Complete hematologic and cytogenetic response to 2-amino-9-beta-D-arabinosyl-6-methoxy-9H-guanine in a patient with chronic myelogeneous leukemia in T-cell blastic phase - A case report and review of the literature

BACKGROUND, T-cell lymphoid blastic phase (BP) transformation is rare in ch ronic myelogenous leukemia (CML). 2-amino-8-beta-D-arabinosyl-6-methexy-9H- guanine (GW506U78), a prodrug of arabinosylguanine (ara-G), is effective in T-cell leukemias. METHODS, The authors present a case of a 48-year-old male with Philadelphia chromosome (Ph) positive CML and T-cell lymphoid BP after 17 months in the chronic phase. RESULTS. Plasma pharmacokinetic studies after an infusion of GW506U78 at a dose of 40 mg/kg showed GW506U78 concentrations of 60 mu M, and a peak ara- G concentration of 260 mu M in the plasma, Cellular ara-G triphosphate (ara -GTP) concentration in the peripheral blood T-lymphoblasts was 80 mu M at t he end of GW506U78 infusion and reached a maximum of 150 mu M. The patient achieved a complete response that lasted 13 months. Severe neurotoxicity re lated to GW506U78 was observed. CONCLUSIONS. GW506U78 showed antileukemic activity against Ph positive T-ce ll BP CML. Neurotoxicity was dose-limiting in this patient. Treatment with GW506U78 and modulation of ara-GTP concentrations are therapeutic strategie s that require further exploration in T-cell malignancies. Investigation of other dosing schedules may limit neurotoxicity. Cancer 1999;85:58-64, (C) 1999 American Cancer Society.