title: A randomized phase II trial comparing tacrolimus and mycophenolate mofetil to tacrolimus and methotrexate for acute graft-versus-host disease prophylaxis.
abstract: Tacrolimus (Tac) plus methotrexate (MTX) is a standard regimen for graft-versus-host disease (GVHD) prophylaxis. Mycophenolate mofetil (MMF) is sometimes used instead of MTX to minimize toxicity, despite the lack of controlled studies demonstrating efficacy. We conducted a single-center, randomized phase II trial comparing Tac + MMF to Tac + MTX. Intent-to-treat analyses included 42 patients randomized to Tac + MMF and 47 to Tac + MTX. Patient characteristics were not different between the study arms. Patients in the Tac + MMF arm were less likely to experience severe mucositis, require narcotic analgesia and parenteral nutrition, and had earlier hospital discharge. The Tac + MMF arm had the same time to neutrophil recovery, but earlier platelet recovery. The cumulative incidence of grade II-IV acute GVHD (aGVHD) at 100 days was similar (P = .8), but grade III-IV aGVHD was higher in the Tac + MMF arm (19% versus 4%; P = .03); this was predominantly seen in unrelated donor transplants (26% versus 4%; P = .04), and less in related donor transplants (11% versus 4%; P = n.s.). Moderate or severe chronic GVHD was similar (P = .71). There were no significant differences between the arms in relapse, nonrelapse mortality, or overall and relapse-free survivals. MMF was associated with less early toxicity than MTX but was not as effective in preventing severe aGVHD, especially in unrelated donor transplants.
authors.affiliation: Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. Janelle.perkins@moffitt.org
authors.forename: Janelle
authors.initials: J
authors.lastname: Perkins
authors.forename: Teresa
authors.initials: T
authors.lastname: Field
authors.forename: Jongphil
authors.initials: J
authors.lastname: Kim
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Kharfan-Dabaja
authors.forename: Hugo
authors.initials: H
authors.lastname: Fernandez
authors.forename: Ernesto
authors.initials: E
authors.lastname: Ayala
authors.forename: Lia
authors.initials: L
authors.lastname: Perez
authors.forename: Mian
authors.initials: M
authors.lastname: Xu
authors.forename: Melissa
authors.initials: M
authors.lastname: Alsina
authors.forename: Leonel
authors.initials: L
authors.lastname: Ochoa
authors.forename: Daniel
authors.initials: D
authors.lastname: Sullivan
authors.forename: William
authors.initials: W
authors.lastname: Janssen
authors.forename: Claudio
authors.initials: C
authors.lastname: Anasetti
mesh_terms: D000328:Adult; D000368:Aged; D004359:Drug Therapy, Combination; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015994:Incidence; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011379:Prognosis; D033581:Stem Cell Transplantation / Q000379:methods*; D016559:Tacrolimus / Q000627:therapeutic use*; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D016559:Tacrolimus; D008727:Methotrexate