Complex and monosomal karyotype are distinct cytogenetic entities with an adverse prognostic impact in paediatric acute myeloid leukaemia. A NOPHO-DBH-AML study

Ninna Bager; Kristian L. Juul-Dam; Julie D. Sandahl; Jonas Abrahamsson; Berna Beverloo; Eveline S.J.M. de Bont; Shau Yin Ha; Kirsi Jahnukainen; Ólafur G. Jónsson; Gertjan L. Kaspers; Zhanna Kovalova; Birgitte Lausen; Barbara De Moerloose; Ulrika Noren-Nyström; Josefine Palle; Kadri Saks; Bernward Zeller; Eigil Kjeldsen; Henrik Hasle

doi:10.1111/bjh.15587

Complex and monosomal karyotype are distinct cytogenetic entities with an adverse prognostic impact in paediatric acute myeloid leukaemia. A NOPHO-DBH-AML study

Ninna Bager, Kristian L. Juul-Dam, Julie D. Sandahl, Jonas Abrahamsson, Berna Beverloo, Eveline S.J.M. de Bont, Shau Yin Ha, Kirsi Jahnukainen, Ólafur G. Jónsson, Gertjan L. Kaspers, Zhanna Kovalova, Birgitte Lausen, Barbara De Moerloose, Ulrika Noren-Nyström, Josefine Palle, Kadri Saks, Bernward Zeller, Eigil Kjeldsen, Henrik Hasle

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Abstract

Data on occurrence, genetic characteristics and prognostic impact of complex and monosomal karyotype (CK/MK) in children with acute myeloid leukaemia (AML) are scarce. We studied CK and MK in a large unselected cohort of childhood AML patients diagnosed and treated according to Nordic Society for Paediatric Haematology and Oncology (NOPHO)-AML protocols 1993–2015. In total, 800 patients with de novo AML were included. CK was found in 122 (15%) and MK in 41 (5%) patients. CK and MK patients were young (median age 2·1 and 3·3 years, respectively) and frequently had FAB M7 morphology (24% and 22%, respectively). Refractory disease was more common in MK patients (15% vs. 4%) and stem cell transplantation in first complete remission was more frequent (32% vs. 19%) compared with non-CK/non-MK patients. CK showed no association with refractory disease but was an independent predictor of an inferior event-free survival (EFS; hazard ratio [HR] 1·43, P = 0·03) and overall survival (OS; HR 1·48, P = 0·01). MK was associated with a poor EFS (HR 1·57, P = 0·03) but did not show an inferior OS compared to non-MK patients (HR 1·14, P = 0·62). In a large paediatric cohort, we characterized AML with non-recurrent abnormal karyotype and unravelled the adverse impact of CK and MK on prognosis.

Original language	English
Pages (from-to)	618-628
Number of pages	11
Journal	British Journal of Haematology
Volume	183
Issue number	4
DOIs	https://doi.org/10.1111/bjh.15587
Publication status	Published - Nov 2018
Externally published	Yes

Keywords*

Acute myeloid leukaemia
complex karyotype
monosomal karyotype
paediatrics
refractory disease

Field of Science*

3.2 Clinical medicine

Publication Type*

1.1. Scientific article indexed in Web of Science and/or Scopus database

Access to Document

10.1111/bjh.15587

Complex and monosomal karyotypFinal published version, 300 KB

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Bager, N., Juul-Dam, K. L., Sandahl, J. D., Abrahamsson, J., Beverloo, B., de Bont, E. S. J. M., Ha, S. Y., Jahnukainen, K., Jónsson, Ó. G., Kaspers, G. L., Kovalova, Z., Lausen, B., De Moerloose, B., Noren-Nyström, U., Palle, J., Saks, K., Zeller, B., Kjeldsen, E., & Hasle, H. (2018). Complex and monosomal karyotype are distinct cytogenetic entities with an adverse prognostic impact in paediatric acute myeloid leukaemia. A NOPHO-DBH-AML study. British Journal of Haematology, 183(4), 618-628. https://doi.org/10.1111/bjh.15587

