Targeting mycophenolate mofetil for graft-versus-host disease prophylaxis after allogeneic blood stem cell transplantation

Bone Marrow Transplant. 2008 Jul;42(2):113-20. doi: 10.1038/bmt.2008.85. Epub 2008 Mar 24.

Abstract

As low trough levels of mycophenolic acid (MPA) have been measured in recipients of allo-SCTs, we performed a pilot study targeting mycophenolate mofetil (MMF) doses according to the MPA area under the concentration (AUC) levels. Twenty-nine patients were transplanted from matched sibling (n=7) and unrelated donors (n=22). Tacrolimus was given orally from day -1 to achieve trough blood levels of 5-10 ng/ml. MMF was started on day 0 at 1500 mg intravenously b.i.d. AUC measurements of MPA by HPLC were scheduled on days 3, 7 and 11 after transplantation. The MMF dose was modified to achieve an MPA AUC of 35-60 microg/ml/h. With the respective adjustments 66 and 75% surpassed the lower AUC target on days 7 and 11, respectively. The cumulative incidence of grade III-IV acute GVHD was 28% (8/29). Eight out of 24 evaluable patients (33%) suffer from limited (n=3) or extensive (n=5) chronic GVHD. Overall, the results of this study suggest that targeting of MPA exposure is feasible early after transplantation. A simplified MMF targeting strategy based on MPA C(max) or C(2h) levels seems to be warranted in future trials involving more patients at later time points in the outpatient setting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Area Under Curve
  • Drug Monitoring
  • Female
  • Graft vs Host Disease / prevention & control*
  • Hematologic Neoplasms / mortality
  • Hematologic Neoplasms / therapy
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Male
  • Middle Aged
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / pharmacokinetics
  • Mycophenolic Acid / therapeutic use
  • Transplantation, Homologous

Substances

  • Immunosuppressive Agents
  • Mycophenolic Acid