Effect of CD34+ cell dose on haploidentical hematopoietic stem cell transplantation for treating malignant hematological diseases / 中国组织工程研究

ABSTRACT

BACKGROUND:Haploidentical hematopoietic stem cell transplantation is associated with a higher rate of graft rejection and therefore often requires a higher CD34+ cell dose,but the findings reported in existing studies regarding the relationship between CD34+ cell dose and study endpoints after allogeneic hematopoietic stem cell transplantation are controversial. OBJECTIVE:To investigate the effect of CD34+ cell dose on clinical outcomes of haploidentical hematopoietic stem cell transplantation for malignant hematological diseases. METHODS:135 patients who underwent haploidentical hematopoietic stem cell transplantation at Hematopoietic Stem Cell Transplantation Center,Department of Hematology,First Affiliated Hospital of Zhengzhou University between January 2019 and December 2021 were included.Combining the results of previous studies and our center's experience,the cohort was divided into two groups using a CD34+ cell count of 5.0×106/kg as the cut-off point.Clinical outcomes related to graft implantation,relapse incidence,non-relapse mortality,overall survival and progression-free survival were evaluated in both groups. RESULTS AND CONCLUSION:(1)CD34+ cell dose correlated with platelet engraftment,with platelets implanted earlier in the high-dose group than in the low-dose group(14 days vs.16 days,P=0.013).(2)There was no significant difference in 3-year overall survival between the two groups(67.5%vs.53.8%,P=0.257);nor was there a significant difference in progression-free survival between the two groups(65.6%vs.44.2%,P=0.106),but stratified analysis based on disease risk index revealed an association with elevated 3-year progression-free survival in the high-dose group among low-risk patients(72.0%vs.49.3%,P=0.036).(3)The cumulative 3-year relapse incidence was smaller in the high-dose group than in the low-dose group(16.0%vs.33.5%,P=0.05).(4)The rate of non-relapse mortality within 100 days was greater in the high-dose group than in the low-dose group,but there was no significant difference(17.3%vs.6.7%,P=0.070);stratified analysis revealed that non-relapse mortality within 100 days was significantly higher in the high-dose group than in the low-dose group(20.0%vs.3.3%,P=0.046).(5)In conclusion,CD34+ cell doses>5.0×106/kg promote early platelet implantation,improve 3-year progression-free survival in low-risk patients at transplantation and reduce the cumulative relapse incidence.However,in high-risk patients,high-dose CD34+ cells result in increased non-relapse mortality within 100 days after transplantation,which is considered to be possibly associated with an increased occurrence of severe acute graft versus host disease in the early post-transplantation period.Therefore,it is considered that graft versus host disease monitoring should be enhanced in patients who transfused high-dose CD34+ cells.