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

Trudy D. Buitenkamp, Shai Izraeli, Martin Zimmermann, Erik Forestier, Nyla A. Heerema, Marry M. Van Den Heuvel-Eibrink, Rob Pieters, Carin M. Korbijn, Lewis B. Silverman, Kjeld Schmiegelow, Der Cheng Liang, Keizo Horibe, Maurizio Arico, Andrea Biondi, Giuseppe Basso, Karin R. Rabin, Martin Schrappe, Gunnar Cario, Georg Mann, Maria MorakRenate Panzer-Grümayer, Veerle Mondelaers, Tim Lammens, Hèléne Cav́, Batia Stark, Ithamar Ganmore, Anthony V. Moorman, Ajay Vora, Stephen P. Hunger, Ching Hon Pui, Charles G. Mullighan, Atsushi Manabe, Gabriele Escherich, Jerzy R. Kowalczyk, James A. Whitlock, C. Michel Zwaan

Research output: Contribution to journalArticlepeer-review

183 Scopus citations


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- Münster 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 3 109/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 DSALLs. 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. (Blood. 2014; 123(1):70-77).

Original languageEnglish
Pages (from-to)70-77
Number of pages8
Issue number1
StatePublished - 2 Jan 2014
Externally publishedYes


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