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Acute lymphoblastic leukemia in children with Down syndrome: a retrospective analysis from the Ponte di Legno study group

Lookup NU author(s): Professor Anthony MoormanORCiD


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Children with Down syndrome (DS) have an increased risk of B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). The prognostic factors and outcome of DS-ALL patients treated in contemporary protocols are uncertain. We studied 653 DS-ALL patients enrolled in 16 international trials from 1995 to 2004. Non-DS BCP-ALL patients from the Dutch Child Oncology Group and Berlin-Frankfurt-Munster were reference cohorts. DS-ALL patients had a higher 8-year cumulative incidence of relapse (26% +/- 2% vs 15% +/- 1%, P < .001) and 2-year treatment-related mortality (TRM) (7% +/- 1% vs 2.0% +/- < 1%, P < .0001) than non-DS patients, resulting in lower 8-year event-free survival (EFS) (64% +/- 2% vs 81% +/- 2%, P < .0001) and overall survival (74% +/- 2% vs 89% +/- 1%, P < .0001). Independent favorable prognostic factors include age <6 years (hazard ratio [HR] = 0.58, P = .002), white blood cell (WBC) count <10 x 10(9)/L (HR = 0.60, P = .005), and ETV6-RUNX1 (HR = 0.14, P = .006) for EFS and age (HR = 0.48, P < .001), ETV6-RUNX1 (HR = 0.1, P = .016) and high hyperdiploidy (HeH) (HR = 0.29, P = .04) for relapse-free survival. TRM was the major cause of death in ETV6-RUNX1 and HeH DS-ALLs. Thus, while relapse is the main contributor to poorer survival in DS-ALL, infection-associated TRM was increased in all protocol elements, unrelated to treatment phase or regimen. Future strategies to improve outcome in DS-ALL should include improved supportive care throughout therapy and reduction of therapy in newly identified good-prognosis subgroups.

Publication metadata

Author(s): Buitenkamp TD, Izraeli S, Zimmermann M, Forestier E, Heerema NA, van den Heuvel-Eibrink MM, Pieters R, Korbijn CM, Silverman LB, Schmiegelow K, Liang DC, Horibe K, Arico M, Biondi A, Basso G, Rabin KR, Schrappe M, Cario G, Mann G, Morak M, Panzer-Grumayer R, Mondelaers V, Lammens T, Cave H, Stark B, Ganmore I, Moorman AV, Vora A, Hunger SP, Pui CH, Mullighan CG, Manabe A, Escherich G, Kowalczyk JR, Whitlock JA, Zwaan CM

Publication type: Article

Publication status: Published

Journal: Blood

Year: 2014

Volume: 123

Issue: 1

Pages: 70-77

Print publication date: 12/11/2013

ISSN (print): 0006-4971

ISSN (electronic): 1528-0020

Publisher: American Society of Hematology


DOI: 10.1182/blood-2013-06-509463


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Funder referenceFunder name
American Lebanese Syrian Associated Charities (SJCRH)
Israel Cancer Research Foundation
Israel Science Foundation iCORE program
Israel Science Foundation Legacy program
KiKa (Erasmus MC-Sophia Children's Hospital)
Women's Auxiliary Millennium Chair in Haematology/Oncology
Ergen Family Chair in Pediatric Cancer
Israel Cancer Association
Waxman Research Foundation
5 P01CA068484National Cancer Institute
CA 21765National Cancer Institute
U24 CA114766