OBJECTIVE: Our previous studies have indicated potentially higher proliferative activity of tumor cells in Chinese patients with mantle-cell lymphoma (MCL) than those in Western. Given the success and tolerability of R-DA-EDOCH immunochemotherapy in treating aggressive B-cell lymphomas, we designed a prospective, phase 3 trial to explore the efficacy and safety of alternating R-DA-EDOCH/R-DHAP induction therapy for young patients with newly diagnosed MCL. The primary endpoint was the complete remission rate (CRR) at the end of induction (EOI). METHODS: A total of 55 patients were enrolled. The CRR at the EOI was 89.1% [95% confidence interval (CI) 78%-96%], and the overall response rate was 98.1% (95% CI 90%-100%). Most patients with bone marrow involvement quickly attained minimal residual disease (MRD) negative status, with a 95.7% rate at the EOI. RESULTS: The 3-year progression-free survival (PFS) and overall survival rates were 66.3% and 83.2%, respectively. No patients discontinued treatment because of adverse events. Univariate analysis identified pathologic morphology and TP53 mutations as risk factors for PFS. However, high tumor proliferative activity and certain cytogenetic abnormalities showed no significant adverse prognostic significance. CONCLUSIONS: Intensive therapy based on a high cytarabine dose and continuously administered EDOCH achieved a high MRD-negative rate and provides an optional induction choice for young patients with MCL with high-risk factors.