重组人血小板生成素促进异基因造血干细胞移植血小板恢复的随机对照临床试验

Recombinant Human Thrombopoietin Improves Platelet Recovery after Allogeneic Hematopoietic Stem Cell Transplantation: A Randomized,Controlled Clinical Trial

目的评价重组人血小板生成素(rhTPO)在异基因造血干细胞移植中促进血小板恢复的临床有效性和移植安全性。方法 123例接受标准骨髓清除性预处理方案的HLA相合同胞及无血缘造血干细胞移植受者,随机进入试验组(n=61)和对照组(n=62)。试验组第7天开始接受rhTPO 1.0μg/kg.d-1皮下注射,至第20天或虽<20 d、但血小板计数(BPC)已≥100×109/L时停药,对照组不用药。结果移植后第3～8周BPC的动态变化,试验组明显快于对照组(P=0.008),累积恢复BPC≥100×109/L,试验组好于对照组(P=0.010),其恢复的中位时间由对照组的移植后33(19～148)d缩短为试验组的28(15～379)d(P=0.008),但在更早的恢复BPC≥20×109/L或50×109/L,两组没有统计学差别。在严格限定的输血条件下,血小板悬液在100 d内的中位输注需求量分别由对照组的8(0～52)u减少为试验组的5(1～39)u(P=0.003),CD 34+细胞的移植数量和rhTPO与血小板计数恢复及血小板悬液输注需求量都明显相关。中位随访时间12.5(0.7～46.5)月,没有发现两组在不良反应、粒细胞植活、急慢性移植物抗宿主病、肝静脉闭塞综合征、肝肾功能动态变化及严重损伤等方面存在显著差异,也没有发现在诸如移植相关死亡、恶性血液病复发、总体生存和无复发生存等方面有显著差异。结论 rhTPO能够促进异基因造血干细胞移植血小板计数的恢复,有效减少血小板悬液的输注需求,并具有良好的移植安全性,值得进一步扩大试验证实。

Objective To evaluate the efficacy and safety of recombinant humanized thrombopietin(rhTPO) treatment in patients receiving allo-HSCT. Methods 123 patients receiving allo-HSCT after standard myeloablative conditioning regimens were randomized to receive rhTPO(n=61) at 1.0 g/kg·d-1 subcutaneously on d 7~20 or when the platelet counts were ≥100×109/L before day 20 or the control group(n=62). Results The rate of platelet recovery was higher with rhTPO than that with the control group(P=0.008) after 3~8 weeks platelet counts monitering,when the platelet counts were ≥100×109/L,rate of platelet recovery was higher with rhTPO than that with the control group 28 d(15~379) vs 33 d(19~148),(P=0.008) either.The median time of platelet recovery in the rhTPO group was significantly more rapid than that in the control group 28 d(15~379) vs 33 d(19~148),P=0.008).But the time of platelet recovery when the platelet counts were ≥20×109/L 28 d(15~379) vs 33 d(19-148),P=0.008.or ≥50×109/L 28 d(15~379) vs 33 d(19~148),P=0.008 were not significant differerce.Under the critically restricted transfusion support.The median number of unites platelets transfused within the 100 d after transplantation was decreased from 8 units(0~52 units) in the control group to 5 units(1~39 units) in the rhTPO group(P=0.003).The number of transplanted CD 34+ cells was correlated with platelet recovery in both groups.After a median follow-up of 12.5(0.7~46.5) months,the occurrence rate of adverse events,granulocyte recovery,acute and chronic graft versus host disease,and hepatic veno-occlusive disease and hepatorenal dysfunction was similar between the two groups.No significant difference was observed between the two groups in transplantation related death,relapsed,and overall survival and relapse free survival during the follow-up. Conclusion rhTPO were well tolerated and could improve platelet recovery post-allo-HSCT and reduce the number of unites platelets transfusion needed.