Childhood Acute Myeloid Leukemia/Other Myeloid Malignancies Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Children with Down Syndrome
Children with Down syndrome have a tenfold to twentyfold increased risk of leukemia compared to children without Down syndrome; the ratio of acute lymphoblastic leukemia to acute myeloid leukemia (AML) is nevertheless typical for childhood acute leukemia. The exception is during the first 3 years of life, when AML, particularly the megakaryoblastic subtype, predominates and exhibits a distinctive biology characterized by GATA1 mutations and increased sensitivity to cytarabine.[1,2,3,4,5,6,7,8,9] Importantly, these risks appear to be similar whether a child has phenotypic characteristics of Down syndrome or whether a child has only genetic bone marrow mosaicism.
In addition to increased risk of AML during the first 3 years of life, about 10% of neonates with Down syndrome may also develop a transient myeloproliferative disorder (TMD) (also termed transient leukemia). This disorder mimics congenital AML, but typically improves spontaneously within the first 3 months of life, though TMD can remit as late as 20 months. Although TMD is usually a self-resolving condition, it can be associated with significant morbidity and may be fatal in 10% to 20% of affected infants.[11,12,13] Infants with progressive organomegaly, visceral effusions, preterm delivery (less than 37-weeks gestation), bleeding diatheses, failure of spontaneous remission, laboratory evidence of progressive liver dysfunction (elevated direct bilirubin), and very high white blood cell count are at particularly high risk for early mortality.[12,14] Death has been reported to occur in 21% of these patients with high-risk TMD. Three risk groups have been identified based on the diagnostic clinical findings of hepatomegaly with or without life-threatening symptoms: (1) low risk includes those with neither finding (38% of patients and 92% ± 8% OS); (2) intermediate risk with hepatomegaly alone (40% of patients and 77% ± 12% OS); and (3) high risk with both characteristics (21% of patients and 51% ± 19% OS). Therapeutic intervention is warranted in patients in whom severe hydrops or organ failure is apparent. Several treatment approaches have been used, including exchange transfusion, leukapheresis, and low-dose cytarabine.
Treatment of refractory chronic lymphocytic leukemia may include the following:
A clinical trial of chemotherapy with stem cell transplant.
A clinical trial of a new treatment.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with refractory chronic lymphocytic leukemia. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General...
The mean time for the development of AML in the 10% to 30% of children who have a spontaneous remission of TMD but then develop AML, has been reported to be approximately 16 months with a range of 1 to 30 months.[11,15,17] Thus, most infants with Down syndrome and TMD who later develop AML will do so within the first 3 years of life. Patients with Down syndrome who develop AML with an antecedent TMD have superior event-free survival (EFS) (91% ± 5%) compared with such children without TMD (70% ± 4%) at 5 years. While TMD is generally not characterized by cytogenetic abnormalities other than trisomy 21, the presence of additional cytogenetic findings may connote an increased risk for developing subsequent AML.