CNS involvement is rare in adults, affecting 5-8% of all cases. This is not an indicator of lowered survival rate, though it has been shown that prophylaxis is necessary to prevent relapse. When no prophylactic therapy is given, the percentage of recurrent disease is between 30 and 50%.

The following risk factors are associated with recurrent CNS involvement: high presence of leukocytes, high LDH, and traumatic lumbar puncture.

There are two different types of prophylactic therapy modalities for CNS involvement including intrathecal chemotherapy, systemic chemotherapy for CNS penetration (such as high-dose methotrexate and cytarabine) and radiotherapy.

Intrathecal chemotherapy maintains concentrations of chemotherapy drugs in the CSF. This is given via lumbar puncture, which makes it necessary to puncture frequently.

The side effects that may occur after administration of intrathecal chemotherapy include headache and confusion.