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Normal karyotype is a poor prognostic factor in myeloid leukemia of Down syndrome: a retrospective, international study

Blink, Marjolein; Zimmermann, Martin; von Neuhoff, Christine; Reinhardt, Dirk; de Haas, Valerie; Hasle, Henrik; O'Brien, Maureen M.; Stark, Batia; Tandonnet, Julie and Pession, Andrea, et al. (2014) In Haematologica 99(2). p.299-307
Abstract
Myeloid leukemia of Down syndrome has a better prognosis than sporadic pediatric acute myeloid leukemia. Most cases of myeloid leukemia of Down syndrome are characterized by additional cytogenetic changes besides the constitutional trisomy 21, but their potential prognostic impact is not known. We, therefore, conducted an international retrospective study of clinical characteristics, cytogenetics, treatment, and outcome of 451 children with myeloid leukemia of Down syndrome. All karyotypes were centrally reviewed before assigning patients to subgroups. The overall 7-year event-free survival for the entire cohort was 78% (+/- 2%), with the overall survival rate being 79% (+/- 2%), the cumulative incidence of relapse 12% (+/- 2%), and the... (More)
Myeloid leukemia of Down syndrome has a better prognosis than sporadic pediatric acute myeloid leukemia. Most cases of myeloid leukemia of Down syndrome are characterized by additional cytogenetic changes besides the constitutional trisomy 21, but their potential prognostic impact is not known. We, therefore, conducted an international retrospective study of clinical characteristics, cytogenetics, treatment, and outcome of 451 children with myeloid leukemia of Down syndrome. All karyotypes were centrally reviewed before assigning patients to subgroups. The overall 7-year event-free survival for the entire cohort was 78% (+/- 2%), with the overall survival rate being 79% (+/- 2%), the cumulative incidence of relapse 12% (+/- 2%), and the cumulative incidence of toxic death 7% (+/- 1%). Outcome estimates showed large differences across the different cytogenetic subgroups. Based on the cumulative incidence of relapse, we could risk-stratify patients into two groups: cases with a normal karyotype (n=103) with a higher cumulative incidence of relapse (21%+/- 4%) than cases with an aberrant karyotype (n=255) with a cumulative incidence of relapse of 9% (+/- 2%) (P=0.004). Multivariate analyses revealed that white blood cell count >= 20x10(9)/L and age >3 years were independent predictors for poor event-free survival, while normal karyotype independently predicted inferior overall survival, event-free survival, and relapse-free survival. In conclusion, this study showed large differences in outcome within patients with myeloid leukemia of Down syndrome and identified novel prognostic groups that predicted clinical outcome and hence may be used for stratification in future treatment protocols. (Less)
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Haematologica
volume
99
issue
2
pages
299 - 307
publisher
Ferrata Storti Foundation
external identifiers
  • wos:000336253900022
  • scopus:84896716441
ISSN
1592-8721
DOI
10.3324/haematol.2013.089425
language
English
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yes
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32c7a8cb-5df3-4637-8a5f-3e7f93b96852 (old id 4559534)
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2014-08-01 07:42:40
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@article{32c7a8cb-5df3-4637-8a5f-3e7f93b96852,
  abstract     = {Myeloid leukemia of Down syndrome has a better prognosis than sporadic pediatric acute myeloid leukemia. Most cases of myeloid leukemia of Down syndrome are characterized by additional cytogenetic changes besides the constitutional trisomy 21, but their potential prognostic impact is not known. We, therefore, conducted an international retrospective study of clinical characteristics, cytogenetics, treatment, and outcome of 451 children with myeloid leukemia of Down syndrome. All karyotypes were centrally reviewed before assigning patients to subgroups. The overall 7-year event-free survival for the entire cohort was 78% (+/- 2%), with the overall survival rate being 79% (+/- 2%), the cumulative incidence of relapse 12% (+/- 2%), and the cumulative incidence of toxic death 7% (+/- 1%). Outcome estimates showed large differences across the different cytogenetic subgroups. Based on the cumulative incidence of relapse, we could risk-stratify patients into two groups: cases with a normal karyotype (n=103) with a higher cumulative incidence of relapse (21%+/- 4%) than cases with an aberrant karyotype (n=255) with a cumulative incidence of relapse of 9% (+/- 2%) (P=0.004). Multivariate analyses revealed that white blood cell count >= 20x10(9)/L and age >3 years were independent predictors for poor event-free survival, while normal karyotype independently predicted inferior overall survival, event-free survival, and relapse-free survival. In conclusion, this study showed large differences in outcome within patients with myeloid leukemia of Down syndrome and identified novel prognostic groups that predicted clinical outcome and hence may be used for stratification in future treatment protocols.},
  author       = {Blink, Marjolein and Zimmermann, Martin and von Neuhoff, Christine and Reinhardt, Dirk and de Haas, Valerie and Hasle, Henrik and O'Brien, Maureen M. and Stark, Batia and Tandonnet, Julie and Pession, Andrea and Tousovska, Katerina and Cheuk, Daniel K. L. and Kudo, Kazuko and Taga, Takashi and Rubnitz, Jeffrey E. and Haltrich, Iren and Balwierz, Walentyna and Pieters, Rob and Forestier, Erik and Johansson, Bertil and van den Heuvel-Eibrink, Marry M. and Zwaan, C. Michel},
  issn         = {1592-8721},
  language     = {eng},
  number       = {2},
  pages        = {299--307},
  publisher    = {Ferrata Storti Foundation},
  series       = {Haematologica},
  title        = {Normal karyotype is a poor prognostic factor in myeloid leukemia of Down syndrome: a retrospective, international study},
  url          = {http://dx.doi.org/10.3324/haematol.2013.089425},
  volume       = {99},
  year         = {2014},
}