Acyclovir susceptibility of herpes simplex virus isolates from transplanted and nontransplanted patients in Rio de Janeiro, Brazil.

Herpes simplex virus (HSV) is prevalent worldwide and known as a notorious opportunistic pathogen ofimmunocompromised patients. During the course of HSV treatment, acyclovir (ACV)-resistant HSV strains may emerge, causing many clinical complications. Because few studies in this area showing the presence and/or frequency ofACV-resistant HSV are available, the authors evaluated the sensitivity of HSV isolated from 3 hematopoietic stem cell transplant recipients and 24 normal patients observed in a University Hospital in Rio de Janeiro, Brazil. Twenty-seven HSV isolated in VERO cells and typed by the direct immunofluorescence assay were tested for their susceptibility to various concentrations ofACV by the dye-uptake method. The susceptibility of the HSV strains was expressed as ED50 (the concentration of drug reducing viral cytophatic effect by 50%). The sensitivity to ACV by the dye-uptake assay revealed that 25 samples (92.6%) were sensitive to ACV concentrations < 1.5 microg/mL. One sample (3.7%) showed intermediate susceptibility (1.56 microg/mL) and one other sample (3.7%) showed resistance to ACV concentrations above the cut-off (2 microg/mL). The presence of resistance in immunocompetent patients could be the result of the frequent use of ACV for the treatment of recurrence. The routine use of HSV susceptibility testing is fundamental in the clinical suspicion of resistance not only for the knowledge of the incidence of HSV resistance in Brazil, but also to understand the mechanism of HSV resistance.

Multiple attacks of transient monocular visual loss in a previously healthy man: a possible complication after COVID-19 vaccination?

BACKGROUND: The present case aims to describe a previously healthy man who presented multiple attacks of transient monocular visual loss after Pfizer-BioNTech COVID-19 vaccination and to discuss the possible mechanisms related to occurrence of this condition. CASE PRESENTATION: We report a case of multiple attacks of transient monocular visual loss in a previously healthy middle-aged man two weeks after Pfizer-BioNTech COVID-19 vaccination. TVL attacks were described as sudden and painless complete visual loss, lasting about one minute, followed by a full recovery. He presented several non-simultaneous attacks in both eyes, 16 in the right eye, and 2 in the left eye on the same day, fifteen days after receiving the second dose of the Pfizer-BioNTech COVID-19 vaccine. The brain's magnetic resonance angiography, echocardiogram, and doppler ultrasound imaging of the carotid and vertebral arteries were non-revealing. The complete blood exam revealed a slightly elevated C-reactive protein test. We assessed fundus examination during the transient visual loss attack and revealed diffuse vascular narrowing for both arterial and venous branches, notably in the emergence of the optic disc in right eye. In addition, the circumpapillary optical coherence tomography angiography (OCTA) vessel density map was reduced. Oral verapamil hydrochloride 60 mg twice daily was initiated, and the attacks of transient visual loss improved after two days. CONCLUSIONS: To date, and the best of our knowledge, this is the first case report of multiple transient monocular visual loss attacks due to retinal vasospasm in a previously healthy middle-aged man documented by fundus retinography and OCTA. We discuss in this article the possible association of retinal vasospasm and Pfizer-BioNTech COVID-19 vaccination, probably related to vaccine-induced inflammation.

Infectious diarrhea in autologous stem cell transplantation: high prevalence of coccidia in a South American center.

BACKGROUND: Diarrhea is frequently seen in autologous stem cell transplantation. Although toxicity related to conditioning is the most common cause, infectious pathogens can play a distinctive role particularly in certain regions and environments. METHODS: The role of enteropathogens was investigated in 47 patients submitted to autologous stem cell transplantation at a Brazilian center between May 2011 and May 2013. All patients who presented with diarrhea consented to stool sample analysis to identify the etiological agents including coccidia, Strongyloides sp., Clostridium difficile and other pathogenic bacteria. RESULTS: Thirty-nine patients (83%) had diarrhea, among whom seven (17.5%) presented with coccidia, three (7.5%) with Candida sp., one (2.5%) with C. difficile, and one (2.5%) with Giardia lamblia. There was a tendency toward a higher incidence of diarrhea in older patients (p-value = 0.09) and those who received conditioning with lomustine, etoposide, cytarabine, and melphalan (p-value = 0.083). Furthermore, the number of days of neutropenia was higher in patients with diarrhea (p-value = 0.06). CONCLUSIONS: The high frequency of diarrhea caused by coccidia shows the importance of investigating and correctly identifying etiological agents and highlights the possible varieties of intestinal infections in patients who undergo autologous stem cell transplantation.

