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

Research output: Contribution to journalArticle

Standard

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; Pession, Andrea; Tousovska, Katerina; Cheuk, Daniel K. L.; Kudo, Kazuko; Taga, Takashi; Rubnitz, Jeffrey E.; Haltrich, Iren; Balwierz, Walentyna; Pieters, Rob; Forestier, Erik; Johansson, Bertil; van den Heuvel-Eibrink, Marry M.; Zwaan, C. Michel.

In: Haematologica, Vol. 99, No. 2, 2014, p. 299-307.

Research output: Contribution to journalArticle

Harvard

Blink, M, Zimmermann, M, von Neuhoff, C, Reinhardt, D, de Haas, V, Hasle, H, O'Brien, MM, Stark, B, Tandonnet, J, Pession, A, Tousovska, K, Cheuk, DKL, Kudo, K, Taga, T, Rubnitz, JE, Haltrich, I, Balwierz, W, Pieters, R, Forestier, E, Johansson, B, van den Heuvel-Eibrink, MM & Zwaan, CM 2014, 'Normal karyotype is a poor prognostic factor in myeloid leukemia of Down syndrome: a retrospective, international study', Haematologica, vol. 99, no. 2, pp. 299-307. https://doi.org/10.3324/haematol.2013.089425

APA

Blink, M., Zimmermann, M., von Neuhoff, C., Reinhardt, D., de Haas, V., Hasle, H., ... Zwaan, C. M. (2014). Normal karyotype is a poor prognostic factor in myeloid leukemia of Down syndrome: a retrospective, international study. Haematologica, 99(2), 299-307. https://doi.org/10.3324/haematol.2013.089425

CBE

Blink M, Zimmermann M, von Neuhoff C, Reinhardt D, de Haas V, Hasle H, O'Brien MM, Stark B, Tandonnet J, Pession A, Tousovska K, Cheuk DKL, Kudo K, Taga T, Rubnitz JE, Haltrich I, Balwierz W, Pieters R, Forestier E, Johansson B, van den Heuvel-Eibrink MM, Zwaan CM. 2014. Normal karyotype is a poor prognostic factor in myeloid leukemia of Down syndrome: a retrospective, international study. Haematologica. 99(2):299-307. https://doi.org/10.3324/haematol.2013.089425

MLA

Vancouver

Author

Blink, Marjolein ; Zimmermann, Martin ; von Neuhoff, Christine ; Reinhardt, Dirk ; de Haas, Valerie ; Hasle, Henrik ; O'Brien, Maureen M. ; Stark, Batia ; Tandonnet, Julie ; Pession, Andrea ; Tousovska, Katerina ; Cheuk, Daniel K. L. ; Kudo, Kazuko ; Taga, Takashi ; Rubnitz, Jeffrey E. ; Haltrich, Iren ; Balwierz, Walentyna ; Pieters, Rob ; Forestier, Erik ; Johansson, Bertil ; van den Heuvel-Eibrink, Marry M. ; Zwaan, C. Michel. / Normal karyotype is a poor prognostic factor in myeloid leukemia of Down syndrome: a retrospective, international study. In: Haematologica. 2014 ; Vol. 99, No. 2. pp. 299-307.

RIS

TY - JOUR

T1 - Normal karyotype is a poor prognostic factor in myeloid leukemia of Down syndrome: a retrospective, international study

AU - Blink, Marjolein

AU - Zimmermann, Martin

AU - von Neuhoff, Christine

AU - Reinhardt, Dirk

AU - de Haas, Valerie

AU - Hasle, Henrik

AU - O'Brien, Maureen M.

AU - Stark, Batia

AU - Tandonnet, Julie

AU - Pession, Andrea

AU - Tousovska, Katerina

AU - Cheuk, Daniel K. L.

AU - Kudo, Kazuko

AU - Taga, Takashi

AU - Rubnitz, Jeffrey E.

AU - Haltrich, Iren

AU - Balwierz, Walentyna

AU - Pieters, Rob

AU - Forestier, Erik

AU - Johansson, Bertil

AU - van den Heuvel-Eibrink, Marry M.

AU - Zwaan, C. Michel

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

U2 - 10.3324/haematol.2013.089425

DO - 10.3324/haematol.2013.089425

M3 - Article

VL - 99

SP - 299

EP - 307

JO - Haematologica-The Hematology Journal

T2 - Haematologica-The Hematology Journal

JF - Haematologica-The Hematology Journal

SN - 1592-8721

IS - 2

ER -