Cold versus warm autoimmune hemolytic anemia in diffuse large B cell lymphoma: pathogenic and therapeutic implications: a case series.

BACKGROUND: Autoimmune hemolytic anemia-associated diffuse large B cell lymphoma is rare, with distinct pathogenic mechanisms and therapeutic responses in cold agglutinin syndrome (CAS) and warm autoimmune hemolytic anemia subtypes poorly characterized. This report highlights two novel cases demonstrating subtype-specific molecular drivers and treatment outcomes, underscoring the necessity for precision management. CASE PRESENTATION: Two patients presented with autoimmune hemolytic anemia: a 29-year-old Han male with cold agglutinin syndrome and a 37-year-old Han female with warm autoimmune hemolytic anemia who had 5-year history of symptoms. Both patients were diagnosed with nongerminal center B cell (nonGCB) diffuse large B cell lymphoma. The male cold agglutinin syndrome-diffuse large B cell lymphoma patient exhibited monoclonal IgM-κ-driven complement-mediated intravascular hemolysis via a direct "tumor-antibody-erythrocyte" axis, accompanied by BCL6 amplification, and achieved rapid remission with rituximab monotherapy. The female warm autoimmune hemolytic anemia-diffuse large B cell lymphoma patient demonstrated polyclonal IgG-mediated macrophage erythrophagocytosis (via the JAK-STAT pathway) and BCL2/BCL6 co-amplification, requiring R-CHOP chemotherapy to control refractory hemolysis. CONCLUSION: These cases reveal distinct molecular mechanisms (BCL6 versus BCL2/BCL6 amplification) and therapeutic vulnerabilities in autoimmune hemolytic anemia-diffuse large B cell lymphoma subtypes, requiring subtype-specific treatment. A screening triad-refractory hemolysis, cytopenia, and lymphatic/splenic involvement-enables early lymphoma detection. Molecular profiling may guide precision therapy, improving outcomes in this rare disease spectrum.