重组人白介素-11治疗化疗所致血小板减少症的疗效和机制

目的观察重组人白介素-11(rhIL-11)治疗化疗后血小板(PLT)减少的疗效和安全性,并探讨其作用机制。方法34例(76周期)化疗后PLT减少患者接受rhIL211治疗,25μg·kg-1·d-1,皮下注射,连用4～16d,或至PLT升高幅度≥50×109/L时停药。观察rhIL211的疗效及不良反应,以ELISA法检测用药前血清IL-11水平,以RT-PCR法检测单个核细胞表面IL-11受体α链mRNA(IL-11Rα)的表达,分析rhIL-11的疗效与血清IL-11水平及IL-11Rα表达的关系。结果第1和第2周期化疗前,PLT基础值分别为(135.0±54.3)×109/L和(259.4±64.5)×109/L;应用rhIL-11的天数分别为7～16d(中位时间12d)和4～10d(中位时间6d),第1和第2周期rhIL-11的应用天数相比,差异有统计学意义(P<0.05);化疗后PLT计数<50×109/L的持续天数分别为7～13d(中位时间10d)和3～8d(中位时间5d),第1和第2周期PLT降低的持续天数相比,差异有统计学意义(P<0.05)。有30个周期PLT计数最高值>300×109/L,PLT计数最高值出现在应用rhIL-11后第10～17天(中位时间14d)。用药前的血清IL-11水平与用药后PLT计数最高值呈负相关。主要不良反应为水肿、乏力、头晕头痛和肌肉、关节疼痛。结论rhIL-11治疗化疗引起的PLT减少安全有效,虽起效缓慢,但作用持久;检测用药前血清IL-11水平对预测rhIL-11

Effectiveness and safety of rhIL-11 in the treatment of chemotherapy-induced thrombocytopenia

OBJECTIVE: To investigate the effectiveness, safety and possible mechanism of recombinate human interleukin 11 (rhIL-11) in the treatment of chemotherapy-induced thrombocytopenia. METHODS: Thirty-four patients (totally 76 cycles) with chemotherapy-induced thrombocytopenia received subcutaneous injection of rhIL-11 at the dose of 25 microg.kg(-1).d(-1) for 4 to 16 days. Serum IL-11 level was measured by ELISA, and IL-11 R alpha expression was detected by RT-PCR. RESULTS: The mean baseline platelet count before chemotherapy was (135.0 +/- 54.3) x 10(9)/L for the 1st cycle and (259.4 +/- 64.5) x 10(9)/L for the 2nd cycle. The time to administer rhIL-11 was 7 to 16 days (median 12 days) in the 1st cycle and 4 to 10 days (median 6 days) in the 2nd, respectively (P < 0.05). The duration of post-chemotherapy platelet count below 50 x 10(9)/L was 7 to 13 days (median 10 days) for the 1st cycle and 3 to 8 days (median 5 days) for the 2nd, respectively (P < 0.05). Platelet count reached 300 x 10(9)/L or above in 30 chemotherapy cycles. The maximum platelet count was found to appear at D10 to D 17 (median D14), and negatively correlated with the pre-chemotherapy serum IL-11 level after administration of rhIL-11. Major adverse reactions included edema, headache, muscle and joint pain. CONCLUSION: rhIL-11 is effective and safe for the treatment of chemotherapy-induced thrombocytopenia, with a relatively slow but sustained effect on the recovery of platelet count. Pre-chemotherpy serum IL-11 level might predict the efficacy of rhIL-11.