Molecular genetic profile in BCR-ABL1 negative pediatric B-cell acute lymphoblastic leukemia can further refine outcome prediction in addition to that by end-induction minimal residual disease detection

Abstract

The recently proposed molecular genetic criteria promise improved risk prediction in B-cell acute lymphoblastic leukemia (B-ALL). This study assesses their utility in BCR-ABL1 negative pediatric B-ALL, particularly with respect to end-induction minimal residual disease (MRD). The DNA was analyzed for copy number alterations in CDKN2A/B, PAX5, IKZF1, and other genes. Seventy-six cases with a median age of 7 years (range: 2 months–18 years) were included. MRD status comprised MRD-positive (24; 32%), MRD-negative standard risk (20; 26%), intermediate risk (20; 26%), and high risk (12; 16%). Risk classification was based on age, initial total leukocyte count, central nervous system involvement, cytogenetics, day 8 prednisolone response, and MRD status after induction chemotherapy. The genetic profile based on Moorman’s criteria identified two subgroups with different event-free survival (EFS) (0.77 vs. 0.38; p = .045) and overall survival (OS) (0.90 vs. 0.30; p = .037) in the MRD-negative intermediate-risk group. The genetic profile also separated two subgroups with different EFS (0.75 vs. 0.41; p = .036) in the MRD-positive group. However, OS was not significantly different (0.75 vs. 0.57; p = .293).