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

Publication ,  Journal Article
Aguayo, A; Cortes, JE; Kantarjian, HM; Beran, M; Gandhi, V; Plunkett, W; Kurtzberg, J; Keating, MJ
Published in: Cancer
January 1, 1999

BACKGROUND: T-cell lymphoid blastic phase (BP) transformation is rare in chronic myelogenous leukemia (CML). 2-amino-9-beta-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 microM, and a peak ara-G concentration of 260 microM in the plasma. Cellular ara-G triphosphate (ara-GTP) concentration in the peripheral blood T-lymphoblasts was 80 microM at the end of GW506U78 infusion and reached a maximum of 150 microM. 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.

Duke Scholars

Published In

Cancer

ISSN

0008-543X

Publication Date

January 1, 1999

Volume

85

Issue

1

Start / End Page

58 / 64

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Remission Induction
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Humans
  • Guanosine Triphosphate
  • Blast Crisis
  • Arabinonucleotides
 

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Aguayo, A., J. E. Cortes, H. M. Kantarjian, M. Beran, V. Gandhi, W. Plunkett, J. Kurtzberg, and M. J. Keating. “Complete hematologic and cytogenetic response to 2-amino-9-beta-D-arabinosyl-6-methoxy-9H-guanine in a patient with chronic myelogenous leukemia in T-cell blastic phase: a case report and review of the literature.Cancer 85, no. 1 (January 1, 1999): 58–64.
Journal cover image

Published In

Cancer

ISSN

0008-543X

Publication Date

January 1, 1999

Volume

85

Issue

1

Start / End Page

58 / 64

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Remission Induction
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Humans
  • Guanosine Triphosphate
  • Blast Crisis
  • Arabinonucleotides