The relationship between the polymorphism (rs6449182) of CD38 and the prognosis of patients with chronic lymphocytic leukemia treated with fludarabine, cyclophosphamide and rituximab (FCR): a 4 year prospective cohort study

Abstract

Background: Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults in Europe and in North America. It is caused by the neoplastic transformation of a population of B-lymphocytes coexpressing CD5, CD19 and CD23. Although the etiology is not well known there is evidence of the existence of a genetical base. CLL is not only caused by the accumulation of B-lymphocytes due to a failure in the apoptosis. It is also caused by the active proliferation of the B-cells in response to the signs sent by the environment. Its clinical course is variable. One third of CLL patients are affected by an indolent form that does not require treatment. Another third of patients with leukemia will require iterative therapies and a small fraction patients develop Richter syndrome that reduces its overall survival to 5 to 8 months. This variability is due to the heterogeneity of the molecules that participate in the pathogenesis. One of these molecules is CD38. Some studies have demonstrated that the presence of this marker confers a worse prognostic, specially the presence of one polymorphism of CD38, rs6449182. Fluradabine, clyclophosphamide and rituximab (FCR) is considered the gold standard therapy for young patients under 65 years with CLL because achieves high percentage of minimal residual disease (MRD). But it has not been studied if in CLL patients with this polymorphism, FCR continues offering these good results. Objective: To analyze the relationship between the polymorphisms of CD38 and treatment outcomes in CLL patients treated with FCR. Methods: The design is a multicenter prospective cohort study. 338 patients will be recruited during 4 years. We will analyze the presence of the polymorphism and evaluate the minimal residual disease (MRD) after the treatment with FCR