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

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 mu g/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.