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Keywords:

  • refractory autoimmune haemolytic anaemia;
  • AIHA;
  • anti-CD20;
  • rituximab

Autoimmune haemolytic anaemia (AIHA) of the warm type results from the production of autoantibodies that bind to red blood cells and lead to their destruction. The established treatment consists of corticosteroids alone or in combination with azathioprine or cyclophosphamide (Schwartz et al, 2000). Refractoriness to these drugs is seen in only a small portion of the patients. Rituximab is an anti-CD20 chimaeric monoclonal antibody that recognizes the CD20 antigen on B-lymphocytes and leads to their lysis. The drug is used to treat patients with indolent non-Hodgkin lymphoma (Onrust et al, 1999), and it has been shown to be helpful in the treatment of some patients with refractory autoimmune disorders including secondary immune thrombocytopenia (Ratanatharathorn et al, 2000), cold agglutinin disease (Lee & Kueck, 1998) and polyneuropathy related to IgM antibodies (Levine & Pestronk, 1999).

We report the 8-year course of a 68-year-old male patient with AIHA. Treatment with prednisolone, azathioprine, cyclophosphamide, mycophenolate-mofetil and pulsed high-dose dexamethasone led to either transient or no responses. Clinical and laboratory examination before treatment with rituximab revealed decompensated haemolytic anaemia. Full blood count before treatment showed haemoglobin (Hb) 8·4 g/dl, white blood count 12·0 × 109/l, platelets 141 × 109/l, neutrophils 10·8 × 109/l, lymphocytes 0·49 × 109/l, CD19-positive cells 4% of lymphocytes, reticulocytes 14·9%, haptoglobin 10 mg/l, total bilirubin 90·63 µmol/l, lactate dehydrogenase (LDH) 759 U/l. Bone marrow biopsy showed hyperplastic erythropoiesis.

After obtaining informed consent, rituximab at 375 mg/m2 was given once a week for 4 weeks to baseline therapy consisting of 15 mg/d prednisolone (Fig 1). Apart from minor chills during the first infusion, there were no side-effects. After the first rituximab infusion, CD19-positive cells in the peripheral blood decreased from 4% to undetectable levels and remained below 0·05% of the lymphocytes during the observation period. Although the direct antiglobulin test remained positive, haemolysis decreased during the 6 months of observation after treatment (Hb 12·3 g/dl versus 8·4 g/dl, LDH 759 U/l vs. 483 U/l, total bilirubin 71·82 µmol/l vs. 90·63 µmol/l). Reticulocyte count and haptoglobin value did not change. The patient is now well and largely asymptomatic. This shows that rituximab may be a tolerable alternative in the treatment of refractory AIHA.

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Figure 1. Haemoglobin concentration after rituximab application (4 × 375 mg/m2) in a patient with refractory autoimmune haemolytic anaemia. Pred, prednisolone; Azt, azathioprine 2 mg/kg/d; Cyc, cyclophosphamide 1·3 mg/kg/d; MMF, mycophenolate-mofetil 2 g/d; Dexa, dexamethasone 40 mg (once).

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References

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  2. References
  • Lee, E.J. & Kueck, B. (1998) Rituxan in the treatment of cold agglutinin disease. Blood, 92, 34903491.
  • Levine, T.D. & Pestronk, A. (1999) IgM antibody-related polyneuropathies: B-cell depletion chemotherapy using rituximab. Neurology, 52, 17011704.
  • Onrust, S.V., Lamb, H.M., Balfour, J.A. (1999) Rituximab. Drugs, 58, 7988; Discussion 89–90.
  • Ratanatharathorn, V., Carson, E., Reynolds, C., Ayash, L.J., Levine, J., Yanik, G., Silver, S.M., Ferrara, J.L., Uberti, J.P. (2000) Anti-CD20 chimeric monoclonal antibody treatment of refractory immune-mediated thrombocytopenia in a patient with chronic graft-versus-host disease. Annals of Internal Medicine, 133, 275279.
  • Schwartz, R.S., Berkman, E.M., Silberstein, L.E. (2000) Autoimmune hemolytic anemias. In: Hematology: Basic Principles and Practice (ed. by R.Hoffmann, E.J.Benz, Jr, S.J.Shattil, B.Furie, H.J.Cohen, L.E.Silberstein & P. McGlave), pp. 611630. Philadelphia.