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 .
Minimal residual disease (MRD) is an independent predictor of relapse risk for childhood acute lymphoblastic leukemia(ALL). The aim of study to investigate impact MRD by real-time quantitative polymerase chain reaction before (day –21) andat +30 ± 10, +60 ± 10, +100 ± 10, +180 ± 10, +365 ± 10 days after hematopoietic stem cell transplantation (HSCT), and PCR-chimerismon transplant outcomes children with ALL. The study was approved by the Independent Ethics Committee and the Scientific Councilof the Belarusian Research Center for Pediatric Oncology, Hematology and Immunology (Republic of Belarus). Fifty one patientswith ALL underwent allogeneic transplantation in remission (period 12.2010–12.2017, median follow-up 2,8 years). 3-years eventfreesurvival (EFS) and cumulative incidence of relapse (CIR) were 71.6 ± 17.1% and 14.3 ± 14.3% respectively for patients (n = 7)with pre-transplant MRD < 10-4 and 0% (n = 4, p = 0.0046) and 50.0 ± 29.2% (p = 0.3111) respectively for MRD ≥ 10-4. After HSCT(n = 29) 3-years EFS and CIR were 22.2 ± 13.9% and 66.7 ± 18.1% respectively for recipients (n = 9) with MRD ≥ 10-4 at leastin one analyzed point. In comparison, patients with MRD < 10-4 at all points (n = 20) had EFS and CIR 70.0 ± 10.2% (p = 0.0172)(HR = 12.3; 95% CI: 2.33–64.87; p = 0.0031), and 5.0±5.0% (p = 0.0004) (HR = 50.7; 2.5–97.5% CI: 1.60–1608.56; p = 0.0260)respectively. Patients with mixed chimerism at least in one analyzed point since day +30 to +365 hadn't significant differences OS,EFS, CIR but were worse (57.1%, 40.0% and 50.0% respectively) in comparison full chimerism patients (79.5% (p = 0.248), 71.4%(p = 0.072) and 20.0% (p = 0.070) respectively). MRD is significant predictor of relapse risk for childhood ALL at time of HSCT.MRD < 10-4 patients have significantly better EFS and CIR in comparison MRD ≥ 10-4 patients before and after HSCT.
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