Philadelphia-like B-Cell Acute Lymphoblastic Leukemia in a Largely Hispanic Population: Disease Features and Outcomes in the Era of Immunotherapy a Single Institutional Study

• Published in: Blood 2023-11, Vol.142 (Supplement 1), p.4208-4208
• Main Authors: Ashouri, Karam, Hom, Brian, Rahimi, Yekta, Resnick, Karen, Nittur, Vinay, Hwang, Jennifer, Adnani, Blake, Chu, Mollee, Ginosyan, Anush Aram, Ireland, Robert, Bragasin, Eljie Isaak, Ye, Shirley, Savitala-Damerla, Lakshmi, Schiff, Kimberly, Chaudhary, Preet M., Siddiqi, Imran, Ladha, Abdullah, Ali, Amir, Woan, Karrune, Tam, Eric, Yaghmour, George
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2023-190716

Introduction: Philadelphia (Ph)-like B-cell acute lymphoblastic leukemia (ALL) is a high-risk subgroup of B- cell ALL with distinct genotypes, unified by a gene expression profile similar to Ph-positive ALL but lacking the BCR: ABL1 fusion. Previous studies have noted the increased prevalence of Ph-like B-cell ALL in Hispanic patients. Our study evaluates Ph-like B- cell ALL clinical/genomic features and outcomes in a predominantly Hispanic population. Methods: This is a retrospective chart review of ALL patients that underwent treatment for B-cell ALL at Norris Comprehensive Cancer Center (NCCC) between 2011 and 2023. Identification of fusions associated with Ph-like B-cell ALL was performed using cumulative results from RNA-seq, conventional cytogenetics, and fluorescence in situ hybridization (FISH) with reflex gene fusion transcript analysis. Additionally, we used the Anchored Multiplex PCR™-based multi-gene NGS assay designed to detect known and novel fusions and elevated gene expression levels using a proprietary algorithm in ALL. Cumulative incidence of relapse (CIR) was evaluated using competing risk regression (Fine-Gray method), with death as a competing outcome. Overall survival (OS) and event-free survival (EFS) were analyzed using Cox proportional hazards model. Events of interest for EFS were relapse, treatment failure, and death. Ph-negative B-cell ALL patients were set as the reference for survival analysis. Results: 253 patients were included with a median age at diagnosis of 42 years (range: 18-80). ALL subtypes included 64(25.3%) Ph-like, 77(30.4%) Ph-positive, and 112(44.3%) Ph-negative. Most were Hispanic (N = 186, 73.5%), and the median follow-up time was 27 months. The 3-year OS, EFS, and CIR were 81.3% (95% CI 75.7-87.4%), 49.1% (95% CI 42.7-56.5%), and 39.9% (95% CI 33.0-46.7%). CRLF2 related mutations constituted 44(68.8%) of Ph-like patients, with 9(14.0%) CRLF2-P2RY8, 24(37.5%) CRLF2-IGH, and 11(17.2%) CRLF2-other gene rearrangements. 19 Ph-like patients had non-CRLF2 mutations consisting of 13(20.3%) IGH, 3(4.7%) ABL1/2, 3(4.7%) JAK2, and 1(1.6%) EPOR rearrangements. Compared to Ph-negative, Ph-like patients were more likely to have a refractory disease (20.6% vs. 6.2% P=0.006) and require Blinatumomab (67.2% vs. 39.3% P