Supplementation with concentrated milk protein in patients undergoing hematopoietic stem cell transplantation.

OBJECTIVE: The aim of this study was to analyze the influence of dietary supplementation with whey protein concentrate (WPC) in the incidence of oral mucositis (OM) in patients undergoing hematopoietic stem cell transplantation (HSCT). METHODS: Patients were supplemented with a daily intake of WPC delivering 50% of the daily protein requirements (DPR) according to the Dietary Reference Intakes and classified later based on the amount of ingested supplement until OM median onset. RESULTS: We evaluated 73 patients. Forty-three were part of the historical control and 30 were supplemented with WPC. The OM had a mean duration of 5.3 d (SD 4.5), ranging from the day of the infusion of stem cells until the 17th day after infusion and a median of 5 d after infusion. OM duration was influenced by the conditioning protocol (P < 0.01) and WPC (P = 0.01). Patients who consumed the WPC in an amount ≥40% of DPR had a 35% reduction in duration of OM, and the incidence of OM grades 3 and 4 was 11 times smaller. Body mass index, serum albumin, and adverse reactions, such as diarrhea, nausea and vomiting, dysphagia, dry mouth and drooling, showed no statistically significant differences. CONCLUSION: WPC intake ≥40% of DPR helped to reduce the severity and duration of OM. The use of WPC in patients undergoing HSCT was shown to be safe, encouraging new studies in this population to assess its action mechanism.

Herpes zoster after autologous hematopoietic stem cell transplantation.

BACKGROUND: The autologous hematopoietic stem cell transplantation procedure involves immunosuppression of the patient. Thus, the patient has an elevated risk for several diseases, such as infections with the varicella-zoster virus. Prevention protocols have been proposed based on the use of acyclovir from the first day of conditioning, and maintaining this drug for 30-100 days after the procedure or for as much as one year. The objective of this work was to evaluate the incidence of herpes zoster after autologous transplantations related to the early suspension of acyclovir. METHODS: A retrospective study was carried out based on the collection of data from 231 medical records of transplant patients in the Bone Marrow Transplant Unit of the teaching hospital of the Universidade Federal de Juiz de Fora in the period between 2004 and 2014. RESULTS: Fourteen (6.1%) patients had herpes zoster in the post-transplant period on average within six months of the procedure. Patients with multiple myeloma (64.3%) were the most affected. There was a statistically significant difference in the age of the patients, with older individuals having a greater chance of developing the infection (p-value=0.002). There were no significant differences for the other variables analyzed. CONCLUSION: The early suspension of acyclovir can be safe in patients who receive autologous hematopoietic stem cell transplants. However some groups may benefit from extended prophylaxis with acyclovir, particularly older patients and patients with multiple myeloma.

A non-randomized comparative study using different doses of acyclovir to prevent herpes simplex reactivation in patients submitted to autologous stem cell transplantation.

The reactivation of Herpes Simplex virus (HSV) occurs in 70% to 80% of patients submitted to autologous stem cell transplantation (ASCT); it increases the severity of chemotherapy-induced mucositis. Therefore, the use of acyclovir in ASCT patients is considered standard practice. However, the minimum dose needed to prevent reactivation is a matter of debate. We compared two doses of acyclovir in a non-randomized fashion in 59 patients submitted to ASCT: 32 patients received a dose of 125 mg/m(2) IV every six hours and the subsequent 27 patients received a dose of 60 mg/m(2) IV every six hours. Viral excretion was evaluated through weekly viral culture of oral swabs. Grade 4 mucositis was more frequent in Group 1 (p= 0.03). The reactivation rates in Groups 1 and 2 were 9% and 4%, respectively (p= 0.62, 95% confidence interval -7 - 18). Prophylaxis with reduced doses of intravenous acyclovir seems to be as effective as a higher dose in inhibiting HSV reactivation, with a significant reduction in cost. Prospective randomized studies are needed to confirm our conclusions.

Advances in cellular technology in the hematology field: What have we learned so far?

