Experts at Children's Mercy Hospital (CMH), led by Alan Gamis,
MD, CMH's chief of the section of oncology, participated in a
national study on a rare childhood cancer and its even rarer
offshoot: its presence in children with Down syndrome (DS). The
results were published in the March 5, 2012 issue of
one of the leading international oncology journals,
Gamis is a specialist in the childhood cancer on which the study
focused, acute myeloid leukemia (AML), and his expertise has made
CMH one of the more well-known centers in the NIH's Children's
Oncology Group (COG). He is also chair of the AML Disease
Scientific Committee, which oversees all COG Research in AML.
"We know that the survival rate in AML children in general is
60-65%, and rises to 80-90% in kids with DS. It's due to a specific
mutation that occurs in DS kids' AML cells called GATA1.
This mutation causes AML in DS kids, but it also confers
sensitivity to chemotherapy," says Gamis.
The question was: could this increased sensitivity mean less
chemo could be used-and still provide the same benefits? The
answers came from this phase-3 trial on DS children with AML, known
as COG A2971, which compared results from the last such trial,
known as CCG2891.
The A2971 trial eliminated two induction drugs and also
eliminated three months of maintenance therapy from the drug
combination known as DCTER. Specifically the follow-up (around 4.8
years of age) showed that in addition to similar remission rates,
the 5-year event-free survival (EFS) rate in A2971 patients was
about 79% compared to 77% in 2891 patients and the disease-free
survival rate (DFS) was 89% vs. 85%.
Age was a key factor. "We found DS children who developed AML at
age 4 or younger had the mutation that made it easier to treat.
Those who developed AML at age 4 or older tended to develop the
tougher to treat variation, requiring the more intense therapy of
other AML patients," says Gamis. He adds that a follow-up to this
study, presented in May 2012, noted that the faster the child goes
into remission (by day 14 of treatment or sooner), the better the
odds of overall survival.
"This was the largest trial for Down syndrome kids with AML to
be performed in the world. It proved that we could continue to cure
almost all of the DS children with AML, while reducing the
intensity of treatment," says Gamis. He concludes: "At CMH, We help
design future AML trials and we have insights into the design of
what's coming down the pike five years from now. Through our
knowledge and oversight of these national trials, we have a
distinctive perspective on taking care of all AML children,
including those with such unique mutations."
NOTE: Citation from CANCER:
Sorrell, A. D., Alonzo, T. A., Hilden, J. M., Gerbing, R. B.,
Loew, T. W., Hathaway, L., Barnard, D., Taub, J. W., Ravindranath,
Yaddanapudi., Smith, F. O., Arceci, R. J., Woods, W. G. and Gamis,
A. S. (2012), Favorable survival maintained in children who have
myeloid leukemia associated with Down syndrome using reduced-dose
chemotherapy on Children's Oncology Group trial A2971. Cancer.