Prognosis and management of acute myeloid leukemia in patients with Down syndrome

Abstract

Children with Down syndrome (DS) are at a substantially increased risk to develop acute myeloid leukemia (AML). This increase in incidence is tempered, however, by favorable overall survival rates of approximately 80%, whereas survival for non-DS children with similar leukemic subtypes is <35%. In this review, the clinical studies that have contributed to this overall high survival will be presented and their individual successes will be discussed. Important issues including intensity of treatment regimens, the role of bone marrow transplants and prognostic indicators will be reviewed. In particular, the roles of high- vs low- vs very low-dose cytarabine will be discussed, as well as potential therapeutic options in the future and the direction of the field over the next 5 years. In summary, children with DS and AML should be treated with a moderate-intensity cytarabine-based regimen with curative intent.

MicroRNA-486-5p is an erythroid oncomiR of the myeloid leukemias of Down syndrome

“…1 These acute megakaryocytic leukemias (AMKLs) often co-express erythroid genes and surface proteins [2][3][4] and have unique clinical and genetic features. [5][6][7][8] They evolve in two distinct clinical stages; up to 10% of affected children are born with a transient myeloid proliferative disorder and in a fifth of these patients, full blown ML-DS is diagnosed by the age of 4 years. 7,9,10 Both the congenital transient leukemia and the established ML-DS are characterized by somatic in utero mutations in the X-chromosome gene GATA1, which arise during fetal liver (FL) hematopoiesis.…”

Long‐term sequelae in survivors of childhood leukemia with Down syndrome: A childhood cancer survivor study report

“…Children with DS and AML fare better than children without DS diagnosed with similar AML subtypes (80% vs 35%), yet children with DS and ALL fare worse compared with children without DS diagnosed with ALL (70% vs 90%). [18][19][20][21][22][23] AML in DS patients, termed Myeloid Leukemia of DS (ML-DS), is specific to trisomy 21 and is clinically and genetically distinct from AML occurring in non-DS patients. Improved survival in DS patients with AML may be due to an increased sensitivity of their leukemia cells to commonly used AML agents like cytosine Original Article Bolded values indicates statistically significant HR results.…”

miR‐155expression in antitumor immunity: The higher the better?

“…Nevertheless, the mortality rate in DS children with TMD is roughly of 20%. Subsequently, 20%‐30% of children with DS with a history of TMD will develop a myeloid leukemia of DS (ML‐DS), the most frequent being acute megakaryoblastic leukemia (AMKL) that occurs during the first 5 years of life in nearly all cases . Thus, it has been estimated that children with DS are at a 500‐fold greater risk to develop AMKL than non‐DS children .…”

“…[89][90][91][92][93] Thus, it has been estimated that children with DS are at a 500-fold greater risk to develop AMKL than non-DS children. 90 Children with ML-DS have a twofold higher disease-free survival than non-DS children treated for AML (roughly 88%-89% vs 42%), and DS-AMKL nevertheless requires less intense chemotherapy than non-DS AMKL. 91 Mutations in GATA1 that produce N-terminal truncated GATA1 factors are present in all cases of TMD and ML-DS and more generally are found in 25%-30% of all newborns with DS.…”