Clinical and therapeutic implications of the mutational status of IgVH in patients with chronic lymphocytic leukemia.

The past 2 decades have brought major advances to clinicians' understanding of the complexities of chronic lymphocytic leukemia (CLL). Novel biologic and genetic markers are providing tools for more accurate prediction of responses, disease progression, and survival of patients across different stages of CLL. Several multivariate analyses have confirmed unmutated IgVH to be an independent adverse prognostic marker in patients with CLL. The presence of unmutated IgVH is strongly associated with poor-risk genomic aberrations and overexpression of CD38 and ZAP-70. Nevertheless, these associations are not absolute. The design of future clinical trials are already incorporating novel prognostic markers such as IgVH, among others, as part of risk-adapted strategies aimed at improving treatment outcomes by tailoring the aggressiveness of the therapy proportional to disease risk. Such a strategy could minimize unnecessary chemotoxicity in patients with favorable prognosis CLL, while reserving more aggressive therapy, including allogeneic hematopoietic cell transplantation, for patients with poor-risk features. (c) 2008 American Cancer Society.