Despite the advances in the hematology field, blood transfusion-related iatrogenesis is still a major issue to be considered during such procedures due to blood antigenic incompatibility. This places pluripotent stem cells as a possible ally in the production of more suitable blood products. The present review article aims to provide a comprehensive summary of the state-of-the-art concerning the differentiation of both embryonic stem cells and induced pluripotent stem cells to hematopoietic cell lines. Here, we review the most recently published protocols to achieve the production of blood cells for future application in hemotherapy, cancer therapy and basic research.

Allogeneic hematopoietic stem cell transplantation in mycosis fungoides.

Mycosis Fungoides is typically an indolent disease in early stages. However, approximately 30% of patients have advanced staged disease at presentation and 20% will develop it at some time. These patients have a poorer prognosis with a median survival of 2-4 years. The only curative option for mycosis fungoides may be hematopoietic allogeneic stem cell transplantation. We report the case of a patient with mycosis fungoides in an advanced stage (IIB), refractory to treatment options. She underwent allogeneic hematopoietic stem-cell transplantation (allo-HSCT). The patient remains in complete remission nineteen months after allo-HSCT. Allogeneic transplantation can alter the natural history of mycosis fungoides and should be considered in patients who have refractory disease or short-lived responses with standard therapies.

Infectious diarrhea in autologous stem cell transplantation: high prevalence of coccidia in a South American center

ABSTRACT Background: Diarrhea is frequently seen in autologous stem cell transplantation. Although toxicity related to conditioning is the most common cause, infectious pathogens can play a distinctive role particularly in certain regions and environments. Methods: The role of enteropathogens was investigated in 47 patients submitted to autologous stem cell transplantation at a Brazilian center between May 2011 and May 2013. All patients who presented with diarrhea consented to stool sample analysis to identify the etiological agents including coccidia, Strongyloides sp., Clostridium difficile and other pathogenic bacteria. Results: Thirty-nine patients (83%) had diarrhea, among whom seven (17.5%) presented with coccidia, three (7.5%) with Candida sp., one (2.5%) with C. difficile, and one (2.5%) with Giardia lamblia. There was a tendency toward a higher incidence of diarrhea in older patients (p-value = 0.09) and those who received conditioning with lomustine, etoposide, cytarabine, and melphalan (p-value = 0.083). Furthermore, the number of days of neutropenia was higher in patients with diarrhea (p-value = 0.06). Conclusions: The high frequency of diarrhea caused by coccidia shows the importance of investigating and correctly identifying etiological agents and highlights the possible varieties of intestinal infections in patients who undergo autologous stem cell transplantation.

Infection profile of patients undergoing autologous bone marrow transplantation in a Brazilian institution.

CONTEXT AND OBJECTIVE: Hematopoietic stem cell transplantation (HSCT) has been widely used for treating oncological and hematological diseases. Although HSCT has helped to improve patient survival, the risk of developing infection during hospitalization is an important cause of morbidity and mortality. This study aimed to analyze the infection profile during hospitalization and the associated risk factors among patients undergoing autologous HSCT at the University Hospital, Universidade Federal de Juiz de Fora. DESIGN AND SETTING: This was a cross-sectional study on patients undergoing autologous HSCT at a public university hospital. METHODS: Patients with febrile neutropenia between 2004 and 2009 were retrospectively evaluated regarding their infection profile and associated risk factors. RESULTS: Infection occurred in 57.2% of 112 patients with febrile neutropenia. The main source of infection was the central venous catheter (25.9%). Infection was chiefly due to Gram-positive bacteria, although Gram-negative-related infections were more severe and caused a higher death rate. Sex, age, skin color, nutritional status and underlying disease were not associated with the development of infection. Patients with severe mucositis (Grades III and IV) had a higher infection rate (P < 0.001). Patients who developed pulmonary complications during hospitalization had higher infection rates (P = 0.002). Infection was the main cause of death (57.1%) in the study sample. CONCLUSION: Strategies aimed at reducing infection-related mortality rates among patients undergoing autologous HSCT are necessary.

