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

作者：Buitenkamp Trudy D; Izraeli Shai; Zimmermann Martin; Forestier Erik; Heerema Nyla A; van den Heuvel Eibrink Marry M; Pieters Rob; Korbijn Carin M; Silverman Lewis B; Schmiegelow Kjeld; Liang Der Cheng; Horibe Keizo; Arico Maurizio; Biondi Andrea; Basso Giuseppe; Rabin Karin R; Schrappe Martin; Cario Gunnar; Mann Georg; Morak Maria; Panzer Grumayer Renate; Mondelaers Veerle; Lammens Tim; Cave Helene; Stark Batia; Ganmore Ithamar; Moorman Anthony V; Vora Ajay

来源：Blood, 2014, 123(1): 70-77.

DOI：10.1182/blood-2013-06-509463

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 %26lt; .001) and 2-year treatment-related mortality (TRM) (7% +/- 1% vs 2.0% +/- %26lt; 1%, P %26lt; .0001) than non-DS patients, resulting in lower 8-year event-free survival (EFS) (64% +/- 2% vs 81% +/- 2%, P %26lt; .0001) and overall survival (74% +/- 2% vs 89% +/- 1%, P %26lt; .0001). Independent favorable prognostic factors include age %26lt;6 years (hazard ratio [HR] = 0.58, P = .002), white blood cell (WBC) count %26lt;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 %26lt; .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.

• 出版日期2014-1-2