Class: Purine nucleoside analog (antimetabolite)
Mechanism of Action:
- Inhibits DNA polymerase and ribonucleotide reductase
- Incorporates into DNA → chain termination and apoptosis
- Causes mitochondrial damage → cytochrome c release → apoptosis
Indications
- Pediatric relapsed/refractory Acute Lymphoblastic Leukemia (ALL) after ≥2 prior regimens
- Off-label: AML, MDS, and investigational combinations in adults
Dosing (Pediatric ALL)
- 52 mg/m² IV daily x 5 days (28-day cycle)
- Adjust for renal dysfunction (renal clearance is primary route)
Key Adverse Effects
- Myelosuppression – neutropenia, anemia, thrombocytopenia
- Infections – bacterial, viral, fungal (high risk)
- Hepatotoxicity – transaminitis, veno-occlusive disease (VOD)
- Capillary leak syndrome – hypotension, edema, pulmonary issues
- Tumor lysis syndrome
- Rash, nausea, mucositis, fever
Monitoring
- CBC with differential (daily during and post-infusion)
- Renal and hepatic function before/during treatment
- Fluid status and blood pressure (capillary leak)
- TLS labs (uric acid, potassium, phosphorus, calcium, creatinine)
- Monitor for signs of infection or VOD
Supportive Measures
- Hydration, allopurinol or rasburicase for TLS prophylaxis
- Anti-infective prophylaxis often needed
- Use caution in hepatic dysfunction or prior HSCT (VOD risk)
Other Notes
- Structurally related to fludarabine and cladribine
- Often used in combination regimens for relapsed/refractory AML or ALL
- Limited use in adults due to toxicity and newer agents