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Chronic Lympthocytic Leukemia

Treatment of severe refractory autoimmune hemolytic anemia in B-cell chronic lymphocytic leukemia with alemtuzumab (humanized CD52 monoclonal antibody)

Abstract

Progressive B-cell chronic lymphocytic leukemia (B-CLL) is often complicated by autoimmune hemolytic anemia (AIHA), which in some cases may be refractory to conventional therapy such as corticosteroids, rituximab and splenectomy. We report here on 5 patients (median age 66 years, range 59–69) with advanced B-CLL, all of whom developed severe transfusion-dependent AIHA resistant to conventional therapy and received subcutaneous (SC) or intravenous (IV) alemtuzumab, a humanized monoclonal antibody that targets the CD52 antigen as salvage treatment for AIHA. Alemtuzumab was well tolerated with only minor ‘first dose’ reactions. All 5 patients responded with a 2.0 g/dl rise in hemoglobin (Hb) concentration, in the absence of further transfusions, after a median time of 5 weeks (range 4–7), and the mean Hb increased from 7.2 g/dl at baseline to 11.9 g/dl at end of treatment. All patients remained stable, without further AIHA episodes, after a median follow-up time of 12 months with a mean Hb of 12.5 g/dl (range 12.2–12.9). For patients with severe, refractory CLL-related AIHA, who have not previously responded to conventional therapy, alemtuzumab is an effective agent.

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References

  1. Diehl LF, Ketchum LH . Autoimmune disease and chronic lymphocytic leukemia: autoimmune hemolytic anemia, pure red cell aplasia, and autoimmune thrombocytopenia. Semin Oncol 1998; 25: 80–97.

    CAS  PubMed  Google Scholar 

  2. Mauro FR, Foa R, Cerretti R, Giannarelli D, Coluzzi S, Mandelli F et al. Autoimmune hemolytic anemia in chronic lymphocytic leukemia: clinical, therapeutic, and prognostic features. Blood 2000; 95: 2786–2792.

    CAS  PubMed  Google Scholar 

  3. Bastion Y, Coiffier B, Dumontet C, Espinouse D, Bryon PA . Severe autoimmune hemolytic anemia in two patients treated with fludarabine for chronic lymphocytic leukemia. Ann Oncol 1992; 3: 171–172.

    Article  CAS  PubMed  Google Scholar 

  4. Juliusson G . Complications in the treatment of CLL with purine analogues. Hematol Cell Ther 1997; 39 (Suppl 1): S41–S44.

    PubMed  Google Scholar 

  5. Weiss RB, Freiman J, Kweder SL, Diehl LF, Byrd JC . Hemolytic anemia after fludarabine therapy for chronic lymphocytic leukemia. J Clin Oncol 1998; 16: 1885–1889.

    Article  CAS  PubMed  Google Scholar 

  6. Efremov DG, Ivanovski M, Siljanovski N, Pozzato G, Cevreska L, Fais F et al. Restricted immunoglobulin VH region repertoire in chronic lymphocytic leukemia patients with autoimmune hemolytic anemia. Blood 1996; 87: 3869–3876.

    CAS  PubMed  Google Scholar 

  7. Kipps TJ, Carson DA . Autoantibodies in chronic lymphocytic leukemia and related systemic autoimmune diseases. Blood 1993; 81: 2475–2487.

    CAS  PubMed  Google Scholar 

  8. Robak T . Monoclonal antibodies in the treatment of autoimmune cytopenias. Eur J Haematol 2004; 72: 79–88.

    Article  CAS  PubMed  Google Scholar 

  9. Keating MJ, Flinn I, Jain V, Binet JL, Hillmen P, Byrd J et al. Therapeutic role of alemtuzumab (Campath-1H) in patients who have failed fludarabine: results of a large international study. Blood 2002; 99: 3554–3561.

    Article  CAS  PubMed  Google Scholar 

  10. Lundin J, Kimby E, Bjorkholm M, Broliden PA, Celsing F, Hjalmar V et al. Phase II trial of subcutaneous anti-CD52 monoclonal antibody alemtuzumab (Campath-1H) as first-line treatment for patients with B-cell chronic lymphocytic leukemia (B-CLL). Blood 2002; 100: 768–773.

    Article  CAS  PubMed  Google Scholar 

  11. Osterborg A, Fassas AS, Anagnostopoulos A, Dyer MJ, Catovsky D, Mellstedt H . Humanized CD52 monoclonal antibody Campath-1H as first-line treatment in chronic lymphocytic leukaemia. Br J Haematol 1996; 93: 151–153.

