Adachi Yoshitaka, Ozeki Kazutaka, Ukai Shun, Sagou Ken, Fukushima Nobuaki, Kohno Akio
Department of Hematology and Oncology, Konan Kosei Hospital, 137, Omatsubara,Takaya-cho, Konan, 483-8704, Aichi, Japan.
Int J Hematol. 2019 Apr;109(4):440-450. doi: 10.1007/s12185-019-02598-x. Epub 2019 Jan 24.
The combination of methotrexate (MTX) and a calcineurin inhibitor is widely used for GVHD prophylaxis in umbilical cord blood transplantation (UCBT). However, the optimal MTX dosage for GVHD prophylaxis in UCBT remains unclear. In the present study, we investigated the impact of MTX dosage on clinical outcomes following UCBT in a single-center retrospective study. Of 70 UCBT recipients included in this study, 37 received MTX at doses of 10 mg/m on day 1, and 7 mg/m on days 3 and 6 (low-dose MTX: LD-MTX), and 33 received MTX at doses of 15 mg/m on day 1, and 10 mg/m on days 3 and 6 (standard-dose MTX: SD-MTX), in addition to tacrolimus (TAC). Grade 3-4 acute GVHD and/or transplant-related complications with endothelial cell damage were considered severe transplant-related complications. Univariate analysis findings revealed that the risk of grade 3-4 acute GVHD was significantly lower in the SD-MTX group than in the LD-MTX group (P = 0.013). Multivariate analysis findings revealed that SD-MTX was significantly associated with a lower incidence of severe transplant-related complications (HR = 0.25; 95% CI, 0.07-0.87; P = 0.029). We conclude that SD-MTX in combination with tacrolimus is optimal for GVHD prophylaxis in UCBT.
甲氨蝶呤（MTX）与钙调神经磷酸酶抑制剂联合应用广泛用于脐带血移植（UCBT）中的移植物抗宿主病（GVHD）预防。然而，UCBT中预防GVHD的最佳MTX剂量仍不清楚。在本项单中心回顾性研究中，我们调查了MTX剂量对UCBT后临床结局的影响。本研究纳入的70例UCBT受者中，37例在第1天接受10mg/m剂量的MTX，在第3天和第6天接受7mg/m剂量的MTX（低剂量MTX：LD-MTX），33例除接受他克莫司（TAC）外，在第1天接受15mg/m剂量的MTX，在第3天和第6天接受10mg/m剂量的MTX（标准剂量MTX：SD-MTX）。3-4级急性GVHD和/或伴有内皮细胞损伤的移植相关并发症被视为严重移植相关并发症。单因素分析结果显示，SD-MTX组3-4级急性GVHD的风险显著低于LD-MTX组（P = 0.013）。多因素分析结果显示，SD-MTX与严重移植相关并发症的发生率较低显著相关（HR = 0.25；95%CI，0.07-0.87；P = 0.029）。我们得出结论，SD-MTX联合他克莫司是UCBT中预防GVHD的最佳方案。
