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

Alvaro Aguayo, Jorge E. Cortes, Hagop M. Kantarjian, Miloslav Beran, Varsha Gandhi, William Plunkett, Joanne Kurtzberg, Michael J. Keating

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)58-64
Number of pages7
JournalCancer
Volume85
Issue number1
DOIs
StatePublished - Jan 1 1999
Externally publishedYes

Fingerprint

T-Cell Leukemia
Guanine
Cytogenetics
T-Lymphocytes
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Chronic Phase
Philadelphia Chromosome
Prodrugs
nelarabine
Appointments and Schedules
Pharmacokinetics
Therapeutics

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

Cite this

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. / Aguayo, Alvaro; Cortes, Jorge E.; Kantarjian, Hagop M.; Beran, Miloslav; Gandhi, Varsha; Plunkett, William; Kurtzberg, Joanne; Keating, Michael J.

In: Cancer, Vol. 85, No. 1, 01.01.1999, p. 58-64.

Research output: Contribution to journalArticle

Aguayo, Alvaro ; Cortes, Jorge E. ; Kantarjian, Hagop M. ; Beran, Miloslav ; Gandhi, Varsha ; Plunkett, William ; Kurtzberg, Joanne ; Keating, Michael J. / 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. In: Cancer. 1999 ; Vol. 85, No. 1. pp. 58-64.
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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.",
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T1 - 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

T2 - A case report and review of the literature

AU - Aguayo, Alvaro

AU - Cortes, Jorge E.

AU - Kantarjian, Hagop M.

AU - Beran, Miloslav

AU - Gandhi, Varsha

AU - Plunkett, William

AU - Kurtzberg, Joanne

AU - Keating, Michael J.

PY - 1999/1/1

Y1 - 1999/1/1

N2 - 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.

AB - 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.

KW - 2-amino-9-β-D-arabinosyl-6-methoxy-9H-guanine

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KW - T-cell blastic phase

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