重组人血小板生成素与重组人白介素-11促进白血病患者异基因造血干细胞移植后血小板恢复的疗效比较

To Comparing the of Recombinant Human Erythropoietin and Recombinant Human Interleukin 11 on Improving the Platelet Recovery After Allogeneic Hematopoietic Stem Cells Transplantation in Patients with Leukemia

目的比较重组人血小板生成素(rhTPO)与重组人白介素-11(rhIL-11)对促进白血病患者异基因造血干细胞移植术后血小板恢复的临床疗效及安全性。方法将114例行异基因造血干细胞移植的白血病患者分为IL-11组、TPO组和空白组,分别为36例、56例和22例,IL-11组及TPO组从移植后第6天开始分别给予rhIL-11 1.5 mg/d及rhTPO 15 000 u/d皮下注射,至血小板上升至100×109/L停药,如使用14 d未达正常亦停用。空白组患者不应用任何升血小板药物,血小板自然恢复。监测血常规并观察记录患者用药后的不良反应及30 d内血小板悬液输注量。结果IL-11组、TPO组和空白组血小板由最低恢复至≥20×109/L的中位时间分别为+13(8～20)d、+12(6～25)d和+19.5(12～32)d,IL-11组、TPO组的恢复时间均快于空白组(P值分别为0.003,0.001),但IL-11组和TPO组两组没有统计学差别(P=0.640);IL-11组、TPO组和空白组血小板由最低恢复至≥50×109/L的中位时间分别为+16.5(10～39)d、+15(11～48)d和+29(15～49)d,IL-11组、TPO组的恢复时间均快于空白组(P值分别为0.002,0.001),IL-11组和TPO组两组亦没有统计学差别(P=0.357);IL-11组、TPO组和空白组血小板由最低恢复至≥100×109/L的中位时间分别为+25(13～69)d、+18(14～48)d和+43(19～64)d,IL-11组、TPO组的恢复时间均快于空白组(P值分别为0.001,0.004),TPO组较IL-11组缩短7 d,两组差异有统计学意义(P=0.033)。+30 d内IL-11组、TPO组及空白组输注血小板悬液的中位数量分别为2(0～6)个治疗量、2(0～4)个治疗量和4(1～4)个治疗量,IL-11组和TPO组的血小板悬液输注量均少于空白组(P值分别为0.005,0.003),但该两组之间差异无统计学意义(P=0.499)。TPO组的不良反应发生率3.6%明显低于IL-11组的77.8%(P<0.001)。结论 rhTPO及rhIL-11均能够促进白血病患者异基因造血干细胞移植术后血小板计数的恢复,有效减少血小板悬液的输注量,降低移植出血相关风险;rhTPO较rhIL-11能缩短血小板升至正常的时间,从而提高患者对移植并发症的耐受性;rhTPO较rhIL-11的不良反应更少,具有良好的安全性,值得临床进一步推广应用。

Objective To compare the clinical efficacy and safety of recombinant human erythropoietin （rhTPO） and recombinant human interleukin 11 （rhIL-11 ） on the platelet recovery after allogeneic hemato- poietic stem cells transplantation in patients with leukemia. Methods 114 leukemia patients treated by allo- geneic hematopoietic stem cell transplantation were divided into IL-11 group, the TPO group and the blank group,respectively,36 patients,56 patients, and 22 patients. Since the sixth day after transplantation the pa- tients were respectively given rhIL-11 1.5 mg/d,rhTPO 15 000 u/d subcutaneous injection,until the platelet rose to 100×10^9/L. If the platelet was not reach to normal after 14 days it is also discontinued. Blank groups of patients were not used any drug and the platelet recovered naturally. We monitored blood routine and recor- ded adverse reactions of the patients after using the drugs and the numbers of unites platelets transfused within 30 days after transplatation. Results Median days of platelet recovered lowestly to 20 × 10^9/L about the rhIL- 11 group, the rhTPO group and the blank group in a time of ＋ 13 （ 8 - 20） d, ＋ 12 （6 - 25 ） d and ＋ 19. 5 （ 12- 32 ） d. The recovery time of IL- 11 group, TPO group are faster than blank group （ P value are 0. 003, 0.001 ）. But there was no statistical differences between IL- 11 group and TPO group （ P = 0.640）. Median days of platelet recovered lowestly to 50 × 10^9/L about the three group in a time of ＋ 16.5 （10 -39） d, ＋ 15 （11 -48） d and ＋29（15 -49） d. The recovery time of IL-I1 group,TPO group are faster than blank group （ P value are 0. 002,0. 001 ）, and IL-11 group and TPO also have no statistical difference （ P = 0. 357 ）. Medi- an days of platelet recovered lowestly to 100 × 10^9/L about the three group in a time of ＋ 25 （13 -69） d, ＋ 18 （ 14 - 48 ） d and ＋ 43 （ 19 - 64 ） d. The recovery time of IL- 11 group, TPO group are faster than blank group （P value are 0. 001, 0. 004 ） , and the recover time of TPO group is less 7 days than IL- 11 group, two groups have statistically significant difference （P = 0. 033 ）. The IL- 11 group, TPO group and blank group ＇ s median numbers of unites platelets transfused within 30 days after transplatation were 2 （0 - 6 ） u, 2 （ 0 - 4 ） u and 4 （ 1 - 4） u. The numbers of unites platelets about IL- 11 group and TPO group are less than blank group （P value are 0. 005,0.003 ） ,but there was no statistical differences between IL-11 group and TPO group （P = 0. 499）. TPO group adverse reactions occurring were 3.6% obviously lower than IL-11 group of 77.8% （P 〈 0. 001 ）. Conclusion rhTPO and rhlL-11 are able to promoting platelet recovery after allogeneic blood stem cells transplantation in patients with leukemia, effectively reduce the number of unites platelets transfused, re- duce the risk of bleeding about transplantation related. Comparing with rhlL-11 rhTPO can shorten the lime that platelet recovered to normal,so it can improve the toleration about transplant related complications;rhTPO has less adverse reaction than rhIL-11 and better safety, and it is worth to further popularize in clinic.