Association of CD123 Expression With High-Risk Disease Characteristics and Outcomes in Pediatric AML

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In an analysis from the Children’s Oncology Group AAML1031 trial reported in the Journal of Clinical Oncology, Lamble et al found that increased CD123 expression was associated with high-risk genetic alterations and poorer treatment outcomes in pediatric patients with newly diagnosed acute myeloid leukemia (AML).

As stated by the investigators, “Increased CD123 surface expression has been associated with high-risk disease characteristics in adult AML but has not been well-characterized in childhood AML.”

Study Details

The study included a cohort of 1,040 uniformly treated patients enrolled in the trial between July 2011 and July 2014. AML blasts in diagnostic bone marrow specimens were prospectively analyzed for CD123 expression by multidimensional flow cytometry immunophenotyping at a central laboratory. The cohort was analyzed according to CD123 expression quartiles (n = 260 in each), with quartile 4 (Q4) having the highest CD123 expression level.

Key Findings

Patients in CD123 expression Q4 vs Q1 to Q3 had a higher prevalence of high-risk genetic alterations, including KMT2A rearrangements (31.8% vs 19.6%, P < .001) and FLT3-ITD mutations (34.2% vs 8.6%, P < .001). They also had a lower prevalence of low-risk alterations, including t(8;21) (3.2% vs 18.3%, P < .001), inv(16) (4.8% vs 11.4%, P = .002), and CEBPA mutations (0.4% vs 8.1%, P < .001).

Patients in CD123 Q1 to Q3 had similar 5-year relapse risk, event-free survival, and overall survival. Those in Q4 vs Q1 to Q3 had higher relapse risk (53% vs 39%, P < .001), poorer event-free survival (49% vs 69%, P < .001), and poorer overall survival (32% vs 50%, P < .001).

On multivariate analysis including all known contemporary high-risk cytogenetic and molecular markers, higher CD123 expression maintained independent significance for relapse risk (hazard ratio [HR] = 1.42, P = .009), event-free survival (HR = 1.51, P < .001), and overall survival (HR = 1.43, P = .005).

The investigators concluded, “CD123 is strongly associated with disease-relevant cytogenetic and molecular alterations in childhood AML. 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.”

Adam J. Lamble, MD, of the University of Washington–Seattle Children's Hospital, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by National Clinical Trials Network grants and St. Baldrick’s Foundation. For full disclosures of the study authors, visit

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