Influence of Minimal Residual Disease at Day 15 of Induction Therapy on Survival of Children with Acute Lymphoblastic Leukemia.

Abstract

The aim of the study was to evaluate the impact of minimal residual disease (MRD) on day 15 of induction therapy (d15) on the treatment outcome in children with acute lymphoblastic leukemia (ALL). The study included 74 patients (1-18 years) with ALL, who were treated at the Pediatric Clinic of the University Clinical Center Banja Luka from January 2011 to May 2021. All patients were treated according to ALL IC-BFM 2009 protocol. MRD on bone marrow was assessed d15, using the multiparameter flow cytometry method (FCM). Of all, 59.46% of patients had MRD d15 0.1-10%, MRD<0.1% had 18.92% of patients, and 21.62% had MRD >10%. Patients with the lowest MRD had the highest 5-year overall survival (OS) and event-free survival (89.5% and 91% respectively) and the lowest cumulative risk for relapse or death (9.7% and 8.1%), in contrast to patients with MRD>10% in whom OS was 80.0%, and the risk of recurrence is 20%. Predicted MRD d15 was significantly associated with prednisone response assessed in the peripheral blood on day 8 (P<0.001) and statistically significantly positive correlation (r=0.498; P<0.001) was found. MRD measurement d15 has a great prognostic significance for patients in the standard and high risk groups, but not for patients in the intermediate risk group. The introduction of additional testing is necessary for better identification of patients with an increased risk of disease recurrence.