Xueya Zhang, Yuyu Zheng, Shijie Cai
Cold agglutinin disease (CAD) and cold agglutinin syndrome (CAS) are currently recognized as distinct clinical entities. CAD is defined as a distinct clonal B-cell lymphoproliferative disorder of the bone marrow. CAD is also a subgroup of autoimmune hemolytic anemia, triggered by cold-reactive immunoglobulin targeting red blood cell surface antigens in its pathogenesis. CAS exhibits similar cold hemolytic anemia; however, it is secondary to hematological malignancies or infectious diseases. For lymphoma-associated CAS, specific types of antilymphoma chemotherapy are required. We report a man in his late 60s with marginal zone lymphoma with IgM kappa positivity and CAS. The patient had no response following two cycles of rituximab monotherapy administered at 375 mg/m2 (2) on day 1 every 21 days. He was then treated with a regimen consisting of rituximab 375 mg/m2 (2) on day 1 and lenalidomide 20 mg daily on days 1-21, administered every 28 days. After four cycles of treatment, the patient's cold agglutinin test turned negative, and no red blood cell agglutination was observed in peripheral blood and bone marrow. After completing six cycles of rituximab and lenalidomide therapy, the condition has remained in complete remission for 24 months. CAS is rare in clinical practice, and effective treatment for underlying diseases is key to improving patient prognosis. The combination therapy of rituximab and lenalidomide is one worthy of clinical practice as a salvage regimen for such diseases, especially for those who are refractory to rituximab monotherapy.