CD123 Expression Is Associated With High-Risk Disease Characteristics in Childhood Acute Myeloid Leukemia: A Report From the Children's Oncology Group

Author:

Lamble Adam J.1ORCID,Eidenschink Brodersen Lisa2ORCID,Alonzo Todd A.34,Wang Jim3,Pardo Laura2ORCID,Sung Lillian5ORCID,Cooper Todd M.1ORCID,Kolb E. Anders6ORCID,Aplenc Richard78ORCID,Tasian Sarah K.78ORCID,Loken Michael R.2ORCID,Meshinchi Soheil9

Affiliation:

1. Division of Hematology/Oncology, Seattle Children's Hospital, University of Washington, Seattle, WA

2. Hematologics Inc, Seattle, WA

3. Children's Oncology Group, Monrovia, CA

4. University of Southern California, Keck School of Medicine, Los Angeles, CA

5. Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, CA

6. Division of Oncology, Nemours/Alfred I. Dupont Hospital for Children, Wilmington, DE

7. Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA

8. Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA

9. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA

Abstract

PURPOSE Increased CD123 surface expression has been associated with high-risk disease characteristics in adult acute myeloid leukemia (AML), but has not been well-characterized in childhood AML. In this study, we defined CD123 expression and associated clinical characteristics in a uniformly treated cohort of pediatric patients with newly diagnosed AML enrolled on the Children's Oncology Group AAML1031 phase III trial ( NCT01371981 ). MATERIALS AND METHODS AML blasts within diagnostic bone marrow specimens (n = 1,040) were prospectively analyzed for CD123 protein expression by multidimensional flow cytometry immunophenotyping at a central clinical laboratory. Patients were stratified as low-risk or high-risk on the basis of (1) leukemia-associated cytogenetic and molecular alterations and (2) end-of-induction measurable residual disease levels. RESULTS The study population was divided into CD123 expression–based quartiles (n = 260 each) for analysis. Those with highest CD123 expression (quartile 4 [Q4]) had higher prevalence of high-risk KMT2A rearrangements and FLT3-ITD mutations ( P < .001 for both) and lower prevalence of low-risk t(8;21), inv(16), and CEBPA mutations ( P < .001 for all). Patients in lower CD123 expression quartiles (Q1-3) had similar relapse risk, event-free survival, and overall survival. Conversely, Q4 patients had a significantly higher relapse risk (53% v 39%, P < .001), lower event-free survival (49% v 69%, P < .001), and lower overall survival (32% v 50%, P < .001) in comparison with Q1-3 patients. CD123 maintained independent significance for outcomes when all known contemporary high-risk cytogenetic and molecular markers were incorporated into multivariable Cox regression analysis. CONCLUSION 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.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

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