From the Guidelines
Lymphoma is associated with several types of hemolytic anemias, primarily autoimmune hemolytic anemia (AIHA), cold agglutinin disease, and paroxysmal cold hemoglobinuria, with AIHA being the most common type, as reported in the most recent study 1.
Types of Hemolytic Anemias
- Autoimmune hemolytic anemia (AIHA): warm AIHA, where IgG antibodies bind to red blood cells at body temperature, causing their removal by the spleen
- Cold agglutinin disease: characterized by IgM antibodies that bind to red cells at lower temperatures, activating complement and causing hemolysis
- Paroxysmal cold hemoglobinuria: though rare, can also occur with lymphomas
Lymphoma Association
- Non-Hodgkin lymphomas, particularly chronic lymphocytic leukemia (CLL), are more commonly associated with hemolytic anemias than Hodgkin lymphoma, as noted in 1
- Lymphoma patients may develop drug-induced immune hemolytic anemia from medications used in treatment
- Microangiopathic hemolytic anemia can occur if lymphoma infiltrates blood vessels, causing mechanical damage to red cells
Treatment
- Treatment typically focuses on addressing the underlying lymphoma while managing the hemolytic process with corticosteroids, rituximab, or other immunosuppressants depending on the specific type of hemolytic anemia, as recommended in 1
- Second-line treatment options for AIHA include splenectomy, intravenous immunoglobulins, and/or immunosuppressive therapy with agents, such as cyclosporine A, azathioprine, or low-dose cyclophosphamide, as mentioned in 1
From the FDA Drug Label
A single occurrence of transient aplastic anemia (pure red cell aplasia) and two occurrences of hemolytic anemia following RITUXAN therapy occurred during the single-arm studies
The types of hemolytic anemias associated with lymphoma mentioned in the drug label are:
- Hemolytic anemia No specific types of hemolytic anemia are mentioned, only that two occurrences of hemolytic anemia were reported in the single-arm studies 2.
From the Research
Types of Hemolytic Anemias Associated with Lymphoma
- Autoimmune hemolytic anemia (AIHA) is an acquired, heterogeneous group of diseases that can be associated with lymphoma 3
- Cold agglutinin disease (CAD) is a type of AIHA that is a clonal lymphoproliferative disorder, which can be associated with lymphoma 4, 5, 6
- Secondary cold agglutinin syndrome (CAS) can also be associated with lymphoma, as it can occur secondary to another distinct clinical disease, including malignancies 4, 5, 6
- Warm antibody AIHA can also be associated with lymphoma, although the pathogenesis is different from CAD and CAS 3, 7
- Mixed AIHA and atypical AIHA are other types of AIHA that can be associated with lymphoma, although less is known about their pathogenesis and treatment 3
Characteristics of Hemolytic Anemias Associated with Lymphoma
- Hemolysis in CAD and CAS is mediated by the classical complement pathway and is predominantly extravascular 4, 6
- The pathogenesis of AIHA is complex and involves T and B cell dysregulation, reduced CD4+ and CD25+ Tregs, and increased clonal expansions of CD8+ T cells 3
- Treatment of AIHA associated with lymphoma should be differentiated and sequenced according to the type of AIHA, and may include rituximab, fludarabine, and bendamustine 5, 7