Allogeneic stem cell transplantation (alloHSCT) is effective curative option for a broad range of primary immunodeficiencies (PIDs). Hematopoietic chimerism monitoring in patients with various PIDs and its connection with the outcome of alloHSCT is of great interest. In this study 16 alloHSCT in patients with PIDs were included. Three-year overall survival was 72.2 ± 12.0 %. Full donor chimerism (FDC) was achieved in 13 (81.25 %) patients. Prolonged persistence of mixed chimerism (MC) was observed in 3 (18.75 %) patients. In patients with MC in the peripheral blood, circulating T-cells are completely or predominantly of donor origin, whereas granulocytes are predominantly or completely recipient cells, and chimerism in B-cells differs significantly from 0 % chimerism to FDC. In patients with PIDs, engraftment of individual cell lines (split chimerism) could be observed. In some patients chimerism decreased during the first year after alloHSCT with its subsequent stabilization. Increasing MC is not associated with transplant rejection in PIDs. FDC in patients with PIDs provides restoration of all cell lines participating in the immune response regardless of the diagnosis, but it is associated with more frequent development of «graft-versus-host» disease (GVHD), which is a serious complication of alloHSCT and can lead to treatment-related mortality (TRM). MC/split chimerism, in which the frequency of development of GVHD is less, can also provide the formation of a full immune response and correction of other disease manifestations, but only when replacing defective cell lines according to the diagnosis.
At the present time, clinical relapses remain the major cause of treatment failure in children with acute lymphoblastic leukemia (ALL) treated by allogeneic hematopoietic stem cell transplantation (allo-HSCT). So far, the requirements for precise quantifi cation of minimal residual disease (MRD) aft er HSCT were did not confi rmed. Th e aim of this study was to evaluate the impact of MRD assays on management and prediction of outcomes aft er allo-HSCT. Patients and methods Th e Ig/TCR markers were identifi ed for MRD monitoring in 37 (82.2%) of 45 patients. Presence of high-level MRD aft er allo-HSCT was an unfavorable prognostic factor for the clinical outcome. Th e 3-year cumulative incidence (CI) of relapse in the patients with negative MRD vs MRD levels of ≤10-3 , and >10-3 proved to be 10.7±7.4%; 14.6±14.6%, and 100%, respectively (p<0.0001). Event-free survival (EFS) was 66.6±11.4% vs 43.8±18.8% vs 0% (p=0.0012) at the respective MRD levels, whereas overall survival (OS) was 83.6±8.8% vs 57.1±18.7% vs 0% (p=0.0083), resp., for undetectable, ≤10-3 , and >10-3 MRD levels. MRD positivity combined with increasing mixed chimerism (MC) was followed by relapse in almost all cases. MRD clearance was more oft en observed in patients with full donor chimerism (FDC) having graft-versus-host disease (GvHD) posttransplant, or aft er donor lymphocyte infusion. Conclusion Positive MRD aft er HSCT is an unfavorable factor for OS and EFS, being associated with ALL re-occurrence. We identifi ed the high-risk group for relapses aft er allo-HSCT among ALL patients, i.e., those cases which showed MRD positivity with mixed chimerism (MC) and absence of GvHD, and/or had MRD>10-3 .
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