The combination of cyclosporine and mycophenolate mofetil is less effective than cyclosporine and methotrexate in the prevention of acute graft-versus host disease after stem-cell transplantation from unrelated donors

Ronit Yerushalmi, Noga Shem-Tov, Ivetta Danylesko, Roni Shouval, Arnon Nagler, Avichai Shimoni

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Acute graft-versus-host disease (GVHD) is the major treatment-related complication after stem-cell transplantation (SCT) from unrelated-donors. Several GVHD prophylaxis regimens have been explored, but no regimen has shown superiority. We analyzed transplantation outcomes in 472 consecutive unrelated-donor SCT recipients, using cyclosporine/methotrexate (MTX, n = 314) or cyclosporine/mycophenolate-mofetil (MMF, n = 158) for GVHD prophylaxis. Neutrophil engraftment was faster after MMF, days 11 and 14, respectively (P =.001). Acute GVHD grade II-IV and III-IV occurred in 47% and 28% after MMF compared to 27% and 12% after MTX, respectively (P <.001). Nonrelapse mortality (NRM) was 44% and 24%, respectively (P <.001). Death associated with GVHD occurred in 25% and 8% (P <.0001), while other NRM causes occurred in 19% and 16%, respectively (P =.39). Relapse mortality was similar. Overall survival was better after MTX, 40% and 29%, respectively (P =.006). However, this difference had only borderline significance when adjusting for differences in patient characteristics (HR, 1.3, P =.08). To minimize potential selection bias we analyzed outcomes on the basis of an intention-to-treat like analysis. During the years 2008-2009, the leading GVHD prophylaxis regimen for unrelated-donor SCT included MMF (89% of transplants). During the other periods, MTX was used predominantly (82% of transplants). The two periods were otherwise well-matched. Acute GVHD occurred more often in 2008-2009. Death associated with GVHD occurred more often, while other NRM causes occurred less often resulting in similar NRM and overall survival. In conclusion, cyclosporine/MMF is associated with faster engraftment and possibly with less organ toxicity than cyclosporine/MTX. However, it is associated with increased rates of acute GVHD and GVHD-associated deaths.

Original languageEnglish
Pages (from-to)259-268
Number of pages10
JournalAmerican Journal of Hematology
Volume92
Issue number3
DOIs
StatePublished - 1 Mar 2017
Externally publishedYes

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© 2017 Wiley Periodicals, Inc.

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