重组人血小板生成素治疗化疗诱导的重度血小板减少的临床研究

目的　评价国产重组人血小板生成素 (rhTPO)对化疗后重度血小板减少 (≤ 2 0×10 9/L)患者治疗的临床疗效和安全性。方法　化疗后血小板≤ 2 0× 10 9/L的 81例实体瘤和完全缓解的白血病患者接受方案和剂量相同的两周期化疗 ,第 1个周期作对照 ,第 2个周期化疗结束后 6～2 4h皮下注射rhTPO 1.0 μg·kg-1·d-1为用药组 ,连续用药最长 14d。监测血尿常规、肝肾功能、凝血功能、胸部X线片、心电图及血清抗rhTPO抗体。结果　用药组血小板最低值及血小板恢复最高值均明显高于对照组 (最低值分别为 13× 10 9/L、12× 10 9/L ,P =0 0 0 2 ;血小板恢复最高值分别为186× 10 9/L和 12 2× 10 9/L ,P <0 0 0 1)。血小板 <5 0× 10 9/L的持续天数用药组和对照组分别为 11d和 13d(P <0 0 5 )。血小板恢复至≥ 75× 10 9/L、≥ 10 0× 10 9/L所需的天数用药组分别为 2 1d和 2 4d ,明显短于对照组的 2 4d和 2 7d(P <0 0 0 1)。血小板输注量用药组少于对照组 ,P <0 0 0 1。用药组和对照组相比 ,化疗后检测血常规、肝肾功能及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。个别患者出现发热、关节痛、头晕、头痛和寒战。结论　rhTPO可减少化疗后重度血小板减少患者血小板降低程度和持续时间 ,减

The clinical study of recombinant human thrombopoietin in the treatment of chemotherapy-induced severe thrombocytopenia

OBJECTIVE: To evaluate the efficacy and safety of recombinant human thrombopoietin (rhTPO) on chemotherapy-induced severe thrombocytopenia. METHODS: In this self-controlled multi-center clinical trial, 81 patients, 23 with solid tumor and 58 with leukemia with complete remission, with the platelet count < or = 20 x 10(9)/L after chemotherapy were given two cycles of the same chemotherapy. The first cycle was non- rhTPO-treated cycle as control, in the second cycle rhTPO of the dosage of 1.0 microg.kg(-1).d(-1) was administered subcutaneously 6-24 hours after the beginning of chemotherapy for at most 14 days. Laboratory tests including complete blood counts, urinalysis, serum chemistry, coagulant test, chest radiography, and electrocardiography were made. Serum samples were screened for anti-rhTPO antibodies. RESULTS: In rhTPO-treated cycle, the platelet count was higher the mean minimal platelet count was 13 x 10(9)/L, significantly higher than that of the control cycle (12 x 10(9)/L, P = 0.002), the mean maximal platelet count was 186 x 10(9) cells/L, significantly higher than that of the control cycle (122 x 10(9)/L, P < 0.001)]. The duration of thrombocytopenia was shorter in the rhTPO-treated cycle than in the control cycle: days with platelet count <50 x 10(9)/L, days with platelet count recovered > or = 75 x 10(9)/L, and days with platelet count recovered > or = 100 x 10(9)/L were 11 days, 21 days, and 24 days respectively, all significantly shorter than those of the control cycle (13 days, 24 days, and 27 days respectively, P < 0.05, P < 0.001, and P < 0.001). The amount of needed platelet transfusion was 10 U in the rhTPO-treated cycle, both significantly less than those in the control cycle (12 U, P < 0.001). No effects of rhTPO on hemoglobin, white blood cells, hepatic function, kidney function and coagulant function were found. Transient low-titer antibody was developed in one patient. Side effects such as fever, knee arthralgia, dizziness, headache and chill were mild and tolerable. CONCLUSION: Administration of rhTPO after chemotherapy significantly reduces the degree and duration of thrombocytopenia and the need for platelet transfusions.