IT Therapy

Intrathecal (IT) Therapy in Leukemia

Purpose

  • Prevents or treats CNS leukemia (common sanctuary site due to poor penetration of many systemic agents).
  • ALL: CNS prophylaxis is mandatory for all patients (B-ALL and T-ALL, with T-ALL being highest risk).
  • AML: IT therapy is not routine; reserved for patients with CNS-positive disease or select high-risk subsets (e.g., infant AML, monocytic AML).

Common IT Agents

  1. Methotrexate (MTX)
    • Folic acid antagonist, S-phase specific
    • Standard agent, often used alone in B-ALL
    • Dose varies by age/weight (e.g., 6–12 mg in children, 12 mg in adults)
  2. Cytarabine (Ara-C)
    • Antimetabolite, inhibits DNA polymerase
    • Dose: ~30–50 mg depending on age
    • Used in combo (triple IT) or for refractory/relapse CNS disease
  3. Hydrocortisone (HC)
    • Glucocorticoid, anti-leukemic + reduces arachnoiditis risk
    • Dose: 10–15 mg (children), 50 mg (adults)

Triple IT therapy (MTX + Ara-C + HC) is the gold standard in T-ALL and in high-risk B-ALL.

Timing by Leukemia Type

Acute Lymphoblastic Leukemia (ALL)

  • Induction: IT at diagnosis (sometimes with diagnostic LP), repeated weekly.
  • Consolidation/Interim Maintenance: Repeated ITs, often alternating with systemic high-dose MTX.
  • Maintenance: Periodic IT dosing continues (less frequent, e.g., every 12 weeks in some pediatric regimens).
  • CNS3 disease: Intensified schedule (2–3× per week until CSF clears, then resume prophylaxis).

Acute Myeloid Leukemia (AML)

  • Routine prophylaxis not given (lower baseline CNS relapse risk).
  • Given only if CNS disease present at diagnosis or relapse.
  • Pediatric AML protocols may add a few ITs in higher-risk cases.

Clinical Considerations

  • Platelet count: Delay LP/IT if <50 × 10⁹/L.
  • Avoid traumatic LPs → increases risk of CNS relapse.
  • Systemic high-dose MTX/Ara-C: Also provide CNS penetration (important synergy with IT).
  • Neurotoxicity risks:
    • IT MTX + cranial irradiation → leukoencephalopathy
    • IT Ara-C → chemical arachnoiditis (mitigated by hydrocortisone)
  • Formulation safety: Only preservative-free preparations should be used intrathecally.

Quick-Reference Table

IT Agent Pediatric Dose (common) Adult Dose Notes
Methotrexate 6–12 mg (age-based) 12 mg CNS prophylaxis, cornerstone drug
Cytarabine 30–50 mg 50 mg Added in triple IT or CNS disease
Hydrocortisone 10–15 mg 50 mg Prevents arachnoiditis, adds efficacy
Triple IT (MTX + Ara-C + HC) Standard in T-ALL Standard in T-ALL & high-risk B-ALL More effective than MTX alone

Key oncology pharmacy point:

  • In ALL → IT prophylaxis is standard for all patients.
  • In AML → IT therapy is only for documented CNS involvement.
  • Use triple IT for higher-risk patients (esp. T-ALL, CNS3, infant ALL).
Synonyms
Intrathecal Therapy
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