Herpes zoster after autologous hematopoietic stem cell transplantation

ABSTRACT Background: The autologous hematopoietic stem cell transplantation procedure involves immunosuppression of the patient. Thus, the patient has an elevated risk for several diseases, such as infections with the varicella-zoster virus. Prevention protocols have been proposed based on the use of acyclovir from the first day of conditioning, and maintaining this drug for 30-100 days after the procedure or for as much as one year. The objective of this work was to evaluate the incidence of herpes zoster after autologous transplantations related to the early suspension of acyclovir. Methods: A retrospective study was carried out based on the collection of data from 231 medical records of transplant patients in the Bone Marrow Transplant Unit of the teaching hospital of the Universidade Federal de Juiz de Fora in the period between 2004 and 2014. Results: Fourteen (6.1%) patients had herpes zoster in the post-transplant period on average within six months of the procedure. Patients with multiple myeloma (64.3%) were the most affected. There was a statistically significant difference in the age of the patients, with older individuals having a greater chance of developing the infection (p-value = 0.002). There were no significant differences for the other variables analyzed. Conclusion: The early suspension of acyclovir can be safe in patients who receive autologous hematopoietic stem cell transplants. However some groups may benefit from extended prophylaxis with acyclovir, particularly older patients and patients with multiple myeloma.

Acute myeloid leukemia: update in diagnosis and treatment in Brazil.

OBJECTIVE: To identify how the Brazilian hematology centers treated and diagnosed cases of acute myeloid leukemia in 2009. METHODS: An epidemiological observational multicenter study of 11 listed Brazilian centers that treat acute myeloid leukemia and perform bone marrow transplantation. Data were collected from clinical charts of patients with acute myeloid leukemia treated at the said centers between 2005 and 2009. The availability for immunophenotyping and cytogenetic tests was assessed. RESULTS: During 2009, a total of 345 new cases of acute myeloid leukemia were diagnosed. Differences were noted in the tests performed between patients who initiated treatment at the center and those referred for treatment. Of the participating centers, 72% conducted some type of molecular study in acute myeloid leukemia upon diagnosis. CONCLUSION: Treatment for acute myeloid leukemia in Brazil shows significantly inferior results when compared to other centers worldwide.

Allogeneic hematopoietic stem cell transplantation in mycosis fungoides / Transplante alogenico de celulas-tronco hematopoieticas em micose fungoide

Mycosis Fungoides is typically an indolent disease in early stages. However, approximately 30% of patients have advanced staged disease at presentation and 20% will develop it at some time. These patients have a poorer prognosis with a median survival of 2-4 years. The only curative option for mycosis fungoides may be hematopoietic allogeneic stem cell transplantation. We report the case of a patient with mycosis fungoides in an advanced stage (IIB), refractory to treatment options. She underwent allogeneic hematopoietic stem-cell transplantation (allo-HSCT). The patient remains in complete remission nineteen months after allo-HSCT. Allogeneic transplantation can alter the natural history of mycosis fungoides and should be considered in patients who have refractory disease or short-lived responses with standard therapies.

Micose Fungoide é tipicamente uma doença indolente em estágios iniciais. No entanto, aproximadamente 30% dos pacientes têm doença avançada na apresentação e 20% irão desenvolvê-la em algum momento. Esses pacientes têm um pior prognóstico com uma sobrevida média de dois a quatro anos. A única possibilidade de cura é o transplante alogênico de células-tronco hematopoiéticas. Relatamos o caso de uma paciente com micose fungoide em estágio avançado (IIB), refratária às opções terapêuticas e que foi submetida a um transplante alogênico de células-tronco hematopoiéticas. A paciente permanece em remissão completa 19 meses após o procedimento. O transplante alogênico é capaz de mudar a história natural da micose fungoide e deve ser considerado em pacientes com doença avançada e refratária aos tratamentos disponíveis.

Infection profile of patients undergoing autologous bone marrow transplantation in a Brazilian institution / Perfil de infecção em pacientes submetidos a transplante autólogo de medula óssea em uma instituição brasileira

