Analysis Of Risk Factors Of Secondary Cytopenias After Allogeneic Hematopoietic Stem.cell Transplantation In 291 Patients

BackgroundSecondary cytopenias were common complications after allogeneic hematopoietic stem cell transplantation,characterized by a reduction of one or more lines of peripheral blood.Severe cytopenias can result in an increased risk of infection and bleeding,which affects the survival and quality of life of transplant patients.Therefore,it is very critical to identity the risk factors of secondary cytopenias after transplantation in order to improve the prognosis of transplant patients.At present,it is considered that the recipients’ age,the intensity of the conditioning regime,HLA matching,the source of donor,CD34+cell dose,CMV infection,acute GVHD and other factors are related to the poor haemopoietic function post transplant.However,more comprehensive risk factors and specific pathogenesis still need to be further elucidated.In addition,it is unclear whether different transplant types,including matched sibling donor HSCT,matched unrelated donor HSCT and haploidentical hematopoietic stem cell transplantation,affect the development of post-transplant secondary cytopenias.ObjectiveTo investigate the incidence and risk factors of secondary cytopenias after allo-HSCT,and to compare the incidence and risk factors of secondary cytopenias among MSD-HSCT group,MUD-HSCT group and Haplo-HSCT group.MethodsWe retrospectively analyzed the clinical data of 291 blood disease patients who underwent allo-HSCT between September 2012 and November 2020 at the first affiliated hospital of Zhengzhou University.Patients were divided into four groups according to the type of reduction in peripheral blood cells post transplant:secondary leukopenia group,secondary anemia group,secondary thrombocytopenia group and secondary pancytopenia group.The risk factors of each group were evaluated by logistic regression analysis.In addition,the incidence and risk factors of secondary cytopenias in patients receiving MSD-HSCT(n=139),MUD-HSCT(n=52)and Haplo-HSCT(n=100)were analyzed.Result1.Hematopoiesis reconstruction:In 291 allo-HSCT patients,the median engraftment time of neutrophils and platelets was+13(+8～+23)day and+15(+9～+37)day,respectively.In MSD-HSCT group(n=139),MUD-HSCT group(n=52)and Haplo-HSCT group(n=100),the median engraftment time of neutrophils was+13 day,+13 day,+14 day(p=0.118),and the median engraftment time of platelets was+14 day,+15 day,+15 day(p=0.03).2.Incidences of CMV infection and aGVHD:In 291 patients,the incidence of CMV infection and grade Ⅱ to Ⅳ aGVHD was 42.3%and 17.2%respectively.The rates of CMV infection in MSD-HSCT group,MUD-HSCT group and Haplo-HSCT group were 26.6%,48.1%and 61%respectively(p＝0.000),and the rates of grade Ⅱto Ⅳ aGVHD were 17.3%,13.5%and 19.2%respectively(p=0.691).3.Incidence of secondary cytopenias:among the 291 patients,107(36.8%)had at least one type of cytopenia and 54(18.6%)had anemia with thrombocytopenia.23(7.9%)developed secondary pancytopenia with a median time of+82(+30～+302)day,including 4 cases in MSD-HSCT group(2.9%),6 cases in MUD-HSCT group(11.5%),and 13 cases in Haplo-HSCT group(13%)(p=0.009),the median time of pancytopenia was+66 day,+82 day,+84 day,respectively(p=0.692).The median time of secondary leukopenia was+77(+29～+3 02)day in 26 cases(8.9%),including 6 cases in MSD-HSCT group(4.3%),7 cases in MUD-HSCT group(13.5%),and 13 cases in Haplo-HSCT group(13%)(P=0.03),the median time was+64 day,+75 days and+82 day,respectively(p=0.44).The median time of secondary anemia was+66(+26-+353)day in 85 cases(29.2%),including 22 cases in MSD-HSCT group(15.8%),24 cases in MUD-HSCT group(46.2%),and 39 cases in Haplo-HSCT group(39%)(p=0.000),the median time was+66 day,+72 day,+61 day(p-0.865).The median time of secondary thrombocytopenia was+65(+30-+591)day in 98 cases(33.7%),including 30 cases in MSD-HSCT group(21.6%),22 cases in MUD-HSCT group(42.3%),and 46 cases in Haplo-HSCT group(46%)(p=0.000),the median time was+59 day,+73 day and+66 day(p=0.563).4.Risk factors:Multivariate analysis showed that grade Ⅱ to Ⅳ aGVHD was a common independent risk factor for both secondary leukopenia and secondary pancytopenia,HLA mismatch,unrelated donors,CMV infection and grade Ⅱ to ⅣaGVHD were identified as independent risk factors for secondary anemia.while the risk factors for secondary thrombocytopenia included CMV infection and acute GVHD grade Ⅱ～Ⅳ.There were differences in risk factors among different transplant groups.In MSD-HSCT group,we identified CMV infection and acute GVHD gradeⅡ-Ⅳ as common independent risk factors for both secondary anemia and secondary thrombocytopenia and only acute GVHD grade Ⅱ-Ⅳ for secondary leucopenia.For Haplo-HSCT recipients,acute GVHD grade Ⅱ-Ⅳ was the only independent risk factor for secondary anemia,no risk factors associated with other types of cytopenia were found.In addition,we did not find any risk factors associated with secondary cytopenias in MUD-HSCT patients.Conclusion1.The risk of secondary cytopenias was higher in MUD-HSCT and Haplo-HSCT than that in MSD-HSCT.2.HLA mismatch,unrelated donor,CMV infection,and grade Ⅱ to Ⅳ aGVHD significantly could increase the risk of secondary cytopenias in allo-HSCT patients.