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.