@article{9b230ea296274c949a3d3cdd5ef22e8f,

title = "Complex and monosomal karyotype are distinct cytogenetic entities with an adverse prognostic impact in paediatric acute myeloid leukaemia. A NOPHO-DBH-AML study",

abstract = "Data on occurrence, genetic characteristics and prognostic impact of complex and monosomal karyotype (CK/MK) in children with acute myeloid leukaemia (AML) are scarce. We studied CK and MK in a large unselected cohort of childhood AML patients diagnosed and treated according to Nordic Society for Paediatric Haematology and Oncology (NOPHO)-AML protocols 1993–2015. In total, 800 patients with de novo AML were included. CK was found in 122 (15%) and MK in 41 (5%) patients. CK and MK patients were young (median age 2·1 and 3·3 years, respectively) and frequently had FAB M7 morphology (24% and 22%, respectively). Refractory disease was more common in MK patients (15% vs. 4%) and stem cell transplantation in first complete remission was more frequent (32% vs. 19%) compared with non-CK/non-MK patients. CK showed no association with refractory disease but was an independent predictor of an inferior event-free survival (EFS; hazard ratio [HR] 1·43, P = 0·03) and overall survival (OS; HR 1·48, P = 0·01). MK was associated with a poor EFS (HR 1·57, P = 0·03) but did not show an inferior OS compared to non-MK patients (HR 1·14, P = 0·62). In a large paediatric cohort, we characterized AML with non-recurrent abnormal karyotype and unravelled the adverse impact of CK and MK on prognosis.",

keywords = "Acute myeloid leukaemia, complex karyotype, monosomal karyotype, paediatrics, refractory disease",

author = "Ninna Bager and Juul-Dam, {Kristian L.} and Sandahl, {Julie D.} and Jonas Abrahamsson and Berna Beverloo and {de Bont}, {Eveline S.J.M.} and Ha, {Shau Yin} and Kirsi Jahnukainen and J{\'o}nsson, {{\'O}lafur G.} and Kaspers, {Gertjan L.} and Zhanna Kovalova and Birgitte Lausen and {De Moerloose}, Barbara and Ulrika Noren-Nystr{\"o}m and Josefine Palle and Kadri Saks and Bernward Zeller and Eigil Kjeldsen and Henrik Hasle",

note = "Funding Information: The study was supported by the Danish Childhood Cancer Foundation. Furthermore, all the work done by the cytogenetic groups in NOPHO is acknowledged. Publisher Copyright: {\textcopyright} 2018 British Society for Haematology and John Wiley & Sons Ltd",

year = "2018",

month = nov,

doi = "10.1111/bjh.15587",

language = "English",

volume = "183",

pages = "618--628",

journal = "British Journal of Haematology",

issn = "0007-1048",

publisher = "Wiley-Blackwell Publishing Ltd",

number = "4",

}

Bager, N, Juul-Dam, KL, Sandahl, JD, Abrahamsson, J, Beverloo, B, de Bont, ESJM, Ha, SY, Jahnukainen, K, Jónsson, ÓG, Kaspers, GL, Kovalova, Z, Lausen, B, De Moerloose, B, Noren-Nyström, U, Palle, J, Saks, K, Zeller, B, Kjeldsen, E & Hasle, H 2018, 'Complex and monosomal karyotype are distinct cytogenetic entities with an adverse prognostic impact in paediatric acute myeloid leukaemia. A NOPHO-DBH-AML study', British Journal of Haematology, vol. 183, no. 4, pp. 618-628. https://doi.org/10.1111/bjh.15587

TY - JOUR

T1 - Complex and monosomal karyotype are distinct cytogenetic entities with an adverse prognostic impact in paediatric acute myeloid leukaemia. A NOPHO-DBH-AML study

AU - Bager, Ninna

AU - Juul-Dam, Kristian L.

AU - Sandahl, Julie D.

AU - Abrahamsson, Jonas

AU - Beverloo, Berna

AU - de Bont, Eveline S.J.M.

