Reduced-dose methotrexate in combination with tacrolimus was associated with rapid engraftment and recovery from oral mucositis without affecting the incidence of GVHD

Toshihiro Matsukawa, Daigo Hashimoto, Junichi Sugita, Seitarou Nakazawa, Takae Matsushita, Haruhiko Kashiwazaki, Hideki Goto, Masahiro Onozawa, Kaoru Kahata, Katsuya Fujimoto, Tomoyuki Endo, Takeshi Kondo, Satoshi Hashino, Yutaka Yamazaki, Takanori Teshima

Research output: Contribution to journalArticle

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Abstract

Allogeneic hematopoietic stem cell transplantation is a curable treatment for hematological diseases. Graft-versus-host disease (GVHD) causes morbidity and mortality after HSCT. Methotrexate (MTX) is used for GVHD prophylaxis, but its appropriate dose remains unclear. In the present study, we compared the efficacy and toxicity of 15-10-10 MTX (day +1: 15 mg/m2; days +3 and +6: 10 mg/m2) with 10-7-7 MTX (day +1: 10 mg/m2; day +3 and +6: 7 mg/m2) in combination with tacrolimus. The cumulative incidence rates of grades II–IV acute GVHD, grades III–IV acute GVHD and chronic GVHD in the 15-10-10 MTX and 10-7-7 MTX groups did not differ to a statistically significant extent. The median time for neutrophil engraftment in the 15-10-10 MTX group was 16 days (range, 11–31 days), while that in the 10-7-7 group was 15 days (range, 12–19 days) (P = 0.024). Moreover, the median time for platelet recovery was significantly shorter in the 10-7-7 MTX group (22 days; range, 13–49 days) than that in the 15-10-10 MTX group (27 days; range, 9–405 days) (P = 0.027). The duration of oral mucositis was significantly shorter in the patients who received a reduced dose of MTX (median, 4.5 vs 13.0 days; P = 0.013). In conclusion, GVHD prophylaxis with a reduced dose of MTX was associated with earlier engraftment and earlier recovery from mucositis in comparison to a standard dose of MTX, without affecting the incidence of GVHD.

Original languageEnglish
Pages (from-to)117-124
Number of pages8
JournalInternational journal of hematology
Volume104
Issue number1
DOIs
Publication statusPublished - Jul 1 2016

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Stomatitis
Tacrolimus
Graft vs Host Disease
Methotrexate
Incidence
Mucositis
Hematologic Diseases
Hematopoietic Stem Cell Transplantation
Neutrophils
Blood Platelets

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

Reduced-dose methotrexate in combination with tacrolimus was associated with rapid engraftment and recovery from oral mucositis without affecting the incidence of GVHD. / Matsukawa, Toshihiro; Hashimoto, Daigo; Sugita, Junichi; Nakazawa, Seitarou; Matsushita, Takae; Kashiwazaki, Haruhiko; Goto, Hideki; Onozawa, Masahiro; Kahata, Kaoru; Fujimoto, Katsuya; Endo, Tomoyuki; Kondo, Takeshi; Hashino, Satoshi; Yamazaki, Yutaka; Teshima, Takanori.

In: International journal of hematology, Vol. 104, No. 1, 01.07.2016, p. 117-124.

Research output: Contribution to journalArticle

Matsukawa, T, Hashimoto, D, Sugita, J, Nakazawa, S, Matsushita, T, Kashiwazaki, H, Goto, H, Onozawa, M, Kahata, K, Fujimoto, K, Endo, T, Kondo, T, Hashino, S, Yamazaki, Y & Teshima, T 2016, 'Reduced-dose methotrexate in combination with tacrolimus was associated with rapid engraftment and recovery from oral mucositis without affecting the incidence of GVHD', International journal of hematology, vol. 104, no. 1, pp. 117-124. https://doi.org/10.1007/s12185-016-1996-0
Matsukawa, Toshihiro ; Hashimoto, Daigo ; Sugita, Junichi ; Nakazawa, Seitarou ; Matsushita, Takae ; Kashiwazaki, Haruhiko ; Goto, Hideki ; Onozawa, Masahiro ; Kahata, Kaoru ; Fujimoto, Katsuya ; Endo, Tomoyuki ; Kondo, Takeshi ; Hashino, Satoshi ; Yamazaki, Yutaka ; Teshima, Takanori. / Reduced-dose methotrexate in combination with tacrolimus was associated with rapid engraftment and recovery from oral mucositis without affecting the incidence of GVHD. In: International journal of hematology. 2016 ; Vol. 104, No. 1. pp. 117-124.
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abstract = "Allogeneic hematopoietic stem cell transplantation is a curable treatment for hematological diseases. Graft-versus-host disease (GVHD) causes morbidity and mortality after HSCT. Methotrexate (MTX) is used for GVHD prophylaxis, but its appropriate dose remains unclear. In the present study, we compared the efficacy and toxicity of 15-10-10 MTX (day +1: 15 mg/m2; days +3 and +6: 10 mg/m2) with 10-7-7 MTX (day +1: 10 mg/m2; day +3 and +6: 7 mg/m2) in combination with tacrolimus. The cumulative incidence rates of grades II–IV acute GVHD, grades III–IV acute GVHD and chronic GVHD in the 15-10-10 MTX and 10-7-7 MTX groups did not differ to a statistically significant extent. The median time for neutrophil engraftment in the 15-10-10 MTX group was 16 days (range, 11–31 days), while that in the 10-7-7 group was 15 days (range, 12–19 days) (P = 0.024). Moreover, the median time for platelet recovery was significantly shorter in the 10-7-7 MTX group (22 days; range, 13–49 days) than that in the 15-10-10 MTX group (27 days; range, 9–405 days) (P = 0.027). The duration of oral mucositis was significantly shorter in the patients who received a reduced dose of MTX (median, 4.5 vs 13.0 days; P = 0.013). In conclusion, GVHD prophylaxis with a reduced dose of MTX was associated with earlier engraftment and earlier recovery from mucositis in comparison to a standard dose of MTX, without affecting the incidence of GVHD.",
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AU - Sugita, Junichi

AU - Nakazawa, Seitarou

AU - Matsushita, Takae

AU - Kashiwazaki, Haruhiko

AU - Goto, Hideki

AU - Onozawa, Masahiro

AU - Kahata, Kaoru

AU - Fujimoto, Katsuya

AU - Endo, Tomoyuki

AU - Kondo, Takeshi

AU - Hashino, Satoshi

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