The association of Down's syndrome and leukemia has been documented for over 50 
years. Multiple studies have established the incidence of leukemia in Down's 
syndrome patients to be 10- to 20-fold higher than that in the general 
population. The age of onset for leukemia in these children is bimodal, peaking 
first in the newborn period and again at 3-6 years. This increased risk extends 
into adulthood. All cytogenetic types of Down's syndrome apparently predispose 
to leukemia. The proportion of acute lymphoblastic leukemia and acute 
nonlymphoblastic leukemia in patients with Down's syndrome is similar to 
non-Down's syndrome leukemia patients matched for age. There are case reports in 
which leukemia, Down's syndrome, and other chromosomal aberrations cluster 
within a family. In these kindreds, there may be a familial tendency toward 
nondisjunction. Congenital leukemia also occurs with increased frequency in 
Down's syndrome patients, and is characterized by a preponderance of acute 
nonlymphoblastic leukemia (similar to non-Down's syndrome patients). Transient 
leukemoid reactions have been observed in Down's syndrome patients, as well as 
in phenotypically normal children with constitutional trisomy 21 mosaicism. The 
transient leukemoid reactions are characterized by a high spontaneous remission 
rate. However, in some Downs syndrome patients with apparent transient leukemoid 
reaction, leukemia relapse following periods of spontaneous remission have been 
reported. Cytogenetic studies of leukemic cells in Down's syndrome patients show 
a tendency toward hyperdiploidy. Besides trisomy 21, there is no other specific 
cytogenetic abnormality that is characteristic of the leukemia cells in Down's 
syndrome patients. The possible mechanisms for leukemogenesis in Down's syndrome 
patients may involve factors at the levels of the organism, the organ/system, 
the cell, the chromosomes or the DNA.