Prolonged sirolimus administration after allogeneic hematopoietic cell transplantation is associated with decreased risk for moderate-severe chronic graft-versus-host disease

Joseph Pidala, Jongphil Kim, Melissa Alsina, Ernesto Ayala, Brian C. Betts, Hugo F. Fernandez, Teresa Field, Heather Jim, Mohamed A. Kharfan-Dabaja, Frederick L. Locke, Asmita Mishra, Taiga Nishihori, Leonel Ochoa-Bayona, Lia Perez, Marcie Riches, Claudio Anasetti

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Effective pharmacological strategies employed in allogeneic hematopoietic cell transplantation should prevent serious chronic graft-versus-host disease and facilitate donor-recipient immune tolerance. Based on demonstrated pro-tolerogenic activity, sirolimus (rapamycin) is an agent with promise to achieve these goals. In a long-term follow-up analysis of a randomized phase II trial comparing sirolimus/tacrolimus versus methotrexate/tacrolimus for graft-versus-host disease prevention in matched sibling or unrelated donor transplant, we examined the impact of prolonged sirolimus administration (≥ 1 year post-transplant). Median follow-up time for surviving patients at time of this analysis was 41 months (range 27-60) for sirolimus/tacrolimus and 49 months (range 29-63) for methotrexate/tacrolimus. Sirolimus/tacrolimus patients had significantly lower National Institutes of Health Consensus moderate-severe chronic graft-versus-host disease (34% vs. 65%; P=0.004) and late acute graft-versus-host disease (20% vs. 43%; P=0.04). While sirolimus/tacrolimus patients had lower prednisone exposure and earlier discontinuation of tacrolimus (median time to tacrolimus discontinuation 368 days vs. 821 days; P=0.002), there was no significant difference in complete immune suppression discontinuation (60-month estimate: 43% vs. 31%; P=0.78). Prolonged sirolimus administration represents a viable approach to mitigate risk for moderate-severe chronic and late acute graft-versushost disease. Further study of determinants of successful immune suppression discontinuation is needed.

Original languageEnglish (US)
Pages (from-to)970-977
Number of pages8
JournalHaematologica
Volume100
Issue number7
DOIs
StatePublished - Jul 6 2015
Externally publishedYes

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