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CD123 Overexpression in the Development of High-Risk Pediatric AML

By: Justine Landin, PhD
Posted: Friday, March 18, 2022

Surface expression of the alpha chain of the interleukin 3 receptor, CD123, may be associated with high-risk disease characteristics in children with acute myeloid leukemia (AML), according to the Children’s Oncology Group phase III AAML1031 trial conducted by Adam J. Lamble, MD, of the University of Washington, Seattle, and colleagues. In fact, CD123 overexpression was associated with high-risk mutations and poor clinical prognosis in this young population. The findings of this study were published in the Journal of Clinical Oncology.

“CD123 is a critical biomarker and promising immunotherapeutic target for children with relapsed or refractory AML, given its prevalent expression and enrichment in patients with high-risk genetic alterations and inferior clinical outcomes with conventional therapy,” stated the study investigators.

Children, adolescents, and young adults with newly diagnosed AML were enrolled (n = 1,040). Blasts within diagnostic bone marrow specimens were obtained and prospectively analyzed for CD123 expression using multidimensional flow cytometry immunophenotyping. Patients were stratified into low- and high-risk groups. High-risk patients exhibited high-risk AML-associated lesions and/or positive end-of-induction measurable residual disease.

Patients were divided into quartiles based upon CD123 expression levels (n = 260/group). Compared with quartiles 1 to 3, patients with the highest levels of CD123 (quartile 4) were found to have the highest levels of high-risk KMT2A rearrangements and FLT3-ITD mutations, with lower levels of low-risk mutations (P < .001 for all). There was no difference found between quartiles 1 to 3 in relapse risk, event-free survival, and overall survival. However, patients in quartile 4 exhibited higher relapse risks (53%) and reduced event-free survival (49%) compared with all other groups (39% and 69%, respectively; P < .001 for all). Of note, overall survival was more than 1.5 times higher in quartiles 1 to 3 (50%) compared with quartile 4 (32%, P < .001).

Disclosure: For full disclosures of the study authors, visit ascopubs.org.


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