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Rituximab is an effective and safe therapeutic alternative in adults with refractory and severe autoimmune hemolytic anemia

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Abstract

Rituximab-induced B-cell depletion has been proven to be a useful therapy for autoimmune hemolytic anemia (AIHA). The aim of this retrospective study was to evaluate the effectiveness of rituximab in the treatment of 36 patients with AIHA refractory to several treatments. These patients had received a median of four (one to eight) previous treatments, and 13 patients had undergone splenectomy. Rituximab was administered by intravenous infusion at a dose of 375 mg/m2 once weekly for four doses in 29 patients, and 7 patients received one to six doses. Overall, 28 (77%) of 36 patients achieved response. Twenty-two patients (61%) reached a complete response (CR), and 6 patients (16%) obtained a partial response. All patients that reached CR (61%) were able to maintain the response during more than 6 months, with a median follow-up of 14 months (1–86 months). Sixteen patients maintained response for more than 1 year. The predictors of maintained response were achievement of CR and negative Coombs test result. Splenectomized patients showed a better response rate than those nonsplenectomized. Rituximab was well tolerated, and only one patient presented a transitory rash during infusion. Rituximab induced clinical responses in multitreated severe refractory both warm and cold AIHA patients with little toxicity, and consequently, this therapy should be considered as an early therapeutic option in this setting.

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References

  1. Gehrs BC, Friedberg RC (2002) Autoimmune hemolytic anemia. Am J Hematol 69:258–271

    Article  PubMed  Google Scholar 

  2. King KE, Ness PM (2005) Treatment of autoimmune haemolytic anemia. Semin Hematol 42:131–136

    Article  CAS  PubMed  Google Scholar 

  3. Petz LD (2001) Treatment of autoimmune hemolytic anemias. Curr Opin Hematol 8:411–416

    Article  CAS  PubMed  Google Scholar 

  4. Garvey B (2008) Rituximab in the treatment of autoimmune haematological disorders. Br J Haematol 141(2):149–169

    Article  CAS  PubMed  Google Scholar 

  5. Semple JW, Freedman J (2005) Autoimmune pathogenesis and autoimmune hemolytic anemia. Semin Hematol 42:122–130

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  7. Berentsen S, Ulvestad E, Gjertsen BT, Hjorth-Hansen H, Langholm R, Knutsen H et al (2004) Rituximab for primary chronic cold agglutinin disease: a prospective study of 37 courses of therapy in 27 patients. Blood 103:2925–2928

    Article  CAS  PubMed  Google Scholar 

  8. Peñalver FJ, Jiménez-Yuste V, Almagro M, Alvarez-Larrán A, Rodríguez L et al (2006) Multi-institutional Retrospective Spanish Study Group on the Use of Rituximab in Refractory ITP. Rituximab in the management of chronic immune thrombocytopenic purpura: an effective and safe therapeutic alternative in refractory patients. Ann Hematol 85(6):400–406

    Article  PubMed  Google Scholar 

  9. Berentsen S (2007) Rituximab for the treatment of autoimmune cytopenias. Haematologica 92:1589–1596

    Article  CAS  PubMed  Google Scholar 

  10. Ramanathan S, Koutts J, Hertzberg MS (2005) Two cases of refractory warm autoimmune hemolytic anemia treated with rituximab. Am J Hematol 78:123–126

    Article  CAS  PubMed  Google Scholar 

  11. Zecca M, Nobili B, Ramenghi U, Perotta S, Amendola G, Rosito P et al (2003) Rituximab for the treatment of refractory autoimmune hemolytic anemia in children. Blood 101:3857–3861

    Article  CAS  PubMed  Google Scholar 

  12. Stasi R, Pagano A, Stipa E, Amadori S (2001) Rituximab chimeric anti-CD20 monoclonal antibody treatment for adults with chronic idiopathic thrombocytopenic purpura. Blood 98:952–957

    Article  CAS  PubMed  Google Scholar 

  13. Zaja F, Iacona I, Masolini P, Russo D, Sperotto A, Prosdocimo S et al (2002) B-cell depletion with rituximab as treatment for immune hemolytic anemia and thrombocytopenia. Haematologica 87:189–195

    CAS  PubMed  Google Scholar 

  14. Bussone G, Ribeiro E, Dechartres A, Viallard JF, Bonnotte B et al (2009) Efficacy and safety of rituximab in adults' warm antibody autoimmune haemolytic anemia: retrospective analysis of 27 cases. Am J Hematol 84(3):153–157

    Article  CAS  PubMed  Google Scholar 

  15. Cooper N, Stasi R, Cunningham-Rundles S, Feuerstein MA, Leonard JP, Amadori S, Bussel JB (2004) The efficacy and safety of B-cell depletion with anti-CD20 monoclonal antibody in adults with chronic immune thrombocytopenic purpura. Br J Haematol 125:232–239

    Article  CAS  PubMed  Google Scholar 

  16. Zaja F, Vianelli N, Sperotto A, Patriarca F, Tani M, Marin L et al (2003) Anti- CD20 therapy for chronic lymphocytic leukemia-associated autoimmune diseases. Leuk Lymphoma 44:1951–1955

    Article  CAS  PubMed  Google Scholar 

  17. Kajouri K, Vesely SK, Terrell DR, George JN (2004) Splenectomy for adults patients with idiopathic thrombocytopenic purpura: a systematic review to assess long-term platelet count response, prediction of response, and surgical complications. Blood 104:2623–2634

