Prophylaxis and treatment with mycophenolate mofetil in children with graft-versus-host disease undergoing allogeneic hematopoietic stem cell transplantation: a nationwide survey in Japan
- 46 Downloads
We investigated the safety and efficacy of mycophenolate mofetil (MMF) in the prevention and treatment of graft-versus-host disease (GVHD) using a nationwide retrospective survey in Japanese children undergoing hematopoietic stem cell transplantation (HSCT). Overall, 141 children undergoing allogeneic HSCT for hematological malignancy (n = 84), non-malignancy (n = 52), and solid tumors (n = 5) were administered MMF orally (median 8 years; range 0–15 years; 89 males and 52 females) during 1995–2011. Donors were primarily unrelated and mismatched related. In the GVHD prophylaxis group, 29% and 8.6% of patients developed grade II–IV and III–IV GVHD, respectively. Of the 32 evaluable patients, 16% developed chronic [limited (n = 4) and extensive (n = 1)] GVHD. In the acute GVHD treatment group, 61% had decreased grade. In the chronic GVHD treatment group, 36% had improved symptoms. Combined immunosuppressant was reduced or discontinued in 61% patients. Major adverse events (AEs) were neutropenia (4.3%), infection (3.5%), thrombocytopenia (2.1%), myelosuppression (2.1%), and diarrhea (1.4%). MMF dosage was reduced in two children due to grade ≥ 3 AEs; two children died from infection. MMF thus may be well tolerated in children, and may be an effective option for prophylaxis and treatment of acute and chronic GVHD.
KeywordsMycophenolate mofetil Graft-versus-host disease Prophylaxis Treatment Pediatric
The authors would like to thank the following collaborating institutions for collecting patient data: Hokkaido University, Sapporo Medical University, Jichi Medical University, Narita Red Cross Hospital, Tokyo Metropolitan Children’s Medical Center, Tokyo Medical Dentinal University, Yokohama City University, Kanagawa Cancer Center, Tokai University, Niigata University, Kanazawa University, Shinshu University, Hamamatsu Medical University, Shizuoka Children’s Hospital, Kyoto University, Kinki University, Osaka University, Osaka City University, Osaka City General Hospital, Osaka Women’s and Children’s Hospital, Matsushita Memorial Hospital, Kobe University, Okayama University, Hiroshima University, Yamaguchi University, Kagawa Children’s Hospital, Kyushu University, and Kyushu Cancer Center (listed from north to south).
Compliance with ethical standards
Conflict of interest
There are no relevant conflicts of interest to disclose.
- 6.Miyamoto T, Takashima S, Kato K, Takase K, Yoshimoto G, Yoshida S, et al. Comparison of cyclosporine and tacrolimus combined with mycophenolate mofetil in prophylaxis for graft-versus-host disease after reduced-intensity umbilical cord blood transplantation. Int J Hematol. 2017;105:92–9.CrossRefGoogle Scholar
- 7.Nakane T, Nakamae H, Yamaguchi T, Kurosawa S, Okamura A, Hidaka M, et al. Use of mycophenolate mofetil and a calcineurin inhibitor in allogeneic hematopoietic stem-cell transplantation from HLA-matched siblings or unrelated volunteer donors: Japanese multicenter phase II trials. Int J Hematol. 2017;105:485–96.CrossRefGoogle Scholar
- 12.Niederwieser D, Maris M, Shizuru JA, Petersdorf E, Hegenbart U, Sandmaier BM, et al. Low-dose total body irradiation (TBI) and fludarabine followed by hematopoietic cell transplantation (HCT) from HLA-matched or mismatched unrelated donors and postgrafting immunosuppression with cyclosporine and mycophenolate mofetil (MMF) can induce durable complete chimerism and sustained remissions in patients with hematological diseases. Blood. 2003;101:1620–9.CrossRefGoogle Scholar
- 13.Osunkwo I, Bessmertny O, Harrison L, Cheung YK, Van de Ven C, del Toro G, et al. A pilot study of tacrolimus and mycophenolate mofetil graft-versus-host disease prophylaxis in childhood and adolescent allogeneic stem cell transplant recipients. Biol Blood Marrow Transplant. 2004;10:246–58.CrossRefGoogle Scholar
- 15.Bhatia M, Militano O, Jin Z, Figurski M, Shaw L, Moore V, et al. An age-dependent pharmacokinetic study of intravenous and oral mycophenolate mofetil in combination with tacrolimus for GVHD prophylaxis in pediatric allogeneic stem cell transplantation recipients. Biol Blood Marrow Transplant. 2010;16:333–43.CrossRefGoogle Scholar
- 24.Burroughs LM, Storb R, Leisenring WM, Pulsipher MA, Loken MR, Torgerson TR, et al. Intensive postgrafting immune suppression combined with nonmyeloablative conditioning for transplantation of HLA-identical hematopoietic cell grafts: results of a pilot study for treatment of primary immunodeficiency disorders. Bone Marrow Transplant. 2007;40:633–42.CrossRefGoogle Scholar
- 27.Militano O, Ozkaynak MF, Mehta B, van deVen C, Hamby C, Cairo MS. Mycophenolate mofetil administered every 8 hours in combination with tacrolimus is efficacious in the prophylaxis of acute graft versus host disease in childhood, adolescent, and young adult allogeneic stem cell transplantation recipients. Pediatr Blood Cancer. 2018;65:e27091.CrossRefGoogle Scholar