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.
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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).
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: The cumulative incidence of transplantation-related morality. The overall transplantation-related mortality (TRM) rate was 0.31, with a median follow-up of 5 years. The TRM rate was 0.28 in the GVHD prophylaxis group, 0.30 in the acute GVHD treatment group, and 0.35 in the chronic GVHD treatment group. TRM was not significantly different among the GVHD prophylaxis and treatment groups. (PDF 426 KB)
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Kawashima, N., Iida, M., Suzuki, R. et al. Prophylaxis and treatment with mycophenolate mofetil in children with graft-versus-host disease undergoing allogeneic hematopoietic stem cell transplantation: a nationwide survey in Japan. Int J Hematol 109, 491–498 (2019). https://doi.org/10.1007/s12185-019-02601-5
- Mycophenolate mofetil
- Graft-versus-host disease