Clinicians have long known that children with Down syndrome carry an elevated risk of developing acute lymphoblastic leukemia (ALL), the most common pediatric cancer. Research also consistently shows that children with Down syndrome are more likely to suffer complications from chemotherapy – and some studies have suggested that children with Down syndrome ALL may have a higher chance of relapsing. What to do with this knowledge has been a source of controversy.
Because of their increased susceptibility to the toxicities of chemotherapy, should ALL patients with Down syndrome receive modified treatment to minimize this risk? Or should they be given the same treatment as other children with ALL, to minimize the chance for relapse? A new study from researchers at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center suggests the latter for patients treated on Dana-Farber Cancer Institute ALL Consortium protocols.
Children with Down syndrome ALL treated on the DFCI protocol without any dose modifications did not have greater risk of relapse or death, although they did experience a higher frequency of certain side effects from chemotherapy, according to study results presented at the recent annual meeting of the American Society of Hematology.
“Without dose reductions or modifications, the Down syndrome patients did just as well as the non-Down syndrome patients,” said Lewis B. Silverman, MD, senior author of the abstract and clinical director of the Hematologic Malignancy Center at Dana-Farber/Boston Children’s. “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.”
Some studies, looking at other treatment regimens, have found that ALL patients with Down syndrome have higher rates of relapse and/or treatment-related mortality, resulting in lower rates of long-term cure. While the Dana-Farber protocol has never modified treatment for children with Down syndrome, Silverman added, other protocols have made dose-adjustments to minimize side effects.
“There has been controversy in the field regarding how Down syndrome children do in terms of their prognosis compared with children who don’t have Down syndrome,” Silverman said. “We found that with our particular treatment approach, we’re not running into problems that others have reported.”
Researchers studied 1,286 children and adolescents with ALL treated on two consecutive DFCI ALL Consortium protocols between 2000 and 2011 at 11 institutions in the United States, Canada, and Puerto Rico. Of these patients, 38 (3 percent) had Down syndrome.
In addition to reporting no treatment-related deaths among the Down syndrome patients, researchers also found no difference in the rate at which children achieved complete remission after the first month of treatment. Researchers also found no statistically significant difference in event-free survival, disease-free survival, or overall survival. Patients with Down syndrome were more likely to suffer treatment-related mouth sores, clots or bleeding, and infection – but there was no difference in the frequency of other side effects.
The bottom line, Silverman said, is that children with Down syndrome may need measures to reduce their risk of complications, but they can still tolerate standard treatment well.
“The target toxicities that one needs to think about are infections and mouth sores,” Silverman said. “With supportive care to try to prevent complications, our overall recommendation is that you can treat children with Down syndrome the same as other children with ALL.”