Prevalence, clinical and haematological profile and outcome of BCR-ABL1-like acute lymphoblastic leukaemia in Indian children: A prospective observational study.

Background: BCR-ABL1-like acute lymphoblastic leukaemia (ALL) represents a perplexing subclass of ALL mainly due to genomic heterogeneity and non-availability of standardized diagnostic tests. The data on prevalence, clinical-haematological profile and outcome are limited, more so from low-middle income countries. Methods: This prospective observational study enrolled children<14 years with B-ALL. Recurrent genetic/chromosomal aberrations were excluded. BCR-ABL1-like aberrations were analysed using Polymerized Chain Reaction (PCR) or Next-Generation Sequencing (NGS). Two groups with/without BCR-ABL1-like ALL (Mut+/Mut-) were compared. Results: Out of 214 eligible children; 75 with "B-other ALL" were analysed for BCR-ABL1-like aberrations. Their prevalence was 34/214 (15.8%) in B-ALL and 34/75 (45.3%) in "B-other" ALL (PCR:33.3% and NGS:53.3%). Majority of the aberrations were JAK2E16 and ILR7e5/ILR7e6 with PCR and RAS pathway and PAX5 fusion with NGS. Baseline demographic, clinical and laboratory parameters including aberrant flowcytometry were comparable in Mut+ and Mut-groups. Children with day-8 absolute blast count (ABC) were higher in Mut+ group. High end-induction minimal residual disease (MRD) was comparable in two groups. Number of NCI-standard risk (SR) at diagnosis with high D-8 ABC or high MRD was higher in Mut+ group. Similar results were found when aberrations were analysed by NGS alone. In all 56 children are alive, 19 had an event (relapse/death). The outcomes were comparable in two groups with median follow-up of 1075 days (IQR: 660-1527); when analysis was based on combined as well as NGS-based methodology alone. Conclusions: We report 15.8% prevalence of BCR-ABL1-like ALL in children by PCR or NGS. High D-8 ABC was associated with BCR-ABL1-like ALL with no impact on outcomes.