Clinicopathologic and molecular profile of Philadelphia like ALL in Hispanic population of Central Valley California.

Abstract

7524 Background: Philadelphia-like Acute B-ALL(PHL) are Ph negative B-ALL(PHN) with molecular signatures that mirrors Ph + B ALL. Studies have shown worse prognosis in this subtype of leukemias, but few have reported outcomes with incorporation of novel agents. Our study seeks to describe clinical and molecular profile of a single center experience. Methods: This is a retrospective study of patients treated for PHL in community referral center in central valley of California from 1/2009 to 12/2019. Of the initial 71 patients, 34 met the inclusion and exclusion criteria. 16 of the 34 patients who had Next Generation Sequencing (NGS) by Foundation Medicine (14) or NeoGenomics (2). Data for 34 PHN and 8 with PHL patients were analyzed. Results: There are no differences in mean ages (36.7 x 36) and gender between the PHN and PHL subgroup. There is over representation of Hispanics in both groups (63% x 65%) with slightly male predominance in PHL group (62%). This ratio is slightly higher than reported by 2010 census of 46%. The BMI 38.4(27.5-48.4) vs. 29.1(26.6-39.1), mean WBC (71 vs. 58), bone marrow CD20+ by flow cytometry (90% vs. 63%) and abnormal cytogenetics (50% vs.15%) are all higher in PHL compared to PHN group. The prevalence rate of PHL signature in 16 tested patients is 8(50%). CRLF2 like subtype accounted for 6/8(75%), with 1 each of ABL-like and JAK-Stat subtype. All patients harbored multiple other mutational abnormalities in addition to those associated with Ph-like genetic signatures (Table). The median number of mutations was 4.55(3-7). The distribution of the 20 other mutation is as shown in table. 6 patients had morphological remission after induction chemotherapy of HyperCVAD (37%) and CALGB 10403 (25%) with measurable MRD in 5 of the patients. 7 patients were exposed to novel therapy; Blinatumomab; 2nd line (6 patients), Cart T cell; 3rd line (2 patients), Inotuzumab; 3rd line (3 patients) and ASCT; (3 Patients post second- or third-line remission). 2 patients died at the time of data cut off, 1 from infection and other from refractory leukemia. Conclusions: Our data shows high incidence of PHL signatures in the cohort. The mutational heterogeneity between and within patients, may represent sub-clonal population vs. passenger and hence poor clinical outcomes. [Table: see text]