CONTEXT AND OBJECTIVE: Hematopoietic stem cell transplantation (HSCT) has been widely used for treating oncological and hematological diseases. Although HSCT has helped to improve patient survival, the risk of developing infection during hospitalization is an important cause of morbidity and mortality. This study aimed to analyze the infection profile during hospitalization and the associated risk factors among patients undergoing autologous HSCT at the University Hospital, Universidade Federal de Juiz de Fora. DESIGN AND SETTING: This was a cross-sectional study on patients undergoing autologous HSCT at a public university hospital. METHODS: Patients with febrile neutropenia between 2004 and 2009 were retrospectively evaluated regarding their infection profile and associated risk factors. RESULTS: Infection occurred in 57.2 percent of 112 patients with febrile neutropenia. The main source of infection was the central venous catheter (25.9 percent). Infection was chiefly due to Gram-positive bacteria, although Gram-negative-related infections were more severe and caused a higher death rate. Sex, age, skin color, nutritional status and underlying disease were not associated with the development of infection. Patients with severe mucositis (Grades III and IV) had a higher infection rate (P < 0.001). Patients who developed pulmonary complications during hospitalization had higher infection rates (P = 0.002). Infection was the main cause of death (57.1 percent) in the study sample. CONCLUSION: Strategies aimed at reducing infection-related mortality rates among patients undergoing autologous HSCT are necessary.

CONTEXTO E OBJETIVO: O transplante de células-tronco hematopoiéticas (TCTH) vem sendo amplamente utilizado no tratamento das doenças onco-hematológicas. Embora o TCTH tenha colaborado para a melhora na sobrevida dos pacientes, o risco de desenvolver infecção no período de internação é uma importante causa de morbi-mortalidade. O presente estudo teve como objetivo analisar o perfil das infecções no período de internação e os fatores de risco associados entre os pacientes submetidos ao TCTH autólogo, no Hospital Universitário da Universidade Federal de Juiz de Fora. TIPO DE ESTUDO E LOCAL: Trata-se de um estudo transversal sobre pacientes submetidos a transplante autólogo, em um hospital público universitário. MÉTODOS: Foram analisados retrospectivamente os pacientes que apresentaram neutropenia febril no período de 2004 a 2009, com relação ao perfil infeccioso e os fatores de risco associados. RESULTADOS: A infecção foi determinada em 57,2 por cento dos 112 pacientes com neutropenia febril. A principal fonte de infecção foi o cateter venoso central (25,9 por cento). A infecção ocorreu principalmente devido a bactérias Gram-positivas, apesar de as infecções causadas por bactérias Gram-negativas terem sido mais graves e causado maior taxa de morte. Sexo, idade, cor da pele, estado nutricional e doença de base não estiveram associados com o desenvolvimento da infecção. Pacientes com mucosite grave (graus III e IV) apresentaram maior taxa de infecção (P < 0.001). Os pacientes que desenvolveram complicações pulmonares durante a internação apresentaram maiores taxas de infecção (P = 0,002). A infecção foi a principal causa do óbito (57,1 por cento) na amostra estudada. CONCLUSÃO: São necessárias estratégias voltadas para a redução da taxa de mortalidade relacionada com infecção entre pacientes submetidos ao TCTH autólogo.

Leucemia mieloide aguda: atualidade brasileira de diagnóstico e tratamento / Acute myeloid leukemia: update in diagnosis and treatment in Brazil

Objective: To identify how the Brazilian hematology centers treated and diagnosed cases of acute myeloid leukemia in 2009. Methods: An epidemiological observational multicenter study of 11 listed Brazilian centers that treat acute myeloid leukemia and perform bone marrow transplantation. Data were collected from clinical charts of patients with acute myeloid leukemia treated at the said centers between 2005 and 2009. The availability for immunophenotyping and cytogenetic tests was assessed. Results:During 2009, a total of 345 new cases of acute myeloid leukemia were diagnosed. Differences were noted in the tests performed between patients who initiated treatment at the center and those referred for treatment. Of the participating centers, 72% conducted some type of molecular study in acute myeloid leukemia upon diagnosis. Conclusion: Treatment for acute myeloid leukemia in Brazil shows significantly inferior results when compared to other centers worldwide.

Objetivo: Identificar como centros de hematologia brasileiros trataram e diagnosticaram os casos de leucemia mieloide aguda no ano de 2009. Métodos: Estudo epidemiológico, observacional, multicêntrico de 11 centros brasileiros cadastrados para tratamento de leucemia mieloide aguda e transplante de medula óssea. Os dados foram coletados a partir de prontuários de pacientes com leucemia mieloide aguda tratados nos centros citados entre os anos de 2005 e 2009. Foi avaliada a disponibilidade para realização de exames de imunofenotipagem e citogenética nos centros estudados. Resultados: Foram diagnosticados 345 casos novos de leucemia mieloide aguda no ano de 2009. Observaram-se diferenças na realização de exames entre pacientes que iniciaram o tratamento no centro em relação àqueles referenciados para tratamento. Dos centros participantes, 72% realizaram algum tipo de pesquisa molecular em leucemia mieloide aguda ao diagnóstico. Conclusão: O tratamento da leucemia mieloide aguda no Brasil apresenta resultados muito inferiores quando comparado a outros centros mundiais.

