Cytogenetic abnormalities in Acute Myeloid Leukemia in Sweden. A population based study.
Author
Summary, in English
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.
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.
Department/s
- Stem Cell Center
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
Publishing year
2015
Language
English
Publication/Series
Lund University Faculty of Medicine Doctoral Dissertation Series
Volume
2016:2
Full text
- Available as PDF - 1017 kB
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Document type
Dissertation
Publisher
Stam Cells Centrum (SCC)
Topic
- Hematology
Keywords
- AML
- karyotype
- population-based studies
- prognosis
- chromosomes
- hyperdiploidy
Status
Published
Research group
- Hematopoietic Stem Cell Laboratory
Supervisor
ISBN/ISSN/Other
- ISSN: 1652-8220
- ISBN: 978-91-7619-227-6
Defence date
20 January 2016
Defence time
13:00
Defence place
Belfragesalen, BMC D15, Klinikgatan 32, Lund
Opponent
- Anthony Moorman (Professor)