BACKGROUND: Despite advances in novel therapeutics, supportive care, and postremission therapy, the outcome of high-risk and elderly patients as well as those with relapsed/refractory acute myeloid leukemia (AML) remains poor. There is likely still room for improvement through optimizing conventional chemotherapy. PATIENTS AND METHODS: Through a pharmacy database search we identified all patients with AML treated at Washington University with cladribine-based regimens. RESULTS: Twenty-four patients were identified that were treated with 2 cladribine-based regimens: CLAG (cladribine [5 mg/m2 days 1-5], cytarabine [2 g/m2 days 1-5] and granulocyte colony-stimulating factor [G-CSF; 300 microg subcutaneously (s.c.) days 0-5]) and CLAM (cladribine [5 mg/m2 days 1-5], cytarabine [2 g/m2 days 1-5], G-CSF [300 mg s.c. days 0-5] and mitoxantrone [10 mg/m2 days 1-3]). Complete responses were achieved in 53% of patients given induction chemotherapy and 44% of those given salvage chemotherapy. The regimens were well tolerated with minimal extramedullary toxicity. CONCLUSION: These data suggest that cladrabine-based regimens should be further explored in both the salvage and first-line setting and might offer an attractive backbone on which to add novel therapies.