Childhood Acute Myeloid Leukemia/Other Myeloid Malignancies Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Children with Down Syndrome
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, although this was not observed in another study. 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.
Outcome is generally favorable for children with Down syndrome who develop AML.[18,19] The prognosis is particularly good (EFS exceeding 80%) in children aged 4 years or younger at diagnosis, the age group that accounts for the vast majority of Down syndrome patients with AML.[18,20] A large study of 451 children with AML and Down syndrome (age >6 months and <5 years) confirmed the generally favorable outcome for this patient population (7-year EFS of 78% and 7-year OS of 79%). Multivariate analyses revealed that white blood cell (WBC) count (≥20 × 109/L) and age (>3 years) were independent predictors for lower EFS, although 7-year EFS for the older population (>3 years) and for the higher WBC count population still exceeded 60%. Absence of leukemia cell cytogenetic abnormalities (other than trisomy 21), observed in approximately 30% of patients, independently predicted for inferior OS and EFS (7-year EFS of 65% compared with 82% for patients with aberrant karyotypes).
Appropriate therapy for younger children (aged ≤4 years) with Down syndrome and AML is less intensive than current standard childhood AML therapy, and hematopoietic stem cell transplant is not indicated in first remission.[3,17,18,20,22,23,24,25]
Children with mosaicism for trisomy 21 are recommended to be treated similarly to those children with clinically evident Down syndrome. Children with Down syndrome who are older than 4 years have a significantly worse prognosis. Although an optimal treatment for these children has not been defined, they are usually treated on AML regimens designed for children without Down syndrome.
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- Blink M, Zimmermann M, von Neuhoff C, et al.: Normal karyotype is a poor prognostic factor in myeloid leukemia of Down syndrome: a retrospective, international study. Haematologica 99 (2): 299-307, 2014.
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