Lower levels of cyclosporine between days 0 and +21 may reduce later relapses without increasing graft-versus-host disease in children and adolescents with acute lymphoblastic leukemia who undergo myeloablative TBI-based allogeneic hematopoietic cell transplantation.

BACKGROUND: The degree of immunosuppression required for adequate graft-versus-host disease (GVHD) prevention, while keeping an adequate graft-versus-leukemia effect, in children with acute leukemia has not been established. We report the results of a retrospective comparison of cyclosporine levels and relapse rate in children and adolescents with acute lymphoblastic leukemia (ALL). METHODS: Patients <21 y/o with ALL in remission who underwent TBI-based hematopoietic cell transplantation from related or unrelated donors between 2008 and 2021 were included. Cyclosporine levels were measured twice a week and we calculated the area under the curve (AUC) from D0 to D + 7, D + 14, and D + 21. RESULTS: We included 76 patients. There was a trend towards a lower incidence of relapse in patients with a mean AUC < 200 ng/ml at D + 21 (HR = 0.41; p = .08). The 5-year relapse rate was 26.9% for patients with a mean AUC < 200 ng/ml at D + 21 and 43.9% for patients with a mean AUC≥200 ng/ml at D + 21. Relapse protection was restricted to relapses happening after D + 120 (HR = 0.21; p = .04). CONCLUSIONS: Our results show evidence that pediatric patients with ALL might benefit from lower cyclosporine levels between D0 and D + 21 without a detectable increase in GVHD. Large prospective studies comparing different cyclosporine levels are awaited.

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. METHODS: 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.

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.

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.

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.

Síndrome metabólica em mulheres submetidas ao transplante de células precursoras hematopoéticas: prevalênciae fatores associados

O agrupamento de obesidade central, hipertensão arterial, hiperglicemia e dislipidemia, conhecido como síndrome metabólica (SM), está associado com aumento no risco de diabetes mellitus tipo 2 e doença cardiovascular. Estudos sugerem maior freqüência desta síndrome em sobreviventes do transplante de células precursoras hematopoéticas (TCPH), porém a prevalência de SM e de resistência insulínica (RI), bem como fatores associados ao seu desenvolvimento permanecem mal definidos nesta população. Objetivos.Comparar a prevalência de SM e de RI em mulheres submetidas ou não ao TCPH; identificar possíveis fatores de risco para SM e RI e avaliar o efeito da terapia hormonal sobre a prevalência destas condições em receptoras de TCPH. Métodos. Cento e treze receptoras de TCPH e 48 controles, entre 18 e 65 anos, foram avaliadas em estudo de corte transversal realizado no Centro de Transplante de Medula Óssea do Instituto Nacional do Câncer, Rio de Janeiro, de junho de 2005 a maio de 2008. As variáveis analisadas foram: componentes da síndrome metabólica conforme os critérios do NCEP-ATPIII e resistência insulínica pelo índice do modelo homeostático para insulino-resistência (HOMA-IR) (dependentes), e tipo dotransplante, doença do enxerto-contra-o-hospedeiro, hipotireoidismo, hipogonadismo, terapia hormonal, uso de imunossupressores, idade, idade ao transplante, tempo pós-transplante, diagnóstico de SM pré-TCPH, regime de condicionamento, cor, status menopausal, tabagismo, índice de massa corpórea, dieta, atividade física e história familiar de doença cardiovascular (independentes). Resultados. A idade mediana foi 36,9 anos, e 30 anos ao transplante. Foram 77 transplantes alogênicos, 2 singênicos e 34 autólogos. Não houve diferença significativa na prevalência de SM entre receptoras de transplante (22,1%) e controles (20,8%). Entretanto, a prevalência de RI foi significativamente maior entre pacientes (20%) que nos controles (6,5%). Os componentes mais frequentes foram hipertensão arterial (36,2%) e obesidade central (32,7%). A SM foi mais prevalente nas mulheres com idade superior a 30 anos ao transplante. Os diagnósticos de SM pré-TCPH e obesidade estiveram significativamente ssociados à SM e à RI, porém hiperinsulinemia e hipogonadismo estiveram relacionados significativamente apenas com SM. O uso de terapia hormonal reduziu em 75% o risco de SM, mas a redução no risco de RI não foi significativa. Conclusões. A prevalência de RI foi significativamente maior entre receptoras de TCPH. Diagnóstico de SM pré-TCPH, obesidade, hiperinsulinemia e hipogonadismo foram preditores independentes de SM. Os únicos preditores independentes de RI oram diagnóstico de SM pré-TCPH e obesidade. Novos estudos serão necessários para definir qual a melhor terapia hormonal para a prevenção destes distúrbios metabólicos em receptoras de TCPH.

Introduction. The clustering of central obesity, arterial hypertension, hyperglycemia and dyslipidemia, known as the metabolic syndrome (MS), is associated with an increased risk for type 2 diabetes mellitus and cardiovascular disease. Studies suggest a higher frequency of this syndrome in survivors of hematopoietic stem cell transplantation (HSCT); however, the prevalence of MS and insulin resistance (IR), as well as of the factors associated with its development, remains ill-defined. Objectives. To compare the prevalence of MS and of IR in women submitted or not to HSCT; to identify possible risk factors for MS and IR and to evaluate the effect of hormone therapy on the risk of these conditions in HSCT recipients. Methods. One hundred and thirteen HSCT recipients and 48 controls, between 18 and 65 years old, were evaluated in a cross-sectional study carried out at Centro de Transplante de Medula Óssea, in Instituto Nacional de Câncer, Rio de Janeiro, Brazil, from June 2005 to May 2008. The variables analyzed were: MS components on the basis of the NCEP-ATPIII criteria and insulin resistance by the homeostasis model assessment insulin resistance index (HOMAIR) (dependents), and transplant type, graft-versus-host disease, hypothyroidism, hypogonadism, hormone therapy, immunosuppressor use, age, age at transplant, time since transplant, MS diagnosis before HSCT, conditioning regimen, race, menopausal status, smoking habits, body mass index, diet, physical activity and family history of cardiovascular disease (independents). Results. The median age was 36.9 years, and 30 years at transplant. There were 77 allogeneic, two syngeneic and 34 autologous transplants. There was no significant difference in the prevalence of MS between transplant recipients (22.1%) and controls (20.8%). However, the prevalence of IR was significantly higher among patients (20%) than controls (6.5%). The most frequent components were arterial hypertension (36.2%) and central obesity (32.7%). MS was more prevalent among women older than 30 years at transplant. MS diagnosis before HSCT and obesity were significantly associated with MS and IR. However, hyperinsulinemia and hypogonadism were significantly related only with MS. Hormone therapy decreased by 75% the risk of MS, but the risk reduction for IR was not significant. Conclusions. The prevalence of IR was significantly higher among HSCT recipients. MS diagnosis before HSCT, obesity, hyperinsulinemia and hypogonadism were independent predictors of MS. Only obesity and MS diagnosis before HSCT were independent predictors of IR. Further studies will be necessary to define the best hormone therapy for prevention of these metabolic disorders in HSCT recipients.