title: A phase II study of sirolimus, tacrolimus and rabbit anti-thymocyte globulin as GVHD prophylaxis after unrelated-donor PBSC transplant.
abstract: We report on a prospective phase II trial of 32 patients who underwent unrelated-donor hematopoietic cell transplantation, with a tacrolimus, sirolimus and rabbit anti-thymoctye globulin GVHD prophylactic regimen. The primary study endpoint was incidence of grades II-IV acute (aGVHD), with 80% power to detect a 30% decrease compared with institutional historical controls. Median age at transplant was 60 (19-71). In total, 23 patients (72%) received reduced-intensity conditioning, whereas the remainder received full-intensity regimens. Median follow-up for surviving patients was 35 months (range: 21-49). The cumulative incidence of aGVHD was 37.3%, and the 2-year cumulative incidence of chronic GVHD was 63%. We observed thrombotic microangiopathy in seven patients (21.8%), one of whom also developed sinusoidal obstructive syndrome (SOS). Four of the 32 patients (12.5%) failed to engraft, and 3 of these 4 died. As a result, enrollment to this trial was closed before the targeted accrual of 60 patients. Two-year OS was 65.5% and EFS was 61.3%. Two-year cumulative incidence of relapse was 12.5% and non-relapse mortality (NRM) was 15.6%. NRM and aGVHD rates were lower than historical rates. However, the unexpectedly high incidence of graft failure requires caution in the design of future studies with this regimen.
authors.affiliation: Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA 91010, USA. skhaled@coh.org
authors.forename: S K
authors.initials: SK
authors.lastname: Khaled
authors.forename: J
authors.initials: J
authors.lastname: Palmer
authors.forename: T
authors.initials: T
authors.lastname: Stiller
authors.forename: D
authors.initials: D
authors.lastname: Senitzer
authors.forename: R
authors.initials: R
authors.lastname: Maegawa
authors.forename: R
authors.initials: R
authors.lastname: Rodriguez
authors.forename: P M
authors.initials: PM
authors.lastname: Parker
authors.forename: A
authors.initials: A
authors.lastname: Nademanee
authors.forename: J L
authors.initials: JL
authors.lastname: Cai
authors.forename: D S
authors.initials: DS
authors.lastname: Snyder
authors.forename: C
authors.initials: C
authors.lastname: Karanes
authors.forename: E
authors.initials: E
authors.lastname: Osorio
authors.forename: S H
authors.initials: SH
authors.lastname: Thomas
authors.forename: S J
authors.initials: SJ
authors.lastname: Forman
authors.forename: R
authors.initials: R
authors.lastname: Nakamura
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods*; D011446:Prospective Studies; D011817:Rabbits; D020123:Sirolimus / Q000627:therapeutic use*; D016559:Tacrolimus / Q000627:therapeutic use*; D061349:Unrelated Donors; D055815:Young Adult
chemical_list: D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D020123:Sirolimus; D016559:Tacrolimus