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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

Date

07/02/2014

Pubmed ID

24982504

Pubmed Central ID

PMC4141519

DOI

10.1182/blood-2014-04-567164

Scopus ID

2-s2.0-84907357105   77 Citations

Abstract

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 www.clinicaltrials.gov 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

Authors

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 Associate Professor in the Medicine department at Medical College of Wisconsin




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

Adolescent
Adult
Allografts
Disease-Free Survival
Female
Follow-Up Studies
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Humans
Immunosuppressive Agents
Male
Methotrexate
Middle Aged
Sirolimus
Stomatitis
Survival Rate
Tacrolimus
Time Factors
jenkins-FCD Prod-409 d1e206b0be345926047b0d9c353c78a4cce4058b