Down's Syndrome and Leukaemia

© Leukaemia Research Fund, 1997
43 Great Ormond Street
London WC1N 3JJ
England
Telephone: 0171 405 0101
   Reprinted with the permission of Ken Campbell
Clinical Information Officer
Leukaemia Research Fund

This leaflet concerns the special features of leukaemia in Down's Syndrome patients. 
This leaflet should be read together with the Leukaemia Research Fund booklet "Acute Leukaemia in Childhood"

Most children with Down's syndrome now live into adolescence and adulthood. Leukaemia is from 10 to 30 times more common in these children than in the general population. All of the different types of Down's syndrome show a similar increased risk of leukaemia. This still only represents about 1 in 150 of Down's children. About 2% of all cases of childhood leukaemia occur in children who have Down's syndrome. 

The age distribution of leukaemia in children with in Down's syndrome is the same as in the general population. 

Transient Abnormal Myelopoiesis
Transient abnormal myelopoiesis (TAM) is almost never seen in children who do not have Down's syndrome. In TAM, which is usually seen at or soon after birth, the blood and bone marrow show changes which appear typical of leukaemia. The blood and bone marrow of children with TAM return to normal without treatment. In about 20 to 30% of cases with these blood and bone marrow changes leukaemia will develop, this is usually acute myeloid leukaemia (AML). There is no test which can distinguish between TAM and leukaemia and the diagnosis of TAM can only be made after the condition has spontaneously cleared up.

Types of Leukaemia
Both acute lymphoblastic leukaemia and acute myeloid leukaemia may be seen in children with Down's syndrome. 

Most patients who have acute lymphoblastic leukaemia (ALL) and Down's syndrome have the common ALL (cALL) sub-type. The leukaemia cells from these children less frequently show chromosome changes of a type regarding as being "poor risk" than in other children with ALL. That is to say that they rarely have changes which would predict a poor response to standard treatment.

Acute myeloid leukaemia is also seen at a higher than normal rate in Down's syndrome and the disease is typically seen at an earlier age than in other children with AML. AML in Down's syndrome is usually of the FAB M7 sub-type which affects mainly the platelet producing cells in the bone marrow. There is often a long period before the diagnosis is made when the blood count is moderately abnormal but there is no clear evidence of leukaemia.

In some of the children with Down's syndrome who eventually develop acute myeloid leukaemia, this is preceded by a bone marrow condition called myelodysplastic syndrome. In patients without Down's syndrome, leukaemia which develops after myelodysplastic syndrome (secondary leukaemia) tends to respond poorly to standard treatment. In Down's syndrome it appears to have no effect on response to treatment whether or not the child has previously had myelodysplastic syndrome.

Treatment
The outlook for children with Down's syndrome and ALL is as good as that for other children with ALL and for AML the outlook is better than for other children. 

Many children with Down's syndrome also have heart abnormalities. There is no evidence at present to indicate whether or not this leads to an increased risk of developing cardiac toxicity when treated with anti-cancer drugs. 
Children with Down's syndrome are more prone to severe side-effects when treated with methotrexate. These side-effects can be greatly reduced by giving high doses of folic acid along with the methotrexate. 

The treatment of Down's syndrome children with leukaemia is largely the same as for other children. They do require particularly careful attention to prevention of infection as they are more at risk of some infections, for example mycoplasma infection, and these will need appropriate intensive treatment.

Revised: January 28, 1998.