Cytogenetic abnormalities in Acute Myeloid Leukemia in Sweden. A population based study.

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    Abstract

    The impact of cytogenetic findings in AML was analyzed in the large population-based Swedish AML
    registry. Karyotypic patterns differed by age: t(8;21), inv(16) and t(11q23) were more common in younger patients,
    whereas loss of 5q, 7q and 17p, monosomal karyotype (MK) and complex karyotype (CK) were more common in
    older patients. Patients with ≥5 chromosome abnormalities had worse overall survival than those with fewer
    abnormalities or normal karyotype in all age groups. Loss of 5q, 7q and/or 17p had, in contrast to MK, a further
    negative impact on survival. Multivariable analyses on risk factors in patients <80 years with cytogenetic
    abnormalities and intensive treatment revealed that age and performance status had the most significant impact
    on survival (both P<0.001), followed by sex (P=0.0135) and a karyotype including -7/del(7q) (P=0.048).
    We compared outcome of AHD-AML and tAML, i.e., secondary (sAML) with de novo AML. The CR rates were
    significantly lower but early death rates similar in sAML vs de novo AML. In a multivariable analysis, AHD-AML
    (HR 1.51; 95% CI 1.26–1.79) and tAML (1.72; 1.38–2.15) were independent risk factors for poor survival. The
    negative impact of AHD-AML and tAML on survival was highly age dependent with a considerable impact in
    younger patients, but without independent prognostic value in the elderly.
    The frequencies of unsuccessful cytogenetics (UC) and unperformed cytogenetics (UPC) were 2.1% and 2.0%,
    respectively. The early death rates differed between the cytogenetic subgroups (P=0.006) with the highest rates in
    patients with UC (14%) and UPC (12%) followed by high-risk (HR) AML, intermediate risk (IR) and standard risk
    (SR) cases successfully karyotyped (8.6%, 5.9%, and 5.8%, respectively). The CR rate was lower in UC and UPC
    and HR compared with the other risk groups (P<0.001). The 5-year OS rates were 25% for UC and 22% for UPC,
    whereas the corresponding frequencies for SR, IR and HR AML patients without UC and UPC were 64%, 31%
    and 15%, respectively. Lack of cytogenetic data translates into a poor prognosis.
    To ascertain the clinical implications of high hyperdiploid (HH; 49–65 chromosomes) and triploid/tetraploid (TT;
    >65 chromosomes) adult AML diagnosed 1997-2014, and 68 (1.9%) were HH (n=50)/TT (n=18). The OS was
    similar between patients with HH/TT and CK AML (median 0.9 years vs. 0.6 years; P=0.082), whereas OS was
    significantly longer (median 1.6 years; P=0.028) for IR AML. The OS was shorter for cases with HH than with TT
    (median 0.6 years vs. 1.4 years; P=0.032) and for HH/TT AMLs with adverse abnormalities (median 0.8 years vs.
    1.1 years; P=0.044). HH/TT AML is associated with a poor outcome, but chromosome numbers >65 and absence
    of adverse aberrations seem to translate into a more favorable prognosis.
    Also, among 23 patients (0.4 %) with trisomy 13 with a median age of 72 years (44-84), there was a striking male
    predominance (80%) with AML-M0 subtype in 37% of patients. Therapy-related AML and MDS/MPN/AML were
    present in 30% of patients. Median OS time was 9.6 months (95 % CI (3.5-13.7), and 13 months for other patients
    (95% CI 11.7-14.04), which was almost identical as in previously published studies.
    Original languageEnglish
    QualificationDoctor
    Awarding Institution
    Supervisors/Advisors
    • Juliusson, Gunnar, Supervisor
    Award date2016 Jan 20
    Publisher
    Print ISBNs978-91-7619-227-6
    Publication statusPublished - 2015

    Bibliographical note

    Defence details

    Date: 2016-01-20
    Time: 13:00
    Place: Belfragesalen, BMC D15, Klinikgatan 32, Lund

    External reviewer(s)

    Name: Moorman, Anthony
    Title: Professor
    Affiliation: Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne

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    Subject classification (UKÄ)

    • Hematology

    Keywords

    • AML
    • karyotype
    • population-based studies
    • prognosis
    • chromosomes
    • hyperdiploidy

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