CRLF2-rearrangement and Extramedullary Disease in B-cell Acute Lymphoblastic Leukemia: A Possible Link?

Cytokine receptor-like factor 2 rearrangement (CRLF2r), an aberration causing a Philadelphia chromosome-like (Ph-like) gene expression profile and a poor prognostic marker in B-cell acute lymphoblastic leukemia (B-ALL), endows relative chemotherapeutic-resistance. Extramedullary disease (EMD), including both central nervous system (CNS) and non-CNS involvement, can also be associated with worse outcomes. The relationship between CRLF2r and EMD is unknown. Based on an initial observation of patients with relapsed/refractory (r/r) CRLF2r B-ALL and EMD, a single-center retrospective review was conducted to evaluate the incidence of EMD in CRLF2-r B-ALL patients. Across 177 children, adolescents, and young adults with r/r B-ALL, 21 (11.9%) harbored CRLF2r of whom 19 (90.5%) had EMD at some point during their treatment course. In contrast, only 78 of 156 (50%) patients without CRLF2r ever had EMD (p=0.0003). In the CRLF2r cohort, 8 (38.1%) presented with EMD at diagnosis: 7 with CNS and 1 with non-CNS EMD. At relapse, 17 (80.9%) had EMD: 4 (19%) had CNS-EMD, 9 (42.9%) had non-CNS-EMD and 4 (19%) had both. Isolated EMD was observed in 2 (11.8%) patients at first relapse and in 3 (17.6%) patients with multiple relapses. Given these findings, further study to evaluate this potential association between EMD and CRLF2r in r/r B-ALL is indicated.