Intrathecal Chemotherapy: Direct CNS Delivery for Leukemia, Lymphoma, and Brain Metastases

Intrathecal (IT) chemotherapy delivers drugs directly into the cerebrospinal fluid (CSF) via lumbar puncture or Ommaya reservoir, bypassing the blood-brain barrier to treat or prevent central nervous system (CNS) disease.

Indications

• Acute lymphoblastic leukemia (ALL) – CNS prophylaxis & treatment
• Aggressive lymphomas (Burkitt, high-risk DLBCL) – prophylaxis/treatment
• Leptomeningeal metastases from solid tumors (breast, lung, melanoma)
• Medulloblastoma, other primary CNS tumors

Common Agents

• Methotrexate (most frequent)
• Cytarabine (Ara-C)
• Thiotepa
• Liposomal cytarabine (DepoCyt) – prolonged exposure

Procedure & Schedule

• Lumbar puncture (L3–L4 or L4–L5) under sterile conditions; CSF pressure measured; drug injected; patient flat 30–60 min.
• Ommaya reservoir (subcutaneous port with ventricular catheter) for repeated access—avoids multiple LPs.
• Schedule varies: ALL protocols use frequent early IT MTX (e.g., days 1, 8, 15, 29); solid tumor leptomeningeal disease often weekly × 4 then monthly.

Side Effects

• Acute: headache (post-LP), nausea, vomiting, fever
• Neurotoxicity: arachnoiditis, cranial neuropathies, seizures, cognitive changes (especially high-dose MTX + IT)
• Infection (meningitis) – rare with sterile technique

Integration

IT chemo is part of multimodal regimens: systemic chemo ± cranial radiation ± targeted therapy. Close neuro-oncology/hematology coordination essential.