Clinical and prognostic significance of CD4 expression in patients with de novo acute myeloid leukemia receiving intensive chemotherapy.

Abstract

Although the lymphoid marker CD4 is aberrantly expressed in acute myeloid leukemia (AML), its clinical and prognostic significance remains poorly characterized. We retrospectively analyzed 217 patients with de novo AML receiving intensive chemotherapy. The clinical characteristics and survival outcomes were analyzed according to CD4 status. CD4 was expressed in 35.5% (77/217) of patients. Compared with CD4-negative patients, CD4-positive patients were more frequently aged ≥60 years (29.9% vs. 17.9%, P = 0.0414), showed higher frequencies of M4/M5 morphology (31.2% vs. 7.1% and 40.3% vs. 2.9%, both P < 0.0001) and RUNX1 mutations (9.1% vs. 2.1%, P = 0.0363), while the favorable-risk CEBPA bZIPinf mutation was markedly less frequent in CD4-positive patients (2.6% vs. 21.4%; P = 0.0002). CD4 positivity was associated with inferior overall survival (OS; P = 0.0011), but not event-free survival (EFS; P = 0.0501), and was not independently associated with either outcome in multivariate analysis. CD4 expression level was also not associated with EFS or OS. Notably, CD4 positivity remained associated with inferior OS within the adverse-risk group (P = 0.0335). In sensitivity analyses restricted to patients without HSCT (n = 166), CD4 positivity remained associated with inferior OS (P = 0.0108), whereas this association was attenuated after excluding patients with CEBPA bZIPinf mutations (HR, 1.389; 95% CI, 0.926-2.083; P = 0.1119). In conclusion, CD4 expression identifies an AML subset with distinct clinical and genomic characteristics, and its association with inferior OS may partly reflect the lower frequency of favorable CEBPA bZIPinf mutations.