Tacrolimus/sirolimus vs tacrolimus/methotrexate as GVHD prophylaxis after matched, related donor allogeneic HCT

摘要: Grades 2-4 acute graft-versus-host disease (GVHD) occurs in approximately 35% of matched, related donor (MRD) allogeneic hematopoietic cell transplantation (HCT) recipients. We sought to determine if the combination tacrolimus and sirolimus (Tac/Sir) was more effective than methotrexate (Tac/Mtx) preventing GVHD early mortality after MRD HCT a phase 3, multicenter trial. The primary end point trial compare 114-day grades GVHD-free survival using an intention-to-treat analysis 304 randomized subjects. There no difference probability day 114 (67% vs 62%, P = .38). similar Tac/Sir Tac/Mtx arms (26% 34%, .48). Neutrophil platelet engraftment were rapid arm (14 16 days, < .001; 19 .03). Oropharyngeal mucositis less severe (peak Oral Mucositis Assessment Scale score 0.70 0.96, .001), but otherwise toxicity similar. Chronic GVHD, relapse-free survival, overall at 2 years different between study (53% 45%, .06; 53% 54%, .77; 59% 63%, .36). Based on long-term outcomes, engraftment, oropharyngeal mucositis, is acceptable alternative HCT. This funded by National Heart, Lung, Blood Institute Cancer Institute; registered www.clinicaltrials.gov as #NCT00406393.