Abstract
PURPOSE
WHO5 (2022) classification of B-lymphoblastic leukemia (B-ALL) incorporates several novel entities requiring high-throughput sequencing for their accurate characterization. The clinical relevance of this classification in the context of contemporary measurable residual disease (MRD)–directed therapy is unclear.
METHODS
We analyzed 533 pediatric B-ALL uniformly treated with Indian Collaborative Childhood Leukaemia group (ICiCLe)-ALL-14 protocol as defined by WHO-2016 and reclassified them as per WHO5 using targeted sequencing, FISH, and cytogenetics.
RESULTS
Subtype-defining genomic abnormalities were identified in 81.2% of the cohort as per the WHO5 classification. Among the new subtypes,
PAX5
alt
and
MEF2D
-r were associated with a trend toward an inferior 3-year event-free survival (EFS) of 32.8% (
P
= .003) and 33.7% (
P
= .091), respectively. We developed a three-tier genomic risk stratification model incorporating 15 genomic subtypes and the
IKZF1
deletion. Children with standard (SGR), intermediate (IGR), and high genomic risk (HGR) demonstrated 3-year EFS of 80.4%, 59.3%, and 45.8% (
P
P
P
v
80.8% PI-MRD–positive patients,
P
= .530). On multivariable analysis, genomic risk (hazard ratio [HR], 1.7 [95% CI, 1.41 to 2.01];
P
P
= .009), and PI-MRD (HR, 2.2 [95% CI, 1.66 to 2.90];
P
CONCLUSION
The study demonstrates the potential role of genomic risk stratification, in conjunction with MRD, in stratifying patients into clinically relevant risk categories.