| Purpose:As the numbers of total nucleated cells(TNC)and CD34+cells in umbilical cord blood are limited,umbilical cord blood transplantation has been facing problems of neutrophil and platelet engraftments'delay or failure.Delayed platelet engraftment(DPE)increases risks of bleeding complications,death and medical costs.In addition,there is a shortage of available infused blood in China,especially infused platelets'supply is far less than clinical demand.This study evaluated efficacy and safety of recombinant human thrombopoietin(rhTPO)for platelet engraftment(platelet recovery to?20×10~9/L without transfusion support for seven consecutive days)after sUCBT with hematologic malignancies.Method:This study is a prospective single-center randomized controlled trials.We enrolled 120 patients with malignant hematological diseases(body weight?30 kg)receiving sUCBT in the first affiliated hospital of University of Science and Technology of China(Anhui Provincial Hospital)from October 20,2016 to March 26,2018.120patients were randomly divided into rhTPO group and controlled group in a ratio of 1:1.rhTPO group received rhTPO subcutaneous injection at a dose of 300 U/kg(maximum dose is 15000 U)once a day from 14 days after transplantation to 28 days,while controlled group did not use rhTPO,and other treatment in two groups both followed principle of treatment in our medical center.The main endpoint of this study was the time of platelet engraftment,and outcomes was evaluated combing cumulative incidence of platelet implantation at 60 days after sUCBT.The safety of rhTPO was analyzed by the incidence of adverse events and transplantation related complications.This trial was registered with the Chinese Clinical Trial Registry(registration number is ChiCTR-IPR-16009357).Result:In rhTPO group,1 patient withdrew immediately after grouping,1 patient died before applying rhTPO,and 2 patients withdrew because they could not tolerate subcutaneous injection.116 patients(96.7%)was analyzed for the efficacy of rhTPO.The median follow-up time in survival patients is 520 days(interquartile[IQR],410-602days),and the cumulative incidence of platelet engraftment at 60 days post-transplantation in rhTPO group was 82.1%(95%confidence interval[CI],68.9-90.1%),significantly higher than that in the controlled group(66.7%,95%CI,53.0-77.2%)(p=0.0222).The cumulative incidence of platelet recovery in rhTPO group(83.9%,95%ci,70.5-91.6%)was significantly higher than the controlled group(73.3%,95%ci,59.7-83.0%)(p=0.0439).The median time of platelet recovery(platelet recovery to?50×109/L without transfusion support for seven consecutive days)in the rhTPO group was 39 days(IQR 43-58 days),significantly shorter than that in the control group(53 days,IQR 42-76.5 days)(P=0.049).In addition,the platelet transfusion from 14days after transplantation to 60 days in rhTPO group was 3 units(IQR,2-5 units),which was significantly lower than the controlled group(4 units,IQR,2-7 units)(p=0.041).Multivariate analysis showed rhTPO[hazard ratio(HR)=1.755,95%CI,1.167-2.638,P=0.0069]was an independent predictor of platelet engraftment.Transplant related complications such as bloodstream infections,fungal infection(confirmed or probable),pre-engraftment syndrome(PES),II-IV degree of acute graft-versus-host disease(aGVHD),III-IV aGVHD,replase,transplant related mortality(TRM)and overall survival(OS),disease-free survival(DFS),graft-versus-host disease-free&relapse-free survival(GRFS)between two groups had no difference.No severe adverse event was observed in all patients.Conclusion:1)rhTPO can improve platelet engraftment after transplantation,as well as platelet recovery,in patients with malignant hematological diseases after sUCBT treatment.2)rhTPO can reduce clinical demand for platelet transfusion in patients with malignant hematological diseases after sUCBT treatment.3)rhTPO is an effective and safe option for promoting platelet engraftment and recovery after sUCBT in patients with hematological malignancies. |
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