Treatment of refractory autoimmune haemolytic anaemia with anti-CD20 (rituximab)

Abstract

Purpose: Autoimmune haemolytic anaemia (AFHA) in patients with warm reactive autoantibodies can usually be controlled through treatment with corticosteroids alone or in combination with azathioprine or cyclophosphamide. Some patients remain refractory to these drugs though and need an alternative therapy. Rituximab is an anti-CD20 chimeric monoclonal antibody that recognises the CD20 antigen on B-lymphocytes and leads to their lysis. The drug is used to treat patients with indolent non-Hodgkin lymphoma, and it has been shown to be helpful in the treatment of a few patients with refractory autoimmune disorders including secondary immune thrombocytopenia, cold agglutinin disease, and polyneuropathy related to IgM antibodies. It is unknown, whether refractory AIHA would respond to anti-CD20 treatment. Methods: We report on a 68-year-old male patient with autoimmune haemolytic anaemia over the last 10 years. Treatment with prednisolone. azathioprine, cyclophosphamide, mycophenolate-mofetil, and pulsed high-dose dexamethasone led only to either transient or no responses. Clinical and laboratory examination prior to treatment with riluximab revealed decompensated haemolytic anaemia (haemoglobin 8.4 g/dl, white blood count 12.0 ·109/1, platelets 141 ·109/1, neutrophils 10.8 ·109/1, lymphocytes 0.49 · 109/l. CD19-positve cells 4 % of lymphocytes, reticulocytes 14.9 %, haptoglobin 1 mg/dl, total bilirubin 5.3 mg/dl, lactate dehydrogenase 759 U/l, and bone marrow biopsy showed hyperplastic erythropoiesis). Results: After obtaining informed consent, rituximab was given once a week for four weeks (375 mg/m2). Apart from minor chills during the first infusion, there were no side effects. After the first rituximab infusion. CD19-positive cells decreased in the peripheral blood from 4 % to not detectable and remained below 0.05 % of the lymphocytes during the observation period. Although the direct antiglobulin test remained positive, haemoglobin-levels raised 191 days after first infusion to 12.3 g/dl, and lactate dehydrogenase and total bilirubin dropped to 483 U/l and 4.2 mg/dl respectively. The response was long lasting and no additional therapy was required until today. Conclusion: Rituximab is well tolerable and may represent an alternative in the treatment of refractory autoimmune haemolytic anaemia.