The effect of the minimum residual disease on the risk of relapse at allogeneic hematopoietic stem cell transplantation in children, adolescents, and young adults with acute lymphoblastic leukemia

Abstract

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.