CD123 Expression Is Associated With High-Risk Disease Characteristics in Childhood Acute Myeloid Leukemia: A Report From the Children's Oncology Group
Adam J Lamble, Lisa Eidenschink Brodersen, Todd A Alonzo, Jim Wang, Laura Pardo, Lillian Sung, Todd M Cooper, E Anders Kolb, Richard Aplenc, Sarah K Tasian, Michael R Loken, Soheil Meshinchi, Adam J Lamble, Lisa Eidenschink Brodersen, Todd A Alonzo, Jim Wang, Laura Pardo, Lillian Sung, Todd M Cooper, E Anders Kolb, Richard Aplenc, Sarah K Tasian, Michael R Loken, Soheil Meshinchi
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.
Conflict of interest statement
Lisa Eidenschink BrodersenEmployment: Hematologics IncLeadership: Hematologics Inc Laura PardoEmployment: Hematologics Inc, Fred Hutchinson Cancer Research Center Todd M. CooperEmployment: Adaptive Biotechnologies (I)Stock and Other Ownership Interests: Juno/Celgene (I) E. Anders KolbTravel, Accommodations, Expenses: Roche/Genentech Richard AplencExpert Testimony: Vorys Sarah K. TasianConsulting or Advisory Role: Aleta Biotherapeutics, Kura OncologyResearch Funding: Incyte, Gilead Sciences, Beam Therapeutics Michael R. LokenEmployment: Hematologics IncLeadership: Hematologics IncStock and Other Ownership Interests: Hematologics IncConsulting or Advisory Role: Newlink GeneticsNo other potential conflicts of interest were reported.
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Source: PubMed