MYELODYSPLASIA AND ACUTE MYELOGENOUS LEUKEMIA IN DOWNS-SYNDROME - A REPORT OF 40 CHILDREN OF THE AML-BFM STUDY-GROUP

Forty children with Down's syndrome have been identified among 633 pat ients in the cooperative pediatric BFM studies for acute myelogenous l eukemia (AML) since 1987. The following features were characteristic f or these patients: (1) a 500-fold higher than expected incidence of me gakaryoblastic leukemia (M7) with a peak incidence under 4 years of ag e; (2) a myelodysplastic prephase with thrombocytopenia lasting for se veral months up to a few years; (3) frequent involvement of the red ce ll lineage as suggested by dyserythropoiesis in the bone marrow; (4) c oexpression of the lymphoid cell surface antigen CD7 on the leukemic b lasts; (5) absence of the translocation t(1;22), instead presence of c omplete or partial trisomies involving chromosomes 8 and 1; and (6) a good response to chemotherapy. Nearly half of the patients did not rec eive any or only palliative chemotherapy and subsequently died. In 21 patients treatment according to the AML-BFM protocols was intended, ho wever, with major dose or protocol reductions in six patients. Four di ed early, 15 (71%) achieved remission. Nine of 11 patients remaining a live for 0.6-6.5 years had received intensive treatment including high -dose cytosine arabinoside (HD-Ara-C). The 5-year survival estimate of 48%+/-12% was similar to patients without Down's syndrome, In conclus ion, these clinical and biological features suggest that M7 leukemia i n children with Down's syndrome (M7-Down) is distinct from megakaryobl astic leukemia in other children. Children with Down's syndrome show a favorable outcome if treated adequately. However, overtreatment shoul d be avoided and life-threatening infections pose a particular problem . Therefore, standard-risk AML therapy (including HD-Ara-C) should be considered in children with Down's syndrome and AML.