K562/GM-CSF immunotherapy reduces tumor burden in chronic myeloid leukemia patients with residual disease on imatinib mesylate

B Douglas Smith, Yvette L. Kasamon, Jeanne Kowalski, Christopher Gocke, Kathleen Murphy, Carole B. Miller, Elizabeth Garrett-Mayer, Hua Ling Tsai, Lu Qin, Christina Chia, Barbara Biedrzycki, Thomas C. Harding, Guang Haun Tu, Richard J Jones, Kristen Hege, Hyam I. Levitsky

Research output: Contribution to journalArticle

Abstract

Purpose: Chronic myeloid leukemia (CML) can be responsive to T-cell-mediated immunity. K562/granulocyte macrophage-colony stimulating factor (GM-CSF) is a GM-CSF producing vaccine derived from a CML cell line that expresses several CML-associated antigens. A pilot study was developed to determine if K562/GM-CSF immunotherapy could improve clinical responses to imatinib mesylate (IM) in patients with chronic myeloid leukemia. Experimental Design: Patients with chronic phase CML who achieved at least a major cytogeneic response but remained with persistent, measurable disease despite one or more years on imatinib mesylate were eligible. Each was given a series of four vaccines administered in three-week intervals, with or without topical imiquimod, while remaining on a stable dose of imatinib mesylate. CML disease burden was measured serially before and after vaccination. Results: Nineteen patients were vaccinated, with a median duration of previous imatinib mesylate therapy of 37 (13-53) months. Mean PCR measurements of BCR-ABL for the group declined significantly following the vaccines (P = 0.03). Thirteen patients had a progressive decline in disease burden, 8 of whom had increasing disease burden before vaccination. Twelve patients achieved their lowest tumor burden measurements to date following vaccine, including seven subjects who became PCR-undetectable. Conclusions: K562/GM-CSF vaccine appears to improve molecular responses in patients on imatinib mesylate, including achieving complete molecular remissions, despite long durations of previous imatinib mesylate therapy.

Original languageEnglish (US)
Pages (from-to)338-347
Number of pages10
JournalClinical Cancer Research
Volume16
Issue number1
DOIs
StatePublished - Jan 1 2010

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Granulocyte-Macrophage Colony-Stimulating Factor
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Tumor Burden
Immunotherapy
Vaccines
imiquimod
Vaccination
Leukemia, Myeloid, Chronic Phase
Polymerase Chain Reaction
Myeloid Cells
Cellular Immunity
Imatinib Mesylate
Research Design
T-Lymphocytes
Antigens
Cell Line
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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K562/GM-CSF immunotherapy reduces tumor burden in chronic myeloid leukemia patients with residual disease on imatinib mesylate. / Smith, B Douglas; Kasamon, Yvette L.; Kowalski, Jeanne; Gocke, Christopher; Murphy, Kathleen; Miller, Carole B.; Garrett-Mayer, Elizabeth; Tsai, Hua Ling; Qin, Lu; Chia, Christina; Biedrzycki, Barbara; Harding, Thomas C.; Tu, Guang Haun; Jones, Richard J; Hege, Kristen; Levitsky, Hyam I.

In: Clinical Cancer Research, Vol. 16, No. 1, 01.01.2010, p. 338-347.

Research output: Contribution to journalArticle

Smith, BD, Kasamon, YL, Kowalski, J, Gocke, C, Murphy, K, Miller, CB, Garrett-Mayer, E, Tsai, HL, Qin, L, Chia, C, Biedrzycki, B, Harding, TC, Tu, GH, Jones, RJ, Hege, K & Levitsky, HI 2010, 'K562/GM-CSF immunotherapy reduces tumor burden in chronic myeloid leukemia patients with residual disease on imatinib mesylate', Clinical Cancer Research, vol. 16, no. 1, pp. 338-347. https://doi.org/10.1158/1078-0432.CCR-09-2046
Smith, B Douglas ; Kasamon, Yvette L. ; Kowalski, Jeanne ; Gocke, Christopher ; Murphy, Kathleen ; Miller, Carole B. ; Garrett-Mayer, Elizabeth ; Tsai, Hua Ling ; Qin, Lu ; Chia, Christina ; Biedrzycki, Barbara ; Harding, Thomas C. ; Tu, Guang Haun ; Jones, Richard J ; Hege, Kristen ; Levitsky, Hyam I. / K562/GM-CSF immunotherapy reduces tumor burden in chronic myeloid leukemia patients with residual disease on imatinib mesylate. In: Clinical Cancer Research. 2010 ; Vol. 16, No. 1. pp. 338-347.
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AU - Murphy, Kathleen

AU - Miller, Carole B.

AU - Garrett-Mayer, Elizabeth

AU - Tsai, Hua Ling

AU - Qin, Lu

AU - Chia, Christina

AU - Biedrzycki, Barbara

AU - Harding, Thomas C.

AU - Tu, Guang Haun

AU - Jones, Richard J

AU - Hege, Kristen

AU - Levitsky, Hyam I.

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N2 - Purpose: Chronic myeloid leukemia (CML) can be responsive to T-cell-mediated immunity. K562/granulocyte macrophage-colony stimulating factor (GM-CSF) is a GM-CSF producing vaccine derived from a CML cell line that expresses several CML-associated antigens. A pilot study was developed to determine if K562/GM-CSF immunotherapy could improve clinical responses to imatinib mesylate (IM) in patients with chronic myeloid leukemia. Experimental Design: Patients with chronic phase CML who achieved at least a major cytogeneic response but remained with persistent, measurable disease despite one or more years on imatinib mesylate were eligible. Each was given a series of four vaccines administered in three-week intervals, with or without topical imiquimod, while remaining on a stable dose of imatinib mesylate. CML disease burden was measured serially before and after vaccination. Results: Nineteen patients were vaccinated, with a median duration of previous imatinib mesylate therapy of 37 (13-53) months. Mean PCR measurements of BCR-ABL for the group declined significantly following the vaccines (P = 0.03). Thirteen patients had a progressive decline in disease burden, 8 of whom had increasing disease burden before vaccination. Twelve patients achieved their lowest tumor burden measurements to date following vaccine, including seven subjects who became PCR-undetectable. Conclusions: K562/GM-CSF vaccine appears to improve molecular responses in patients on imatinib mesylate, including achieving complete molecular remissions, despite long durations of previous imatinib mesylate therapy.

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