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 Miyamoto

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)2579-2591
Number of pages13
JournalAnnals of Hematology
Volume98
Issue number11
DOIs
Publication statusPublished - Nov 1 2019

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Mycophenolic Acid
Graft vs Host Disease
Fetal Blood
Methotrexate
Transplantation
Incidence
Neutrophils
Calcineurin Inhibitors
Hematologic Neoplasms
Blood Platelets

All Science Journal Classification (ASJC) codes

  • Hematology

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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. / Yoshida, Shuro; Ohno, Yuju; Nagafuji, Koji; Yoshimoto, Goichi; Sugio, Takeshi; Kamimura, Tomohiko; Ohta, Takanori; Takase, Ken; Henzan, Hideho; Muta, Tsuyoshi; Iwasaki, Hiromi; Ogawa, Ryosuke; Eto, Tetsuya; Akashi, Koichi; Miyamoto, Toshihiro.

In: Annals of Hematology, Vol. 98, No. 11, 01.11.2019, p. 2579-2591.

Research output: Contribution to journalArticle

Yoshida, Shuro ; Ohno, Yuju ; Nagafuji, Koji ; Yoshimoto, Goichi ; Sugio, Takeshi ; Kamimura, Tomohiko ; Ohta, Takanori ; Takase, Ken ; Henzan, Hideho ; Muta, Tsuyoshi ; Iwasaki, Hiromi ; Ogawa, Ryosuke ; Eto, Tetsuya ; Akashi, Koichi ; Miyamoto, Toshihiro. / 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. In: Annals of Hematology. 2019 ; Vol. 98, No. 11. pp. 2579-2591.
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abstract = "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.",
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AU - Yoshida, Shuro

AU - Ohno, Yuju

AU - Nagafuji, Koji

AU - Yoshimoto, Goichi

AU - Sugio, Takeshi

AU - Kamimura, Tomohiko

AU - Ohta, Takanori

AU - Takase, Ken

AU - Henzan, Hideho

AU - Muta, Tsuyoshi

AU - Iwasaki, Hiromi

AU - Ogawa, Ryosuke

AU - Eto, Tetsuya

AU - Akashi, Koichi

AU - Miyamoto, Toshihiro

PY - 2019/11/1

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N2 - 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.

AB - 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.

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