环孢素血药浓度水平对重型再生障碍性贫血患者免疫抑制治疗近期疗效的影响

Effects of concentration of cyclosporine A on the early response to immunosuppressive therapy in severe aplastic anemia

目的研究环孢素（CsA）血药浓度水平是否影响重型和（或）极重型再生障碍性贫血（SAA／VSAA）患者免疫抑制治疗（IST）早期疗效，探讨CsA的合理使用方法。方法回顾性分析兔源抗胸腺细胞球蛋白（r—ATG）联合CsA方案初始治疗的90例SAA／VSAA患者临床资料，分别比较IST后6个月获得治疗反应和未获治疗反应患者间CsA血药浓度水平的差异，以及不同CsA血药浓度对SAA／VSAA患者获得治疗反应的影响。结果①初始CsA血药浓度对SAA／VSAA患者近期IST疗效无影响，但与SAA患者更早获得治疗反应相关；②获得治疗反应组患者IST第3个月CsA谷值血药浓度（C0）和峰值血药浓度（C2）均较未获治疗反应组患者明显增高（P值分别为0．024和0．009），IST其他时间段CsA血药浓度平均水平两组间差异无统计学意义（P〉0．05）。（3）IST第3个月G≥200μg／L组患者治疗反应率为82．4％，明显高于C0150～200μg／L组的55．6％（P=0．023）和C0〈150μg／L组的59．3％（P=0．046）；IST第3个月C2≥700μg/L组患者治疗反应率为80．5％，明显高于C2〈700μg/L组的55．3％（P=0．012）。结论CsA血药浓度水平影响SAA／VSAA患者近期疗效；IST第3个月CsA血药浓度水平对患者获得早期疗效尤为重要，维持CsA血药浓度C0≥200μg/L、C2≥700μg／L或可进一步提高SAA／VSAA患者IST治疗反应率。

Objective To evaluate the effects of cyclosporine A （CsA） whole-blood concentration on the early response to immunosuppressive therapy （ IST ） in severe and very. severe aplastic anemia （ SAA/ VSAA）. Methods Ninety SAA/VSAA patients treated with rabbit antithymocyte globulin （ATG） plus CsA as first line therapy in our hospital were retrospectively analysed. CsA levels between the response group and non-response group, and response rates of patients with variant CsA levels were compared respectively. Resuits （1）There was no significant difference in the beginning unmodified CsA blood concentration between IST responded and non-responded SAA/VSAA patients. The beginning unmodified C0 133.91 μg/L in IST 2- month responders was higher than that of 49.9 μg/L in non-responded SAA patients （ P = 0. 009 ） ; （2）The mean CsA C0 and C2 levels during the third month following IST were significantly different in responders and non-responders（ 197.52 μg/L vs 161.49 μg/L, P =0. 024, and 738.76 μg/L vs 615.46 μg/L,P =0. 009）, and no significant difference in other periods of IST（P 〉 0.05 ） （3）The response rate （87.5%） was significantly higher in patients with CsA C0 ≥200μg/L the third month following IST than those of 55.6% in patients with CsA C0 150-200 μg/L（P =0.023） and 59.3% in patients with CsA C0 〈 150 μg/L（P = 0. 046） , respectively. The response rate was significantly higher of C2 ≥ 700 μg/L group than that of C2 〈 700 μg/L group（80.5%vs 55.3% ,P=0.012）. Conclusions The CsA concentration related to the early IST response. The third month CsA concentrations was the most important for the response and maintainingCsA levels with C0 ≥200 μg/L and C2≥700 μg/L may improve the response to IST in SAA/VSAA.