Factors influencing a second myeloid malignancy in patients with Philadelphia-negative-7 or del(7q) clones during tyrosine kinase inhibitor therapy for chronic myeloid leukemia

Michael J. Groves, Mark Sales, Lee Baker, Michael Griffiths, Norman Pratt, Sudhir Tauro

    Research output: Contribution to journalArticle

    12 Citations (Scopus)

    Abstract

    The detection of Philadelphia-negative (Ph-neg) cells with non-random karyotypic abnormalities after tyrosine kinase inhibitor (TKI) therapy of chronic myeloid leukaemia (CML) can be associated with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). To our knowledge, however, there have been no studies on variables influencing the risk of MDS/AML in patients with specific Ph-neg karyotypes. We systematically examined studies reporting -7 or del(7q) within Ph-neg cells in TKI-treated CML patients, and abstracted clinical and cytogenetic data from individual reports into a standardized format for further analysis. Of 53 patients, 43 had Ph-neg -7 clones [as the sole abnormality (-7(sole)) in 29, or with other clones (-7(dual)) in 14], and del(7q) was present in 10. A total of 16/51 evaluable patients, all with -7, transformed to MDS/AML. Transformation was more frequent (15/16 patients) within 6 months of Ph-neg -7 detection rather than subsequently (P < 0.0001). At first detection after TKI therapy, Ph-neg abnormal clones comprised >= 50% of Ph-neg cells in a greater proportion of patients with -7 than del(7q) (P = 0.035). Upon comparing -7(sole) and -7(dual), the latter was likely to be transient (P = 0.004), and AML was frequently observed with persistent -7 clones (P = 0.03). By logistic regression analysis (n = 36), clone size (P = 0.017), time-to-detection longer than 15 months (P = 0.02), and CML response (P = 0.085) were associated with MDS/AML. Validation of these novel associations in registry-based studies will help develop predictive criteria that define the MDS/AML risk in individual patients.

    Original languageEnglish
    Pages (from-to)39-44
    Number of pages6
    JournalCancer Genetics
    Volume204
    Issue number1
    DOIs
    Publication statusPublished - Jan 2011

    Keywords

    • -7
    • del(7q)
    • tyrosine kinase inhibitor
    • MDS
    • AML
    • CML
    • Philadelphia negative
    • CHRONIC MYELOGENOUS LEUKEMIA
    • CHROMOSOME-NEGATIVE CELLS
    • IMATINIB MESYLATE THERAPY
    • COMPLETE CYTOGENETIC RESPONSE
    • CHRONIC MYELOCYTIC-LEUKEMIA
    • CHRONIC PHASE
    • CML PATIENTS
    • INTERFERON-ALPHA
    • ABNORMAL CLONES
    • PH-CELLS

    Cite this

    @article{848d6479b5824264ad38f921a27b5cba,
    title = "Factors influencing a second myeloid malignancy in patients with Philadelphia-negative-7 or del(7q) clones during tyrosine kinase inhibitor therapy for chronic myeloid leukemia",
    abstract = "The detection of Philadelphia-negative (Ph-neg) cells with non-random karyotypic abnormalities after tyrosine kinase inhibitor (TKI) therapy of chronic myeloid leukaemia (CML) can be associated with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). To our knowledge, however, there have been no studies on variables influencing the risk of MDS/AML in patients with specific Ph-neg karyotypes. We systematically examined studies reporting -7 or del(7q) within Ph-neg cells in TKI-treated CML patients, and abstracted clinical and cytogenetic data from individual reports into a standardized format for further analysis. Of 53 patients, 43 had Ph-neg -7 clones [as the sole abnormality (-7(sole)) in 29, or with other clones (-7(dual)) in 14], and del(7q) was present in 10. A total of 16/51 evaluable patients, all with -7, transformed to MDS/AML. Transformation was more frequent (15/16 patients) within 6 months of Ph-neg -7 detection rather than subsequently (P < 0.0001). At first detection after TKI therapy, Ph-neg abnormal clones comprised >= 50{\%} of Ph-neg cells in a greater proportion of patients with -7 than del(7q) (P = 0.035). Upon comparing -7(sole) and -7(dual), the latter was likely to be transient (P = 0.004), and AML was frequently observed with persistent -7 clones (P = 0.03). By logistic regression analysis (n = 36), clone size (P = 0.017), time-to-detection longer than 15 months (P = 0.02), and CML response (P = 0.085) were associated with MDS/AML. Validation of these novel associations in registry-based studies will help develop predictive criteria that define the MDS/AML risk in individual patients.",
    keywords = "-7, del(7q), tyrosine kinase inhibitor, MDS, AML, CML, Philadelphia negative, CHRONIC MYELOGENOUS LEUKEMIA, CHROMOSOME-NEGATIVE CELLS, IMATINIB MESYLATE THERAPY, COMPLETE CYTOGENETIC RESPONSE, CHRONIC MYELOCYTIC-LEUKEMIA, CHRONIC PHASE, CML PATIENTS, INTERFERON-ALPHA, ABNORMAL CLONES, PH-CELLS",
    author = "Groves, {Michael J.} and Mark Sales and Lee Baker and Michael Griffiths and Norman Pratt and Sudhir Tauro",
    year = "2011",
    month = "1",
    doi = "10.1016/j.cancergencyto.2010.08.017",
    language = "English",
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    Factors influencing a second myeloid malignancy in patients with Philadelphia-negative-7 or del(7q) clones during tyrosine kinase inhibitor therapy for chronic myeloid leukemia. / Groves, Michael J.; Sales, Mark; Baker, Lee; Griffiths, Michael; Pratt, Norman; Tauro, Sudhir.

