Rituximab Therapy for Treatment of Chronic Warm Autoimmune Hemolytic Anemia

Abstract

Autoimmune hemolytic anemia (AIHA) is a disorder in which auto antibodies are directed against red blood cells resulting in severe anemia. It is a relatively uncommon disorder with an estimated incidence of 1–3 cases per 100,000 persons per year. These disorders are classified as either warm AIHA or cold AIHA depending on the temperature at which the auto antibodies show maximal binding. First line therapy for patients (pts) with warm AIHA is corticosteroids, 20% achieve complete remission most patients require maintenance treatment. Splenectomy is the usual second line treatment. Cytotoxic and immunosuppressive medications can be tried. Rituximab a monoclonal antibody against CD 20 has also shown efficacy in pt with chronic AIHA.In this study we retrospectively studied 2 cases of chronic warm AIHA. Case 1 was a female diagnosed with AIHA at the age of 15 years with a history of vasculitis. AIHA had a relapsing and a remitting course. She was treated with steroids, splenectomy, cytotoxic therapy with cyclophosphamide and immunosuppressive therapy with azathioprine with no long-term remission. At 36 yr of age she had a relapse, steroids induced a minimal response, cyclophosphamide induced a partial response. She developed hemorrhagic cystitis hence cyclophosphamide was discontinued. Rituximab was administered at 375mg/m2 weekly for 3 doses with minimal response. After 4 weeks she was given 3 more doses of weekly rituximab with minimal response. 2 weeks after the last Rituximab dose, pt developed pancytopenia, gram-negative sepsis and died.Case 2 was also a female who was diagnosed with AIHA at the age of 21 years, etiology was considered idiopathic. She had a relapsing remitting course as well. She had been treated with steroids, splenectomy, cytotoxic therapy and immunosuppressive therapy. At 41 years of age she relapsed, this episode was, not responsive to steroids, Rituximab 375mg/m2 was infused weekly for 3 weeks with minimal improvement, after 6 weeks, 3 more doses of Rituximab were infused. She had a gradual improvement of her hemoglobin over 4 months and pt has been in remission since. She has had a sustained response for over 24 months.There have been a few case series published about the effects of Rituximab in pt with warm AIHA, with an estimated complete response ranging from 40 – 100%. The toxicities of this therapy in this pt population has been not been well documented. We conclude that Rituximab must be used cautiously in pt with AIHA. Prospective Randomized clinical trails are needed to assess the efficacy of Rituximab in pt with warm AIHA.