Drug monitoring for mycophenolic acid in graft-vs-host disease prophylaxis in cord blood transplantation

Br J Clin Pharmacol. 2020 Dec;86(12):2464-2472. doi: 10.1111/bcp.14354. Epub 2020 May 30.

Abstract

Aims: We performed the retrospective analysis to clarify the significance of drug monitoring for mycophenolic acid (MPA), the active form of mycophenolate mofetil (MMF), in prophylaxis for graft-vs-host disease (GVHD) in cord blood transplantation.

Methods: We retrospectively analysed the data of 46 patients who underwent first cord blood transplantation and received GVHD prophylaxis with tacrolimus plus MMF. MPA levels were measured on days 7 and 21, and 24-hour areas under the curve (AUC0-24 ) were estimated.

Results: The engraftment and 3-year overall survival rates of all patients were 94% and 78%, respectively. The cumulative incidence of sepsis before engraftment was higher in patients with AUC0-24 on day 7 of >60 μg h/mL than in other patients (33 vs 6%, P = .02). The cumulative incidence of grade II-IV acute GVHD was higher in patients with AUC0-24 on day 21 of ≤30 μg h/mL than in other patients (80 vs 50%, P = .04). The cumulative incidence of human herpesvirus 6 reactivation was higher in patients with AUC0-24 on day 21 of ≤48 μg h/mL (median) than in other patients (50 vs 19%, P = .03).

Conclusion: Blood level of MPA was associated with risk of acute GVHD and infection. A prospective trial evaluating the benefit of personalized MMF dosing using MPA levels is needed.

Keywords: cord blood transplantation; drug monitoring; mycophenolic acid.

MeSH terms

  • Adult
  • Antibiotics, Antineoplastic* / therapeutic use
  • Cord Blood Stem Cell Transplantation* / adverse effects
  • Drug Monitoring*
  • Female
  • Graft vs Host Disease* / epidemiology
  • Graft vs Host Disease* / prevention & control
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Immunosuppressive Agents
  • Male
  • Mycophenolic Acid* / therapeutic use
  • Prospective Studies
  • Retrospective Studies

Substances

  • Antibiotics, Antineoplastic
  • Immunosuppressive Agents
  • Mycophenolic Acid