Updates on lymphoblastic leukemia/lymphoma classification and minimal/measurable residual disease analysis

Lymphoblastic leukemia/lymphoma (ALL/LBL), especially certain subtypes, continues to confer morbidity and mortality despite significant therapeutic advances. The pathologic classification of ALL/LBL, especially that of B-ALL, has recently substantially expanded with the identification of several distinct and prognostically important genetic drivers. These discoveries are reflected in both current classification systems, the World Health Organization (WHO) 5th edition and the new International Consensus Classification (ICC). In this article, novel subtypes of B-ALL are reviewed, including DUX4, MEF2D and ZNF384-rearranged B-ALL; the rare pediatric entity B-ALL with TLF3::HLF, now added to the classifications, is discussed; updates to the category of B-ALL with BCR::ABL1-like features (Ph-like B-ALL) are summarized; and emerging genetic subtypes of T-ALL are presented. The second half of the article details current approaches to minimal/measurable residual disease (MRD) detection in B-ALL and T-ALL and presents anticipated challenges to current approaches in the burgeoning era of antigen-directed immunotherapy.