This article concerns the special features of Leukemia in Down's Syndrome patients and is based on the Leukemia Research Fund leaflet on this topic. There is a Leukemia Research Fund booklet Acute Leukemia in Childhood which can be obtained from:

Leukemia Research Fund
43 Great Ormond Street,
London WC1N 3JJ
Tel: 020 7 405 0101

• Most children with Down's syndrome now live into adolescence and adulthood.
• Leukemia 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 Leukemia.
• This still only represents about 1 in 150 of Down's children.
• About 2% of all cases of childhood leukemia occur in children who have Down's Syndrome.
• The age distribution of leukemia in children on with Down's syndrome is the same as in the general population.

Transient Abnormal Myelopoiesis (TAM)

Transient abnormal myelopoiesis (TAM) is a condition which 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 Leukemia. 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 leukemia will develop, this is usually acute myeloid leukemia (AML). There is no test which can distinguish between TAM and leukemia and the diagnosis of TAM can only be made after the condition has spontaneously cleared up. It is very likely that the same mechanism(s) explain both the excess number of cases of leukemia seen in Down's syndrome and TAM. It is probable that all these cases commence in a similar way. For some unexplained reason, possibly a further genetic abnormality, in some children the condition progresses and becomes full-blown leukemia while in other children it resolves.

Types of Leukemia seen in Down's Syndrome

Both acute lymphoblastic leukemia and acute myeloid leukemia are seen in children with Down's Syndrome.

Most patients who have acute Iymphoblastic leukemia (ALL) and Down's Syndrome have the common ALL (cALL) sub.type. The leukemia cells from these children Iess frequently show chromosome changes of a type regarded 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. Children with Down's syndrome and ALL usually have a good response to treatment and a good chance of a cure. It is very important that parents should discuss this with their child's specialist, who is the only person who can give a reliable prediction of the individual child's chances of a cure.

Acute myoloid leukemia is also seen in 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 Syndromes 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 this diagnosis is made when the blood count is moderately abnormal there is no clear evidence of Leukemia.

When a very young child has changes which would usually suggest Leukemia it is important to rule out TAM in case any unnecessary treatment is given. This may be a very difficult period for parents and close liaison with the hospital, preferably with one named nurse or doctor, may help.

In some of the children with Down's syndrome who eventually develop acute myeloid Leukemia, this is proceeded by a bone marrow condition called myelodysplastic syndrome. In patients without Down's syndrome, leukemia which develops after myelodysplastic syndrome (secondary leukemia) 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. Doctors treating children with Down's syndrome will keep a particularly careful watch for any signs of heart problems.

Children with Down's syndromes are more prone to serious side-effects when treated with methotrexate. These side effects can be greatly reduced by giving doses of folic acid along with the methotrexate.

The treatment of Down's syndrome children with leukemia is largely the same as for other children. They do require particular 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.

Depending on the child's degree of understanding, there may be some difficulties in ensuring that appropriate drugs are taken. Here it is clear that schoolteachers and any others involved in care of the child with Down's syndrome must be enlisted as part of the care team.

Professor Judith Chessells of the world famous Great Ormond Street Hospital for Sick Children, and the Institute of Child Health, has a special interest in the phenomenon of leukemia occurring in association with Down's syndrome and is carrying out research into the exact reason(s) why there is an excess of leukemia in these children.