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

Philadelphia chromosome( Ph)-like acute lymphoblastic leukemia ( ALL) is a high-risk subtype of ALLin children. There are conflicting data on the incidence and prognosis of Ph-like ALLin adults. Patients with newly diagnosed B-cell ALL(B- ALL) who received frontline chemotherapy at MD Anderson Cancer Center underwent gene expression profiling of leukemic cells. Of 148 patients, 33.1% had Ph-like, 31.1% had Ph+ , and 35.8% had other B- ALLsubtypes (B-other). Within the Ph-like ALLcohort, 61% had cytokine receptor-like factor 2 (CRLF2) overexpression. Patients with Ph-like ALLhad significantly worse overall survival (OS), and event-free survival compared with B-other with a 5-year survival of 23% (vs 59% for B-other, P = .006). Sixty-eight percent of patients with Ph-like ALLwere of Hispanic ethnicity. The following were associated with inferior OS on multivariable analysis: age (hazard ratio [HR], 3.299; P P = .017), platelet count (HR, 7.437; P = .005), and Ph-like ALL(HR, 1.818; P = .03). Next-generation sequencing of the CRLF2 + group identifiedmutations in the JAK-STAT and Ras pathway in 85% of patients, and 20% had a CRLF2 mutation. Within the CRLF2 + group, JAK2 mutation was associated with inferior outcomes. Our findings show high frequency of Ph-like ALLin adults, an increased frequency of Ph-like ALLin adults of Hispanic ethnicity, significantly inferior outcomes of adult patients with Ph-like ALL, and significantly worse outcomes in the CRLF2 + subset of Ph-like ALL. Novel strategies are needed to improve the outcome of these patients.