Acute megakaryoblastic leukemia and clonal trisomy 21 in a phenotypically normal infant.

Kojima et al recently reported 20 patients with Down’s syndrome and acute leukemia.’ Of these 20 patients, 14 who were 3 years old and less were diagnosed as having acute megakaryoblastic leukemia (AMKL). They were characterized by the presence of bone marrow fibrosis, a history of myelodysplastic syndrome (MDS), and a poor response to chemotherapy. Ten of the 14 patients were male, and platelet count ranged from 0.2 to 108 X 109/L (median 25.0 x 109/L). The median observation time between initial diagnosis and moment of overt leukemia for the seven patients with MDS was 6 months with a range of 3 to 9 months. All but one MDS-AMKL patients achieved a complete remission with anthracycline and cytosine arabinoside, but the duration of complete remission was short. We recently observed a phenotypically normal 10-month-old boy with a white blood cell (WBC) count of 70 X 10y/L, hemoglobin 7.4 g/dL, and platelet count 107 x 109/L, whose bone marrow showed ANAE, and PAS staining and reacted with anti CD33, CD42, and CD4S monoclonal antibodies. Following unsuccesful treatment with anthracycline and cytosine arabinoside, he received mitoxantrone and etoposide and achieved complete remission of short duration. Repeated follow-up chromosome studies during remission persistently showed normal karyotype on cells from both the peripheral blood and the bone marrow until relapse. In the infants with phenotypically evident Down’s syndrome the likely outcome of an illness resembling congenital leukemia is spontaneous recovery. Transient leukemoid reaction and trisomy 21 mosaicism had been reported in a phenotypically normal newborn.2 Transient myeloproliferative disorder of the Down type was observed recently in two infants showing trisomy 21 apparently restricted to the leukemic clone, never detected in either PHA-stimulated peripheral blood cells or bone marrow, or in myeloid progenitor cells after resolution of the transient myeloproliferative di~order .~ According to the present knowledge, occurrence of any type of myeloproliferative disorders, both the transient leukemoid reaction or the AMKL, is not confined to infants with partial or complete abnormalities in the three cell lines. Chromosome analysis showed normal male karyotype from peripheral blood phytohemagglutinin (PHA)-stimulated cells, but 47,XY,t(6;16)(923;q22),+21 karyotype on unstimulated blast cells from the peripheral blood and the bone marrow. After an observation time of 3 weeks, during systemic trisomy 21, but can occur in genetically normal newborns or infantswhose leukemic cells contain a third chromosome 21.