Congenital leukemia refers to leukemia that presents at birth or during the first month of life. However, because numerous cases of leukemia appearing later in infancy have been linked to chromosomal rearrangements that occurred in utero, most, if not all, cases of infant leukemia are now thought to be congenital in origin. Leukemias in the neonate and infant have different clinical and biologic features than those of older children. Acute myelocytic leukemia (AML) is more common than acute lymphocytic leukemia (ALL) in the neonate, in contradistinction to older children; acute megakaryocytic leukemia (AMKL) and acute erythroblastic leukemia occur less commonly. There is an equal incidence among males and females, though females with ALL have a markedly worse prognosis. Alcohol consumption by the birthing parent has been associated with increased risk of infant leukemia, particularly AML.

The characteristic clinical presentation of all subtypes in the neonatal period is leukemia cutis and hepatosplenomegaly, with a majority of patients also demonstrating hyperleukocytosis and evidence of meningeal involvement. When leukemias present later in infancy, signs and symptoms are often less specific and include low-grade fever, pallor, lethargy, hepatosplenomegaly, bleeding diathesis, diarrhea, or failure to thrive. The prognosis of neonatal / infant leukemia is generally bleak, with or without chemotherapy.