The Prognostic Impact Philadelphia Like (CRLF2) Gene on the Outcome of Adult Acute Lymphoblastic Leukaemia

Abstract

Treatment outcomes of adult patients with B-cell acute lymphoblastic leukemia (B-ALL) remain suboptimal with long-term disease-free survival (DFS) of around 40% to 45%. This is in contrast to childhood B-ALL where DFS of > 90% is routinely achieved, the inferior outcome of older patients has been linked to several factors, both disease-related (higher frequency of high-risk genomic subgroups such as Philadelphia chromosome [Ph+]) and patient-related (poor tolerance to chemotherapy). A high-risk subgroup of B-ALL called Ph-like ALL was identified in children and adolescents and young adults (AYAs). The leukemic cell gene expression profile of Ph-like ALL is similar to that of Ph+ ALL; however, instead of BCR-ABL1, such patients harbor a highly diverse range of genetic alterations activating tyrosine kinase signaling. Ph-like ALL comprises up to 15% of childhood B-ALL, and 20% to 25% in AYAs, These patients have a very high rate of disease relapse and poor overall survival (OS). Our study shows a high frequency of Ph-like ALL in adults and significantly worse outcomes in the CRLF2+ subset of Ph-like ALL. Patients with CRLF2 rearrangement tended to be older and with higher WBC counts, lower hemoglobin and platelet counts at presentation than non-CRLF2 ALL. Patients with Ph-like ALL also had significantly worse OS and DFS