The prognosis for patients with chronic myeloid leukemia who have clonal cytogenetic abnormalities in philadelphia chromosome-negative cells

Authors

  • Michael W. N. Deininger MD, PhD,

    Corresponding author
    1. Division of Hematology and Medical Oncology, Oregon Health & Science University Cancer Institute, Portland, Oregon
    • Oregon Health and Science University Cancer Institute, L592, 3181 SW Sam Jackson Park Road, Portland, OR 97239
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    • Fax: (503) 494-3688

    • Dr. Deininger has acted as a consultant for Bristol-Myers Squibb and Novartis, and has received research support from SGX and Calistoga.

  • Jorge Cortes MD,

    1. Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Ron Paquette MD,

    1. Division of Hematology/Oncology, University of California–Los Angeles, Los Angeles, California
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    • Dr. Paquette has received honoraria from Novartis and Bristol-Myers Squibb for speaking engagements.

  • Byung Park PhD,

    1. Biostatistics Shared Resource, Oregon Health & Science University Cancer Institute, Portland, Oregon
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  • Andreas Hochhaus MD,

    1. Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
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    • Dr. Hochhaus has received research support from Novartis and Bristol-Myers Squibb.

  • Michele Baccarani MD,

    1. Department of Hematology and Oncology “L. and A. Serágnoli,” S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
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    • Dr. Baccarani has received honoraria and grants from Novartis and Bristol-Myers Squibb.

  • Richard Stone MD,

    1. Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts
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    • Dr. Stone has received clinical research support from Novartis and Bristol-Myers Squibb and has acted as a member of the Speakers Bureau for Bristol-Myers Squibb.

  • Thomas Fischer MD,

    1. III. Medical Department, Johannes Gutenberg University, Mainz, Germany
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  • Hagop Kantarjian MD,

    1. Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Dietger Niederwieser MD,

    1. Department of Hematology and Oncology, University of Leipzig, Leipzig, Germany
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  • Carlo Gambacorti-Passerini MD,

    1. Department of Internal Medicine, University of Milano Bicocca, Monza, Italy
    2. Department of Hematology, McGill University, Montreal, Quebec, Canada
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  • Charlene So PharmD,

    1. Clinical Development, Novartis Pharma, Basel, Switzerland
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    • Ms. So is an employee of Novartis and has stock ownership.

  • Insa Gathmann MSc,

    1. Biostatistics Department, Novartis Pharma, Basel, Switzerland
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    • Ms. Gathmann is an employee of Novartis Pharma AG and owns shares.

  • John M. Goldman DM,

    1. Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland
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    • Dr. Goldman has acted as a consultant for and has received honoraria from Bristol-Myers Squibb and Novartis.

  • Douglas Smith MD,

    1. Division of Hematologic Malignancies, Kimmel COmprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland
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  • Brian J. Druker MD,

    1. Division of Hematology and Medical Oncology, Oregon Health & Science University Cancer Institute, Portland, Oregon
    2. Howard Hughes Medical Institute, Chevy Chase, Maryland
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    • Dr. Druker has received consulting fees from Ambit Biosciences, Avalon Pharmaceuticals, Bristol-Myers Squibb, Cephalon Inc, Cylene Pharmaceuticals, Geron Corporation, Great Point Partners, ICOS Corporation, Kereos Inc, KeyBio LLC, Portola Pharmaceuticals, Prolexys, SGX Pharmaceuticals, TargeGen, Upstate Biotechnology, and Vertex Pharmaceuticals. He also owns stock options in Breakthrough Therapeutics and was a scientific founder of Molecular MD.

  • François Guilhot MD

    1. Department of Oncology Hematology and Cell Therapy, University Miletrie Hospital, Clinical Research Center, Poitiers, France
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Abstract

BACKGROUND.

Clonal cytogenetic abnormalities (CCA) were detected in Philadelphia chromosome (Ph)-negative cells in some patients with chronic myeloid leukemia (CML) who attained a cytogenetic response to imatinib mesylate. In some patients, CCA/Ph-negative status was associated with myelodysplasia or acute myeloid leukemia. The objective of the current study was to determine the prognostic impact of CCA/Ph-negative cells.

METHODS.

The authors compared the pretherapeutic risk factors (Kruskall-Wallis test), exposure to cytotoxic drugs (chi-square test), and overall and progression-free survival (Kaplan-Meyer and logistic regression analysis, respectively) of 515 patients with mostly chronic-phase CML who were treated with imatinib mesylate after failure of interferon-α according to whether they attained a major cytogenetic response (MCR) (n = 324 patients), an MCR with CCA/Ph-negative status (n = 30 patients), or no MCR (n = 161 patients).

RESULTS.

CCA/Ph-negative status most frequently involved chromosomes Y, 8, and 7. No significant differences in pretherapeutic risk factors were detected between patients who attained an MCR with and without CCA/Ph-negative cells, except that exposure to alkylating agents was more frequent in patients with CCA/Ph-negative cells, and overall and progression-free survival were identical. With a median follow-up of 51 months, only 2 patients developed myelodysplastic syndromes (MDS).

CONCLUSIONS.

The overall prognosis for patients who had CML with CCA/Ph-negative status was good and was driven by the CML response to imatinib mesylate. Isolated CCA/Ph-negative cells in the absence of morphologic evidence of MDS do not justify a change in therapy. Cancer 2007. © 2007 American Cancer Society.

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