Prognostic impact of CD123 overexpression on the outcome of pediatric acute myeloid leukemia.

BACKGROUND AND AIMS: Despite advances in acute myeloid leukemia (AML) therapy, outcomes remain poor. CD123 overexpression influences proliferation and enhanced survival of leukemic cells. Its impact on the outcome is still debatable. This study aimed to assess CD123 overexpression frequency in pediatric AML, its relation with disease features, and its impact on outcomes. METHODS: This retrospective study included pediatric patients with de novo AML (≤18 years) treated with a protocol adapted from COGAAML 1031. CD123 expression ≥20% on AML blasts assessed by multicolor flow cytometry was considered positive. Survival outcomes were analyzed using Kaplan-Meier estimates, with cumulative incidence of relapse in the competing risk setting compared by Gray's test, and multivariable associations assessed through Cox regression. RESULTS: Among 403 patients, 141 (35%) were CD123+ve, showing a median expression level of 46%. CD123+ve was significantly associated with higher white blood cell count (P = 0.003), percentage of bone marrow blasts (P = 0.02), M4/M5 FAB subtypes (P < 0.001), FLT3-ITD (P = 0.001), and inversely related with t(8;21) (P = 0.02). Conversely, CD123+ve did not show significant association with age, sex, initial risk and other genetic abnormalities and did not influence the response to induction therapy, whether assessed morphologically or by minimal residual disease levels. No significant differences in survival outcomes were observed between CD123+ve and CD123-ve patients in both univariate and multivariable analyses. The 3-year EFS was 45.3% (95% CI; 37.8-54.3) for CD123+ve compared to 42.2% (95% CI; 36.6-48.7) in CD123-ve patients (P = 0.5) and the 3-year OS was 51.7% (95% CI; 44.1-60.7) versus 49% (95% CI; 43.2-55.5), respectively (P = 0.6). The cumulative incidence of relapse at 3 years for CD123+ve was 24.1% (95% CI; 17.4-31.5), comparable to 23.7% (95% CI; 18.7-29) for CD123-ve patients (P = 0.9). CONCLUSIONS: The association of CD123+ve with initial higher disease burden and FLT3-ITD, implies that it may mark a biologically distinct and more aggressive leukemia subtype. Although its prognostic impact remains unclear, its high incidence supports its potential as a therapeutic target, necessitating further large-scale studies.