Risk stratification for indolent lymphomas / Estratificação de risco dos linfomas indolentes

Indolent B-cell lymphomas account for approximately 40 percent of all non-Hodgkin lymphomas (NHLs). Advances in technology have contributed to improvements in the diagnosis and classification of indolent non-Hodgkin lymphomas. Follicular Lymphomas are the most common although the frequency varies significantly throughout the world. The description of the Follicular Lymphoma International Prognostic Index (FLIPI) was an important step in identifying patient subgroups, but its use in the clinical practice has not been established yet. The use of a larger number of paraffin active monoclonal antibodies for immunohistochemistry, molecular cytogenetic studies including standard cytogenetics, multi-color fluorescence in-situ hybridization (FISH), polymerase chain reaction and locus-specific fluorescence insitu hybridization as well as developments in high-resolution techniquesincluding microarray gene expression profiling allow more accurate diagnosis andprecise definition of biomarkers of value in risk stratification. The identification ofdiseasespecific gene lists resulting from expression profiling provides a number ofpotential protein targets that can be validated using immunohistochemistry. Analysesof gene expression profiles or constitutive gene variations may also provide additional insight for prognostication in the near future. A comprehensive understanding of the biology of these distinct lymphoid tumors will allow us to identify novel diseaserelated genes and should facilitate the development of improved diagnosis, outcome prediction, and personalized approaches to treatment.

Os linfomas de células B indolentes representam aproximadamente 40 por cento do total de linfomas não Hodgkin (LNHs). O avanço das tecnologias novas tem contribuído para a melhora no diagnóstico e classificação dos LNH indolentes. O linfoma folicular é o mais comum e sua frequência varia significantemente pelo mundo. Adescrição do Índice Internacional de Prognóstico dos linfomas folicular (FLIPI) representa um passo importante na identificação de subgrupos de pacientes, mas seu uso na prática clínica ainda necessita ser estabelecido. O uso de um número maior de anticorpos monoclonais para imunoistoquímica, estudo citogenético incluindo citogenética convencional ou hibridização in-situ por fluorescência (FISH), bem como o desenvolvimento de técnicas de alta resolução incluindo a expressão por microarray possibilita maior acurácia no diagnóstico e definição precisa dos biomarcadores com valor na estratificação de risco. A identificação de genes específicos para os diversos tipos de linfomas permite o reconhecimento de potenciais proteínas alvo que podem ser validadas usando imunoistoquímica. Análises da expressão do perfil de genes ou variações genéticas constitutivas pode também prover conhecimentos adicionais para o prognóstico em um futuro próximo. Um entendimento da biologia desses distintos tumores linfoides permite-nos identificar novos grupos de genes relacionados à doença e deve facilitar o desenvolvimento diagnóstico, predizendo a evolução e permitindo tratamentos personalizados.

Transplante de células-tronco hematopoéticas em gamopatias monoclonais / Hematopoietic stem cell transplantation for monoclonal gammopathies

O transplante de células-tronco hematopoéticas (TCTH) é um procedimento de fundamental importância na estratégia terapêutica das gamopatias monoclonais. No mieloma múltiplo, em particular, o TCTH autólogo está indicado como estratégia de primeira linha para pacientes até 70 anos de idade. Nesta capítulo serão discutidas as indicações, estratégias e recomendações envolvendo o TCTH em gamopatias monoclonais, amiloidose e POEMS, frutos da Reunião de Consenso da Sociedade Brasileira de Transplante de Medula Óssea.

Hematopoietic stem cell transplantation (HSCT) is an important strategy in the treatment of monoclonal gammopathies. For multiple myeloma, in particular, autologous HSCT is indicated as first line therapy for under 70-year-old patients. In this chapter we will discuss indications, strategies and recommendations involving HSCT for monoclonal gammopathies from the Consensus Meeting of the Brazilian Society of Bone Marrow Transplantation.