Patients will receive RCD or PCD combination as induction treatment followed by rituximab or velcade maintenance therapy, as the investigators try to compare the, very good partial remission (VGPR) rate, complete remission (CR) rates, Overall remission rate (MR+CR + VGPR + partial remission (PR) rate), major reaction rate (MRR, PR+VGPR+CR) at the end of the research.

This is an open-label, single-centre, randomised study, looking at a series of 40 patients up to the age of 75 with newly diagnosed Waldenstrom's macroglobulinemia (WM) not previously treated. Patients will receive RCD or PCD combination as induction treatment followed by rituximab or velcade maintenance therapy, as the investigators try to compare the, very good partial remission (VGPR) rate, complete remission (CR) rates, Overall remission rate (MR+CR + VGPR + partial remission (PR) rate), major reaction rate (MRR, PR+VGPR+CR) at the end of the research.

Inclusion Criteria:

• Recently diagnosed WM according to the second 2002 WM international working group
• Not previously treated, apart from not regularly received by Chlorambucil
• Aged from 18 to 75 years, both male and female
• Ability to give signed informed consent
• Negative pregnancy test at inclusion (if necessary)
• ECOG from 0 to 2

Exclusion Criteria:

• Known hypersensitivity to rituximab or velcade or cyclophosphamide
• Uncontrolled infection including bacteria, virus and fungus, including active HBV infection
• Organic dysfunction: Bilirubin > 1.5 x normal above, Renal failure requiring dialysis, glutamic pyruvic transaminase (ALT) and Glutamic-Oxaloacetic Aminotransferase (AST) > 2.5 x normal above
• Positive HIV serology
• Serious psychiatric item in the history