    Article  CAS  PubMed  Google Scholar 

  12. Osterborg A, Dyer MJ, Bunjes D, Pangalis GA, Bastion Y, Catovsky D et al. Phase II multicenter study of human CD52 antibody in previously treated chronic lymphocytic leukemia. European Study Group of CAMPATH-1H treatment in chronic lymphocytic leukemia. J Clin Oncol 1997; 15: 1567–1574.

    Article  CAS  PubMed  Google Scholar 

  13. Lundin J, Porwit-MacDonald A, Rossmann ED, Karlsson C, Edman P, Rezvany MR et al. Cellular immune reconstitution after subcutaneous alemtuzumab (anti-CD52 monoclonal antibody, CAMPATH-1H) treatment as first-line therapy for B-cell chronic lymphocytic leukaemia. Leukemia 2004; 18: 484–490.

    Article  CAS  PubMed  Google Scholar 

  14. Lundin J, Karlsson C, Celsing F . Alemtuzumab therapy for severe autoimmune hemolysis in a patient with B-cell chronic lymphocytic leukemia. Med Oncol 2006; 23: 137–139.

    Article  PubMed  Google Scholar 

  15. Cheson BD, Bennet JM, Grever M, Kay N, Keating MJ, O'Brien S et al. National Cancer Institute – sponsored Working Group guidelines for chronic lymphocytic leukemia: Revised guidelines for diagnosis and treatment. Blood 1996; 87: 4990–4997.

    CAS  PubMed  Google Scholar 

  16. Shanafelt TD, Madueme HL, Wolf RC, Tefferi A . Rituximab for immune cytopenia in adults: idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, and Evans syndrome. Mayo Clin Proc 2003; 78: 1340–1346.

    Article  CAS  PubMed  Google Scholar 

  17. Narat S, Gandla J, Hoffbrand AV, Hughes RG, Mehta AB . Rituximab in the treatment of refractory autoimmune cytopenias in adults. Haematologica 2005; 90: 1273–1274.

    CAS  PubMed  Google Scholar 

  18. Gupta N, Kavuru S, Patel D, Janson D, Driscoll N, Ahmed S et al. Rituximab-based chemotherapy for steroid-refractory autoimmune hemolytic anemia of chronic lymphocytic leukemia. Leukemia 2002; 16: 2092–2095.

    Article  CAS  PubMed  Google Scholar 

  19. Willis F, Marsh JC, Bevan DH, Killick SB, Lucas G, Griffiths R et al. The effect of treatment with Campath-1H in patients with autoimmune cytopenias. Br J Haematol 2001; 114: 891–898.

    Article  CAS  PubMed  Google Scholar 

  20. Cheung WW, Hwang GY, Tse E, Kwong YL . Alemtuzumab induced complete remission of autoimmune hemolytic anemia refractory to corticosteroids, splenectomy and rituximab. Haematologica 2006; 91: 21–22.

    Google Scholar 

  21. Marsh JC, Gordon-Smith EC . CAMPATH-1H in the treatment of autoimmune cytopenias. Cytotherapy 2001; 3: 189–195.

    Article  CAS  PubMed  Google Scholar 

  22. Schützinger C, Gaiger A, Thalhammer R, Vesely M, Fritsche-Polanz R, Schwarzinger I et al. Remission of pure red cell aplasia in T-cell receptor γδ-large granular lymphocyte leukemia after therapy with low-dose alemtuzumab. Leukemia 2005; 19: 2005–2008.

    Article  PubMed  Google Scholar 

  23. Rodon P, Breton P, Courouble G . Treatment of pure red cell aplasia and autoimmune haemolytic anaemia in chronic lymphocytic leukaemia with Campath-1H. Eur J Haematol 203; 70: 319–321.

    Article  Google Scholar 

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Acknowledgements

This study was supported by grants from the Swedish Cancer Society, The Cancer Society in Stockholm and The Karolinska Institutet Foundations.

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Correspondence to J Lundin.

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Karlsson, C., Hansson, L., Celsing, F. et al. Treatment of severe refractory autoimmune hemolytic anemia in B-cell chronic lymphocytic leukemia with alemtuzumab (humanized CD52 monoclonal antibody). Leukemia 21, 511–514 (2007). https://doi.org/10.1038/sj.leu.2404512

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