Ph-like acute lymphoblastic leukemia: a high-risk subtype in adults.

Ph-like acute lymphoblastic leukemia (ALL) is a high-risk subtype of ALL in children. There are limited and conflicted data on the incidence and prognosis of Ph-like ALL in adults. Patients with newly-diagnosed B-ALL who received frontline chemotherapy at MD Anderson Cancer Center underwent gene expression profiling of leukemic cells to identify Ph-like ALL. Patients received hyper-CVAD (80%) or augmented-BFM (20%) regimen. Of 148 patients, 33.1% had Ph-like, 31.1% had Ph+, and 35.8% had other B-ALL subtypes (B-other). Within the Ph-like ALL cohort, 61% had CRLF2 overexpression. Patients with Ph-like ALL had significantly worse overall survival (OS), event-free survival, and remission duration compared to B-other with a 5-year survival of 23% (vs. 59% for B-other, p=0.006). Sixty-eight percent of patients with Ph-like ALL were of Hispanic ethnicity (78% among the CRLF2+ group). The following were independently associated with inferior OS on multivariable analysis: age (hazard ratio [HR] 3.299, p<0.001); WBC count (HR 1.910, p=0.017); platelet count (HR 7.437, p=0.005) and Ph-like ALL (HR 1.818, p=0.03). Next-generation sequencing of the CRLF2+ group identified mutations in JAK-STAT and Ras pathway in 85% of patients, and 20% had a mutation of CRLF2 Within the CRLF2+ group, JAK2 mutation was associated with inferior outcomes. Our findings show high frequency of Ph-like ALL in adults; an increased frequency of Ph-like ALL in adults of Hispanic ethnicity; significantly inferior outcomes of adult patients with Ph-like ALL; and significantly worse outcomes in CRLF2+ subset of Ph-like ALL. Novel strategies are needed to improve the outcome of these patients.