Extramedullary sites of disease in B-cell acute lymphoblastic leukemia: incidence, biology, and treatment

Treatment outcomes of relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) have improved with the introduction of targeted agents and immunotherapeutics that allow successful bridging to allogeneic hematopoietic cell transplantation. Nonetheless, the risk of subsequent relapse remains significant. Although the most common site of relapse after salvage therapies is the bone marrow, extramedullary relapse is increasingly reported both in the central nervous system (CNS) and in non-CNS sites, especially after treatment with blinatumomab. Extramedullary relapse represents a challenge and warrants additional research to prevent and manage effectively. Chimeric antigen receptor T-cell therapy has demonstrated unprecedented success in the treatment of relapsed/refractory B-cell ALL, including disease at extramedullary sites, and it has emerged as a valuable therapeutic option in this setting. In this review, we discuss the incidence of extramedullary relapse in various clinical settings, postulated mechanisms of this phenomenon in ALL, and therapeutic strategies.