Factors Affecting Hematopoietic Reconstitution After Allogeneic Peripheral Blood Stem Cell Transplantation With Total Body Irradiation Conditioning:A Single-center Study Of 279 Cases

Backgrounds:Allogeneic hematopoietic stem cell transplantation(allo-HSCT)is the most effective treatment for various hematologic malignancies.HCT recipients must achieve donor cell implantation within the first month after transplant to obtain an anti-leukemia/lymphoma effect.Rapid and durable hematopoietic reconstitution(HR)is an important requirement for a successful HSCT,which can significantly reduce transplant-related complications and is also associated with long-term prognosis.Bone marrow structure and function damage induced by the conditioning regimen will have different degrees of influence on hematopoietic recovery.Recent advances in immunosuppressive therapy,GVHD prophylaxis,donor sources and various supportive care may have an impact on HR in the HCT setting containing TBI.So far,the reports focused on HR after peripheral blood stem cell transplantation(PBSCT)in patients with acute myeloid leukemia(AML)and acute lymphoblastic leukemia(ALL)are limited.Objective:To analyze the correlative factors and prognostic significance of HR after TBI conditioning allo-PBSCT,and to review relevant literature.Methods:Medical data about 279 acute leukemia patients who underwent the first allo-PBSCT with TBI combined with CY conditioning in our center were retrospectively collected.The Excel software and social science statistical software packages were used to process relevant data.Descriptive statistics were used to summarize the data,including demographics,clinical features,and transplant results.HR was assessed by the number of days required for neutrophils and platelets to recover following PBSCT.The significance of each independent variable between the two groups of patients who achieved early HR and who did not was statistically determined using the chi-square test.In a multivariate analysis,significant variables(p<0.05)in a univariate analysis were compared using a logistic regression.The cumulative time-to-engraftment curves of neutrophils and platelets was calculated using the Kaplan-Meier method based on the donor CD34+cell doses.Differences between cumulative engraftment rate curves were estimated using the log-rank test.Results:The median number of days for neutrophil and platelet engraftment in 279patients was 15 days(range,10-36 days)and 17 days(range,9-122 days),respectively.The median number of days for platelet counts over 50×10~9/L was 20 days(range,10-125 days).The overall proportion of patients who achieved engraftment at 30 days post-HSCT was 97.1%for neutrophil and 91.8%for platelet.Univariate analysis found that factors associated with rapid engraftment of ANC and PLT included gender,GVHD prophylaxis,stratification of prognosis,disease status before HSCT,donor type(related or unrelated),HLA matching,CD3+cells and CD34+cells.Multivariate analysis showed that the dose of CD34+cells was the only independent factor affecting the rapid engraftment of ANC and PLT,and less dose of CD34+cells was less likely to achieve rapid engraftment(neutrophil,OR=0.218,95%Confidence Interval(CI)[0.106–0.449],p<0.001;Platelet,OR=0.412,95%CI[0.190–0.894],p=0.025).Cumulative time-to-engraftment curves showed that CD34+cells≥5.0 x 10~6/kg can achieve faster implantation and higher engraftment rates(neutrophil,p=0.001;platelet,p=0.003),and rapid HR was associated with good prognosis(p<0.01).Given the heterogeneity of immunological backgrounds and CD34+cell number available due to different donor types,the subgroups of donors were further analyzed by quartiles of CD34+cell doses.Results showed HR after transplant was more significantly affected by the dose of CD34+cells derived from unrelated donors than from related donors(neutrophil,p<0.001 vs p=0.639;platelet,p<0.001 vs p=0.545).Moreover,there was a statistical difference in the HR of unrelated groups,while this difference was not observed in the related donors.Our results may be valuably informative regarding the number of infused peripheral blood stem cells in the universal clinical practice.Conclusion:HR was satisfactory in MAC allo-PBSCT with TBI,and the dose of CD34+cells was the only factor affecting rapid engraftment.The HR of HSCT from unrelated donors depended more on the dose of CD34+cells.Rapid HR may predict better overall survival for patients with acute leukemia receiving allo-PBSCT.