Nelarabine is the
prodrug of 9-beta-arabinofuranosylguanine (
ara-G) and is therapeutically classified as a
purine nucleoside analog.
Nelarabine is converted to
ara-G by
adenosine deaminase and transported into cells by a
nucleoside transporter.
Ara-G is subsequently phosphorylated to
ara-G triphosphate (
ara-GTP), thereby initiating the
therapeutic effect by inhibiting
DNA synthesis.
Nelarabine has been extensively studied in regards to its pharmacokinetics, and the data have demonstrated that
ara-GTP preferentially accumulates in malignant T-cells. Clinical responses to
nelarabine have been demonstrated in various T-cell
malignancies and appear to correlate with a relatively high intracellular concentration of
ara-GTP compared to nonresponders. Therefore, this unique
drug feature of
nelarabine accounts for clinical utilization in treating adult and pediatric patients with relapsed or refractory T-cell
acute lymphoblastic leukemia or T-cell
lymphoblastic lymphoma. Neuropathy is the most predominant adverse effect associated with
nelarabine and the incidence correlates with the dose administered. Myelosuppression has been observed, with
thrombocytopenia and
neutropenia as the most common hematologic complications. This article reviews the pharmacology, mechanism of action, and pharmacokinetic properties of
nelarabine, as well as
nelarabine's clinical efficacy in
T-ALL, T-LBL, and other
hematologic malignancies. The toxicity profile, dosage, and administration, and areas of ongoing and future research, are also presented.