Area-under-the-Curve-Based Mycophenolate Mofetil Dosage May Contribute to Decrease the Incidence of Graft-versus-Host...

Acute graft-versus-host disease (GvHD) remains the second leading cause of death, after disease relapse, in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). The medical records of 112 pediatric patients who underwent allo-HSCT from matched unrelated and haploidentical donors were analyzed. Patients were divided into two groups, according to the GvHD prophylactic regimen used. In the control group, GvHD prophylaxis consisted of cyclosporine A (CsA) and methotrexate (MTX) or CsA and mycophenolate mofetil (MMF) at a standard daily dose of 30 mg/kg. All subjects in the study group received tacrolimus (FK506) and MMF. In this group, MMF was subjected to therapeutic drug monitoring (TDM) through mycophenolic acid (MPA) area under the curve AUC_0-12. We found a statistically significant difference in both overall acute GvHD (p < 0.0001) and overall chronic GvHD (p < 0.05) incidence between the study and the control group. The initial daily MMF dose and the age at transplant in the study group proved to be inversely correlated (r = -0.523, p < 0.0001). The children under six years of age required a significantly higher daily MMF dose (p < 0.008). This study showed that pharmacological monitoring of MPA AUC_0-12 concentration allowed a reduction in the incidence of acute and chronic GvHD. MMF showed age-dependent pharmacokinetics due to greater drug clearance in younger children.