Long-term Analysis Of Chimerism And Intervention Of Mixed Chimerism After Hematopoietic Stem Cell Transplantation For Thalassemia Major

Objectives: This study summarized the long-term outcome of chimera after hematopoietic stem cell transplantation for thalassemia major.Donor lymphocytes infusions was administered to some patients with unstable mixed chimerism.To provide the theoretical and clinical evidence of hematopoietic stem cell transplantaion for thalassemia major.Methods: 1.A total of 306 patients of thalassemia major who recieved allogeneic hematopoietic stem cell transplantation and had regular follow-up with chimerism in our hospital were retrospectively analyzed from September2012 to December 2020.The median age was 6 years old(range 2～19 years).185 patients were male,121 patients were female.The median follow up period was 45 months(range 16～111 months).Fluorescence in situ hybridization(FISH)was performed on PB when host and donor were sex mismatched.STR-PCR was performed when host and host were sex-matched.2.The patients with unstable mixed chimerism after hematopoietic stem cell transplantation were treated donor lymphocyte infusions(DLI).The infusion dosages of mononuclear cells was 1-2*10^8/kg.The cytopenia、 graft versus host disease(GVHD)、change of chimerism and survival associated DLI were observed.Results: 1.The neutrophil engraftment time was 12.49±2.38 days and11.67±2.22 days in mixed chimerism group and complete chimerism group respectively.The platelet engraftment time was 17.90±7.62 days and 201815.28±7.80 days in mixed chimerism group and complete chimerism group respectively.44/306(14.4%)had mixed chimerism(MC)in the last follow-up.Fourteen(4.6%)patients had MC at +1 month after transplantation.16(5.2%)patients had MC at +2 months after transplantation.25(8.2%)patients had MC at +6 months after transplantation.17(5.5%)patients had MC at +12months after transplantation.12(3.9%)patients had persistent MC in the last follow-up.Uni-and multivariate logistic regression analysis showed male、age below 6 years old and cord combined bone marrow transplantation were high-risk factors for MC.Once the chimerism of grade Ⅱ was determined,the immunosuppressive agent was tapered and stopped.No patients developed Gv HD.The chimerism of 22 patients was reversed from mixed chimerism to complete chimerism.12 patients were persistent mixed chimerism in the last follw-up.One patient received interferon injection and the chimerism rate was improved.9 patients received donor lymphocyte infusions and the chimerism of 9 patients was reversed to complete chimerism.6 patients developed DLI-related acute GVHD.None had donor lymphocyte infusion related cytopenia.The median follow-up period was 45 months(range: 16–111).31 patients reversed to complete chimerism.12 patients maintained persistent mixed chimerism.1 patient rejected the graft.2.A total of 23 patients received donor lymphocyte infusions.The cumulative incidence of acute graft versus host disease was 43.7%.The cumulative incidence of chronic graft versus host disease was 26%.3 patients occurred DLI related cytopenia.20 patients reversed to CC and 1 patient evolved from grade Ⅱ mixed chimerism to grade Ⅰ mixed chimerism.2 patients rejected graft.The effective rate of DLI that reversed unstable mixed chimerism was 91.3%.Conclusion: 1.Mixed chimerism existed after allogeneic hematopoietic stem cell transplantation for thalassemia major.The chimera required regular follow-up.2.The risk factors for MC was male、 age below 6 years old and cord combined bone marrow transplantation.3.On tapering immunosuppressive agents and donor lymphocyte infusions could promote the transition from mixed chimerism to complete chimerism.The graft rejection could prevented.4.Donor lymphocyte infusions was an effective treatment for unstable mixed chimerism after hematopoietic stem cell transplantation for thalassemia major.