Down’s Syndrome and Megakaryoblastic Leukemia

Recent reports estimate an approximately 20-fold higher incidence of leukemia in children with Down’s syndrome compared to non-Down’s syndrome children and a marked increase of the megakaryoblastic subtype (FAB M7)[l]. Twenty-six of 42 children with Down’s syndrome were enrolled in our studies since 1987 were classified as FAB M7 or presented with a preleukemic phase (myelodysplastic syndrome, MDS) with increased megakaryoblasts. All patients were under 3 years (0.4-2.6 median 1.8 years) and generally had a low leukocyte count (1.6-177 median 7.75 x 103/mm3) and a low platelet count (4.0-210 median 26.0 x 103/mm3). Karyotype abnormalities other than +21c or [t(21;21)c] were found in 11/15 patients, predominantly trisomies (8/15) involving the chromosomes #8 (n = 5), #21 (n = 2), #11 (n = 2), #10, #14, #18, #19, and #22 (n = 1). Only nine children initially presented with > 30% blasts in the bone marrow (BM). In ten patients diagnosis of M7 leukemia was based on morphology alone, and in 16 patients confirmed by immunophenotyping. A preleukemic phase with thrombocytopenia for at least 2 months was recorded in nine of the 17 patients presenting with a low blast count (≤30%) and myelodysplasia in the BM. Four children had a history of transient neonatal leukemia. Sixteen children were left untreated or received only minimal treatment and subsequently died due to progressing leukemia. In two of the untreated patients, a spontaneous improvement or a stable disease (with retinoids) lasting for several months was observed. Ten patients were treated. Three out of ten had an end-stage disease and received inadequate dosages of therapy and died early. Six of seven children treated according to the AML-BFM protocols including high-dose cytosine arabinoside were in continuous complete remission for 0.2-4.6 years. We conclude that M7 leukemia in Down’s syndrome is often preceded by a preleukemic phase with thrombocytopenia. Patients treated according to the AML protocol showed good results. Further studies are warranted to clarify whether Down’s syndrome patients with a preleukemic phase of M7 would also benefit from an early and intensive treatment.