PBSC).

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%) met the criteria of overlap syndrome and eight (24%) the classic subcategory. The overall severity of disease was moderate in 21 (62%) and severe in 13 (38%) 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%. 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 sangue de cordão umbilical - SCU

The frequent use of umbilical cord blood as the source of hematopoietic stem cells, both in children and adults who do not have related donors, has led to the establishment of a better standardization of selection criteria aiming at improving the results. The choice of the umbilical cord blood unit should be based on the total number of nucleated cells and the number of differences in the human leukocyte antigen (HLA) system. When a unit has minimal cellularity, the use of a double cord blood transplant should be considered. When two or more units have similar characteristics, the choice may be determined by the CD34 count, ABO compatibility and the quality and speed to obtain the unit.

Diretrizes para o diagnóstico, classificação, profilaxia e tratamento da doença enxerto contra hospedeiro crônica

A falta de criterios diagnosticos padronizados, amplamente utilizados, pode comprometer tanto a avaliacao real da incidencia da doenca contra hospedeiro cronica bem como a correlacao de sua gravidade com a taxa de mortalidade pos-transplante. Na I Reuniao de Diretrizes da Sociedade Brasileira de Transplante de Medula Ossea, realizada em junho de 2009, o Grupo de Estudos de DECH Brasil - Seattle (GEDECH), baseado na realidade dos Centros brasileiros, apresentou as recomendacoes para diagnostico, classificacao, profilaxia e tratamento da doenca enxerto contra hospedeiro cronica propostas pelo National Institutes of Health. Estas propostas incluiram padronizacao das caracteristicas utilizadas no diagnostico e ferramentas para a pontuacao dos orgaos envolvidos e avaliacao global da gravidade a serem utilizados em estudos clinicos da doenca enxerto contra hospedeiro cronica. Estes criterios sao uteis para uma melhor analise da incidencia desta doenca, alem de poder avaliar a gravidade do comprometimento de um orgao ou sitio envolvido e a influencia na mortalidade tardia do transplante. A profilaxia e os tratamentos propostos para esta importante complicacao dos transplantes de celulas-tronco hematopoeticas foram discutidos e graduados de acordo com niveis de evidencia estabelecidos pelo National Institutes of Health.

Seleção de doador de medula óssea ou sangue periférico

A compatibilidade HLA e o fator mais valorizado na escolha do doador de medula ossea voluntario, preconizando-se a realizacao de HLA de alta resolucao nos locos HLA-A,B,C, DRB1 e DQB1. Tem sido dado preferencia para o doador com consanguinidade alelica 8x8 (A,B,C, DRB1). Na presenca de incompatibilidade na classe-I sugere-se a busca de doador com compatibilidade DQB1 (9x10). Ja as incompatibilidades dos locos DPB1 nao constituem criterio de exclusao de doador, exceto quando existir presenca de anticorpo contra o loco HLA-DP do doador.

Prolonged viremia in dengue virus infection in hematopoietic stem cell transplant recipients and patients with hematological malignancies

Fever, skin rash, headache, and thrombocytopenia are considered hallmarks of dengue infection. However, these symptoms are frequently observed in infectious and non‐infectious complications of hematopoietic stem cell transplant recipients and oncohematological patients. Thus, laboratory confirmation of dengue is relevant for prompt intervention and proper management of dengue in endemic and non‐endemic regions. Because no prospective study of dengue has been conducted in these populations, the actual morbidity and mortality of dengue is unknown. In the present series, we describe five cases of dengue in patients living in endemic areas, emphasizing the prolonged course of the disease and the occurrence of prolonged viremia.

Brazilian workshop model to train investigators in chronic graft-versus-host disease clinical trials according to the 2005-2006 National Institutes of Health recommendations

Background The lack of standardization of clinical diagnostic criteria, classification and severity scores of chronic graft-versus-host disease led the National Institutes of Health to propose consensus criteria for the purpose of clinical trials. Method Here we describe a one-day workshop model conducted by the Chronic Graft-versus-Host Disease Brazil-Seattle Consortium Study Group to train investigators interested in participating in multicenter clinical trials in Brazil. Workshop participants included eight transplant physicians, one dermatologist, two dentists, three physical therapists and one psychologist from five institutions. Workshop participants evaluated nine patients with varying degrees of severity of mucocutaneous lesions and other manifestations of the disease followed by a training session to review and discuss the issues encountered with the evaluation and scoring of patients and in the methods used to evaluate grip strength and the 2-minute walk test. Results Most participants had difficulties in rating the percentage of each type of mucocutaneous lesion and thought 20 minutes was insufficient to evaluate and record the scores of each patient using the National Institutes of Health criteria and other cutaneous assessments. Several specific areas of difficulties encountered by the evaluators were: 1) determining the percentage of erythema in movable and non-movable sclerosis, 2) whether to score all cutaneous findings in a particular area or just the dominant lesion; 3) clarification of the definition of poikiloderma in chronic graft-versus-host disease; 4) discrepant interpretation of the mouth score and 5) clarification on the methodology used for the evaluation of grip strength and the 2-minute walk tests. Conclusions Results of this workshop support the need to train investigators participating in clinical trials on chronic graft-versus-host disease.