Pediatric Patients With Down Syndrome and ALL Can Be Safely, Effectively Treated With Standard Regimens

Treatment modifications and dose reductions are common strategies in managing pediatric patients with Down syndrome and acute lymphocytic leukemia (ALL). According to results from a study presented at the 2016 ASH Annual Meeting by Uma H. Athale, MD, though, ALL patients with Down syndrome have comparable survival outcomes and toxicity profiles to ALL patients without Down syndrome.

Dr. Athale, from the Division of Hematology/Oncology at McMaster Children’s Hospital and Hamilton Health Sciences in Ontario, Canada, and authors analyzed data from 1,286 children with de novo ALL (age range = 1-18 years), including 38 with Down syndrome (3%), who underwent treatment under Dana Farber Cancer Institute ALL Consortium protocol between 2000 and 2011. This protocol included treatment with vincristine, dexamethasone, 6-mercaptopurine, and low-dose methotrexate.

Patients with Down syndrome had a complete response rate of 100 percent, compared with 95 percent among those without Down syndrome (p=0.47). After a median follow-up of 6.2 years, five-year overall survival and event-free survival rates were also higher among those with Down syndrome (97.1% vs. 91% and 91% vs. 82%, respectively). There was no significant difference in the proportion of patients in each group with low end-of-induction minimal residual disease.

“Without dose reductions or modifications, the Down syndrome patients did just as well as the non-Down syndrome patients,” said Lewis B. Silverman, MD, the study’s senior author. “They were able to tolerate full-dose chemotherapy based on their risk group and did well despite biologic differences in their disease compared with other children’s disease.”

Toxicity profiles were similar between children with and without Down syndrome; however, higher rates of grade ≥3 mucositis (52% vs. 12%; p<0.001), non-central nervous system thrombosis/bleed (18.4% vs. 8.2%; p=0.036), and seizures (15.8% vs. 4.7%; p=0.01) occurred in patients with Down syndrome. Bacterial and fungal infections also occurred more frequently (55.3% vs. 41%), but the difference was not statistically significant (p=0.096).

“The target toxicities that one needs to think about are infections and mucositis,” Dr. Silverman said. “Using supportive care interventions to try to prevent these complications, our recommendation is that you can treat children with Down syndrome the same as other children with ALL.”

Source: Athale UH, Puligandla M, Stevenson KE, et al. Excellent outcome of children with down syndrome (DS) and acute lymphoblastic leukemia (ALL) treated on Dana-Farber Cancer Institute (DFCI) ALL consortium protocols 00-001 and 05-001. Abstract #761. Presented at the 2016 ASH Annual Meeting, December 5, 2016; San Diego, CA; Dana-Farber Cancer Institute press release, December 5, 2017.