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

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 ¼ 7) and unrelated donors (n ¼ 22). Tacrolimus was given orally from day À1 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 lg/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 ¼ 3) or extensive (n ¼ 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.

Pharmacokinetics-based optimal dose prediction of donor source-dependent response to mycophenolate mofetil in unrelated hematopoietic cell transplantation

“…2, 3, 4). The day on which to check the MPA C 2h after allo-SCT may not be necessarily rigid because AUCs on days 2, 9, and 16 were similar in each individual because of the relatively low intra-patient variability [15,24]. Although day 16 C 2h might be much too simplified to extract the highrisk population of relapse in CBT, this study raises the possibility of significantly improving allo-SCT outcome with an individualized MMF administration strategy by checking this simple parameter.…”

Recipient Pretransplant Inosine Monophosphate Dehydrogenase Activity in Nonmyeloablative Hematopoietic Cell Transplantation

“…(10, 30) Pharmacodynamic data suggest a relationship between clinical outcomes and MPA plasma exposure (as reviewed in McDermott et al (31), and some HCT centers personalize MMF doses to a target MPA exposure. (32) We recently observed that low total MPA plasma exposure was associated with increased grades 3–4 acute GVHD and increased non-relapse mortality in nonmyeloabative HCT recipients with an unreIated donor graft. In patients receiving a related donor graft after nonmyeloablative conditioning, however, total MPA plasma exposure was not associated with clinical outcomes and additional biomarkers, such as recipient pretransplant IMPDH activity, are of interest.…”

Graft-versus-host disease after allogeneic hematopoietic stem cell transplantation in children

“…Блокада пролиферации Т-клеток достигается назначе-нием метотрексата и микофенолата, что используется для успешной профилактики РТПХ, особенно при раннем назначении препарата [13]. Токсичность микофенолата значительно ниже, чем метотрексата, поэтому при его назначении реже регистрируется лекарственный мукозит [14].…”