How I prevent and treat central nervous system disease in adults with acute lymphoblastic leukemia

Abstract

The central nervous system (CNS) is the most important site of extramedullary disease in adults with acute lymphoblastic leukemia (ALL). Although CNS disease is identified only in a minority of patients at the time of diagnosis, subsequent CNS relapses (either isolated or concurrent with other sites) occur in some patients even after the delivery of prophylactic therapy targeted to the CNS. Historically, prophylaxis against CNS disease has included intrathecal (IT) chemotherapy and radiotherapy (RT), although the latter is being used with decreasing frequency. Treatment of a CNS relapse usually involves intensive systemic therapy and cranial or craniospinal RT along with IT therapy and consideration of allogeneic hematopoietic cell transplant. However, short- and long-term toxicities can make these interventions prohibitively risky, particularly for older adults. As new antibody-based immunotherapy agents have been approved for relapsed/refractory B-cell ALL, their use specifically for patients with CNS disease is an area of keen interest not only because of the potential for efficacy but also concerns of unique toxicity to the CNS. In this review, we discuss data-driven approaches for these common and challenging clinical scenarios as well as highlight how recent findings potentially support the use of novel immunotherapeutic strategies for CNS disease.

Graphical abstract

Figure 1.

Modalities for CNS prophylaxis and treatment of active CNS disease. (A) In most patients, there is no evidence of CNS disease at diagnosis. Here, prevention of CNS relapse depends primarily on IT therapy (most commonly with MTX) and CNS-penetrating systemic therapy (traditional cytotoxic chemotherapy [CHEMO] as well as the ABL TKI dasatinib, the latter for use in Ph⁺ disease). (B) In cases of overt CNS disease at diagnosis or of a CNS relapse, many of the same tools used in the prophylaxis setting, such as IT and systemic chemotherapy, are used. Additional tools include RT, CD19 CAR-modified T-cells, and consolidative HCT. Figure created with BioRender.com.