Mycophenolate mofetil combined with tacrolimus and minidose methotrexate after unrelated donor bone marrow transplantation with reduced-intensity conditioning.
We evaluated the efficacy of a post-grafting immunosuppressive regimen consisting of tacrolimus, methotrexate, and mycophenolate mofetil (MMF) in 21 adults (median age, 55 years) with poor-risk hematologic malignancy who underwent unrelated bone marrow transplantation after fludarabine-based reduced-intensity conditioning (RIC). In combination with intravenous tacrolimus and minidose methotrexate (5 mg/m2 on days 1, 3, and 6), MMF was orally administered at 30 mg/kg daily in three divided doses between days 7 and 27. All patients achieved neutrophil recovery with donor-type chimerism at a median of 19 days (range, 13-35). Cumulative incidences of grades II-IV and III-IV acute graft-versus-host disease (GVHD) were 33% (95% CI, 15-53%) and 5% (95% CI, 0.3-20%), respectively. Five of 20 evaluable patients developed extensive chronic GVHD. Toxicities associated with the use of MMF were acceptable, although one patient experienced intractable GVHD immediately after the cessation of MMF. With a median follow-up of 24 months, overall survival at 3 years was 38% (95% CI, 14-63%). No late graft failure was observed. In conclusion, post-transplant MMF combined with tacrolimus and methotrexate was well tolerated and conferred stable donor cell engraftment, low risk of severe acute GVHD, and encouraging overall survival in unrelated donor marrow transplantation after RIC regimens.
Mizumoto
Chisaki
C
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawaharacho, Sakyo-ku, Kyoto, 606-8507, Japan.
Kanda
Junya
J
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawaharacho, Sakyo-ku, Kyoto, 606-8507, Japan.
Ichinohe
Tatsuo
T
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawaharacho, Sakyo-ku, Kyoto, 606-8507, Japan. nohe@kuhp.kyoto-u.ac.jp.
Ishikawa
Takayuki
T
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawaharacho, Sakyo-ku, Kyoto, 606-8507, Japan.
Matsui
Masashi
M
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawaharacho, Sakyo-ku, Kyoto, 606-8507, Japan.
Kadowaki
Norimitsu
N
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawaharacho, Sakyo-ku, Kyoto, 606-8507, Japan.
Kondo
Tadakazu
T
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawaharacho, Sakyo-ku, Kyoto, 606-8507, Japan.
Imada
Kazunori
K
Department of Hematology, Kokura Memorial Hospital, Kita-kyushu, Japan.
Hishizawa
Masakatsu
M
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawaharacho, Sakyo-ku, Kyoto, 606-8507, Japan.
Kawabata
Hiroshi
H
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawaharacho, Sakyo-ku, Kyoto, 606-8507, Japan.
Nishikori
Momoko
M
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawaharacho, Sakyo-ku, Kyoto, 606-8507, Japan.
Yamashita
Kouhei
K
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawaharacho, Sakyo-ku, Kyoto, 606-8507, Japan.
Takaori-Kondo
Akifumi
A
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawaharacho, Sakyo-ku, Kyoto, 606-8507, Japan.
Hori
Toshiyuki
T
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawaharacho, Sakyo-ku, Kyoto, 606-8507, Japan.
Uchiyama
Takashi
T
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawaharacho, Sakyo-ku, Kyoto, 606-8507, Japan.
D000208:Acute Disease; D000328:Adult; D000368:Aged; D016026:Bone Marrow Transplantation / Q000276:immunology; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D007938:Leukemia / Q000276:immunology / Q000601:surgery; D008727:Methotrexate / Q000009:adverse effects / Q000494:pharmacology*; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D015996:Survival Rate; D016559:Tacrolimus / Q000009:adverse effects / Q000494:pharmacology*; D019172:Transplantation Conditioning
D009173:Mycophenolic Acid; D016559:Tacrolimus; D008727:Methotrexate