rituximab + fludarabine + alemtuzumab

A multi-agent chemoimmunotherapy regimen combining the anti-CD20 monoclonal antibody rituximab, the purine analog antimetabolite fludarabine, and the anti-CD52 monoclonal antibody alemtuzumab. It has been investigated primarily in chronic lymphocytic leukemia and related B‑cell lymphoid malignancies to deepen responses after fludarabine+rituximab induction or to treat relapsed/refractory disease. Rituximab targets CD20 on B cells to mediate complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, and apoptosis. Fludarabine is phosphorylated intracellularly to F-ara-ATP, inhibiting DNA polymerase, ribonucleotide reductase, and DNA primase, causing DNA synthesis inhibition and apoptosis. Alemtuzumab targets CD52 on lymphocytes, inducing profound lymphocyte depletion via complement and cellular cytotoxicity. This combination can increase complete response and MRD-negative rates but carries high risk of infectious complications due to profound immunosuppression.