Haemolytic anaemia triggered by antitumoural “biological agents” and immunotherapies with monoclonal antibodies: short review of the literature

Special Report

In the last decade, many novel immunomodulating therapies and “biologicals”, usually acting as signal transduction inhibitors, came into routine therapy in cancer. Mostly, these substances are well tolerated, and there is a typical spectrum of common side effects to be considered with these therapies. A rather rarely seen toxic effect associated with the administration of these agents is haemolytic anaemia (HA). Here, we shortly summarize current knowledge on HA potentially triggered by these substances. Furthermore, an impressive case of myelodysplastic syndrome with 5q deletion which received lenalidomide and developed autoimmune haemolytic anaemia (AIHA) is presented.


Haemolytic anaemia biologicals therapeutic antibodies lenalidomide 


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  1. 1.
    List A, Kurtin S and Roe DJ et al. (2005). Efficacy of lenalidomide in myelodysplastic syndromes. N Engl J Med 352: 549–557 CrossRefPubMedGoogle Scholar
  2. 2.
    Darabi K, Kantamnei S, Wiernik PH. Lenalidomide-induced warm autoimmune hemolytic anemia. J Clin Oncol, 24: e59, 2006.Google Scholar
  3. 3.
    Sun WL, Koeck L, Walder A, et al. Successful treatment of MDS with lenalidomide, complicated by transient autoimmune hemolysis. Anna Hematol, Epub ahead of printGoogle Scholar
  4. 4.
    Faderl S, Rai K and Gribben J et al. (2006). Phase II study of single-agent Bortezomib for the treatment of patients with fludarabine-refractory B-cell chronic lymphocytic leukemia. Cancer 107: 916–924 CrossRefPubMedGoogle Scholar
  5. 5.
    Novaretti MCZ, Fonseca GHH and Conchon M et al. (2003). First case of immune- mediated haemolytic anaemia associated to imatinib mesylate. Eur J Haematol 71: 455–458 CrossRefPubMedGoogle Scholar
  6. 6.
    De Arriba JJ, Nerin C and Garcia E et al. (2003). Severe hemolytic anemia and skin reaction in a patient treated with imatinib. Ann Oncol 14: 962 CrossRefPubMedGoogle Scholar
  7. 7.
    Jain R, Mathew P and Wood CG et al. (2008). Sunitinib-induced acute hemolysis without hypertension: a case report. Clin Genitourin Cancer 6: 122–123 CrossRefPubMedGoogle Scholar
  8. 8.
    Berchem G, Dewilde S and Mahassen P (2009). A case of acute haemolysis with 2 diff erent multi target thyrosine kinase inhibitors in a patient with renal cancer. Bull Soc Sci Med Grand Duche Luxemb 1: 7–9 PubMedGoogle Scholar
  9. 9.
    Ruch J, McMahon B and Ramsey G et al. (2009). Catastrophic multiple organ ischemia due to an anti-Pr cold agglutinin developing in a patient with mixed cryoglobulinemia after treatment with rituximab. Am J Hematol 84: 120–122 CrossRefPubMedGoogle Scholar
  10. 10.
    Ramamoorthy SK, Marangolo M and Durrant E et al. (2006). Unusual reaction to Rituximab with intra-vascular hemolysis, rhabdomyolysis, renal failure and bone marrow necrosis. Leuk Lymphoma 47: 747–750 CrossRefPubMedGoogle Scholar
  11. 11.
    Jourdan E, Topart D and Richard B et al. (2003). Severe autoimmune hemolytic anemia following rituximab therapy in a patient with a lymphoproliferative disorder. Leuk Lymphoma 44: 889–890 CrossRefPubMedGoogle Scholar
  12. 12.
    Elimelakh M, Dayton V and Park KS et al. (2007). Red cell aplasia and autoimmune hemolytic anemia following immunosuppression with alemtuzumab, mycophenolate, and daclizumab in pancreas transplant recipients. Haematologica 92: 1029–1036 CrossRefPubMedGoogle Scholar
  13. 13.
    Kako S, Kanda Y and Oshima K et al. (2008). Late onset of autoimmune hemolytic anemia and pure red cell aplasia after allogeneic hematopoietic stem cell transplantation using in vivo alemtuzumab. Am J Hematol 83: 247–249 CrossRefPubMedGoogle Scholar
