RESUMO
The Blood and Marrow Transplant Clinical Trials Network (BMT CTN) conducts large, multi-institutional clinical trials with the goal of improving the outcomes of hematopoietic cell transplantation (HCT) for patients with life-threatening disorders. Well-designed HCT trials benefit from standardized criteria for defining diagnoses, treatment plans, and graft source selection. In this perspective, we summarize evidence supporting criteria for the selection of related and unrelated adult volunteer progenitor cell donors or umbilical cord blood units. These standardized criteria for graft source selection have been adopted by the BMT CTN to enhance the interpretation of clinical findings within and among future clinical protocols.
Assuntos
Transplante de Medula Óssea , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Antígenos HLA/análise , Transplante de Células-Tronco Hematopoéticas , Teste de Histocompatibilidade/normas , Doadores de Tecidos , Ensaios Clínicos como Assunto , Consenso , Humanos , Transplante HomólogoRESUMO
The introduction of reduced-intensity conditioning (RIC) regimens made it possible to offer allogeneic hematopoietic cell transplantation (alloHCT) to older patients with myelodysplastic syndromes (MDS). However, the relative risks and benefits of alloHCT compared with novel nontransplant therapies continue to be the source of considerable uncertainty. We will perform a prospective biologic assignment trial to compare RIC alloHCT with nontransplant therapies based on donor availability. Primary outcome is 3-year overall survival. Secondary outcomes include leukemia-free survival, quality of life, and cost-effectiveness. Four hundred patients will be enrolled over roughly 3 years. Planned subgroup analyses will evaluate key biologic questions, such as the impact of age and response to hypomethylating agents on treatment effects. Findings from this study potentially may set a new standard of care for older MDS patients who are considered candidates for alloHCT.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Análise de Intenção de Tratamento , Síndromes Mielodisplásicas/terapia , Condicionamento Pré-Transplante/métodos , Fatores Etários , Idoso , Análise Custo-Benefício , Metilação de DNA/efeitos dos fármacos , Feminino , Teste de Histocompatibilidade , Humanos , Masculino , Pessoa de Meia-Idade , Agonistas Mieloablativos/uso terapêutico , Síndromes Mielodisplásicas/imunologia , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/patologia , Prognóstico , Estudos Prospectivos , Qualidade de Vida , Fatores de Risco , Análise de Sobrevida , Transplante Homólogo , Doadores não RelacionadosRESUMO
INTRODUCTION: The epidemiology of chronic myeloid leukemia (CML) in low and middle income countries is limited. As a result, we analyzed a contemporary cohort of patients from low and middle income countries treated with Imatinib through The Glivec(®) International Patient Assistance Program (GIPAP). METHODS: Generalized estimating equations (GEE) and Kaplan-Meier estimation were utilized to test for regional variations in age at diagnosis and overall survival among 33,985 patients from 94 countries. RESULTS: Patients participated from Asia (79.2%), Africa (9.4%), Latin America (8.7%) and Southern/Eastern Europe (2.5%). Sixty-one (61.2%) percent were male. Mean age at diagnosis was 38.5 years (9.4% <20 years and only 4.7% ≥65 years). Using GEE, Asians were youngest (38.3 years), followed by Africans (39.5 years), Southern/Eastern Europeans (41.1 years) and Latin Americans (41.3 years; p < 0.0001). Diagnoses were predominately in chronic stage (78.3%). In 2002, 85.2% of patients had a delay in treatment >1 year; decreasing to 15.5% in 2010 (p < 0.0001). The 3-year overall survival probability was 89.4% (95% CI, 88.9-89.9). In multivariate analysis, risk of death increased among patients 65 years or older at diagnosis (p < 0.0001), time from diagnosis to treatment >1-year (p < 0.0001), diagnoses in the accelerated or blast crisis (p < 0.0001), initial dose of Imatinib >400 mg (p < 0.0001) and among Latin Americans and Africans (p < 0.0001). CONCLUSION: The GIPAP cohort is the largest series of patients with CML described from low and middle income countries. Differences in age at diagnosis and overall survival exist within and between regions. Additional epidemiological studies should be conducted to assess for possible environmental factors associated with the earlier age at onset.