Prognostic value of immunoglobulin variable heavy chain gene mutation status: long term follow-up in a series of chronic lymphocytic leukemia patients

B-cell chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease, with many patients surviving for decades with minimal or no treatment, whereas others succumb rapidly to their disease despite therapy. Classical staging systems and laboratory features help predict survival in CLL, but they do not distinguish patients who will progress from those whose disease will remain indolent. In recent years, new molecular prognostic factors have emerged that have significantly improved prediction of the risk for disease progression. The mutational status of the immunoglobulin variable heavy chain genes (VH) is one of the major molecular prognostic factors. In this study we evaluated the association between the immunoglobulin VH gene mutation status and the clinical characteristics and outcome in 65 CLL patients that had been followed for a considerably long period at our institution. At diagnosis, patients with unmutated VH genes had higher median lymphocyte counts (P=0.001), higher total tumor mass score (P=0.001) and more often presented at an advance clinical stage (P=0.005) compared to patients utilizing mutated VH genes. Moreover, the median survival of patients with unmutated VH genes was considerably shorter (VH unmutated, 56 months, VH mutated, 125 months; P0.001). These data confirmed the prognostic value of immunoglobulin VH genes mutational status in CLL, which divides the disease in two prognostic subsets in terms of overall survival and clinical characteristics of the disease. Analysis of the mutational status of the immunoglobulin VH genes may allow for an individualized approach to CLL treatment in the near future.