Outcomes in Children, Adolescents, and Young Adults With Down Syndrome and ALL: A Report From the Children's Oncology Group.

Purpose: Patients with Down syndrome (DS) and B-ALL experience increased rates of relapse, toxicity, and death. We report results for patients with DS B-ALL enrolled on Children's Oncology Group trials between 2003 and 2019.

Methods: We analyzed data for DS (n = 743) and non-DS (n = 20,067) patients age 1-30 years on four B-ALL standard-risk (SR) and high-risk trials.

Results: Patients with DS exhibited more frequent minimal residual disease (MRD) ≥0.01% at end induction (30.8% 21.5%; < .001). This difference persisted at end consolidation only in National Cancer Institute (NCI) high-risk patients (34.0% 11.7%; < .0001). Five-year event-free survival (EFS) and overall survival (OS) were significantly poorer for DS versus non-DS patients overall (EFS, 79.2% ± 1.6% 87.5% ± 0.3%; < .0001; OS, 86.8% ± 1.4% 93.6% ± 0.2%; < .0001), and within NCI SR and high-risk subgroups. Multivariable Cox regression analysis of the DS cohort for risk factors associated with inferior EFS identified age >10 years, white blood count >50 × 10/μL, and end-induction MRD ≥0.01%, but not cytogenetics or overexpression. Patients with DS demonstrated higher 5-year cumulative incidence of relapse (11.5% ± 1.2% 9.1% ± 0.2%; = .0008), death in remission (4.9% ± 0.8% 1.7% ± 0.1%; < .0001), and induction death (3.4% 0.8%; < .0001). Mucositis, infections, and hyperglycemia were significantly more frequent in all patients with DS, while seizures were more frequent in patients with DS on high-risk trials (4.1% 1.8%; = .005).

Conclusion: Patients with DS-ALL exhibit an increased rate of relapse and particularly of treatment-related mortality. Novel, less-toxic therapeutic strategies are needed to improve outcomes.