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Tacrolimus/sirolimus vs tacrolimus/methotrexate as GVHD prophylaxis after matched, related donor allogeneic HCT. Blood 2014 Aug 21;124(8):1372-7



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Scopus ID

2-s2.0-84907357105   99 Citations


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

Author List

Cutler C, Logan B, Nakamura R, Johnston L, Choi S, Porter D, Hogan WJ, Pasquini M, MacMillan ML, Hsu JW, Waller EK, Grupp S, McCarthy P, Wu J, Hu ZH, Carter SL, Horowitz MM, Antin JH


Mary M. Horowitz MD, MS Center Director, Professor in the Medicine department at Medical College of Wisconsin
Brent R. Logan PhD Director, Professor in the Institute for Health and Equity department at Medical College of Wisconsin
Marcelo C. Pasquini MD, MS Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Disease-Free Survival
Follow-Up Studies
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Immunosuppressive Agents
Middle Aged
Survival Rate
Time Factors
jenkins-FCD Prod-480 9a4deaf152b0b06dd18151814fff2e18f6c05280