重组人血小板生成素治疗白血病患者化疗诱导血小板减少73例

Recombinant human thrombopoietin (rhTPO) in treatment of chemotherapy-induced thrombocytopenia in patients with leukemia

目的:评价国产重组人血小板生成素(rhTPO)对白血病患者化疗后血小板减少的疗效和安全性。方 法:73例完全缓解白血病患者进行自身对照多中心临床试验,均接受方案和剂量相同的2个周期化疗,第1个周期 作对照,第2个周期化疗结束后6～24h皮下注射rhTPO 1.0μg·kg-1·d-1,连续用药最长14d。实验室检测血尿常规、肝肾功能、凝血功能、胸片、心电图及血清抗rhTPO抗体。结果:用药周期与对照周期化疗后血小板最低值分别为20.8×109和16.3×109·L-1(P>0.05);血小板恢复最高值分别为226.9×109和144.9×109·L-1(P<0.001),用药周期明显高于对照周期。用药周期和对照周期化疗后血小板<50×109·L-1的持续时间分别为10.9和12.8d(P<0.05)。用药周期化疗后血小板恢复至≥75×109和≥100×109·L-1所需的时间分别为22.0和24.1d,明显短于对照周期25.0和27.8d(P分别<0.01和<0.001)。用药周期血小板输注次数及剂量少于对照周期(P<0.05)。2个周期相比,化疗后血红蛋自(Hb),白细胞(WBC)及肝肾功能和凝血功能的变化无明显差异。1例患者产生低滴度血清抗rhTPO抗体。不良反应有发热、关节痛、头晕和头痛。结论:白血病患者化疗后给予国产rhTPO,可减少血小板降低程度和持续时间,促进血小板恢复,减少血小板输注。

Objective: To evaluate the efficacy and safety of domestic rhTPO in treatment of chemotherapy-induced thrombocytopenia in patients with leukemia. Methods: 73 patients with leukemia who had been completely remitted were enrolled into the self-controlled multi-center trial. They were given 2 cycles of same chemotherapy, the first cycle was used as control and at 2-14h after the end of the second cycle they were given subcutaneouly rhTPO in a dose of 1.0μg·kg-1·d-1 for 14 consecutive day at the longest. Laboratory tests including blood and urine routine examination, hepatic function,kidney function, coagulation function, chest radiography, and electrocardiography were com-pleted.Serum samples were screened for anti-rhTPO antibody. Results:The mean minimal and maximal platelet count in rhTPO treated cycle was significantly higher than those of control cycle. The platelet count of <50×109·L-1 maintained for 10.9d in rhTPO treated cycle versus 12.8d in control cycle (P<0.05). The time needed to achieve a recovery of platelet count of ≥75×109·L-1 and ≥100×109·L-1 was 22.0d and 24.1d respectively for rhTPO treated cycle versus 25.0d and 27. 8d re-spectively for control cycle, these values in rhTPO cycle were significantly shorter than those of control cycle (P<0.01 and P<0. 001). Times and doses of platelet infusion needed in rhTPO treated cycle was significantly smaller than those of control cycle (P<0.05).No significant difference in Hb,WBC, liver function and function of blood coagulation between cycles was observed. Transient low-titer anti-body was developed in a patient and fever,knee arthralgia,dizziness and headache were occurred in the study.Conclusion:The degree and duration of thrombocytopenia and platelet infusion needed in patient with leukemia who have received chemotherapy can be reduced and the recovery of their platelet count can be promoted. It seems safe to receive rhTPO treatment after chemotherpy.