Nelarabine – A New Age in the Management of Lymphoid Malignancies

Nelarabine is the 6-methoxy prodrug of 9-b-D-arabinofuranosylguanine (ara-G)11 Nelarabine is a substrate for adenosine deaminase, which cleaves the methoxy group to form ara-G (Figure 1). Ara-G is taken up by the cell and is then triphosphorylated by two enzymes, deoxycytidine kinase and deoxyguanosine kinase2 (Figure 2). Ara-G triphosphate (ara-GTP) competes with deoxy-GTP in malignant cells for incorporation into DNA.3 Once incorporation occurs, ara-GTP results in chain termination and apoptosis.2 Ara-GTP accumulates to a greater extent in T-cells compared with B-cells. This may explain Nelarabine’s greater activity in T-cell malignancies than B-lymphocyte malignancies. Elimination half-life of ara-GTP is longer in leukemic T-cells than in leukemic B-cells.4