Abstract
BACKGROUND. T-cell lymphoid blastic phase (BP) transformation is rare in chronic myelogenous leukemia (CML). 2-amino-9-β-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 μM, and a peak ara-G concentration of 260 μM in the plasma. Cellular ara-G triphosphate (ara-GTP) concentration in the peripheral blood T- lymphoblasts was 80 μM at the end of GW506U78 infusion and reached a maximum of 150 μM. 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.
Original language | English (US) |
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Pages (from-to) | 58-64 |
Number of pages | 7 |
Journal | Cancer |
Volume | 85 |
Issue number | 1 |
DOIs | |
State | Published - Jan 1 1999 |
Externally published | Yes |
Keywords
- 2-amino-9-β-D-arabinosyl-6-methoxy-9H-guanine
- Arabinosylguanine
- Chronic myelogenous leukemia
- Compound 506
- T-cell blastic phase
ASJC Scopus subject areas
- Oncology
- Cancer Research