Six New High-Risk Alterations Identified for Pediatric AML
Adam Lamble, MD, Attending Physician, Cancer and Blood Disorders Center, Seattle Children’s Hospital, discusses a recent study that lists six high-risk alterations of acute myeloid leukemia (AML) that ought to be included in Children's Oncology Group’s (COG) contemporary risk classification system. These findings were recently presented at this year’s American Society of Hematology Meeting & Exposition (ASH 2022).
AML is a rare progressing blood cancer that most often occurs in people over the age of 40 years but it can occur in children as well. Signs and symptoms can vary but for many patients, the cancer can be very aggressive and may require intensive treatment.
As Dr. Lamble explains, diagnostic specimens from 2 sequential COG phase 3 trials for pediatric AML (AAML0531 and AAML1031) were retrospectively tested with next generation sequencing. This data was combined with a central review of structural and molecular alterations to identify candidates for risk adjustment (i.e., 5-year event-free survival (EFS) inferior to similarly treated patients with noninformative cytomolecular genetics with and/or without censoring for stem cell transplant in first complete remission.) Candidate alterations were then incorporated into an updated risk classification which was retrospectively applied to assess impact on treatment allocation.
Of 1944 patients in , 137 (7%) patients with 1 of 6 newly defined alterations met the predefined criteria for risk adjustment. These included:
• CEBPA co-occurring with CSF3R (n=18, EFS: 33%),
• CREBBP mutations (n=40, EFS: 18%),
• TP53 mutations (n=20, EFS: 0%),
• KMT2A-partial tandem duplications (n=21, EFS: 43%),
• IDH1/2 mutations in the absence of NPM1 (n=36, EFS: 31%), and
• Fusions involving the ETS family, excluding previously high-risk defined members (n=13, EFS: 43%).
As a group, patients with these alterations had an EFS of 28% and relapse risk of 70%, which were worse than contemporarily defined standard-risk patients and analogous to contemporarily defined high-risk patients.
The study concluded that “before these alterations can be considered high-risk, further investigation is required, including corroboration from other large pediatric and adult consortium trials and the benefit of this re-allocation will need to be validated prospectively.”
To learn more about AML and other rare cancers, visit checkrare.com/diseases/cancers/
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