You Make the Call: Would rituximab re-treatment help this patient with hemolytic anemia?

Edward J. Benz Jr., MD
President and CEO Emeritus, Dana-Farber Cancer Institute; Richard and Susan Smith Distinguished Professor of Medicine, Harvard Medical School

This month, Edward Benz Jr., MD, discusses treatment of Coombs-positive hemolytic anemia in a patient who declines to undergo splenectomy.


I am caring for a 57-year-old man with idiopathic Coombs-positive hemolytic anemia (with no underlying lymphoproliferative disease) who requires 5-10 mg of prednisone daily to keep his hemoglobin level above 7 g/dL. He refuses splenectomy. He has received treatment with rituximab once with no apparent benefit. Is there any evidence that a second treatment with rituximab might be beneficial?


Until recently, the usual protocol for reducing or eliminating the immune-mediated hemolysis of autoimmune hemolytic anemia (AIHA) consisted of initial treatment with corticosteroids, followed by splenectomy in the event of primary resistance or relapse. Unfortunately, treatment failure or relapse can occur despite employment of both modalities, and splenectomy has both a morbidity and mortality risk.

Rituximab has gained accept- ance as second-line therapy before employing splenectomy1,2 and has also been advocated on the basis of small clinical trials as firstline combination therapy in conjunction with corticosteroids. Splenectomy is then usually pursued if treatment with corticosteroids followed by rituximab is ineffective or relapse occurs. Deployment of other immunosuppressive agents such as azathioprine or cyclosporine in the most refractory situations has yielded mixed results with more toxicity issues and should be reserved for the most difficult situations.

This patient’s reluctance to undergo splenectomy despite the persistence of low-level but daily prednisone and one round of rituximab therapy leads to a difficult choice. Would it be better to give rituximab another try before resorting to more aggressive and toxic immunosuppressive agents? While I have not had personal experience with the use of a second round of rituximab, one can find precedent for trying a second round in the literature.3,4 Response rates after second use, however, are considerably lower after a first unsuccessful attempt. Thus, prior experience suggests that it is unlikely that your patient will respond.

Still, given the relative safety of rituximab, a second effort seems reasonable here. That said, this patient might well require splenectomy to restore his red cell status to more sustainable levels as he ages.


  1. Reynaud Q, Durieu I, Dutertre M, et al. Efficacy and safety of rituximab in auto-immune hemolytic anemia: A meta-analysis of 21 studies. Autoimmun Rev. 2015;14:304-13.
    Rodrigo C, Rajapakse S, Gooneratne L. Rituximab in the treatment of autoimmune haemolytic anaemia. Br J Clin Pharmacol. 2015;79:709–719.
  2. Abadie K, Hege KM. Severe refractory autoimmune hemolytic anemia with five-year complete hematologic response to third course of treatment with rituximab: a case report. J Med Case Reports. 2014;8:175.
  3. Dierickx D, Kentos A, Delannoy A. The role of rituximab in adults with warm antibody autoimmune hemolytic anemia. Blood. 2015;125:3223–3229.

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