A newborn infant, one day old, presented with the following blood count:
Hb 140 g/L, MCV 111.3 fL, WBC 112.5 x 109/L and platelet count 191 x 109/L
The white cell differential included 87 percent blast cells.
The blasts were large with rounded nuclei and moderate amounts of basophilic cytoplasm. Cytoplasmic blebs were present. Some of the blasts contained coarse azurophilic granules. The blast cells on this blood film appeared to be megakaryoblasts. The red cell precursors showed marked dysplastic changes.
Flow cytometry was performed on the peripheral blood. A bone marrow aspiration was not attempted. The immunophenotype of the blast cells was as follows:
HLD-DR–, CD7+, CD13–, CD33+, CD45–, CD41+ and CD61+
Cytogenetics were performed. In addition to the presence of trisomy 21 found in Down syndrome there was an additional chromosome 8 (trisomy 8).
A provisional diagnosis of Transient Abnormal Myelopoiesis (TAM) was made on this infant.
Newborn infants with Down syndrome have an increased disposition for acute leukaemia. The leukaemia is predominantly acute megakaryoblastic leukaemia. Acute lymphoblastic leukaemia may occur but is less common.
Acute leukaemia in the newborn is initially labelled as TAM.
TAM is characterised by an uncontrolled proliferation of blast cells that regress spontaneously over weeks and months. However, in 25 to 30 percent of cases TAM will persist, in which case a diagnosis of congenital acute leukaemia will be made. Approximately 25 percent of cases with TAM will go on to develop acute megakaryoblastic leukaemia by the age of three years.
Leukaemia associated with Down syndrome is often preceded by a myelodysplastic-like syndrome, as is the case in this patient.
Most children with Down syndrome and acute myeloid leukaemia have an abnormal karyotype, most commonly trisomy 8 or less commonly trisomy 1 and 19 or tetrasomy 21.
As the absolute blast cell count on this infant was extremely high, chemotherapy was commenced. Low-dose of cytarabine therapy was administered. The infant responded well initially but relapsed some weeks later before dying from its disease.