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Immune Reconstitution And Clinical Outcome Relevance Of Allogeneic Hematopoietic Stem Cell Transplantation For Acute Leukemia

Posted on:2024-01-01Degree:MasterType:Thesis
Country:ChinaCandidate:L L ZhangFull Text:PDF
GTID:2544307091476824Subject:Internal medicine
Abstract/Summary:PDF Full Text Request
Research background and purpose:Reconstitution of the donor-derived immune system is critical to the success of allogeneic hematopoietic stem cell transplantation.Poor long-term immune reconstitution is an important cause after transplant infections,graft versus host disease(GVHD)and relapse.The widespread clinical use of haploid grafts,particularly prolonged immunodeficiency due to delayed immune cell reconstitution caused by massive T-cell depletion,has serious implications for long-term survival and prognosis.In order to better understand and enforce the regulation of immune cell reconstitution from different graft sources,the reconstitution features of CD4+T cells,CD8+T cells,B cells and NK cells at 90d,180d,270d and 360d after transplantation were compared between the two transplant types by reviewing the data of acute leukemia receiving haploidentical hematopoietic stem cell transplantation or matched sibling donor hematopoietic stem cell transplantation and the donor;analysed the association of different immune cells with overall survival(OS);and the reconstitution characteristics of different immune cells in the context of acute graft versus host disease.Materials and Methods:General clinical data(patient’s disease diagnosis type,gender,age at transplantation,CD34+cell transfusion,MNC transfusion)were collected from September 2017 to December 2022 from acute leukemia patients(n=116)who received haploidentical or matched sibling donor at The General Hospital of Western Theater Command PLA,and absolute cell count assay values of CD4+T cells,CD8+T cells,B cells,and NK cells in peripheral blood on days 90,180,270,and 360 after transplantation in patients with both transplant types,and absolute cell count assay values of CD4+T cells,CD8+T cells,B cells,and NK cells in peripheral blood from 18 donors as healthy control groups;combined with the overall survival the statistical analysis was performed by SPSS to compare the characteristics of different immune cells in the two transplant types at 3 months,6 months,9 months and 12 months after transplantation,and the differences with the healthy control groups,as well as the dynamic changes of individual immune cells at different times to observe the reconstruction characteristics of different immune cells;a binary logistic analysis was applied to analyse whether there was any correlation between the number of immune cells at different testing time points and OS.The correlation between the number of immune cells and OS at different time points was analyzed by binary logistic analysis.Result:1.Comparison of different immune cell reconstitution at 3,6,9 and 12 months after transplantation between the two transplant types:at 3,6,9 and 12 months after transplantation,the absolute cell counts of CD4+T were statistically lower in patients than in matched sibling donor hematopoietic stem cell transplantation(P<0.05);at 3 months after transplantation the absolute cell counts of B cells were statistically lower in patients than in MSD-HSCT(P<0.05);The rest was not statistically significant(P>0.05).2.Comparison of immune cells between the two modalities of HSCT and healthy subject groups at month 3,6,9 and 12 after transplantation:(1)matched sibling donor hematopoietic stem cell transplantation:absolute cell counts of CD4+T and B cells at month 3,6,9 and 12 after transplantation were statistically lower than those of healthy control groups(P<0.05);the absolute cell counts of NK cells were statistically lower than those of the healthy control groups at month 3,6,9 and 12 after transplantation(P<0.05),but the rest were not statistically significant(P>0.05);(2)haploidentical transplantation:the absolute cell counts of CD4+T,B cells and NK cells were statistically lower than those of the healthy control groups at 3,6,9 and 12 months after transplantation(P<0.05),but the rest were not statistically significant(P>0.05).3.The results of different immune cell changes at month 3,6,9 and 12 after transplantation in both transplantation modes:CD4+T and B cell numbers gradually recovered from the 3 months after transplantation after all-phase and haploidentical transplantation,and were still lower than those of healthy control groups until the 12 months after transplantation,in a significantly delayed state;NK cell numbers reached a basic plateau from the 3 months after transplantation and were able to reach the level of healthy controls;CD8+T cell numbers gradually increased from the 3 months after transplantation and reached and exceeded the level of healthy controls in the 12 months after transplantation.4.Correlation between haploidentical transplantation of different immune cells and OS:(1)OS:1)recovery of CD4+T cells from day 360 after transplantation was positively correlated with OS and was a good predictor;2)survival analysis showed that posttransplantation CD4+T-360d≥ 218/μL had better OS compared to patients with CD4+T360d<218/μL(2 year expected OS rate:85.70±8.00%vs 63.60± 10.30%,P=0.026).
Keywords/Search Tags:Allogeneic hematopoietic stem cell transplantation, Haploidentical hematopoietic stem cell transplantation, Matched sibling donor hematopoietic stem cell transplantation, Immune reconstruction
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