Acute myeloid leukemia and Down syndrome evolution of modern therapy--state of the art review

Over the past decade, a series of clinical reports have described the experience of Down syndrome (DS) children treated for acute myeloid leukemia (AML). Whereas prior to the first reports in the early 1980's it was felt that DS children with AML had poor outcomes, these clinical trials concluded that DS had a better outcome than non-DS (NDS) children with AML. With these recent reports, it is clear that DS children have a better outcome utilizing less intensive chemotherapy regimens. They also tolerate the more intensive regimens less well than the NDS children. This review focuses upon the six multi-institutional reports that described the DS and AML experience in order to better ascertain the chemotherapy combinations that may be useful in the future for these children. Regimens of varying intensity have all had similar outcomes. In general, the remission rates are approximately 90% with event-free survival (EFS) approximating 70-80%. Most recently, the clinical trials have been large enough to explore prognostic factors specifically in the DS children. This has identified that the younger DS children fair significantly better than the older children. AML in DS is unique and these differences in comparison to NDS children are highlighted. The significantly better outcomes for DS children likely represents a combination of the unique AML seen in DS children and the heightened sensitivity to cytarabine that DS AML cells have. Future trials should focus on age-stratified approaches that exploit the greater sensitivity of DS AML to cytarabine.