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Clinical Implications of a Complex Karyotype in AML in Children

By: Lauren Harrison, MS
Posted: Monday, August 2, 2021

Complex karyotypes were identified as a risk factor for reduced survival among children with acute myeloid leukemia (AML). Liming Bao, MD, PhD of the University of Colorado Anschutz Medical Campus in Aurora, and colleagues published data in Molecular Cytogenetics that shed light on the cytogenetic and mutational profile of childhood AML.

Researchers studied a population of 284 children with de novo AML who were diagnosed at the Children’s Hospital of Chongqing Medical University in China. Patients were treated with daunorubicin, cytarabine, and etoposide. Patient samples were analyzed using fluorescence in situ hybridization to look for a variety of mutations. Tumor cells were given the label of complex karyotype if there were three or more chromosomal aberrations other than abnormalities defined by the World Health Organization as recurrent AML mutations [such as t(8;21), t(15;17)]. Genetic mutations were subsequently analyzed using polymerase chain reaction.

Within the study population, 34 (12%) met the criteria for complex karyotype AML. There were 16 patients with three to four abnormalities, and the rest had five or more aberrations. The only major difference in clinical features between the patients with complex karyotypes and those without was that patients with complex karyotypes tended to be younger (2.5 years vs. 5 years). The WT1 gene had the highest mutational incidence (13%) in the complex karyotype group, followed by CEBPA, FLT3/ITD, and IDH1 genes (6% each). Atypical complex karyotypes, with -5/5q, -7/7q, and/or 17p aberrations, were seen more frequently than typical complex karyotypes.

Outcome information was available for 80 patients in this cohort, including 20 with complex karyotypes. Those with complex karyotypes were less likely to reach complete remission (60% vs. 83%) and had shorter 5-year overall survival (26.7 months vs. 37.5 months) than the patients without complex karyotypes. Further, those with five or more chromosomal aberrations had an inferior overall survival (13.6 months vs. 50.0 months) and event-free survival (13.6 months vs. 50.0 months) than patients with up to four aberrations.

Disclosure: The study authors reported no conflicts of interest.



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