CD34 Expression Is Associated with an Adverse Outcome in Patients with NPM1-Positive Acute Myeloid Leukemia
Harry Dang, Macy Chen, Joseph Brandwein, Hong Chang. University Health Network, Toronto, ON, Canada
Background: Acute myeloid leukemia (AML) patients harboring an NPM1 mutation exhibit distinctive clinicopathologic and biologic features and account for approximately 35% of all AML cases. Recent studies have shown that the absence of FLT3 internal tandem duplication (FLT3-ITD) mutation confers a favorable prognosis in NPM1-positive AML. Since NPM1+ patients have a heterogeneous clinical outcome, the identification of prognostic parameters will aid in the stratification of these patients.
Design: We retrospectively reviewed 228 de novo AML patients who were tested for NPM1 mutation by multiplex RT-PCR at our institution. 85 patients who were positive for NPM1 were analyzed for FLT3 mutation status, immunophenotypic profile, and correlated with their clinical features and survival outcomes. Immunophenotypes were determined by multi-parameter flow cytometry.
Results: Of 85 NPM1 positive cases, CD7, CD15, CD34, CD56, and HLA-DR were expressed in 31%, 49%, 16%, 19% and 56%, respectively. Complete remission (CR) was achieved in 79% of patients with a median event-free survival (EFS) of 23.4 months, and a median overall survival (OS) of 36.4 months. Univariate analysis identified older age (≥60), high leukocyte count (>30×109/L), FLT3-ITD, CD7, and CD34 expression were significant parameters. Multivariate analysis adjusting for the aforementioned parameters revealed that only high leukocyte count is an independent predictor of CR (hazard ratio HR = 0.20, P=0.019). Older age (HR = 2.12, P=0.035), high leukocyte count (HR = 2.99, P=0.008), FLT3-ITD (HR = 2.72, P=0.012), and CD34 expression (HR = 3.18, P=0.006) all were independent predictors of shorter EFS. High leukocyte count (HR = 2.64, P=0.014), FLT3-ITD (HR = 3.18, P=0.005), and CD34 expression (HR = 2.31, P=0.047) all were independent predictors of a shorter OS.
Conclusions: In addition to FLT3-ITD mutation and high leukocyte count, we identified CD34 expression as an independent adverse prognostic factor for OS and EFS in NPM1+ AML patients. Incorporation of CD34 would be helpful in the risk stratifiction of this subgroup.
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 226, Wednesday Morning