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Acute lymphoblastic leukemia in children with Down syndrome: a retrospective analysis from the Ponte di Legno study
Trudy D Buitenkamp1, Shai Izraeli, Martin Zimmermann
1Pediatric Oncology/Hematology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands;
Insights
Children with Down syndrome (DS) have poorer outcomes for B-cell acute lymphoblastic leukemia (ALL) due to higher relapse rates and treatment-related mortality (TRM). Improved supportive care and reduced therapy for good-prognosis subgroups are key to improving survival in DS-ALL.
Area of Science:
- Pediatric Oncology
- Hematology
- Genetics
Background:
- Children with Down syndrome (DS) exhibit a higher risk of B-cell precursor acute lymphoblastic leukemia (BCP-ALL).
- Prognostic factors and treatment outcomes for DS-ALL in contemporary protocols remain uncertain.
- DS-ALL patients require specific considerations due to unique biological and clinical characteristics.
Purpose of the Study:
- To investigate the prognostic factors and outcomes of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) in children with Down syndrome (DS).
- To compare the outcomes of DS-ALL patients with non-DS BCP-ALL patients.
- To identify key factors influencing event-free survival (EFS) and treatment-related mortality (TRM) in DS-ALL.
Main Methods:
- Analysis of 653 DS-ALL patients from 16 international trials (1995-2004).
- Comparison with non-DS BCP-ALL reference cohorts from the Dutch Child Oncology Group and Berlin-Frankfurt-Münster.
- Statistical analysis to determine independent prognostic factors for EFS and relapse-free survival.
Main Results:
- DS-ALL patients showed a higher 8-year cumulative incidence of relapse (26% vs 15%) and TRM (7% vs 2.0%) compared to non-DS patients.
- Eight-year EFS (64% vs 81%) and overall survival (74% vs 89%) were significantly lower in DS-ALL patients.
- Favorable prognostic factors for EFS included age <6 years, WBC count <10 × 10(9)/L, and ETV6-RUNX1.
- Favorable prognostic factors for relapse-free survival included age, ETV6-RUNX1, and high hyperdiploidy (HeH).
- Infection-associated TRM was increased in DS-ALL, irrespective of treatment phase or regimen.
Conclusions:
- Relapse is the primary driver of poorer survival in DS-ALL.
- Treatment-related mortality, particularly from infections, is a significant concern in DS-ALL.
- Future strategies should focus on enhancing supportive care and tailoring therapy intensity for favorable-risk DS-ALL subgroups to improve outcomes.
Abstract:
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.
