Risk factors for acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: retrospective analysis of 73 patients who received cyclosporin A
Risk factors for acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: retrospective analysis of 73 patients who received cyclosporin A
复制标题
DOI：
10.1038/sj.bmt.1705834
复制
发表时间：
2007-11-01
影响因子：
4.8
通讯作者：
Aizawa, Y.
中科院分区：
文献类型：
--
作者：
Izumi, N.;Furukawa, T.;Aizawa, Y.
环孢菌素A（CsA）作为一种免疫抑制剂已被广泛用于预防移植物抗宿主病（GVHD）。为探讨包括CsA血药浓度在内的II ~ IV级急性GVHD的危险因素，我们回顾性分析了1989年3月至2001年7月在我院接受异基因造血干细胞移植的患者资料。73例患者（47例男性和26例女性）接受CsA和短期甲氨蝶呤预防GVHD。CsA 1.5 mg/kg，从第-1天开始每天输注2次，每次3小时，直至患者从毒性胃肠道并发症中恢复。甲氨蝶呤在第1天以15 mg/m2的剂量给药，在第3、6和11天以10 mg/m2的剂量给药。18例（24.7%）发生Ⅱ ~ Ⅳ级急性GVHD。多变量考克斯回归分析显示，急性GVHD发生前较高的C-5（开始输注后5 h的全血CsA浓度）降低了II-IV级急性GVHD的发生，每增加1 ng/ml，风险比为0.994（95%置信区间0.989-0.999）。我们的数据表明，CsA暴露不足可能是发生急性GVHD的重要风险。从我们的研究结果，我们认为，精确监测CsA浓度和调整CsA剂量使用的浓度可能是有效的，以防止严重的急性GVHD的发生。为了证实这一发现，还需要进一步的前瞻性研究。
Cyclosporin A (CsA) has been used most widely as an immunosuppressive agent for preventing graft-versus-host disease (GVHD). To explore the risk factors including CsA blood levels for grades II-IV acute GVHD, we retrospectively analyzed the data of patients who underwent allogeneic hematopoietic stem cell transplantation in our hospital between March 1989 and July 2001. Seventy-three patients ( 47 males and 26 females) received CsA and short-term methotrexate for GVHD prophylaxis. CsA 1.5 mg/kg was administered as a 3-h infusion twice daily from day -1 until the patient recovered from the toxic gastrointestinal complication. Methotrexate was given at a dose of 15 mg/m(2) on day 1 and 10 mg/m2 on days 3, 6 and 11. Grades II-IV acute GVHD occurred in 18 patients ( 24.7%). Multivariate Cox regression analysis revealed that higher C-5 ( the whole-blood CsA concentration at 5 h after the start of infusion) before the onset of acute GVHD reduced the onset of grades II-IV acute GVHD with a hazard ratio of 0.994 (95% confidence interval 0.989-0.999) for every increase of 1 ng/ml. Our data indicate that inadequate exposures of CsA can be a vital risk for developing acute GVHD. From our results, we consider that precise monitoring of CsA concentrations and adjustment of CsA dose using the concentration may be effective to prevent the onset of severe acute GVHD. To confirm this finding, further prospective study will be needed.