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

Marjolein Blink, Martin Zimmermann, Christine von Neuhoff, Dirk Reinhardt, Valerie de Haas, Henrik Hasle, Maureen M. O'Brien, Batia Stark, Julie Tandonnet, Andrea Pession, Katerina Tousovska, Daniel K.L. Cheuk, Kazuko Kudo, Takashi Taga, Jeffrey E. Rubnitz, Iren Haltrich, Walentyna Balwierz, Rob Pieters, Erik Forestier, Bertil JohanssonMarry M. van den Heuvel-Eibrink, C. Michel Zwaan

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)


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 ≥20×109/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.

Original languageEnglish
Pages (from-to)299-307
Number of pages9
Issue number2
Publication statusPublished - 01-02-2014
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Hematology


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