RESUMO
PURPOSE: To characterize the impact of graft T-cell composition on outcomes of reduced-intensity conditioned (RIC) allogeneic hematopoietic stem-cell transplantation (alloHSCT) in adults with hematologic malignancies. PATIENTS AND METHODS: We evaluated associations between graft T-cell doses and outcomes in 200 patients who underwent RIC alloHSCT with a peripheral blood stem-cell graft. We then studied 21 alloHSCT donors to identify predictors of optimal graft T-cell content. RESULTS: Higher CD8 cell doses were associated with a lower risk for relapse (adjusted hazard ratio [aHR], 0.43; P = .009) and improved relapse-free survival (aHR, 0.50; P = .006) and overall survival (aHR, 0.57; P = .04) without a significant increase in graft-versus-host disease or nonrelapse mortality. A cutoff level of 0.72 × 10(8) CD8 cells per kilogram optimally segregated patients receiving CD8(hi) and CD8(lo) grafts with differing overall survival (P = .007). Donor age inversely correlated with graft CD8 dose. Consequently, older donors were unlikely to provide a CD8(hi) graft, whereas approximately half of younger donors provided CD8(hi) grafts. Compared with recipients of older sibling donor grafts (consistently containing CD8(lo) doses), survival was significantly better for recipients of younger unrelated donor grafts with CD8(hi) doses (P = .03), but not for recipients of younger unrelated donor CD8(lo) grafts (P = .28). In addition, graft CD8 content could be predicted by measuring the proportion of CD8 cells in a screening blood sample from stem-cell donors. CONCLUSION: Higher graft CD8 dose, which was restricted to young donors, predicted better survival in patients undergoing RIC alloHSCT.
Assuntos
Linfócitos T CD8-Positivos , Seleção do Doador , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Idoso , Feminino , Citometria de Fluxo , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Agonistas Mieloablativos/uso terapêutico , Recidiva , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Transplante Homólogo , Resultado do Tratamento , Doadores não RelacionadosRESUMO
BACKGROUND: Although intensive induction and autologous stem cell transplantation (ASCT) prolong survival in younger patients with mantle cell lymphoma (MCL), benefit in older patients remains uncertain because data supporting these approaches come almost exclusively from younger cohorts. PATIENTS AND METHODS: We reviewed outcomes for 38 patients with MCL aged ≥ 60 years who received R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) (n = 19) or R-HyperCVAD (rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine) (n = 19) with or without ASCT. RESULTS: Median progression-free survival (PFS) of R-CHOP + ASCT (3.2 years) and R-HyperCVAD alone (4.0 years) was longer than that for R-CHOP alone (1.6 years; P = .013 and P = .009, respectively). R-CHOP + ASCT and R-HyperCVAD resulted in similar PFS (P = .66). R-HyperCVAD induction led to a higher incidence of toxicity, including therapy discontinuation and need for transfusions, compared with R-CHOP, although rates of adverse events were similar for R-HyperCVAD alone and R-CHOP + ASCT. CONCLUSION: R-CHOP alone is less effective therapy for fit older patients with MCL. Intensifying therapy with R-HyperCVAD induction or ASCT consolidation after R-CHOP is associated with prolonged PFS and similar rates of toxicity. Consideration should be given to individual preferences regarding the differing method of administration and relative timing of toxicity with each regimen.