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

Research output: ThesisDoctoral Thesis (compilation)

Bibtex

@phdthesis{42cb09386bd14067b00e9304500ccaa1,
title = "Cytogenetic abnormalities in Acute Myeloid Leukemia in Sweden. A population based study.",
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.",
keywords = "AML, karyotype, population-based studies, prognosis, chromosomes, hyperdiploidy",
author = "Vladimir Lazarevic",
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 ---",
year = "2015",
language = "English",
isbn = "978-91-7619-227-6",
series = "Lund University Faculty of Medicine Doctoral Dissertation Series",
publisher = "Stam Cells Centrum (SCC)",
school = "Stem Cell Center",

}