Revisiting the role of cladribine in acute myeloid leukemia: an improvement on past accomplishments or more old news?

Originally studied in lymphoid diseases, cladribine (CdA) is an adenosine deaminase resistant analog of adenosine that was later discovered to induce myeloid cell apoptosis. The activity of CdA in myeloid malignancies was first reported in relapsed/refractory (RR) pediatric acute myeloid leukemia (AML) with complete response (CR) rates of up to 47%. Consequently, several studies have confirmed the efficacy of single agent CdA or CdA combination regimens in AML. Established CR rates for combination regimens in RR adults are approximately 50%, while CR rates for newly diagnosed (ND) adults are approximately 70% and show similar toxicity profiles to previously used regimens. Despite these promising data, many centers have yet to adopt CdA combination regimens for these difficult to treat populations. We review the pharmacology, pharmacokinetics, clinical data, and safety of CdA monotherapy and combination regimens for the management of pediatric and adult ND and RR-AML.