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 consistently shows that children with Down syndrome are more likely to suffer complications from chemotherapy. At the same time, some studies have suggested that children with Down syndrome and ALL may have a higher chance of relapsing.
What to do with this knowledge has been a source of controversy. Should patients with ALL and Down syndrome receive treatment modified to minimize toxicity from chemotherapy? Or should they be given the same treatment as other children with ALL to minimize the chance for relapse? Recent study results from Dana-Farber/Boston Children’s Cancer and Blood Disorders Center suggest that full-dose chemo is preferable.
The researchers studied 1,286 children and adolescents with ALL treated on two consecutive Dana-Farber Cancer Institute 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 and were treated without dose modifications.
The children with Down syndrome did not have a greater risk of relapse or death than the other children with ALL, although they did experience a higher frequency of certain side effects from chemotherapy, according to results reported 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.”
Safety concerns allayed
Some prior 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. The Dana-Farber protocol has never modified treatment for children with Down syndrome, Silverman notes, but 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.”
Not only were there no treatment-related deaths among the Down syndrome patients, but there also was no difference in the rate of complete ALL remission after the first month of treatment. After a median follow-up of 6.2 years, the 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, says Silverman, 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 these complications, our overall recommendation is that you can treat children with Down syndrome the same as other children with ALL.”
Learn more about ALL treatment at Dana-Farber/Boston Children’s.