Kanda Yoshinobu, Hyo Rie, Yamashita Takuya, Fujimaki Katsumichi, Oshima Kumi, Onoda Masahiro, Mori Takehiko, Sakura Toru, Tanaka Masatsugu, Sakai Miwa, Taguchi Jun, Kurakawa Mineo, Maruta Atsuo, Okamoto Shinichiro, Sakamaki Hisashi
Department of Hematology, Cell Therapy and Transplantation Medicine, University of Tokyo, Graduate School of Medicine and Hospital, Tokyo, Japan.
Am J Hematol. 2006 Nov;81(11):838-44. doi: 10.1002/ajh.20710.
We retrospectively evaluated the effect of the blood cyclosporine (CsA) concentration on the outcome of allogeneic hematopoietic stem cell transplantation from an HLA-matched sibling donor in 171 patients who received a continuous infusion of CsA and short-course methotrexate to prevent graft-versus-host disease (GVHD). CsA was started at 3.0 mg/kg/day and the dose was adjusted to maintain the blood CsA concentration between 250 and 350 ng/ml. The actual dose of CsA averaged 1.9 mg/kg/day at the 3rd week after transplantation. The incidence of grade II-IV acute GVHD was 29.9%. Patient age and sex were identified as independent significant risk factors for acute GVHD. The CsA concentration during the 3rd week after transplantation most strongly affected the incidence of grade II-IV acute GVHD (RR 0.995 for an increase in CsA concentration by 1 ng/ml, P = 0.037) adjusted for other risk factors. The incidence of acute GVHD was significantly lower in patients with a 3rd-week CsA concentration higher than 300 ng/ml than in those with values between 200 and 300 ng/ml (20% vs. 35%, P = 0.036). We concluded that the blood CsA concentration at peri-engraftment period may be important in preventing acute GVHD.
我们回顾性评估了171例接受环孢素（CsA）持续输注和短疗程甲氨蝶呤以预防移植物抗宿主病（GVHD）的患者中，血中环孢素（CsA）浓度对来自HLA匹配同胞供者的异基因造血干细胞移植结局的影响。CsA起始剂量为3.0mg/kg/天，并调整剂量以维持血CsA浓度在250至350ng/ml之间。移植后第3周时，CsA的实际剂量平均为1.9mg/kg/天。II-IV级急性GVHD的发生率为29.9%。患者年龄和性别被确定为急性GVHD的独立显著危险因素。在调整其他危险因素后，移植后第3周的CsA浓度对II-IV级急性GVHD的发生率影响最为强烈（CsA浓度每增加1ng/ml，相对危险度为0.995，P=0.037）。移植后第3周CsA浓度高于300ng/ml的患者急性GVHD发生率显著低于CsA浓度在200至300ng/ml之间的患者（20%对35%，P=0.036）。我们得出结论，植入期的血CsA浓度在预防急性GVHD中可能很重要。
