Risk Factors For Acute Graft-Versus-Host Disease In Children With Thalassemia Major After Allogeneic Hematopoietic Stem Cells Transplantation

Objective To analysis risk factors for acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation in 338 patients with thalassemia major。Method We retrospectively analyzed clinical information from 338 patients with thalassemia major who underwent allogeneic hematopoietic stem cell transplantation at the Pediatric Transplantation Center of Nanfang Hospital Southern Medical University from January 2014 to December 2018.Univariate analysis and multivariate analysis were used to identify the risk factors for aGVHD after transplantation,including patient age,patient gender,differences in sex and ABO blood group between donor-recipient pairs,pretransplantation serum ferritin level,the degree of human leukocyte antigen(HLA)matching between donors and recipients,graft source,mononuclear cell(MNC)dose and cytomegalovirus(CMV)infection.Result 338 patients with thalassemia major received transplants with grafts from HLA-matched(n=247),HLA-mismatched(one or two HLA allelic mismatch,n=50),and HLA-haploidentical(more than 3 HLA allelic mismatch,n=41)donors.Acute graft-versus-host disease occured in 71 patients,with a median time of 27.3(2-84)days,and the incidence of garde Ⅱ～Ⅳ aGVHD was 12.5%,of which 22 cases(6.7%)were in grade Ⅱ,11 cases(3.4%)in grade Ⅲ,and 8 cases(2.4%)in grade Ⅳ.60 cases involved skin,28 involved intestinal,4 involved liver,14 involved both skin and intestine,1 involved both skin and liver,3 involved skin,liver and intestine.Univariate analysis showed that CMV infection and the degree of HLA matching were risk factors for garde Ⅱ～Ⅳ and garde Ⅲ～Ⅳ aGVHD.Logistic regression analysis showed that CMV infection(OR=3.62,95%CI=[1.80-7.25],P<0.01)was independent risk factors for grade Ⅱ～Ⅳ aGVHD.Also CMV infection(OR=6.64,95%CI=[2.55-17.30],P<0.01)was independent risk factors for gardeⅢ～Ⅳ aGVHD.328 patients survived among 338 patients,10 patients relapsed,and 10 patients died,of which 2 patients died of grade Ⅳ aGVHD.The Kaplan-Meier method was used to analyze transplant-related mortality.The transplant-related mortality of grade 0～I aGVHD and garde Ⅱ～Ⅳ aGVHD was 1.7%and 12.2%,respectively.Conclusion 1.NF-14-TM HSCT protocol can reduce incidence of aGVHD,and HLA-haploidentical hematopoietic stem cell transplantation is a safe and effective way to cure children with thalassemia major in the absence of proper donors.In complementary transplantation increasing MNC dose has no obvious correlation with the incidence of aGVHD.2.CMV infection is an independent risk factor for aGVHD.Improving the prevention of CMV infection may reduce the incidence and severity of aGVHD.3.aGVHD is an risk factor for transplant-related mortality.Strengthening the prevention and treatment of moderate to severe aGVHD can effectively improve overall survival.