Anti-CD20 Treatment of Autoimmune Hemolytic Anemia Refractory to Corticosteroids and Azathioprine: A Pediatric Case Report and Mini Review

Abstract

Autoimmune hemolytic anemia (AIHA) is a relatively uncommon hematological entity in children and sometimes is characterized by a severe course requiring more than one line course therapy. Treatment decisions depend on the severity and chronicity of the anemia and the characteristics of the autoantibodies. Immunosuppression with corticosteroids is the first-line treatment, especially in warm-reactive AIHA. Refractory cases are treated with immunosuppressive drugs, cytotoxic agents, androgens, or splenectomy, with various side effects and questionable efficacy. Another second-line option is rituximab, an anti-CD20 monoclonal antibody, which has been used as an off-label agent with encouraging results from small limited studies or case reports. Herein, we add our experience on the safety and clinical efficacy of rituximab by presenting the case of a boy with warm-type AIHA resistant to corticosteroids and azathioprine, successfully treated with rituximab. We also offer a review of the relevant literature.

Adverse Reactions to Drugs of Special Interest in a Pediatric Oncohematology Service

“…Rituximab was the most frequently drug used off-label. In children, rituximab has been used in a wide range of autoimmune diseases that require lymphocyte B depletion, and observational studies have been published in patients with immune thrombocytopenia, hemolytic anemia, multiple sclerosis or nephrotic syndrome ( Zecca et al, 2003 ; O’Connor et al, 2013 ; Maratea et al, 2016 ; Makis et al, 2018 ). The main indications for rituximab in our cohort were the treatment of Epstein-Barr virus infection and hemolytic anemia.…”

Respiratory failure and shock in an infant with severe anemia

“…Initial treatment with corticosteroids has been widely practiced 6,7 . Their initial mechanism of action is to block the phagocytic Fc receptor, leading to decreased red cell destruction within 24–48 h 1 . A later effect of corticosteroids is decreased autoantibody production, although this can take several weeks.…”

“…A later effect of corticosteroids is decreased autoantibody production, although this can take several weeks. Typically, once hemolysis improves and the patient's hemoglobin stabilizes, a slow wean off corticosteroids over weeks to months is initiated 1,7 . Approximately 80% of patients will respond initially to corticosteroids 1‐3,8 .…”

“…There is no consensus on the best treatment for steroid‐refractory pediatric cases of warm AIHA. A variety of approaches have been tried, including immunosuppressive drugs, cytotoxic agents, androgens, and splenectomy 1,6 . Emerging evidence in adults has suggested that rituximab, a monoclonal antibody against the CD20 antigen on B lymphoblasts has been effective in patients with warm AIHA.…”

“…His clinical evaluation and laboratory results supported a diagnosis of warm autoimmune hemolytic anemia (AIHA). AIHA is caused by the presence of autoantibodies (usually IgG) that develop against erythrocyte surface antigens leading to their subsequent destruction by the macrophages in the reticuloendothelial system 1 . Patients presenting with AIHA have systemic symptoms of hemolysis, including pallor, jaundice, fever, and lethargy 2,3 .…”