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

TitleCD123 Expression Is Associated With High-Risk Disease Characteristics in Childhood Acute Myeloid Leukemia: A Report From the Children's Oncology Group.
Publication TypeJournal Article
Year of Publication2021
AuthorsLamble AJ, Brodersen LEidenschin, Alonzo TA, Wang J, Pardo L, Sung L, Cooper TM, E Kolb A, Aplenc R, Tasian SK, Loken MR, Meshinchi S
JournalJ Clin Oncol
PaginationJCO2101595
Date Published2021 Dec 02
ISSN1527-7755
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 rearrangements and -ITD mutations ( < .001 for both) and lower prevalence of low-risk t(8;21), inv(16), and mutations ( < .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% 39%, < .001), lower event-free survival (49% 69%, < .001), and lower overall survival (32% 50%, < .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.

DOI10.1200/JCO.21.01595
Alternate JournalJ Clin Oncol
PubMed ID34855461