| Objectives To investigate the early immune reconstitution of adult acute leukemia with umbilical cord blood transplantation(UCBT)and allogeneic peripheral blood stem cell transplantation(allo-PBSCT).Methods This study consistant of clinical and experimental components.(1)Clinical study:65 adults with acute leukemia who underwent UCBT or allo-PBSCT at a hospital from February 2017 to December 2018.All patients underwent a myeloablative preconditioning regimen using cyclosporine.Cyclosporin A(CsA)and mycophenolate mofetil(MMF)were used to prevent aGVHD.After UCBT and allo-PBSCT,the pre-engraftment syndrome(PES),hematopoietic reconstitution,aGVHD,Infection,cGVHD,relapse,death,and immune function reconstruction of the two groups were compared and analyzed.(2)Experimental study:At 1,3,6,9,and 12 months after transplantation,lymphocytes,CD3~+T cells,CD4~+T cells,CD8~+T cells,NK cells,the ratio and absolute number of CD19~+B cells,Treg cells and Breg cells in the peripheral blood of the two groups were assessed by eight-color flow cytometry.Screening and collecting two groups of non-cGVHD patients with 5ml of peripheral blood from 6 to 9months after HSCT and CD19~+B cell gene sequencing.Results(1)Clinical results:From February 2017 to December 2018,65 adult-patient with acute leukemia were treated with allogeneic transplantation,including 45 cases of UCBT and 20 cases of HLA-matched sibling donor allo-PBSCT.Gender(P=0.185),age(P=0.148),body weight(P=0.246),blood type,disease type(P=0.658),and disease status(P=1.000)in the two groups with no significant difference.In the UCBT group,the engraftment time of neutrophil count(ANC)and platelet count(PLT)were 16(11~33)d and 40(15~96)d,respectively,and in HLA-matched sibling donor allo-PBSCT group,engraftment time of ANC and PLT were 10(9~14)d and 11(8~40)d respectively.There was a statistically significant difference in the engraftment time of neutrophils and platelets between the two groups(P<0.01).There were 27 cases of PES in the UCBT group and 0 cases of HLA-matched sibling donor allo-PBSCT,the difference was statistically significant(P<0.01).There were 18 cases(40%)of aGVHD in UCBT group and 4 cases(21%)of aGVHD in HLA-matched sibling donor allo-PBSCT group(P=0.148).There were 3 patients and 11 patients with cGVHD in the UCBT group and the HLA-matched sibling donor allo-PBSCT group,the 2-year cumulative incidence of cGVHD was 6.7%and 55%,respectively,and the difference was statistically significant(P<0.01).In the UCBT group,38 cases(84.4%)were infected with cytomeglovirus(CMV),and 8 cases(40%)were in the HLA-matched sibling donor allo-PBSCT group.the difference was statistically significant(P<0.05).The relapse and death of the UCBT group were 3(6.7%)and 6(13.3%),and in the HLA-matched sibling donor allo-PBSCT group were 1(5.3%)and 3(10%),respectively,there was no significant difference in relapse and death(P>0.05).The1-year cumulative survival rates of the two groups were 79.4%±7.3%and 81%±10.5%,respectively,and the difference was no statistically significant(P>0.05).(2)Experimental results:Peripheral blood immune function was monitored and compared between the two groups at 1,3,6,9,and 12 months after transplantation.(?)The median CD3~+T cells,,CD4~+T cells,CD8~+T cells and Treg cells in the 1M recipients were significantly slower than the HLA-matched sibling donor allo-PBSCT in the 1M after transplantation,the difference was statistically significant(P<0.05).There was no significant difference in T cell reconstitution between the two groups after 3,6,9 and 12after transplantation(P>0.05).(?)The NK cells in the UCBT group and the HLA-matched sibling donor allo-PBSCT group had similar reconstitution speeds in the1,3,6,9 and 12M groups after transplantation,and the difference was no statistically significant(P>0.05).(?)The early reconstitution speed of CD19~+B and Breg cells in UCBT group and HLA-matched sibling donor allo-PBSCT group was similar,and the difference was no statistically significant(P>0.05).(?)The median value of CD19~+B cells after transplantation was divided into CD19~+B cell high group and low group,3M and 6M after transplantation in UCBT group,3M after transplantation,and CD19~+B cells in group of allo-PBSCT group.The incidence of high-level cGVHD was significantly lower than that of the low CD19~+B cells(P<0.05).B cell gene sequencing in 6M after transplantation,CD200 expression in B cells of UCBT group was significantly higher than that in allo-PBSCT group.Conclusions(1)The long-term survival rate of UCBT in adult acute leukemia was not statistically different from that of HLA-matched sibling donor allo-PBSCT,suggesting that cord blood can be used as an effective alternative donor for adult patients without HLA-matched donors.(2)The early reconstitution of CD3~+T,CD8~+T and CD4~+T cell subsets in UCBT patients was slower than that of HLA-matched sibling donor allo-PBSCT.The early CMV infection rate of UCBT patients was significantly higher than that of allo-PBSCT group.(3)Early reconstitution of CD19~+B cells in patients after transplantation suggests a lower incidence of cGVHD.(4)The expression of CD200 in B cells of UCBT patients was significantly higher than that of allo-PBSCT patients in6M after transplantation,suggesting that the expression of CD200 on B cells after transplantation in UCBT patients may play an important role in reducing the occurrence of cGVHD. |
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