Analysis Of Risk Factors And Outcomes Of Delayed Platelet Engraftment After Cord Blood Transplantation For Patients With Hematologic Malignancies

BackgroundPresently,allogeneic hematopoietic stem cell transplantation（allo-HSCT）is considered as an significant treatment for patients with hematologic malignancies.Delayed platelet engraftment（DPE）is one of the usual complications after allo-HSCT.Umbilical cord blood,as a readily available donor with a low relapse rate,has been continuously developed as one of the main alternative donor sources for the treatment of high-risk hematologic malignancies.Compared with other types transplantation,delayed platelet engraftment was more likely to happen after umbilical cord blood transplantation,and it needs to be controlled as obviously impacts on the treatment prognosis.To investigate the risk factors and outcomes of DPE after umbilical cord blood transplantation for patients with hematologic malignancies is extremely urgent.Objective We retrospectively investigated the risk factors and outcomes of DPE after single-units cord blood transplantation（CBT）whose myeloablative conditioning regimen without antithymocyte globulin（ATG）for patients with hematologic malignancies.Methods Characteristic of 399 patients with hematological malignancies who received single-unit CBT at An Hui Provinal Hospital between January 2017 and February 2019 were retrospectively analyzed.All patients were treated with a myeloablative conditioning regimen without ATG.According to the inclusion and exclusion standard,318 patients were included finally and were divided into the delayed platelet engraftment（DPE）group（70 cases）and the normal（non-DPE）group（248cases）,depending on the time of platelet engraftment.The day of umbilical cord blood transfusion was defined as day 0 after transplantation.We compared and analyzed the clinical characteristics between these two groups,aimed to find the risk factors of DPE after CBT and its influence on the prognosis and survival after transplantation.Results This study included 318 patients who received CBT for hematologic malignancies,as the median age was 16（IQR,7-31）years and the median body weight of receptor was 48（IQR,24-61）kg.139 patients with less than 6/8 human leukocyte antigen（HLA）matched and 179 patients with greater than or equal to 6/8 HLA.The median infused TNC count was 3.12（IQR,2.33-4.70）×10~7/kg,and the median infused CD34⁺cell count was 1.7（IQR,1.21-2.71）×10~5/kg（baesd on the body weight of receptor）.Among all the 318 patients,108 patients developed grades II-IV a GVHD before platelet engraftment,and the cumulative incidence of grades II-IV a GVHD before platelet engraftment was 64.3%（95%CI 51.1%-73.9%）in the DPE group was significantly higher than 25.4%（95%CI 19.8%-30.6%）（P<0.001）in the non-DPE group（P<0.001）.In this study,70 cases developed DPE among all the 318 patients,and the incidence of DPE was 22.01%.Eventually,Only 35 patients in the DPE group developed platelet engraftment,and the median platelet engraftment time was 93（IQR,69-123）days.Another 35 patients died without platelet engraftment after CBT（+60 days）.33 patients died before platelet engraftment,with a median OS time of 142（IQR,87-174）days,and 2 patients had relapse or progress the primary disease before platelet engraftment.In the non-DPE group,the median platelet engraftment time was 32（IQR,13-60）days among all the 248 patients.Multivariate analysis showed that HLA mismatched（<6/8）,infused lower CD34⁺cell count（≤1.7×10~5/kg）,CMV viremia and grades II-IV a GVHD before platelet engraftment were high risk factors for DPE.The probability of 3-year overall survival（OS）was 32.9%（95%CI 22.2%-43.9%）in the DPE group and 74.0%（95%CI 68.0%-79.1%）in the non-DPE group（P<0.001）.The probability of 3-year disease-free survival（DFS）was 32.9%（95%CI 22.2%-43.9%）in the DPE group and 68.1%（95%CI 61.9%-73.5%）in the non-DPE group（P<0.001）..Respectively,The 3-year cumulative incidence of relapse（RI）was 10.0%（95%CI4.3%-18.5%）in the DPE group and 21.8%（95%CI 16.9%to 27.1%）in the non-DPE group（P=0.031）.The 3-year cumulative incidence of transplant-related mortality（TRM）was 57.1%（95%CI 44.6%-67.9%）in the DPE group,which was significantly higher than 10.1%（95%CI 6.7%-14.2%）in the non-DPE group（P<0.001）.Conclusion1.The rate of delayed platelet engraftment after umbilical cord blood transplantation is significantly higher than other types allo-HSCT for patients with hematologic malignancies;2.HLA mismatched（<6/8）,infused lower CD34⁺cell count（≤1.7×10~5/kg）,CMV viremia and grades II-IV a GVHD before platelet engraftment were high risk factors for DPE;3.The occurrence of DPE after CBT was associated with the increase of TRM,worse OS and DFS but lower RI.