Outcome of children and adolescents with Down syndrome treated on Dana-Farber Cancer Institute Acute Lymphoblastic Leukemia Consortium protocols 00–001 and 05-001

Background: Children and adolescents with Down syndrome (DS) and acute lymphoblastic leukemia (ALL) are reported to have increased relapse rates and therapy-related mortality (TRM). Treatment regimens for DS-ALL patients often include therapy modifications. Dana-Farber Cancer Institute (DFCI) ALL Consortium protocols have used same risk-stratified treatment for patients with and without DS. Procedures: We compared clinical and outcome data of DS (n = 38) and non-DS (n = 1,248) patients enrolled on two consecutive DFCI ALL trials 00–001 (2000–2004) and 05-001 (2005–2011) with similar risk adapted therapy regardless of DS status. Results: There was no difference in demographic or presenting clinical features between two groups except absence of T-cell phenotype and lower frequency of hyperdiploidy in DS-ALL group. All DS-ALL patients achieved complete remission; four relapsed and one subsequently died. There was no TRM in DS-ALL patients. DS-ALL patients had significantly higher rates of mucositis (52% vs. 12%, p < 0.001), non-CNS thrombosis (18% vs. 8%; p = 0.036), and seizure (16% vs. 5%, p = 0.010). Compared to non-DS-ALL patients, DS-ALL patients had a higher incidence of infections during all therapy phases. The 5-year event-free and overall survival rates of DS-ALL patients were similar to non-DS-ALL patients (91% [95% confidence interval (CI), 81–100] vs. 84% [95% CI, 82–86]; 97% [95% CI, 92–100] vs. 91% [95% CI, 90–93]). Conclusion: The low rates of relapse and TRM indicate that uniform risk-stratified therapy for DS-ALL and non-DS-ALL patients on DFCI ALL Consortium protocols was safe and effective, although the increased rate of toxicity in the DS-ALL patients highlights the importance of supportive care during therapy.