Children with Down syndrome, ALL at higher risk for poor outcomes
Children with Down syndrome and acute lymphoblastic leukemia continue to experience poorer outcomes than children with ALL who do not have Down syndrome, according to study results presented during the ASCO20 Virtual Scientific Program.
“Children with Down syndrome have a 10-fold increased risk for developing ALL — the most common childhood cancer — and historically have had poorer outcomes compared with children without Down syndrome,” Karen R. Rabin, MD, PhD, associate professor in the department of pediatric hematology/oncology and director of the leukemia program at Texas Children’s Cancer Center, told Healio. “As treatment regimens have become more intensive in recent years, this has led to overall improvements in cure rates for ALL. However, survival among children with Down syndrome has lagged due to increased risk for relapse and an increase in life-threatening complications when treated with intensive chemotherapy.”
Rabin and colleagues assessed outcomes of 22,446 individuals aged 1 to 30 years who had newly diagnosed ALL and participated in four Children’s Oncology Group trials (standard-risk trials AALL0331 and AALL0932 and high-risk trials AALL0232 and AALL1131). In this cohort, 743 patients (3.3%) had Down syndrome and 21,703 (96.7%) did not.
Individuals with Down syndrome included in both AALL0932 and AALL1131 had significantly higher end-of-induction minimal residual disease (MRD) than those without Down syndrome. This difference persisted at the end of the consolidation treatment phase in the AALL1131 trial only, with fewer patients with Down syndrome and end-of-induction MRD demonstrating end-of-consolidation MRD of less than 0.01% (76.1% vs. 88%; P = .001).
Among all trials, patients with Down syndrome had significantly lower rates of 5-year EFS (79.6% vs. 86.3%) and 5-year OS (86.5% vs. 93.1%) than those without Down syndrome (P < .0001 for both). Researchers observed a similar pattern in the individual trials.
Age older than 10 years and end-of-induction MRD of less than 0.01% appeared associated with inferior EFS among patients with Down syndrome. However, cytogenetics and cytokine receptor-like factor 2 status did not appear associated with shorter EFS among these patients.
Patients with Down syndrome experienced more induction deaths (3.4% vs. 0.8%; P < .0001) and deaths in remission (4.8% vs. 1.8%; P < .0001) than those without Down syndrome.
“For deaths in remission, the increased frequency occurred pre-maintenance and in patients taken off protocol therapy, but not during maintenance, in contrast to prior reports,” Rabin and colleagues wrote in the study abstract.
Grade 3 or higher adverse events — including mucositis, infections and hyperglycemia — occurred at significantly higher rates among children with Down syndrome across all four trials. Grade 3 or higher seizures were significantly more common among children with Down syndrome only in high-risk trials (4.1% vs. 1.7%; P = .001) and occurred across all pre-maintenance phases.
“Children with Down syndrome continue to experience poorer outcomes, partly because children with Down syndrome and ALL are less likely to have leukemia with favorable cytogenetic changes that make it more responsive to chemotherapy and partly due to a higher risk for death from treatment-related complications — primarily infection,” Rabin told Healio. “Our study shows that we are making progress in the treatment of this vulnerable group of patients, but there is still a need for further improvement.”
Targeted therapy and immunotherapy are exciting areas of treatment, and children with ALL and Down syndrome stand to gain from these advances, Rabin added.
“An ongoing Children’s Oncology Group trial for newly diagnosed ALL is testing the utility of blinatumomab [Blincyto, Amgen],” Rabin said. “We are excited that children with Down syndrome are able to participate in this trial and have access to this exciting new therapy. We are also working to improve their access to investigational drugs on clinical trials for relapsed ALL, and we are studying risk factors that predict life-threatening infectious complications that may suggest strategies for prevention and management.” – by Jennifer Southall
Reference:
Rabin KR, et al. Abstract 10510. Presented at: ASCO20 Virtual Scientific Program; May 29-31, 2020.
Disclosures: The NIH funded this study. Rabin reports no relevant financial disclosures. Please see the abstract for all other researchers’ relevant financial disclosures.
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Rabin KR, et al. Abstract 10510. Presented at: ASCO20 Virtual Scientific Program; May 29-31, 2020.
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