It is unclear why CD38 positivity is associated with a short patient survival and poor responsiveness to chemotherapy. It is possible that CD38 expression confers to B-CLL of a more malignant cellular phenotype. This seems plausible given that the antigen has an important role as a modulator of intracellular signaling and that cross-linking of CD38 up-regulates BCL-2 and inhibits apoptosis in normal mature B cells. Indeed, CD38/CD3l interactions lead to increased B-CLL proliferation and survival. This study has been designed to recruit patients with progressive or refractory B-CLL of whom, in line with the literature, about 50% will be CD38+.