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

Research output: Contribution to journalArticleAcademicpeer-review

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 languageEnglish
Pages (from-to)618-628
JournalBritish Journal of Haematology
Volume183
Issue number4
DOIs
Publication statusPublished - 2018

Cite this

Bager, Ninna ; Juul-Dam, Kristian L. ; Sandahl, Julie D. ; Abrahamsson, Jonas ; Beverloo, Berna ; de Bont, Eveline S. J. M. ; Ha, Shau-Yin ; Jahnukainen, Kirsi ; Jónsson, Ólafur G. ; Kaspers, Gertjan L. ; Kovalova, Zhanna ; Lausen, Birgitte ; de Moerloose, Barbara ; Noren-Nyström, Ulrika ; Palle, Josefine ; Saks, Kadri ; Zeller, Bernward ; Kjeldsen, Eigil ; Hasle, Henrik. / Complex and monosomal karyotype are distinct cytogenetic entities with an adverse prognostic impact in paediatric acute myeloid leukaemia. A NOPHO-DBH-AML study. In: British Journal of Haematology. 2018 ; Vol. 183, No. 4. pp. 618-628.
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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.",
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 Shau-Yin Ha 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",
year = "2018",
doi = "10.1111/bjh.15587",
language = "English",
volume = "183",
pages = "618--628",
journal = "British Journal of Haematology",
issn = "0007-1048",
publisher = "Wiley-Blackwell",
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Bager, N, Juul-Dam, KL, Sandahl, JD, Abrahamsson, J, Beverloo, B, de Bont, ESJM, Ha, S-Y, 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

Complex and monosomal karyotype are distinct cytogenetic entities with an adverse prognostic impact in paediatric acute myeloid leukaemia. A NOPHO-DBH-AML study. / Bager, Ninna; Juul-Dam, Kristian L.; Sandahl, Julie D.; Abrahamsson, Jonas; Beverloo, Berna; de Bont, Eveline S. J. M.; Ha, Shau-Yin; Jahnukainen, Kirsi; Jónsson, Ólafur G.; Kaspers, Gertjan L.; Kovalova, Zhanna; Lausen, Birgitte; de Moerloose, Barbara; Noren-Nyström, Ulrika; Palle, Josefine; Saks, Kadri; Zeller, Bernward; Kjeldsen, Eigil; Hasle, Henrik.

In: British Journal of Haematology, Vol. 183, No. 4, 2018, p. 618-628.

Research output: Contribution to journalArticleAcademicpeer-review

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

PY - 2018

Y1 - 2018

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.

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UR - https://www.ncbi.nlm.nih.gov/pubmed/30406946

U2 - 10.1111/bjh.15587

DO - 10.1111/bjh.15587

M3 - Article

VL - 183

SP - 618

EP - 628

JO - British Journal of Haematology

JF - British Journal of Haematology

SN - 0007-1048

IS - 4

ER -