What is the management for central nervous system (CNS) involvement in a child with acute lymphoblastic leukemia (ALL) and cerebrospinal fluid (CSF) positive for lymphoblasts?

Management of CNS Involvement in Pediatric ALL

The answer is D: Intrathecal chemotherapy is the primary treatment for CNS involvement in a child with acute lymphoblastic leukemia presenting with lymphoblasts in the CSF. 1

Rationale for Intrathecal Chemotherapy

CNS-directed therapy with intrathecal chemotherapy (methotrexate, cytarabine, and/or corticosteroids) is the cornerstone of treatment because systemic chemotherapy cannot adequately penetrate the blood-brain barrier to clear leukemic cells from the CNS. 1 This child has confirmed CNS involvement based on the presence of lymphoblasts in the CSF, which classifies them as having CNS disease requiring specific CNS-directed treatment. 1

Why Other Options Are Inadequate

Anticonvulsants (Option A)

• While anticonvulsants may be needed for symptomatic management of seizures, they do not address the underlying leukemic infiltration of the CNS 1
• Convulsions are a symptom of CNS leukemia, not the primary problem requiring treatment 1
• Anticonvulsants alone would allow progression of CNS disease and eventual death 1

Systemic Chemotherapy Alone (Option B)

• Systemic chemotherapy cannot adequately cross the blood-brain barrier to achieve therapeutic concentrations in the CSF 1
• The NCCN explicitly states that the aim of CNS treatment is to clear leukemic cells "within sites that cannot be readily accessed by systemic chemotherapy due to the blood-brain barrier" 1
• While high-dose systemic agents (methotrexate, cytarabine) are part of comprehensive CNS-directed therapy, they must be combined with intrathecal therapy 1

VP Shunt (Option C)

• A VP shunt addresses hydrocephalus but does not treat leukemic cells in the CSF 1
• There is no indication for VP shunt placement in the management of CNS leukemia 1

Specific Treatment Approach

Age-based intrathecal dosing should be used rather than body surface area-based dosing to achieve consistent CSF drug concentrations and reduce neurotoxicity: 2

• Age <1 year: 6 mg
• Age 1 year: 8 mg
• Age 2 years: 10 mg
• Age ≥3 years: 12 mg

The intrathecal regimen typically includes methotrexate, cytarabine, and corticosteroids (triple intrathecal therapy). 1, 2, 3 Treatment frequency is every 2-5 days until CSF cell count normalizes, followed by one additional dose. 2

Comprehensive CNS-Directed Strategy

All patients with ALL require CNS prophylaxis, as over 50% would develop CNS leukemia without CNS-directed therapy. 1 The complete approach includes:

• Intrathecal chemotherapy (primary modality) 1
• High-dose systemic chemotherapy with CNS penetration (methotrexate, cytarabine, pegaspargase/calaspargase) 1
• Cranial radiation (18 Gy at 1.5-1.8 Gy/fraction) is reserved for specific protocols and CNS-3 disease, but is increasingly avoided due to late neurotoxic effects 1

Critical Pitfalls to Avoid

Do not delay intrathecal therapy while waiting for systemic chemotherapy to take effect - the blood-brain barrier prevents adequate systemic drug penetration, and CNS disease will progress. 1

Monitor for systemic toxicity from intrathecal chemotherapy - intrathecally administered methotrexate appears in systemic circulation and can cause systemic toxicity, requiring adjustment of concurrent systemic therapy. 2

Recognize that focal CNS involvement may not respond to intrathecal therapy alone and may require radiotherapy. 2, 3