Complete hematologic and cytogenetic response to 2-amino-9-β-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
✍ Scribed by Alvaro Aguayo; Jorge E. Cortes; Hagop M. Kantarjian; Miloslav Beran; Varsha Gandhi; William Plunkett; Joanne Kurtzberg; Michael J. Keating
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 97 KB
- Volume
- 85
- Category
- Article
- ISSN
- 0008-543X
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✦ Synopsis
BACKGROUND.
T-cell lymphoid blastic phase (BP) transformation is rare in chronic myelogenous leukemia (CML). 2-amino-9--D-arabinosyl-6-methoxy-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 M, and a peak ara-G concentration of 260 M in the plasma. Cellular ara-G triphosphate (ara-GTP) concentration in the peripheral blood T-lymphoblasts was 80 M at the end of GW506U78 infusion and reached a maximum of 150 M. The patient achieved a complete response that lasted 13 months. Severe neurotoxicity related to GW506U78 was observed.
CONCLUSIONS. GW506U78 showed antileukemic activity against
Ph positive T-cell BP CML. Neurotoxicity was dose-limiting in this patient. Treatment with GW506U78 and modulation of ara-GTP concentrations are therapeutic strategies that require further exploration in T-cell malignancies. Investigation of other dosing schedules may limit neurotoxicity.