title: 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.
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.
authors.affiliation: The Division of Hematology and Bone Marrow Transplantation, Tel-Aviv University, Chaim Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Ronit
authors.initials: R
authors.lastname: Yerushalmi
authors.affiliation: The Division of Hematology and Bone Marrow Transplantation, Tel-Aviv University, Chaim Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Noga
authors.initials: N
authors.lastname: Shem-Tov
authors.affiliation: The Division of Hematology and Bone Marrow Transplantation, Tel-Aviv University, Chaim Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Ivetta
authors.initials: I
authors.lastname: Danylesko
authors.affiliation: The Division of Hematology and Bone Marrow Transplantation, Tel-Aviv University, Chaim Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Roni
authors.identifier: http://orcid.org/0000-0001-9827-8032
authors.initials: R
authors.lastname: Shouval
authors.affiliation: The Division of Hematology and Bone Marrow Transplantation, Tel-Aviv University, Chaim Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
authors.affiliation: The Division of Hematology and Bone Marrow Transplantation, Tel-Aviv University, Chaim Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Avichai
authors.identifier: http://orcid.org/0000-0001-8782-6160
authors.initials: A
authors.lastname: Shimoni
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic; D016572:Cyclosporine; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008727:Methotrexate; D008875:Middle Aged; D009026:Mortality; D009173:Mycophenolic Acid; D009504:Neutrophils / Q000166:cytology; D011292:Premedication / Q000379:methods; D012189:Retrospective Studies; D033581:Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D061349:Unrelated Donors; D055815:Young Adult
chemical_list: D000903:Antibiotics, Antineoplastic; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D008727:Methotrexate