Mycophenolate mofetil for treatment of steroid‐refractory acute graft‐versus‐host disease after pediatric hematopoietic stem cell transplantation

Abstract

A standard treatment is yet to be established for steroid-refractory acute aGVHD following HSCT. The effects of MMF have not been well studied in children with aGVHD. We evaluated the effectiveness of oral MMF in 14 children with steroid-refractory aGVHD (grade II in one patient, grade III to IV in 13 patients). The median initial dose of MMF was 40 mg/kg/day (range, 30-74) and was increased by 1.5-2 times if manifestations of GVHD did not improve. Within four wk of treatment, seven patients (50%) achieved CR, and four (29%) had a PR. Within eight wk, 11 patients (79%) achieved CR without using additional agents. Overall, 12 patients are alive and in remission with a median follow-up of 35 months (range, 14-86). The median maximum dose of MMF was 60 mg/kg/day (range, 34-107). No fatal toxicity was observed, including MMF-related infections. MMF appears to be highly effective for steroid-refractory aGVHD when used at a higher dose than has been described previously. Larger studies and pharmacokinetic analysis are required to evaluate its efficacy and toxicity and find the optimal dose of MMF in children.

Ruxolitinib in steroid refractory graft-vs.-host disease: a case report

“…The weighted average 6-month survival from 25 retrospective studies or phase II trials was 49 % [ 2 ]. Among others, agents used included anti-thymocyte globulin, mycophenolate mofetil, anti-CD25 monoclonal antibody (basiliximab), anti-tumor necrosis factor alpha (infliximab and etanercept), anti-interleukin 2 receptor-alpha (inolimomab), anti-CD52 (alemtuzumab), pentostatin, m-Tor inhibitors and extracorporeal photoapheresis [ 5 – 13 ]. Since clinical trials in SR-GvHD are difficult to design given the heterogeneity of treatment policies, direct comparisons of different agents have not been possible.…”

Revisiting mycophenolate mofetil for steroid‐refractory acute graft‐versus‐host disease: Is higher dosing effective in children?

“…For example, it is possible that agents that previously failed to show benefit for initial GVHD treatment, such as MMF, may yet prove efficacious when tested only in high‐risk patients, especially if dosing is determined based on pharmacokinetics. If this is indeed the case, it could help reconcile the current contradictory results between the present positive study and the negative randomized controlled trial .…”

“…It is in this context that Inagaki et al. studied mycophenolate mofetil (MMF) as a treatment for steroid‐refractory acute GVHD as reported in this issue of Pediatric Transplantation .…”

“…Unfortunately, there are no proven treatments for steroid-refractory acute GVHD despite over 40 yr of clinical trials. It is in this context that Inagaki et al (6) studied mycophenolate mofetil (MMF) as a treatment for steroidrefractory acute GVHD as reported in this issue of Pediatric Transplantation.…”

Therapeutic targets and emerging treatment options in gastrointestinal acute graft-versus-host disease

“…[33] Encouraging results of MMF as primary treatment for GVHD were observed in several small series, [54,55] including multi-center, randomized, Phase II trial. [56] However, a randomized, placebo-controlled trial was closed to accrual early for futility.…”