Unrelated Donor Granulocyte Colony-Stimulating Factor-Mobilized Peripheral Blood Mononuclear Cell Transplantation After Nonmyeloablative Conditioning: The Effect of Postgrafting Mycophenolate Mofetil Dosing

Biol Blood Marrow Transplant. 2006 Apr;12(4):454-65. doi: 10.1016/j.bbmt.2005.12.030.

Abstract

We previously reported results in 71 patients with advanced hematologic malignancies given HLA-matched unrelated granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cell (G-PBMC) grafts after fludarabine 90 mg/m(2), 2 Gy of total body irradiation, and postgrafting mycophenolate mofetil (MMF) 15 mg/kg twice daily and cyclosporine 6.25 mg/kg twice daily orally. Graft rejection was 15%; the cumulative probability of acute graft-versus-host disease (GVHD) was 52%. According to MMF pharmacokinetic studies, which showed a short half-life of its active metabolite, mycophenolic acid, we increased MMF dosing from 15 mg/kg twice daily to 15 mg/kg 3 times daily to increase immunosuppression and reduce the incidence of both graft rejection and acute GVHD. Among 103 patients so treated, graft rejection occurred in 5%, whereas acute GVHD remained at 53%. Outcomes were compared with results of previous G-PBMC recipients given MMF twice daily. Infection rates were slightly higher with MMF 3 times daily than with MMF twice daily. Nevertheless, 2-year nonrelapse mortality and overall and progression-free survivals were similar for MMF 3-times-daily and twice-daily patients (19%, 58%, and 49% versus 20%, 48%, and 37%, respectively). Nonmyeloablative conditioning with postgrafting cyclosporine and MMF given 3 times daily allowed 95% durable engraftment of unrelated donor G-PBMC grafts.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cyclosporine / administration & dosage
  • Disease-Free Survival
  • Female
  • Graft Rejection / mortality
  • Graft Rejection / prevention & control
  • Graft Survival / drug effects
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / mortality
  • Granulocyte Colony-Stimulating Factor / administration & dosage*
  • Hematologic Neoplasms / complications
  • Hematologic Neoplasms / mortality*
  • Hematologic Neoplasms / therapy
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Male
  • Middle Aged
  • Mycophenolic Acid / administration & dosage
  • Mycophenolic Acid / analogs & derivatives*
  • Myeloablative Agonists / administration & dosage
  • Peripheral Blood Stem Cell Transplantation* / mortality
  • Recombinant Proteins
  • Remission Induction
  • Survival Rate
  • Transplantation Conditioning* / methods
  • Transplantation Conditioning* / mortality
  • Vidarabine / administration & dosage
  • Vidarabine / analogs & derivatives

Substances

  • Immunosuppressive Agents
  • Myeloablative Agonists
  • Recombinant Proteins
  • Granulocyte Colony-Stimulating Factor
  • Cyclosporine
  • Vidarabine
  • Mycophenolic Acid
  • fludarabine