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

Corey Cutler, Brent Logan, Ryotaro Nakamura, Laura Johnston, Sung Choi, David Porter, William Hogan, Marcelo Pasquini, Margaret L. MacMillan, Jack W. Hsu, Edmund K. Waller, Stephan Grupp, Philip McCarthy, Juan Wu, Zhen Huan Hu, Shelly L. Carter, Mary M. Horowitz, Joseph H. Antin

Research output: Contribution to journalArticle

78 Citations (Scopus)

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 MRDHCT.

Original languageEnglish (US)
Pages (from-to)1372-1377
Number of pages6
JournalBlood
Volume124
Issue number8
DOIs
StatePublished - Aug 21 2014

Fingerprint

Cell Transplantation
Tacrolimus
Graft vs Host Disease
Sirolimus
Methotrexate
Grafts
Disease-Free Survival
Mucositis
Stomatitis
Intention to Treat Analysis
Platelets
Multicenter Studies
Toxicity
Neutrophils
Blood Platelets
Recurrence
Mortality

ASJC Scopus subject areas

  • Immunology
  • Biochemistry
  • Hematology
  • Cell Biology

Cite this

Cutler, C., Logan, B., Nakamura, R., Johnston, L., Choi, S., Porter, D., ... Antin, J. H. (2014). Tacrolimus/sirolimus vs tacrolimus/methotrexate as GVHD prophylaxis after matched, related donor allogeneic HCT. Blood, 124(8), 1372-1377. https://doi.org/10.1182/blood-2014-04-567164

Tacrolimus/sirolimus vs tacrolimus/methotrexate as GVHD prophylaxis after matched, related donor allogeneic HCT. / Cutler, Corey; Logan, Brent; Nakamura, Ryotaro; Johnston, Laura; Choi, Sung; Porter, David; Hogan, William; Pasquini, Marcelo; MacMillan, Margaret L.; Hsu, Jack W.; Waller, Edmund K.; Grupp, Stephan; McCarthy, Philip; Wu, Juan; Hu, Zhen Huan; Carter, Shelly L.; Horowitz, Mary M.; Antin, Joseph H.

In: Blood, Vol. 124, No. 8, 21.08.2014, p. 1372-1377.

Research output: Contribution to journalArticle

Cutler, C, Logan, B, Nakamura, R, Johnston, L, Choi, S, Porter, D, Hogan, W, Pasquini, M, MacMillan, ML, Hsu, JW, Waller, EK, Grupp, S, McCarthy, P, Wu, J, Hu, ZH, Carter, SL, Horowitz, MM & Antin, JH 2014, 'Tacrolimus/sirolimus vs tacrolimus/methotrexate as GVHD prophylaxis after matched, related donor allogeneic HCT', Blood, vol. 124, no. 8, pp. 1372-1377. https://doi.org/10.1182/blood-2014-04-567164
Cutler, Corey ; Logan, Brent ; Nakamura, Ryotaro ; Johnston, Laura ; Choi, Sung ; Porter, David ; Hogan, William ; Pasquini, Marcelo ; MacMillan, Margaret L. ; Hsu, Jack W. ; Waller, Edmund K. ; Grupp, Stephan ; McCarthy, Philip ; Wu, Juan ; Hu, Zhen Huan ; Carter, Shelly L. ; Horowitz, Mary M. ; Antin, Joseph H. / Tacrolimus/sirolimus vs tacrolimus/methotrexate as GVHD prophylaxis after matched, related donor allogeneic HCT. In: Blood. 2014 ; Vol. 124, No. 8. pp. 1372-1377.
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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 MRDHCT.",
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AU - Johnston, Laura

AU - Choi, Sung

AU - Porter, David

AU - Hogan, William

AU - Pasquini, Marcelo

AU - MacMillan, Margaret L.

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AU - McCarthy, Philip

AU - Wu, Juan

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