他克莫司替代环孢素治疗非重型再生障碍性贫血28例临床研究

Tacrolimus as a substitute for Cyclosporine A in treatment of non-severe aplastic anemia: a clinical trial of 28 cases

目的探讨他克莫司(FK506)替代治疗环孢素A(CsA)无效或不能耐受的非重型再生障碍性贫血(NSAA)患者临床疗效。方法收集2009年3月至2012年9月苏州大学附属第一人民医院NSAA患者28例,CsA无效22例(其中10例合并CsA不良反应),CsA有效但不能耐受6例,均换用FK506治疗。维持FK506血药谷质量浓度在4～6μg/L,定期复查血常规、肝肾功能、血药浓度,评估血液学疗效及不良反应。结果 CsA无效22例换药后12例(54.54%)获血液学改善,中位起效时间8周,其中10例的CsA不良反应均改善,肾功能恢复中位时间13周,肝功能恢复中位时间6.5周,牙龈增生改善时间6周。CsA不能耐受6例换药后不良反应均改善,肾功能恢复正常的中位时间10周,牙龈增生改善中位时间6周,1例换用FK506后失去疗效死亡。结论 CsA治疗无效的NSAA患者换用FK506治疗部分患者血液学改善,且CsA继发的肝、肾功能损害等其他不良反应均改善。

Objective To investigate the efficiency of substituting Tacrolimus （FKS06） for Cyclosporine A （CsA） in trea- ting non-severe aplastic anemia （NSAA） patients who were resistant or intolerant to CsA. Methods Twenty eighty patients with NSAA were treated with FK506 after using CsA more than six months. Among the 28 cases ,22 patients （ 10 with CsA- related side-effects） had no responses to CsA ,while the other 6 cases were intolerant to CsA despite being responsive to it. The blood concentration of FKS06 was maintained at 4 - 6 ng/mL, and the side-effects, blood cell count, and hepatic and re- nal function were examined regularly. Results Of the 22 patients not responded to CsA, hematological improvement was found in 12 cases （54. 54% ） and the median response time was 8 weeks. All the side-effects related to CsA in the 10 cases were alleviated,and the median time for hepatic recovery and renal functional recovery were 13 weeks and 6. 5 weeks re- spectively. Gingival hyperplasia （CIGH） was remitted after use of FKS06 ,and the media remission time was 6 weeks. In the 6 intolerant patients, the side-effects were also remitted, and the median time for renal function recovery and gingival hyper- plasia remission were 10 weeks and 6 weeks respectively. One of the 6 patients relapsed and then died after FKS06 was used although the side-effects were remitted. Conclusion Tacrolimus might be an alternative immunosuppressive substitute for CsA in treatment of patients with NSAA, especially of patients who were refractory or intolerant to CsA.