Reduced-dose methotrexate in combination with tacrolimus was associated with rapid engraftment and recovery from oral mucositis without affecting the incidence of GVHD.
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/m(2); days +3 and +6: 10 mg/m(2)) with 10-7-7 MTX (day +1: 10 mg/m(2); day +3 and +6: 7 mg/m(2)) 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.
Department of Hematology, Hokkaido University Graduate School of Medicine, N15 W7, Kita-Ku, Sapporo, 060-8638, Japan. t-matsukawa@med.hokudai.ac.jp.
Toshihiro
T
Matsukawa
Department of Hematology, Hokkaido University Graduate School of Medicine, N15 W7, Kita-Ku, Sapporo, 060-8638, Japan.
Daigo
D
Hashimoto
Department of Hematology, Hokkaido University Graduate School of Medicine, N15 W7, Kita-Ku, Sapporo, 060-8638, Japan.
Junichi
J
Sugita
Gerodontology, Department of Oral Health Science, Graduate School of Dental Medicine, Hokkaido University, N13 W7, Kita-Ku, Sapporo, 060-8586, Japan.
Seitarou
S
Nakazawa
Gerodontology, Department of Oral Health Science, Graduate School of Dental Medicine, Hokkaido University, N13 W7, Kita-Ku, Sapporo, 060-8586, Japan.
Takae
T
Matsushita
Gerodontology, Department of Oral Health Science, Graduate School of Dental Medicine, Hokkaido University, N13 W7, Kita-Ku, Sapporo, 060-8586, Japan.
Haruhiko
H
Kashiwazaki
Department of Hematology, Hokkaido University Graduate School of Medicine, N15 W7, Kita-Ku, Sapporo, 060-8638, Japan.
Hideki
H
Goto
Department of Hematology, Hokkaido University Graduate School of Medicine, N15 W7, Kita-Ku, Sapporo, 060-8638, Japan.
Masahiro
M
Onozawa
Department of Hematology, Hokkaido University Graduate School of Medicine, N15 W7, Kita-Ku, Sapporo, 060-8638, Japan.
Kaoru
K
Kahata
Department of Hematology, Hokkaido University Graduate School of Medicine, N15 W7, Kita-Ku, Sapporo, 060-8638, Japan.
Katsuya
K
Fujimoto
Department of Hematology, Hokkaido University Graduate School of Medicine, N15 W7, Kita-Ku, Sapporo, 060-8638, Japan.
Tomoyuki
T
Endo
Department of Hematology, Hokkaido University Graduate School of Medicine, N15 W7, Kita-Ku, Sapporo, 060-8638, Japan.
Takeshi
T
Kondo
Health Care Center, Hokkaido University, N16 W7, Kita-Ku, Sapporo, 060-0816, Japan.
Satoshi
S
Hashino
Gerodontology, Department of Oral Health Science, Graduate School of Dental Medicine, Hokkaido University, N13 W7, Kita-Ku, Sapporo, 060-8586, Japan.
Yutaka
Y
Yamazaki
Department of Hematology, Hokkaido University Graduate School of Medicine, N15 W7, Kita-Ku, Sapporo, 060-8638, Japan.
Takanori
T
Teshima
D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D006085:Graft Survival / Q000187:drug effects*; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006801:Humans; D015994:Incidence; D008727:Methotrexate / Q000008:administration & dosage*; D013280:Stomatitis / Q000150:complications / Q000628:therapy*; D016559:Tacrolimus / Q000008:administration & dosage*; D013997:Time Factors
D016559:Tacrolimus; D008727:Methotrexate
Engraftment; GVHD prophylaxis; Methotrexate; Oral mucositis