  14. 14.
    Fiegl M, Falkner A and Hopfinger G et al. (2006). Routine clinical use of alemtuzumab in patients with heavily pretreated B-cell chronic lymphocytic leukemia. Cancer 107: 2408–2416 CrossRefPubMedGoogle Scholar
  15. 15.
    Wierda WG, Kipps TJ, Keating MJ, et al. Self-administered, subcutaneous alemtuzumab to eliminate residual disease in patients with CLL. Blood, 108(abstract 2839), 2006.Google Scholar
  16. 16.
    Frangie C, Lefaucheur C and Medioni J et al. (2007). Renal thrombotic microangiopathy caused by anti-VEGF-antibody treatment for metastatic renal-cell carcinoma. Lancet Oncol 8: 177–178 CrossRefPubMedGoogle Scholar
  17. 17.
    Eremina V, Jefferson JA and Kowalewska J et al. (2008). VEGF inhibition and renal thrombotic microangiopathy. N Engl J Med 358: 1129–1136 CrossRefPubMedGoogle Scholar
  18. 18.
    Galesic K, Bozic B and Racic I et al. (2006). Thrombotic microangiopathy associated with σ-interferon therapy for chronic myeloid leukemia. Nephrology 11: 49–52 CrossRefPubMedGoogle Scholar
  19. 19.
    Sacchi S, Kantarjian H, O’Brien S, Cohen PR, Pierce S and Talpaz M (1995). Immune-mediated and unusual complications during interferon alfa therapy in chronic myelogenous leukemia. J Clin Oncol 13: 2401–2407 PubMedGoogle Scholar
  20. 20.
    Takase K, Nakano T, Hamada M, Shiraki K, Oohashi Y, Kihira T and Tameda Y (1995). Hemolytic anemia provoked by recombinant alpha-interferon. J Gastroenterol 30: 795–797 CrossRefPubMedGoogle Scholar
  21. 21.
    Cauli C, Serra G and Chessa L et al. (2006). Severe autoimmune hemolytic anemia in a patient with chronic hepatitis C during treatment with peginterferon alfa-2a and ribavirin. Haematologica 91: e76–e77 Google Scholar
  22. 22.
    Lambotte O, Gelu-Simeon M and Maigne G et al. (2005). Pegylated interferon alpha-2a-associated life-threatening Evens’ syndrome in a patient with chronic hepatitis C. J Infection 51: e113–e115 CrossRefGoogle Scholar
  23. 23.
    Weiss RB, Freiman J and Kweder SL et al. (1998). Hemolytic anemia after fludarabine therapy for chronic lymphocytic leukemia. J Clin Oncol 16: 1885–1889 PubMedGoogle Scholar
  24. 24.
    Borthakur G, O’Brien S and Wierda WG et al. (2007). Immune anaemias in patients with chronic lymphocytic leukaemia treated with fludarabine, cyclophosphamide and rituximab – incidence and predictors. Br J Haematol 136: 800–805 CrossRefPubMedGoogle Scholar
  25. 25.
    Robak T (2004). Monoclonal antibodies in the treatment of autoimmune cytopenias. Eur J Haematol 72: 79–88 CrossRefPubMedGoogle Scholar
  26. 26.
    Giagounidis AA, Haase S and Germing U et al. (2005). Autoimmune disorders in two patients with myelodysplastic syndrome and 5q deletion. Acta Haematol 113: 146–149 CrossRefPubMedGoogle Scholar
  27. 27.
    Novaretti MC, Sopelete CR and Velloso ER et al. (2001). Immunohematological findings in myelodysplastic syndrome. Acta Haematol 105: 1–6 CrossRefPubMedGoogle Scholar
  28. 28.
    Wolf D. (2009). IMiDs induce pleiotropic anti-cancer effects.. memo Suppl 1: 10–12 CrossRefGoogle Scholar

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© Springer 2010

Authors and Affiliations

  1. 1.Department of Internal Medicine/OncologyAcademic Natters HospitalNattersAustria
  2. 2.Department of Hematology, Xuanwu HospitalCapital Medical UniversityBeijingChina
  3. 3.Department of Internal MedicineCounty Hospital of LienzLienzAustria
  4. 4.Department of Internal Medicine V, Division of Hematology and OncologyMedical University of InnsbruckInnsbruckAustria

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