NOTCH1 mutations Identify a chronielymphocytic leukeima patient subset with worse prognosis in tie setting of a rituximab-based induction and consolidation treatment

摘要

Induction therapy with fludarabine followed by rituximab and consolidation plus maintenance with rituximab improved response duration (RD) and overall survival (OS) in our patients with chronic lymphocytic leukemia (CLL). The aim of our study was to investigate the clinical impact of NOTCH 1 mutations in this setting of patients. The study included 123 progressive CLL patients homogeneously assigned to first-line induction treatment with fludarabine followed by rituximab. Fifty-nine patients either in complete remission (CR) minimal residual disease positive (MRD+) after induction (n=39) or in partial remission (PR. n=20) underwent consolidation/maintenance therapy with rituximab. Sixteen patients in CR MRD+or PR underwent observation only. The presence of NOTCH1 mutations was investigated by amplification refractory mutation system (ARMS) PCR and by Sanger sequencing. NOTCH1 mutations occurred in 20 out of 123 (16.3%) cases. Consolidated patients showed longer OS than unconsolidated patients (p=0.030).