Central Nervous System Prophylaxis, or CNS prophylaxis, is a type of chemotherapy for patients at risk of cancer metastasis into the central nervous system (CNS).[1] Prophylaxis originated from the Greek word “phulaxis”, meaning the act of guarding.[2] CNS prophylaxis refers to preventative measures that kill cancer cells potentially in the intrathecal space and the organs of the central nervous system.[1]
CNS involvement is observed in 5% of acute leukaemia patients. It is regarded as an indicator of poor prognosis, and increased difficulty in treatment due to the drug-expelling properties of the blood-brain barrier (BBB).[3] Preventative treatment may be recommended for more aggressive lymphomas and leukaemias, including non-Hodgkin lymphoma, of which Diffuse Large B-cell lymphoma (DLBCL) is the most common subtype.[4]
The most widely-used prophylactic drug is methotrexate (MTX), which is normally administered by one of two methods: intravenous injection (IV HD-MTX) and intrathecal injection (IT-MTX).[1][4] Intravenous injection requires a direct injection of high-dose MTX into a patient’s vein;[4] Intrathecal injection, i.e. injection of the drug into the intrathecal space holding cerebrospinal fluid (CSF), is either administered via the Ommaya reservoir, an implanted container passing fluid into the brain, or by lumbar puncture.[1]
IT-MTX and IV HD-MTX pose different side effects in addition to that of normal dose MTX. While IV HD-MTX poses higher risks of hepatotoxicity and nephrotoxicity, IT-MTX also leads to adverse effects characteristic of Ommaya reservoir implantation or lumbar puncture.[5]
Clinically, the CNS-International Prognostic Index (CNS-IPI) is used to assess a patient’s need for prophylaxis.[6][7] Clinical and biological risk factors, as well as baseline screening provides additional insight into risk stratification. In the past decade, research has also raised some controversies, particularly on the effectiveness of current CNS prophylaxis strategies for DLBCL.[7]