Vergilio A.R. Colturato

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.

The monitoring of hematopoietic stem cell transplant donors and recipients from endemic areas for malaria

Malaria is an unusual complication after hematopoietic stem cell transplantation in non-endemic countries. However, transplant candidates, recipients and donors living in endemic regions frequently report previous episodes of malaria. This fact could represent an important risk for immunosuppressed recipients that could develop severe malaria cases. We report a case of hematopoietic stem cell transplant (HSCT) in which the donor had a history of previous malaria, and close monitoring was performed before and after procedure by parasitological and molecular tests. The donor presented Plasmodium vivax in thick blood smears one month after transplant and was treated according to Brazilian Health Ministry guidelines. The polymerase chain reaction (PCR) was able to detect malaria infection in the donor one week earlier than thick blood film. Even without positive results, the recipient was pre-emptively treated with chloroquine in order to prevent the disease. We highlight the importance of monitoring recipients and donors in transplant procedures with the aim of reducing the risk of malaria transmission.

Estudo retrospectivo do tratamento de leucemia mielóide aguda com o transplante de medula óssea: a experiência brasileira

Data from the International Bone Marrow Transplant Registry (IBMTR) contribute for the improvement of Bone Marrow Transplant (BMT) worldwide. We studied the Brazilian experience in BMT for AML to compare this with international data. We performed a retrospective study by sending questionnaires to 16 BMT centers regarding clinical and treatment variables. Statistical analyses concerning autologous BMT (autoBMT) and allogeneic BMT (alloBMT) were performed using the Kaplan-Meier method and the log-rank test. All p-values were two-tailed. We collected data from 731 patients (205 autoBMT and 526 alloBMT). Median overall survival (OS) for autoBMT patients was longer than alloBMT patients (1035 vs. 466 days, p=0.0012). AlloBMT stem cell source (SCS): 73% bone marrow stem cell (BMSC), 23% peripheral blood stem cells (PBSC) and 4% umbilical cord blood. Among the autoBMT patients, the SCS was 63% PBSC, 22% BMSC and 15% both. The SCS did not impact on OS. There was no difference in OS between different FAB classifications in the alloBMT group, but in the autoBMT the M3 patients had longer survival. As expected, the main cause of mortality among autoBMT patients was related to disease relapse (60%), while in the alloBMT, to infection (38%). In both groups we found longer OS in first complete remission (1CR) compared to second (2CR) and other (p<0.0001), and longer OS in de novo AML than in secondary. In the alloBMT group we found more patients with advanced disease (60%), while in the autoBMT group, we found more M3 patients (24%), which could explain the difference in OS. Most of our results are in accordance with IBMTR data. One should consider the fact that this is a retrospective study and our findings should be analysed with caution.

Zika and chikungunya virus infections in hematopoietic stem cell transplant recipients and oncohematological patients

Aedes mosquitoes are well adapted in domestic environments and widespread in tropical regions. Since 2015, Brazil has been experiencing a triple epidemic of dengue (DENV), chikungunya (CHKV), and Zika (ZIKV) viruses. The last 2 viruses are likely following the path of DENV, which has been endemic in most parts of the country since the 1980s. Given this triple epidemic, we proposed a prospective and collaborative study to assess the prevalence, morbidity, and mortality of DENV, CHKV, and ZIKV infections in hematopoietic stem cell transplant (HSCT) recipients and oncohematological patients. A case definition strategy (fever and rash) was used to prompt diagnostic investigation of DENV, ZIKV, and CHKV, which was accomplished by real-time polymerase chain reaction with plasma and urine samples. Clinical follow-up was performed 7 and 30 days after symptom onset. We report here the first cases of ZIKV and CHKV infections diagnosed in this ongoing study. From February to May 2016, 9 of the 26 patients (34.6%) fulfilling case definition criteria were diagnosed with DENV (3 cases), ZIKV (4 cases), or CHKV (2 cases) infections. Prolonged viremia and viruria were observed in dengue and Zika fever cases, respectively. Thrombocytopenia was the most frequent complication. Delayed engraftment was noted in 1 patient who acquired ZIKV 25 days before HSCT. All patients survived without sequelae. With the geographic expansion of arboviruses, donor and recipient screening may become mandatory. Patients living in areas where these viruses are not endemic are also at risk, since these viruses can be transmitted by blood as well as organ or tissue 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.

Indicações em transplante de células-tronco hematopoéticas em pacientes adultos com leucemia linfoide aguda

In acute lymphoblastic leukemia, accumulation and proliferation of immature cells infiltration characterise a heterogeneous entity, featuring a wide variety of clinical and biological aspects. In the adult LLA concentration of high-risk prognosis factors such as age, B-cell, chromosomic changes, and chiefly the presence of chromosome positive Ph. Considerations of high morbidity and mortality rates related to haematopoietic stem cell transplantation (TCTH) have generated controversy about this therapeutic modality in adult patients with LLA in first remission (1st RC). The results of conventional therapy with chemotherapy in contrast with different risk groups of patients with LLA, has been used for the indication of TCTH. Thus we present the algorithm indications of haematopoietic stem cell transplantation in adult patients with LLA. Rev.

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.

Seleção de doador não aparentado

Apesar da presenca de anticorpos anti-HLA em transplantes de orgaos solidos estar associada a rejeicao, essa correlacao nao havia sido pesquisada em transplante alogenico de celulas progenitoras hematopoeticas (TCPH). Estudos mais recentes na literatura tem demonstrado que a falencia da enxertia no TCPH pode ser mediada por aloanticorpos anti-HLA doador especifico (DSA). A especificidade desses anticorpos pode ser evidenciada pelas tecnicas de fase solida, onde os antigenos HLA unicos sao aderidos a perolas de poliestireno, que permite a realizacao da prova cruzada virtual. Na presenca de DSA, e recomendavel selecionar outro doador ou realizar as estrategias de remocao dos anticorpos.

Paradoxes of hematology: When the old disappears and the new does not arrive

Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular (ABHH), Comitê de Mieloma Múltiplo, Brazil International Myeloma Foundation-Latin America (IMF), Brazil Sociedade Brasileira de Transplante de Medula Óssea (SBTMO), Brazil Latin American Bone Marrow Transplant Association (LABMT), Brazil Sociedade Brasileira de Oncologia Pediátrica (SOBOPE), Brazil Santa Casa de Porto Alegre, Unidade de Hematologia/Oncologia Pediátrica, Porto Alegre, RS, Brazil Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular (ABHH), Brazil Sociedade Brasileira de Oncologia Clínica (SBOC), Brazil Universidade de São Paulo (USP), Faculdade de Medicina, São Paulo, SP, Brazil Hospital Israelita Albert Einstein, Programa de Hematologia e Transplante de Medula Óssea, São Paulo, SP, Brazil Associação Brasileira de Linfoma e Leucemia (ABRALE), Brazil