A phase II trial of autologous activated macrophages (MAKs) coated with a humanized anti-CD20 antibody (rituximab) was performed, focusing on its safety and its capacity to eradicate minimal residual disease (MRD).MAKs/anti-CD20 treatment in heavily pretreated chronic lymphocytic leukemia (CLL) patients displayed promising efficiency, with no noteworthy toxicity.In addition, it was unlikely that the use of low cumulative dose of anti-CD20 could alone have induced a durable response, as single-agent rituximab therapy has limited activity in both previously untreated and refractory/relapsed CLL.The mechanisms underlying the antitumor effect of MAKs/anti-CD20 were not investigated, but MAK-induced phagocytosis was probably a major factor, as demonstrated in vitro.The results generally suggest that MAKs/anti-CD20 (rituximab) therapy is efficient and safe in heavily treated CLL patients with MRD, and could be used to eliminate MRD, although a direct effect of rituximab itself could not be ruled out.