Clinical manifestations of hematologic and oncologic disorders in patients with Down syndrome

Abstract

Hematologic abnormalities are common in individuals with Down syndrome (DS). Increased erythrocyte mean corpuscular volume (MCV) is frequently found among DS infants and remains elevated throughout life in two-thirds of patients, making interpretation of red cell indices for diagnosis of nutritional anemias or bone marrow failure disorders more challenging. Transient myeloproliferative disorder (TMD) associated with pancytopenia, hepatosplenomegaly, and circulating immature WBCs, is found almost exclusively in DS infants with an incidence of approximately 10%. In most cases, TMD regresses spontaneously within the first 3 months of life, but in some children, it can be life threatening or even fatal. Despite the high rate of spontaneous regression, TMD can be a preleukemic disorder in 20-30% of children with DS. The types of malignancy, response to therapy, and clinical outcome in children with DS are also unique. There is an increased risk of leukemia with an equal incidence of lymphoid and myeloid leukemia. Acute megakaryocytic leukemia (AMKL) subtype is the most common form of acute myeloid leukemia (AML) in this setting, and is uncommon in children without DS. Somatic mutations of the gene encoding the hematopoetic growth factor GATA1 have been shown to be specific for TMD and AMKL in children with DS. Myelodysplastic syndrome can precede AML. Children with DS and leukemia are more sensitive to some chemotherapeutic agents such as methotrexate than other children which requires careful monitoring for toxicity. Although the risk for leukemia is higher in individuals with DS, these patients have a lower risk of developing solid tumors, with the exception of germ cell tumors, and perhaps retinoblastoma and lymphoma.

Health Supervision for Children With Down Syndrome

“…20 Polycythemia is also common in infants with Down syndrome (18%-64%) 21 and may require careful management. Infants with TMD and polycythemia should be followed according to subspecialty consultation recommendations.…”

Treatment and prognostic impact of transient leukemia in neonates with Down syndrome

“…4,5 Hematologic abnormalities, such as polycythemia, anemia, thrombocytopenia, thrombocytosis, or increased erythrocyte mean corpuscular volume, are common findings in patients with DS. 6 In addition, 13% to 33% of the patients with TL develop acute myeloid leukemia (AML) within the first 4 years of life. 5,7,8 The unique type of AML in DS is referred to as myeloid leukemia of DS (ML-DS), 8 which is characterized by the frequent occurrence of acute megakaryoblastic leukemia (AMKL or FAB M7-like), a low diagnostic white blood cell (WBC) count, and young age.…”

Evaluation of hematological findings in children with Down syndrome

“…8,9 Studies have shown that thrombocytopenia and thrombocytosis are not associated with bleeding disorders and thrombosis in DS patients. 10 No hemorrhagic symptoms were present except for present cases diagnosed with acute leukemia and myelofibrosis and present cases with severe thrombocytopenia due to hypersplenism. No cases of thrombosis were observed in present cases.…”