Annals of Hematology

, Volume 98, Issue 11, pp 2579–2591 | Cite as

Comparison of calcineurin inhibitors in combination with conventional methotrexate, reduced methotrexate, or mycophenolate mofetil for prophylaxis of graft-versus-host disease after umbilical cord blood transplantation

  • Shuro Yoshida
  • Yuju Ohno
  • Koji Nagafuji
  • Goichi Yoshimoto
  • Takeshi Sugio
  • Tomohiko Kamimura
  • Takanori Ohta
  • Ken Takase
  • Hideho Henzan
  • Tsuyoshi Muta
  • Hiromi Iwasaki
  • Ryosuke Ogawa
  • Tetsuya Eto
  • Koichi Akashi
  • Toshihiro MiyamotoEmail author
Original Article


Umbilical cord blood transplantation (UCBT) is a curative treatment for hematological malignancies. However, appropriate prophylaxis against graft-versus-host disease (GVHD), aimed at obtaining rapid and stable engraftment and avoiding toxicity, remains controversial in UCBT. We retrospectively compared outcomes in 409 patients who received calcineurin inhibitors (CIs) plus conventional-dose methotrexate (conv-MTX/CIs, n = 77; methotrexate, 10 mg/m2 on day 1, 7 mg/m2 on days 3 and 6) with those who received CIs plus reduced-dose methotrexate (reduced-MTX/CIs, n = 209; methotrexate, 5 mg/m2 or 5 mg/body on days 1, 3, and 6) or CIs with mycophenolate mofetil (MMF/CIs, n = 123) for GVHD prophylaxis after UCBT. The cumulative incidence of neutrophil engraftment was significantly higher in the reduced-MTX/CI (82.3%) and MMF/CI (86.6%) groups than the conv-MTX/CI (71.4%) group (p = 0.014), although there were no differences in platelet recovery or infectious complications among the three groups. The incidence and severity of GVHD were comparable among the three groups, and there were no significant differences in transplantation-related mortality among the three groups. In conclusion, GVHD prophylaxis with reduced-dose methotrexate and MMF was closely associated with high incidence of neutrophil engraftment without an effect on the incidence and severity of GVHD, which was compared to GVHD prophylaxis with conventional-dose methotrexate.


GVHD Prophylaxis Reduced-dose Methotrexate MMF UCBT 



We thank the medical and nursing staff working on the Fukuoka Blood and Marrow Transplantation Group for providing patients’ information. This work was supported, in part, by a Grant-in-Aid for Scientific Research to T.M. (No. 16H05340 to T.M.)

Compliance with ethical standards

The ethics committees of the participating institutions approved this study (Kyushu University Graduate School and Faculty of Medicine; approval nos. 23027-1 and 23027-2).

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Shuro Yoshida
    • 1
  • Yuju Ohno
    • 2
  • Koji Nagafuji
    • 3
  • Goichi Yoshimoto
    • 4
  • Takeshi Sugio
    • 4
  • Tomohiko Kamimura
    • 5
  • Takanori Ohta
    • 2
  • Ken Takase
    • 6
  • Hideho Henzan
    • 1
  • Tsuyoshi Muta
    • 7
  • Hiromi Iwasaki
    • 6
  • Ryosuke Ogawa
    • 7
  • Tetsuya Eto
    • 1
  • Koichi Akashi
    • 4
  • Toshihiro Miyamoto
    • 4
    Email author
  1. 1.Department of Hematology, |Hamanomachi HospitalFukuokaJapan
  2. 2.Department of Internal MedicineKitakyushu Municipal Medical CenterKitakyushuJapan
  3. 3.Division of Hematology/OncologyKurume University School of MedicineKurumeJapan
  4. 4.Department of Medicine and Biosystemic Science, Graduate School of Medical ScienceKyushu UniversityFukuokaJapan
  5. 5.Department of HematologyHarasanshin HospitalFukuokaJapan
  6. 6.Department of HematologyNational Kyushu Medical CenterFukuokaJapan
  7. 7.Department of HematologyJapan Community Health Care Organization Kyushu HospitalKitakyushuJapan

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