Clinical Study On Sequential Monitoring Of Chimerism Following Allogeneic Hematopoietic Stem Cell Transplantation

Objective:To evaluate monitoring of chimerism of cell subsets in the estimation of engraftment and occurrence of acute graft versus host disease(GVHD) and in the prevention and treatment of graft rejection and disease relapse following allo-HSCT.Methods:Sixty five patients received allo-HSCT, including acute myeloid leukemia(n=22), acute lymphoblastic leukemia(n=8), chronic myeloid leukemia(n=21), multiple myeloma(n=6), aplastic anemia(n=3), myelodysplastic syndrome(n=2), non-Hodgkin lymphoma(n=1), paroxysmal nocturnal hemoglobinuria(n=1) and oophoroma(n=1). All of their chimerism of peripheral blood and bone marrow were monitored at regular intervals. The chimerism of Fluorescence-activated cell sorter(FACS)sorted CD3+T lymphocytes of 65 cases, CD3-CD56+CD16+NK lymphocytes of 52 cases, CD15+ granulocytes of 32 cases and CD19+B lymphocytes of 20 cases post transplants were analyzed by polymerase chain reaction amplification of short tandem repeats(PCR-STR).Results:On day 7 posttransplant, NK cell donor chimerism (55.5%)was higher than other cell subsets. T lymphocyte was the latest one to reach full donor chimerism(FDC) on median day 21 posttransplant. Patients whose donor T lymphoctes chimerism more than 70% on day 7 posttransplant and more than 95% on day 14 were at high risk of acute GVHD. In all cases except B-ALL, the decreasing DC in T lymphocyte was observed before molecular or hematological relapse occurred. It is possible to evaluate the effect of treatment and direct further immunotherapy by analyzing kinetic donor chimerism.Conclusion:The results demonstrated that serial and quantitative T cell chimerism analysis provided a reliable and rapid screening method for the early detection of engraftment, graft rejection, disease relapse and occurrence of acute GVHD. It is therefore a prognostic tool to identify patients at high risk of acute GVHD and disease relapse following allo-HSCT.