Cancer Treatment Today

Cold-agglutinin-induced autoimmune hemolytic anemia (AIHA)  is difficult to treat.  It is also called cold agglutinin disease. Cold agglutinin disease is a group of disorders that are characterized by antierythrocyte autoantibodies that bind red blood cells at cold temperatures (< 37° C), causing hemagglutination. The antibodies are usually of the IgM type but may also be of the immunoglobulin G (IgG) or immunoglobulin A (IgA) type. Symptoms include Raynaud’s phenomena (vasospasm of peripheral arterioles) and acrocyanosis (intra-arteriolar agglutination of red blood cells in the fingers, feet, nose and earlobes, causing numbness, stiffness and pain in these areas). A phase II study of Rituxan is currenlty ongoing in cryoglobulinemia, which is a related disorder.

Rituximab has been used for the treatment of chronic cold agglutinin disease in several case studies and in 1 small trial was 375 mg/m2 weekly for 4 doses. However until a randomized study can be conducted, it remains an investigational option. A 2007 review concluded: “The preliminary results are encouraging, but further studies are required in order to allow firm conclusions.”

Gertz MA. Management of cold haemolytic syndrome. Br J Haematol. 2007;138:422–9.

Lee EJ, Kueck B. Rituxan in the treatment of cold agglutinin disease. Blood 1998;92:3490-3491.

Zaja F, Russo D, Fuga G, et al. Rituximab in a case of cold agglutinin disease. Brit J Haematol. 2001;115:232.

Mori A, Tamaru J, Sumi H, Kondo H. Beneficial effects of rituximab on primary cold agglutinin disease refractory to conventional therapy. Eur J Haematol. 2002;68:243-246.

Cohen Y, Polliack A, Zelig O, Goldfarb A. Monotherapy with rituximab induces rapid remission of recurrent cold agglutinin-mediated hemolytic anemia in a patient with indolent lympho-plasmacytic lymphoma. Leuk Lymphoma. 2001;42:1405-1408. Abstract

Sparling TG, Andricevic M, Wass H. Remission of cold hemaggluinin disease induced by rituximab therapy. CMJ. 2001;164:1405.

Engelhardt M. Jakob A, Ruter B, et al. Severe cold hemagglutinin disease (CHD) successfully treated with rituximab. Blood. 2002;100:1922-1923.

Berentsen S, Tjonnfjord GE, Brudevold R, et al. Favourable response to therapy with the anti-CD20 monoclonal antibody rituximab in primary chronic cold agglutinin disease. Brit J Haematol. 2001;115:79-83

G, Fabris M, Ferraccioli G, De Vita S.Rituximab treatment for glomerulonephritis in HCV-associated mixed cryoglobulinaemia: efficacy and safety in the absence of steroids.Rheumatology (Oxford). 2006 Jul;45(7):842-6.
Comment in:
Rheumatology (Oxford). 2006 Jun;45(6):783-4; author reply 784-5

Berentsen S, Ulvestad E, Tjønnfjord GE.B-lymphocytes as targets for therapy in chronic cold agglutinin disease.Cardiovasc Hematol Disord Drug Targets. 2007 Sep;7(3):219-27.