Children with Down syndrome have a 10 percent to 20 percent increased risk of developing acute lymphocytic leukemia and acute myeloid leukemia compared to children without Down syndrome. They are considered to have one of the highest risks of developing leukemia and require focused treatment protocols that differ from those for children with the syndrome, according to a study recently published by a Wayne State University pediatrician.
Jeffrey Taub, M.D., F.A.A.P., professor of Pediatrics for the Wayne State University School of Medicine and chief of Oncology for Children’s Hospital of Michigan, was the principal investigator of the study, “Improved outcomes for myeloid leukemia of Down syndrome: a report from the Children’s Oncology Group AAML0431 trial,” published in the June 29 edition of Blood, a weekly medical journal published by the American Society of Hematology.
The study enrolled 204 children from 2007 to 2011 through the Children’s Oncology Group, an international organization that links all major pediatric oncology centers in the United States, Canada and other countries to develop treatments for children with cancer.
Dr. Taub said children with Down syndrome and AML or ALL have special needs, and there have been concerns that they suffer more side effects from treatments compared to children without Down syndrome. These children require treatment protocols that focus on their clinical needs to provide effective and safe treatments. Children with Down syndrome represent 15 percent of all pediatric AML cases, which is significant as they represent about one in 800 children in the general population.
The study showed that the overall cure rate of Down syndrome patients was 93 percent, while deaths from side effects were very low. The most common side effects experienced by patients were infections that occurred when their white blood cell counts were low. No children died due to cardiac complications that had been reported previously (44 percent of children in the study had congenital heart defects).
An important part of the study also addressed the assessment of a test known as minimal residual disease, or MRD, monitoring. The test can detect one leukemia cell amongst 10,000 normal blood cells in the bone marrow. This is a more sensitive and accurate way of detecting leukemia cells compared to the standard approach of looking at bone marrow slides under a microscope. Patients who had a MRD level of less than .01 percent after the first course of chemotherapy experienced exceptionally high cure rates. Patients who had detectable MRD rates of greater than .01 percent had worse outcomes.
This is the first time that a laboratory test can potentially identify how children with Down syndrome and AML will respond to chemotherapy (this has been used previously for children without Down syndrome and AML). Patients with a negative MRD test had cure rates of 92.7 percent compared to 76.2 percent for patients with a positive test.
“Based on the results of this study, MRD testing is now being used in the new Children’s Oncology Group 1531 study for children with Down syndrome. Children who have a negative MRD test, will receive lower doses of chemotherapy (particularly cytarabine) to try to reduce side effects further while maintaining high cure rates. Patients who have a positive MRD test, will receive more intensive chemotherapy,” Dr. Taub said.
Research conducted at the Children’s Hospital of Michigan DMC and the Karmanos Cancer Institute/Wayne State University has shown that leukemia cells from children with Down syndrome and with AML are more sensitive to the main chemotherapy drugs used in protocols (e.g. cytarabine-araC; daunoubicin).
“We can more effectively use these drugs to improve cure rates and decrease side effects (in this protocol, the dose of daunorubicin was reduced by 25 percent compared to past protocols as it is linked to cardiac side effects),” Dr. Taub said. “Down syndrome children require longer intervals between chemotherapy courses to allow their blood counts to recover to higher levels compared to children without Down syndrome. This would potentially reduce the infection risk."
For parents who have a child with Down syndrome who have ALL or AML, Dr. Taub said being treated at a major children’s hospital is important as patients not only benefit from being treated on a clinical trial protocol, the doctors have had the experience of treating other Down syndrome children and are aware of the special clinical supportive care they require.