ACUTE MYELOGENOUS LEUKEMIA IN CHILDREN WITH DOWNS-SYNDROME

Forty-four children, aged between 0.4 and 16.2 years (median 2.0 years) with Down's syndrome and acute myelogenous leukemia (AML) including subacute megakaryoblastic leukemia (M7) were diagnosed between 1980 and 1986 (group 1, n = 16) or between 1987 and 1992 (group 2, n = 28). The leukemic blasts from Down's syndrome patients often proved difficult to classify. In group 1 the most frequent diagnoses were FAB M5 (6 pts.), M6 (3 pts.), in 3 patients the morphological diagnosis of M7 can retrospectively be assumed. In group 2, 15 of 28 patients were classified as M7, in 3 patients based on morphology alone, and in the other 12 patients confirmed by immunophenotyping or biopsy. The other children in group 2 were classified as: FAB MO (3 pts.), M1 (1 pt.), M4 (2 pts.), M5 (2 pts.), M6 (4 pts.), M6/M7 (1 pt.). Initially, the latter and 10 of the patients with M7 presented with <30% of blasts in the bone marrow. Karyotyping in 12 of 13 children frequently revealed numeric abnormalities, particularly trisomies involving chromosomes 8 (n = 6), 11 (n = 3), 21 (n = 3) and 14 (n = 1) in addition to the constitutional +21 c. Six patients in group 1 received no specific treatment, while 10 children were treated according to the protocols AML-BFM-78 or -83. Four of them are still alive for more than 5 years, two others died from infections in remission after 1.0. and 3.8 years. Fourteen of the 28 patients in group 2 did not receive any chemotherapy (10 with M7), and subsequently died. Fourteen patients were treated according to protocol AML-BFM-87, 7 with treatment reduction, e.g. omission of HD-Ara-C courses. Despite reduced therapy, 8 of these patients are still alive (probability of 5-year survival: p = 55%, SE 14%). Three children died of relapse or partial response, two of infection or bleeding in aplasia, and one in CCR. Six of the 7 children receiving 1 or 2 courses of HD-Ara-C are in CCR. In conclusion, FAB M7 is the predominant subtype found in children with Down's syndrome, followed by atypical AML with immature and/or erythroid features which are rarely seen in non-Down's syndrome patients, and thought to be associated with an unfavorable outcome. Survival of patients with Down's syndrome, however, is similar or even better than of non-Down patients, if the are treated adequatly (including HD-Ara-C cycles), and life-threatening infections can be avoided.