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

Lazarevic, Vladimir LU (2015) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2016:2.
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Professor Moorman, Anthony, Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne
organization
publishing date
type
Thesis
publication status
published
subject
keywords
AML, karyotype, population-based studies, prognosis, chromosomes, hyperdiploidy
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2016:2
pages
56 pages
publisher
Stam Cells Centrum (SCC)
defense location
Belfragesalen, BMC D15, Klinikgatan 32, Lund
defense date
2016-01-20 13:00
ISSN
1652-8220
ISBN
978-91-7619-227-6
language
English
LU publication?
yes
id
42cb0938-6bd1-4067-b00e-9304500ccaa1 (old id 8261459)
date added to LUP
2015-12-18 12:30:44
date last changed
2016-09-19 08:44:47
@phdthesis{42cb0938-6bd1-4067-b00e-9304500ccaa1,
  abstract     = {The impact of cytogenetic findings in AML was analyzed in the large population-based Swedish AML<br/><br>
registry. Karyotypic patterns differed by age: t(8;21), inv(16) and t(11q23) were more common in younger patients,<br/><br>
whereas loss of 5q, 7q and 17p, monosomal karyotype (MK) and complex karyotype (CK) were more common in<br/><br>
older patients. Patients with ≥5 chromosome abnormalities had worse overall survival than those with fewer<br/><br>
abnormalities or normal karyotype in all age groups. Loss of 5q, 7q and/or 17p had, in contrast to MK, a further<br/><br>
negative impact on survival. Multivariable analyses on risk factors in patients &lt;80 years with cytogenetic<br/><br>
abnormalities and intensive treatment revealed that age and performance status had the most significant impact<br/><br>
on survival (both P&lt;0.001), followed by sex (P=0.0135) and a karyotype including -7/del(7q) (P=0.048).<br/><br>
We compared outcome of AHD-AML and tAML, i.e., secondary (sAML) with de novo AML. The CR rates were<br/><br>
significantly lower but early death rates similar in sAML vs de novo AML. In a multivariable analysis, AHD-AML<br/><br>
(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<br/><br>
negative impact of AHD-AML and tAML on survival was highly age dependent with a considerable impact in<br/><br>
younger patients, but without independent prognostic value in the elderly.<br/><br>
The frequencies of unsuccessful cytogenetics (UC) and unperformed cytogenetics (UPC) were 2.1% and 2.0%,<br/><br>
respectively. The early death rates differed between the cytogenetic subgroups (P=0.006) with the highest rates in<br/><br>
patients with UC (14%) and UPC (12%) followed by high-risk (HR) AML, intermediate risk (IR) and standard risk<br/><br>
(SR) cases successfully karyotyped (8.6%, 5.9%, and 5.8%, respectively). The CR rate was lower in UC and UPC<br/><br>
and HR compared with the other risk groups (P&lt;0.001). The 5-year OS rates were 25% for UC and 22% for UPC,<br/><br>
whereas the corresponding frequencies for SR, IR and HR AML patients without UC and UPC were 64%, 31%<br/><br>
and 15%, respectively. Lack of cytogenetic data translates into a poor prognosis.<br/><br>
To ascertain the clinical implications of high hyperdiploid (HH; 49–65 chromosomes) and triploid/tetraploid (TT;<br/><br>
&gt;65 chromosomes) adult AML diagnosed 1997-2014, and 68 (1.9%) were HH (n=50)/TT (n=18). The OS was<br/><br>
similar between patients with HH/TT and CK AML (median 0.9 years vs. 0.6 years; P=0.082), whereas OS was<br/><br>
significantly longer (median 1.6 years; P=0.028) for IR AML. The OS was shorter for cases with HH than with TT<br/><br>
(median 0.6 years vs. 1.4 years; P=0.032) and for HH/TT AMLs with adverse abnormalities (median 0.8 years vs.<br/><br>
1.1 years; P=0.044). HH/TT AML is associated with a poor outcome, but chromosome numbers &gt;65 and absence<br/><br>
of adverse aberrations seem to translate into a more favorable prognosis.<br/><br>
Also, among 23 patients (0.4 %) with trisomy 13 with a median age of 72 years (44-84), there was a striking male<br/><br>
predominance (80%) with AML-M0 subtype in 37% of patients. Therapy-related AML and MDS/MPN/AML were<br/><br>
present in 30% of patients. Median OS time was 9.6 months (95 % CI (3.5-13.7), and 13 months for other patients<br/><br>
(95% CI 11.7-14.04), which was almost identical as in previously published studies.},
  author       = {Lazarevic, Vladimir},
  isbn         = {978-91-7619-227-6},
  issn         = {1652-8220},
  keyword      = {AML,karyotype,population-based studies,prognosis,chromosomes,hyperdiploidy},
  language     = {eng},
  pages        = {56},
  publisher    = {Stam Cells Centrum (SCC)},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Cytogenetic abnormalities in Acute Myeloid Leukemia in Sweden. A population based study.},
  volume       = {2016:2},
  year         = {2015},
}