Peripheral blood monitoring of chronic myeloid leukemia during treatment with imatinib, second-line agents, and beyond

Authors

  • Lisa Lima MS,

    1. Department of Hematology and Medial Oncology, Emory University School of Medicine and Winship Cancer Institute of Emory University, Atlanta, Georgia
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  • Leon Bernal-Mizrachi MD,

    1. Department of Hematology and Medial Oncology, Emory University School of Medicine and Winship Cancer Institute of Emory University, Atlanta, Georgia
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  • Debra Saxe PhD,

    1. Department of Pathology and Laboratory Medicine, Emory University School of Medicine and Winship Cancer Institute of Emory University, Atlanta, Georgia
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  • Karen P. Mann MD,

    1. Department of Pathology and Laboratory Medicine, Emory University School of Medicine and Winship Cancer Institute of Emory University, Atlanta, Georgia
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  • Mourad Tighiouart PhD,

    1. Department of Biostatistics and Bioinformatics, Emory University School of Medicine and Winship Cancer Institute of Emory University, Atlanta, Georgia
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  • Martha Arellano MD,

    1. Department of Hematology and Medial Oncology, Emory University School of Medicine and Winship Cancer Institute of Emory University, Atlanta, Georgia
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  • Leonard Heffner MD,

    1. Department of Hematology and Medial Oncology, Emory University School of Medicine and Winship Cancer Institute of Emory University, Atlanta, Georgia
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  • Morgan McLemore MD,

    1. Department of Hematology and Medial Oncology, Emory University School of Medicine and Winship Cancer Institute of Emory University, Atlanta, Georgia
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  • Amelia Langston MD,

    1. Department of Hematology and Medial Oncology, Emory University School of Medicine and Winship Cancer Institute of Emory University, Atlanta, Georgia
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  • Elliott Winton MD,

    1. Department of Hematology and Medial Oncology, Emory University School of Medicine and Winship Cancer Institute of Emory University, Atlanta, Georgia
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  • Hanna Jean Khoury MD

    Corresponding author
    1. Department of Hematology and Medial Oncology, Emory University School of Medicine and Winship Cancer Institute of Emory University, Atlanta, Georgia
    • Department of Hematology and Medical Oncology, WinshipCancer Institute-Emory University, 1365 Clifton Road NE, Suite C1152, Atlanta, GA 30322
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    • Fax: (404) 778-4755


Abstract

BACKGROUND:

The current study was conducted to compare simultaneously obtained bone marrow (BM) cytogenetics (CTG), peripheral blood (PB) and BM fluorescence in situ hybridization (FISH), and quantitative real-time polymerase chain reaction (Q-PCR) for BCR-ABL1 in monitoring response to treatment with tyrosine kinase inhibitors and homoharringtonine (HHT) in patients with chronic myeloid leukemia (CML).

METHODS:

PB and BM FISH (n = 112 samples) and/or Q-PCR (n = 132 samples) for BCR-ABL1 were simultaneously obtained in 70 patients with Philadelphia chromosome-positive (Ph+) CML in chronic (68%), accelerated (16%), and blast phase (16%) before the initiation of therapy and during the course of treatment with imatinib (IM) (n = 40 patients), dasatinib (n = 20 patients), nilotinib (n = 4 patients), bosutinib (n = 18 patients), or HHT (n = 4 patients) for patients with newly diagnosed (n = 13 patients), IM-sensitive (n = 34 patients), IM-resistant (n = 30 patients), or IM-intolerant (n = 9 patients) disease. Eighteen patients were found to have Ph+ variants or karyotypic abnormalities in addition to the Ph+.

RESULTS:

Excellent correlations (r) were observed between PB and BM FISH (r = 0.95) and PB and BM Q-PCR (r = 0.87), as well as BM CTG and PB FISH (r = 0.89) and PB Q-PCR (r = 0.82). This correlation was not affected by the presence of the Ph+ variant or additional chromosomal abnormalities, the presence of ABL1 kinase domain mutations, phase of the disease, or treatment.

CONCLUSIONS:

PB FISH and Q-PCR appear to be reliable methods with which to monitor response to modern therapy in patients with all phases of CML. Cancer 2011. © 2010 American Cancer Society.

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