    In: Cancer Genetics, Vol. 204, No. 1, 01.2011, p. 39-44.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Factors influencing a second myeloid malignancy in patients with Philadelphia-negative-7 or del(7q) clones during tyrosine kinase inhibitor therapy for chronic myeloid leukemia

    AU - Groves, Michael J.

    AU - Sales, Mark

    AU - Baker, Lee

    AU - Griffiths, Michael

    AU - Pratt, Norman

    AU - Tauro, Sudhir

    PY - 2011/1

    Y1 - 2011/1

    N2 - The detection of Philadelphia-negative (Ph-neg) cells with non-random karyotypic abnormalities after tyrosine kinase inhibitor (TKI) therapy of chronic myeloid leukaemia (CML) can be associated with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). To our knowledge, however, there have been no studies on variables influencing the risk of MDS/AML in patients with specific Ph-neg karyotypes. We systematically examined studies reporting -7 or del(7q) within Ph-neg cells in TKI-treated CML patients, and abstracted clinical and cytogenetic data from individual reports into a standardized format for further analysis. Of 53 patients, 43 had Ph-neg -7 clones [as the sole abnormality (-7(sole)) in 29, or with other clones (-7(dual)) in 14], and del(7q) was present in 10. A total of 16/51 evaluable patients, all with -7, transformed to MDS/AML. Transformation was more frequent (15/16 patients) within 6 months of Ph-neg -7 detection rather than subsequently (P < 0.0001). At first detection after TKI therapy, Ph-neg abnormal clones comprised >= 50% of Ph-neg cells in a greater proportion of patients with -7 than del(7q) (P = 0.035). Upon comparing -7(sole) and -7(dual), the latter was likely to be transient (P = 0.004), and AML was frequently observed with persistent -7 clones (P = 0.03). By logistic regression analysis (n = 36), clone size (P = 0.017), time-to-detection longer than 15 months (P = 0.02), and CML response (P = 0.085) were associated with MDS/AML. Validation of these novel associations in registry-based studies will help develop predictive criteria that define the MDS/AML risk in individual patients.

    AB - The detection of Philadelphia-negative (Ph-neg) cells with non-random karyotypic abnormalities after tyrosine kinase inhibitor (TKI) therapy of chronic myeloid leukaemia (CML) can be associated with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). To our knowledge, however, there have been no studies on variables influencing the risk of MDS/AML in patients with specific Ph-neg karyotypes. We systematically examined studies reporting -7 or del(7q) within Ph-neg cells in TKI-treated CML patients, and abstracted clinical and cytogenetic data from individual reports into a standardized format for further analysis. Of 53 patients, 43 had Ph-neg -7 clones [as the sole abnormality (-7(sole)) in 29, or with other clones (-7(dual)) in 14], and del(7q) was present in 10. A total of 16/51 evaluable patients, all with -7, transformed to MDS/AML. Transformation was more frequent (15/16 patients) within 6 months of Ph-neg -7 detection rather than subsequently (P < 0.0001). At first detection after TKI therapy, Ph-neg abnormal clones comprised >= 50% of Ph-neg cells in a greater proportion of patients with -7 than del(7q) (P = 0.035). Upon comparing -7(sole) and -7(dual), the latter was likely to be transient (P = 0.004), and AML was frequently observed with persistent -7 clones (P = 0.03). By logistic regression analysis (n = 36), clone size (P = 0.017), time-to-detection longer than 15 months (P = 0.02), and CML response (P = 0.085) were associated with MDS/AML. Validation of these novel associations in registry-based studies will help develop predictive criteria that define the MDS/AML risk in individual patients.

    KW - -7

    KW - del(7q)

    KW - tyrosine kinase inhibitor

    KW - MDS

    KW - AML

    KW - CML

    KW - Philadelphia negative

    KW - CHRONIC MYELOGENOUS LEUKEMIA

    KW - CHROMOSOME-NEGATIVE CELLS

    KW - IMATINIB MESYLATE THERAPY

    KW - COMPLETE CYTOGENETIC RESPONSE

    KW - CHRONIC MYELOCYTIC-LEUKEMIA

    KW - CHRONIC PHASE

    KW - CML PATIENTS

    KW - INTERFERON-ALPHA

    KW - ABNORMAL CLONES

    KW - PH-CELLS

    U2 - 10.1016/j.cancergencyto.2010.08.017

    DO - 10.1016/j.cancergencyto.2010.08.017

    M3 - Article

    VL - 204

    SP - 39

    EP - 44

    JO - Cancer Genetics

    JF - Cancer Genetics

    SN - 2210-7762

    IS - 1

    ER -