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Haploidentical Peripheral Blood Stem Cell Transplantation For Hematologic Malignancies:Prognostic Analysis

Posted on:2020-02-09Degree:DoctorType:Dissertation
Country:ChinaCandidate:J WangFull Text:PDF
GTID:1364330602970665Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
IntroductionAllogeneic hematopoietic stem cell transplantation(allo-HSCT)is considered the treatment of first choice for intermediate-risk and high-risk hematologic malignancies in there first complete remission.Because of nearly all patients have HLA-haploidentical related donors,haploidentical hematopoietic stem cell transplantation(haplo-HSCT)is widely used in clinical.Haplo-HSCT is commonly used T-Replete protocol in China,using the "GIAC" system:G-CSF-stimulation of the donor;Intensified immunosuppression through post-transplantation CsA,mycophenolate mofetil(MMF),and short-course methotrexate;Antithymocyte globulin(ATG)added to conditioning to help prevent GVHD and aid engraftment;Combination of peripheral blood stem cell and bone-marrow grafts.This study retrospectively reviewed the outcomes of patients with hematologic malignancies underwent peripheral blood stem cell transplantation(PBSCT)at the Hematopoietic Stem Cell Transplantation Center of the First Affiliated Hospital of Zhengzhou University,we comparative analyzed the efficacy of haplo-PBSCT combined with HLA-identical sibling transplantation,the incidence of GVHD and other complications,risk factors affecting prognosis after haplo-PBSCT were also analyzed.MethodPatients data:176 patients with hematologic malignancies receiving PBSCT from either HLA-identical sibling donor(ISD,n=78)or haploidentical donor(HID,n=98)between April 2011 and August 2018 were enrolled.Patients in the ISD group were older than those in the HID group(p=0.001),and the male ratio was lower in the ISD group,p=0.025.The disease distribution and the disease remission status before transplantation were basically the same between the two groups.The conditioning therapy was modified BuCy protocol,ATG was added in the HID group.CsA?MMF and short-term MTX were administered to prevent graft-versus-host disease.ResultsThe median follow-up time of 176 patients was 314(36-1810)days.The 1-year and 3-year cumulative overall survival(OS)rates were lower in the HID group than in the ISD group,[(49.2±5.7)%vs.(73.5±5.3)%,p<0.001;(39.11±6.1)%vs(61.8 ±6.0)%,p=0.001].The 1-year relapse rate(RR)in the HID group was higher than in the ISD group[(35.7±6.2)%vs.(17.4±4.6)%,p=0.004],and the cumulative disease-free survival(DFS)rate and cumulative non-recurrence in the two groups.There were no statistically significant differences in disease-free survival(DFS)and nonrelapse mortality(NRM).Engraftment:the granulocytes were all successfully engraftment,There were no significant differences in neutrophil engraftment,platelet engraftment,and erythroid engraftment between the two groups.The HID group received more platelet transfusion at(0-100)days after HSCT than the ISD group,[10(2-57)U ? 6(1-27)U,p=0.000].There were no statistically significant differences in red blood cell transfusion between the two groups.GVHD:the cumulative incidence of aGVHD in in the HID group was higher than in the ISD group(53.1%vs 23.1%,p<0.001),but there was no statistically significant difference in cumulative incidence of ?-? degree aGVHD between the two groups(9.8%vs 3.8%,p=0.181).Cytomegalovirus(CMV)infection:the cumulative incidence of CMV infection was higher in the HID rroup[67.3%vs 31.3%,p=0.000],and CMV infection occurred earlier than in the ISD group,p=0.004.Prognosis analysis:1,compared with the standard-risk group,OS and DFS were lower and NRM was higher in the high-risk group,p values were 0.041,0.045 and 0.002,respectively;2,compared with patients without or with grade ? to ? aGVHD,OS and DFS for patients with grade ? to ? aGVHD were lower,and NRM was higher,the p values were 0.000,0·000,and 0.000;3,OS?DFS for PLT<50×109/L group at+60 day were lower,and NRM was higher than PLT>50×109/L group,p values were 0.049,0.032,and 0.007,respectively;4,transfusion of RBC more than the median number(?6 U)was associated with higher risk of NRM,p=0.040;5,OS?DFS were lower and NRM was higher in EBV reactivation group than non-EBV reactivation group,p values were 0.006,0.009 and 0.017,respectively.Multivariate analysis showed that high-risk strata was an independent risk factor for OS,DFS and RR,grade ?-? aGVHD was an independent risk factor for DFS.In 92 patients who survived more than 60 days after transplantation,the median count of neutrophils,hemoglobin and platelet were 2.5(0.2-14.7)×109/L,98.5(49-143)g/L and 56.5(7-259)×109/L at+60 day after transplantation,the incidence of poor function of platelet(30?PLT<80×109/L)was significantly higher than neutropenia(ANC<1.5×109/L)and hemoglobin reduction(Hb<80g/L)(48.9%vs 21.7%,p<0.001;48.9%vs 22.8%,p<0.001).The incidence of thrombocytopenia(PLT?29×109/L)at+60 day and+ 100 day after transplantation were 23.9%and 17.3%,respectively.Compared with the poor function of platelet group and platelet recovery group,OS and DFS were lower,NRM was higher in thrombocytopenia group at+60 day;OS was lower,NRM was higher in the thrombocytopenia group at+100 day.Multivariate analysis showed that grade ?-? aGVHD increased the risk of thrombocytopenia at+60 day.Multivariable analysis showed that PLT?29×109/L at+60 day was an independent risk factor for NRM,p value was 0.012;high-risk strata was an independent risk factor for RR,p value was 0.012;PLT ?29×109/L at+60 day and high-risk strata were risk factors for OS and DFS.Conclusion1 Compared with the HLA-identical sibling PBSCT,the cumulative OS rate decreased,and the 1-year cumulative relapse rate increased,but there were no statistically significant differences in the cumulative DFS rate and NRM rate after Haplo-PBSCT.The incidence of CMV infection rate and aGVHD increased,but the cumulative incidence of ?-? aGVHD not increased after Haplo-PBSCT.2 The incidence of thrombocytopenia after haplo-PBSCT was high,PLT?29×109/L at+60 day was an independent risk factor for NRM,and it was also a risk factor for OS and DFS.Grade ? to ? aGVHD was an independent risk factor for thrombocytopenia.3 High-risk strata was an independent risk factor for RR,and it was also a risk factor for OS and DFS.
Keywords/Search Tags:haploidentical peripheral blood stem cell transplantation, hematologic malignancies, thrombocytopenia, Grade ? to ? aGVHD, Red Blood Cell transfusion, efficacy, prognosis
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