Buitenkamp, Trudy D2; Izraeli, Shai2; Zimmermann, Martin2; Forestier, Erik2; Heerema, Nyla A2; van den Heuvel-Eibrink, Marry M2; Pieters, Rob2; Korbijn, Carin M2; Silverman, Lewis B2; Schmiegelow, Kjeld1; Liang, Der-Cheng2; Horibe, Keizo2; Arico, Maurizio2; Biondi, Andrea2; Basso, Giuseppe2; Rabin, Karin R2; Schrappe, Martin2; Cario, Gunnar2; Mann, Georg2; Morak, Maria2; Panzer-Grümayer, Renate2; Mondelaers, Veerle2; Lammens, Tim2; Cavé, Hélène2; Stark, Batia2; Ganmore, Ithamar2; Moorman, Anthony V2; Vora, Ajay2; Hunger, Stephen P2; Pui, Ching-Hon2; Mullighan, Charles G2; Manabe, Atsushi2; Escherich, Gabriele2; Kowalczyk, Jerzy R2; Whitlock, James A2; Zwaan, C Michel2
1 Department of Paediatrics and Adolescent Medicine, Juliane Marie Centre, Rigshospitalet, The Capital Region of Denmark2 unknown
a retrospective analysis from the Ponte di Legno study group
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 × 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.