重组人血小板生成素治疗慢性难治性特发性血小板减少性紫癜的多中心临床试验

目的 评价国产重组人血小板生成素(rhTPO)对慢性难治性特发性血小板减少性紫癜(ITP)的疗效和安全性。方法 慢性难治性ITP患者皮下注射rhTPO 1.0μg/kg,1次/d,疗程14 d。结果 82例患者用药前血小板计数中位数为15.5(6.0-24.0)×109/L,给药起(5、7、15)d时分别升至27.5(16.0～47.0)×109/L、35.0(20.5-78.0)×109/L和77.0(41.8-119.5)×109/L,与用药前相比(P值均<0.01)。停药后血小板计数逐渐回落,至给药起第28天,血小板计数中位数降至76.5(35～120.3)×109/L,但仍明显高于治疗前(P<0.01)。近期有效率85.3％,其中显效58.5％(血小板≥100×109/L,无出血症状),良效26.8％(血小板升至50×109/L或较原水平上升30×109/L以上,无或基本无出血症状)。仅3例出现轻微临床不良反应。16例中1例在给药起21 d和28 d的血清中检测出低滴度抗TPO抗体,但不具有中和活性。结论 rhTPO可一过性升高慢性难治性ITP患者的血小板计数,不良反应轻微。

A multi-center clinical trial of recombinant human thrombopoietin in chronic refractory idiopathic thrombocytopenic purpura

OBJECTIVE: To evaluate the efficacy and safety of human recombinant thrombopoietin (rhTPO, a product of Sunshine Pharmaceutical Co Ltd, China) in chronic refractory idiopathic thrombocytopenic purpura. METHODS: Eighty-two patients with chronic refractory idiopathic purpura received daily subcutaneous administration of rhTPO at a dose of 1.0 micro g/kg for a maximum of 14 doses. RESULTS: After the beginning of treatment, the median platelet counts increased from 15.5 (6.0 - 24.0) x 10(9)/L to 27.5 (16.0-47.0) x 10(9)/L, 35.0 (20.5-78.0) x 10(9)/L and 77.0 (41.8-119.5) x 10(9)/L on the fifth, seventh and fifteenth day, respectively (P < 0.01). After the discontinuation of rhTPO administration, the platelet count decreased gradually. On the twenty-eighth day, the median platelet count was 76.5 (35-120.3) x 10(9)/L, which was still significantly higher than the level before the treatment (P < 0.01). The overall response rate was 85.3%. The rate in the group with remarkable response (platelet count > or = 100 x 10(9)/L without bleeding) was 58.5% and that in the good response group (platelet count > or = 50 x 10(9)/L or 30 x 10(9)/L higher than the count before the treatment, without bleeding) was 26.8%. Only 3 patients had mild clinical untoward reactions. Low titer (1:5) of anti-TPO antibody in serum was detected with ELISA in one of the sixteen patients who received the test on the twenty-first and twenty-eighth day. Neutralizing test using TPO-dependent cell line showed that the positive serum had no neutralizing activity on rhTPO. CONCLUSION: Consecutive subcutaneous injection of rhTPO for a maximum of 14 days was associated with a temporary elevation in platelet counts in patients with chronic refractory ITP with tolerable adverse effects.