Mycophenolate mofetil combined with tacrolimus and minidose methotrexate after unrelated donor bone marrow transplantation with reduced-intensity conditioning

Int J Hematol. 2009 May;89(4):538-545. doi: 10.1007/s12185-009-0306-5. Epub 2009 Apr 11.

Abstract

We evaluated the efficacy of a post-grafting immunosuppressive regimen consisting of tacrolimus, methotrexate, and mycophenolate mofetil (MMF) in 21 adults (median age, 55 years) with poor-risk hematologic malignancy who underwent unrelated bone marrow transplantation after fludarabine-based reduced-intensity conditioning (RIC). In combination with intravenous tacrolimus and minidose methotrexate (5 mg/m2 on days 1, 3, and 6), MMF was orally administered at 30 mg/kg daily in three divided doses between days 7 and 27. All patients achieved neutrophil recovery with donor-type chimerism at a median of 19 days (range, 13-35). Cumulative incidences of grades II-IV and III-IV acute graft-versus-host disease (GVHD) were 33% (95% CI, 15-53%) and 5% (95% CI, 0.3-20%), respectively. Five of 20 evaluable patients developed extensive chronic GVHD. Toxicities associated with the use of MMF were acceptable, although one patient experienced intractable GVHD immediately after the cessation of MMF. With a median follow-up of 24 months, overall survival at 3 years was 38% (95% CI, 14-63%). No late graft failure was observed. In conclusion, post-transplant MMF combined with tacrolimus and methotrexate was well tolerated and conferred stable donor cell engraftment, low risk of severe acute GVHD, and encouraging overall survival in unrelated donor marrow transplantation after RIC regimens.

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Bone Marrow Transplantation* / immunology
  • Chronic Disease
  • Dose-Response Relationship, Drug
  • Graft vs Host Disease / drug therapy
  • Graft vs Host Disease / immunology
  • Humans
  • Leukemia / immunology
  • Leukemia / surgery
  • Methotrexate / adverse effects
  • Methotrexate / pharmacology*
  • Middle Aged
  • Mycophenolic Acid / adverse effects
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / pharmacology
  • Survival Rate
  • Tacrolimus / adverse effects
  • Tacrolimus / pharmacology*
  • Transplantation Conditioning*

Substances

  • Mycophenolic Acid
  • Tacrolimus
  • Methotrexate