title: Sirolimus and mycophenolate mofetil as GVHD prophylaxis in myeloablative, matched-related donor hematopoietic cell transplantation.
abstract: We investigated sirolimus and mycophenolate mofetil (MMF) as GVHD prophylaxis in patients with advanced hematological malignancies receiving myeloablative hematopoietic cell transplantation (HCT) from HLA-identical sibling donors. On the basis of pre-study stopping rules, the trial was closed to accrual after enrollment of 11 adult patients. In all, 7 of the 11 patients received BU-containing preparative regimens. Sirolimus was discontinued in three patients because of the toxicity-related events of severe sinusoidal obstructive syndrome, portal vein thrombosis, altered mental status and in one patient because of the risk of poor wound healing. In all, 6 of the 11 patients developed grade II-IV acute GVHD (AGVHD) a median of 15.5 days post HCT. Two of three patients with grade IV AGVHD had sirolimus discontinued by 9 days post HCT. All patients responded to AGVHD therapy without GVHD-related deaths. There were two non-relapse- and two relapse-related deaths. At a median follow-up of 38 months (2-47 months), 7 of 11 patients were alive without disease. MMF and sirolimus GVHD prophylaxis did not reduce the risk of AGVHD, however, there were no GVHD-related deaths. The severe toxicities in the patients receiving the BU-containing preparative regimens limited the continued use of sirolimus and MMF for the prevention of AGVHD.
authors.affiliation: Department of Medicine, Stanford University, Stanford, CA, USA. laura.johnston@stanford.edu
authors.forename: L
authors.initials: L
authors.lastname: Johnston
authors.forename: M
authors.initials: M
authors.lastname: Florek
authors.forename: R
authors.initials: R
authors.lastname: Armstrong
authors.forename: J S
authors.initials: JS
authors.lastname: McCune
authors.forename: S
authors.initials: S
authors.lastname: Arai
authors.forename: J
authors.initials: J
authors.lastname: Brown
authors.forename: G
authors.initials: G
authors.lastname: Laport
authors.forename: R
authors.initials: R
authors.lastname: Lowsky
authors.forename: D
authors.initials: D
authors.lastname: Miklos
authors.forename: J
authors.initials: J
authors.lastname: Shizuru
authors.forename: K
authors.initials: K
authors.lastname: Sheehan
authors.forename: P
authors.initials: P
authors.lastname: Lavori
authors.forename: R
authors.initials: R
authors.lastname: Negrin
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000401:mortality / Q000517:prevention & control*; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D020123:Sirolimus / Q000008:administration & dosage*; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D061349:Unrelated Donors
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D020123:Sirolimus