AU - Ha, Shau Yin

AU - Jahnukainen, Kirsi

AU - Jónsson, Ólafur G.

AU - Kaspers, Gertjan L.

AU - Kovalova, Zhanna

AU - Lausen, Birgitte

AU - De Moerloose, Barbara

AU - Noren-Nyström, Ulrika

AU - Palle, Josefine

AU - Saks, Kadri

AU - Zeller, Bernward

AU - Kjeldsen, Eigil

AU - Hasle, Henrik

N1 - Funding Information: The study was supported by the Danish Childhood Cancer Foundation. Furthermore, all the work done by the cytogenetic groups in NOPHO is acknowledged. Publisher Copyright: © 2018 British Society for Haematology and John Wiley & Sons Ltd

PY - 2018/11

Y1 - 2018/11

N2 - Data on occurrence, genetic characteristics and prognostic impact of complex and monosomal karyotype (CK/MK) in children with acute myeloid leukaemia (AML) are scarce. We studied CK and MK in a large unselected cohort of childhood AML patients diagnosed and treated according to Nordic Society for Paediatric Haematology and Oncology (NOPHO)-AML protocols 1993–2015. In total, 800 patients with de novo AML were included. CK was found in 122 (15%) and MK in 41 (5%) patients. CK and MK patients were young (median age 2·1 and 3·3 years, respectively) and frequently had FAB M7 morphology (24% and 22%, respectively). Refractory disease was more common in MK patients (15% vs. 4%) and stem cell transplantation in first complete remission was more frequent (32% vs. 19%) compared with non-CK/non-MK patients. CK showed no association with refractory disease but was an independent predictor of an inferior event-free survival (EFS; hazard ratio [HR] 1·43, P = 0·03) and overall survival (OS; HR 1·48, P = 0·01). MK was associated with a poor EFS (HR 1·57, P = 0·03) but did not show an inferior OS compared to non-MK patients (HR 1·14, P = 0·62). In a large paediatric cohort, we characterized AML with non-recurrent abnormal karyotype and unravelled the adverse impact of CK and MK on prognosis.

AB - Data on occurrence, genetic characteristics and prognostic impact of complex and monosomal karyotype (CK/MK) in children with acute myeloid leukaemia (AML) are scarce. We studied CK and MK in a large unselected cohort of childhood AML patients diagnosed and treated according to Nordic Society for Paediatric Haematology and Oncology (NOPHO)-AML protocols 1993–2015. In total, 800 patients with de novo AML were included. CK was found in 122 (15%) and MK in 41 (5%) patients. CK and MK patients were young (median age 2·1 and 3·3 years, respectively) and frequently had FAB M7 morphology (24% and 22%, respectively). Refractory disease was more common in MK patients (15% vs. 4%) and stem cell transplantation in first complete remission was more frequent (32% vs. 19%) compared with non-CK/non-MK patients. CK showed no association with refractory disease but was an independent predictor of an inferior event-free survival (EFS; hazard ratio [HR] 1·43, P = 0·03) and overall survival (OS; HR 1·48, P = 0·01). MK was associated with a poor EFS (HR 1·57, P = 0·03) but did not show an inferior OS compared to non-MK patients (HR 1·14, P = 0·62). In a large paediatric cohort, we characterized AML with non-recurrent abnormal karyotype and unravelled the adverse impact of CK and MK on prognosis.

KW - Acute myeloid leukaemia

KW - complex karyotype

KW - monosomal karyotype

KW - paediatrics

KW - refractory disease

UR - http://www.scopus.com/inward/record.url?scp=85056203633&partnerID=8YFLogxK

U2 - 10.1111/bjh.15587

DO - 10.1111/bjh.15587

M3 - Article

C2 - 30406946

AN - SCOPUS:85056203633

SN - 0007-1048

VL - 183

SP - 618

EP - 628

JO - British Journal of Haematology

JF - British Journal of Haematology

IS - 4

ER -

Complex and monosomal karyotype are distinct cytogenetic entities with an adverse prognostic impact in paediatric acute myeloid leukaemia. A NOPHO-DBH-AML study

Abstract

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