Cladribine

Class: Antimetabolite – purine nucleoside analog (adenosine deoxyadenosine analog).

Mechanism of Action (MOA):

  • Intracellularly phosphorylated → active triphosphate form.
  • Resistant to degradation by adenosine deaminase.
  • Incorporated into DNA → strand breaks + inhibition of DNA synthesis.
  • Also causes depletion of lymphocytes (esp. CD4+ and CD8+ T-cells).

Result: Cytotoxic to both dividing and resting lymphocytes → profound immunosuppression.

Indications (Oncology):

  • Hairy Cell Leukemia (HCL) → standard first-line.
  • Other uses (off-label/rare):
    • Chronic lymphocytic leukemia (CLL)
    • Low-grade non-Hodgkin’s lymphoma
    • Pediatric: Langerhans Cell Histiocytosis (LCH), some leukemias

Dosing (Oncology):

  • Adults (HCL): 0.09 mg/kg/day IV continuous infusion over 24h for 7 days

    OR 0.14 mg/kg IV daily over 2h for 5 days.
  • Pediatric (LCH/other): 5–9 mg/m²/day IV x5 days (protocol-based).
  • Adjustments:
    • Renal: Avoid if CrCl < 50 mL/min.
    • Hepatic: Caution; data limited.

Toxicities:

🔹 Dose-limiting: Myelosuppression + Immunosuppression

🔹 Other toxicities:

  • Fever (common, self-limiting).
  • Fatigue, nausea, headache.
  • Rash.
  • Rare neurotoxicity (high doses).

Monitoring:

  • CBC (baseline + weekly during cycles).
  • Infection signs/symptoms.
  • Renal/hepatic function.
  • Prophylaxis: PJP prophylaxis + antiviral (e.g., acyclovir) often recommended during therapy and for several months after due to prolonged lymphopenia.

Clinical Pearls for Pharmacists:

  • Highly effective in hairy cell leukemia (CR rates >85%).
  • Long-lasting remission possible after single cycle.
  • Causes prolonged lymphocyte depletion → always ensure infection prophylaxis.
  • Avoid live vaccines during and after therapy until immune recovery