Class: Antimetabolite – purine nucleoside analog
Mechanism of Action:
- Prodrug of ara-G (9-β-D-arabinofuranosylguanine)
- Incorporated into DNA → inhibits DNA synthesis → apoptosis
- Selectively toxic to T-cell lymphoblasts
Indications
- T-cell Acute Lymphoblastic Leukemia (T-ALL)
- T-cell Lymphoblastic Lymphoma (T-LBL)
- Used in relapsed/refractory settings (approved in both adults and children)
Dosing
- Adults: 1,500 mg/m² IV over 2 hours on days 1, 3, 5 (every 21 days)
- Pediatrics: 650 mg/m² IV daily × 5 days (every 21 days)
- Adjust for renal function; use caution in hepatic impairment
Key Adverse Effects
- Neurotoxicity (dose-limiting and serious):
- Somnolence, peripheral neuropathy, seizures, Guillain-Barré-like syndrome
- Myelosuppression (neutropenia, thrombocytopenia, anemia)
- Elevated liver enzymes (AST/ALT)
- Nausea, vomiting, fatigue
- Infections (secondary to immunosuppression)
Monitoring
- Neurologic exam before and during treatment (very important)
- CBC with differential
- Liver and renal function
- Monitor for infections
- Electrolytes and hydration status
Supportive Care
- Antiemetics as needed
- Seizure precautions in patients with prior CNS disease
- Infection prophylaxis (if prolonged cytopenias)
- Consider dose modification or discontinuation for neurotoxicity
Other Important Notes
- Reserved for T-cell disease, not effective in B-ALL
- Penetrates CNS — may have activity in CNS disease
- Neurotoxicity is cumulative; avoid in combination with other neurotoxic agents
Synonyms
Arranon, Atriance