Inferior Outcomes in Acute Lymphoblastic Leukemia With Translocation (14;18).

Abstract

Introduction: The (14;18)(q32;q21) chromosomal translocation leading to IGH::BCL2 rearrangement, has been rarely described in B-cell acute lymphoblastic leukemia (B-ALL), mainly in association with MYC rearrangement. The outcome of B-ALL harboring t(14;18)(q32;q21) without MYC rearrangement remains unknown.

Methods: We retrospectively reviewed 2778 cases of B-ALL treated at our institution and identified those harboring a t(14;18)(q32;q21) by karyotype. Cases with concomitant MYC rearrangement and cases of lymphoma were excluded. Three patients with no MYC rearrangement by karyotype but without further confirmation by Fluorescence In Situ Hybridization (FISH), were included.

Results: Five patients were included in this analysis, with a median age of 35 years (range, 19-58); 1 patient had central nervous system involvement at diagnosis. Induction therapy consisted of hyper-CVAD in 3 patients, hyper-CVAD with inotuzumab ozogamicin in 1 patient, and asparaginase-based regimen in 1 patient. Four patients (80%) responded, with a median duration of response of 12.9 months (range, 5.1-32.9); 1 patient had primary refractory disease. None of the patients proceeded to an allogeneic hematopoietic stem cell transplantation (HSCT). Four patients received salvage chemotherapy and eventually progressed and died. One patient received salvage therapy with subcutaneous blinatumomab and achieved complete remission with negative measurable residual disease (MRD) by next-generation sequencing (NGS) after 3 courses of therapy. After a median follow-up of 13.4 months, the 2-year event-free survival and overall survival rates were 20% and 25%, respectively.

Conclusion: The outcome of B-ALL with t(14;18)(q32;q21) is poor. Incorporating immune-therapies, chimeric antigen receptor (CAR)-T cell therapy, with or without HSCT, into the treatment regimens, might further improve outcomes.