    Article  Google Scholar 

  18. Kakaiya R (2003) New therapy with anti-CD20 antibody (rituximab) for autoimmune hemolytic anemia. Blood Therapies in Medicine 3:91–96

    Google Scholar 

  19. Gupta V, Tilak A, Bhatia BD (2008) Immune thrombocytopenic purpura. Indian J Pediatr 75:723–728

    Article  CAS  PubMed  Google Scholar 

  20. Gertz MA (2007) Management of cold haemolytic syndrome. Br J Haematol 138:422–429

    Article  PubMed  Google Scholar 

  21. Shanafelt TD, Madume HL, Wolf RC, Tefferi A (2003) Rituximab for immune cytopenia in adults: idiopathic thrombocytopenic purpura, autoimmune haemolytic anemia, and Evans syndrome. Mayo Clin Proc 78:1340–1346

    Article  CAS  PubMed  Google Scholar 

  22. Berentsen S, Ulvestad E, Gjertsen BT, Hjorth-Hansen H, Langholm R, Knutsen H et al (2004) Rituximab for primary chronic cold agglutinin disease: a prospective study of 37 courses of therapy in 27 patients. Blood 103:2925–2928

    Article  CAS  PubMed  Google Scholar 

  23. Schöllkopf C, Kjeldsen L, Bjerrum OW, Mourits-Andersen HT, Nielsen JL, Christensen BE et al (2006) Rituximab in chronic cold agglutinin disease: a prospective study of 20 patients. Leuk Lymphoma 47:253–260

    Article  PubMed  Google Scholar 

  24. Shan D, Ledbetter JA, Press OW (2000) Signaling events involved in anti-CD20- induced apoptosis of malignant human B cells. Cancer Immunol Immunother 48:673–683

    Article  CAS  PubMed  Google Scholar 

  25. Alas S, Emmanouilides C, Bonavida B (2001) Inhibition of interleukin 10 by rituximab results in down-regulation of bcl-2 and sensitization of B-cell non-Hodgkin’s lymphoma to apoptosis. Clin Cancer Res 7:709–723

    CAS  PubMed  Google Scholar 

  26. Virgolini L, Marzocchi V (2004) Rituximab in autoimmune diseases. Biomed Pharmacother 58:299–309

    Article  CAS  PubMed  Google Scholar 

  27. Schwartz J, Leber MD, Gillis S, Giunta A, Eldor A, Bussel JB (2003) Long-term follow-up after splenectomy performed for immune thrombocytopenic purpura (ITP). Am J Hematol 72:94–98

    Article  PubMed  Google Scholar 

  28. Rao A, Kelly M, Musselman M, Ramadas J, Wilson D, Grossman W, Shenoy S (2008) Safety, efficacy, and immune reconstitution after rituximab therapy in pediatric patients with chronic or refractory hematologic autoimmune cytopenias. Pediatr Blood Cancer 50:822–825

    Article  PubMed  Google Scholar 

  29. Kimby E (2005) Tolerability and safety of rituximab (MabThera). Cancer Treat Rev 31:456–473

    Article  CAS  PubMed  Google Scholar 

  30. Bengston KL, Skinner MA, Ware RE (2003) Successful use of anti-CD20 (Rituximab) in severe, life-threatening childhood immune thrombocytopenic purpura. J Pediatr 143:670–673

    Article  Google Scholar 

  31. Gürcan HM, Keskin DB, Stern JN, Nitzberg MA, Shekhani H, Ahmed AR (2009) A review of the current use of rituximab in autoimmune diseases. Int Immunopharmacol 9(1):10–25

    Article  PubMed  Google Scholar 

  32. Aksoy S, Harputluoglu H, Kilickap S, Dede DS, Dizdar O, Altundag K, Barista I (2007) Rituximab-related viral infections in lymphoma patients. Leuk Lymphoma 48(7):1307–1312

    Article  CAS  PubMed  Google Scholar 

  33. Carson KR, Evens AM, Richey EA et al (2009) Progressive multifocal leukoencephalopathy following rituximab therapy in HIV negative patients: a report of 57 cases from the Research on Adverse Drug Event and Reports (RADAR) project. Blood 113:4834–4840

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

Other members of the Spanish Study Group on the use of rituximab in refractory AIHA: M. Subirá, Hospital Sant Joan de Deu, Barcelona; M. Canales; Hospital Universitario La Paz; Madrid; E. González, Institut Catalá d´Oncologia, Barcelona; J. Nieto, Hospital Morales Meseguer, Murcia; M. Herrera, Hospital Nuestra Señora de la Candelaria, Tenerife; M. A. García, Hospital Perpetuo Socorro, Badajoz; M. J. Rodríguez, Hospital Universitario de Canarias, Tenerife; R. Hernández (C. Menchaca), Hospital Txagorritxu, Vitoria; J. I. Olalla, Hospital Sierrallana, Cantabria; Luis Palomera; Hospital Clínico Lozano Blesa, Zaragoza; who should also be considered as authors of this study.

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Authors and Affiliations

  1. Hospital Universitario Fundación Alcorcón, C/Budapest, 1, 8922, Alcorcón, Madrid, Spain

    Francisco Javier Peñalver

  2. Hospital Clinic, Barcelona, Spain

    Alberto Alvarez-Larrán

  3. Hospital Gregorio Marañon, Madrid, Spain

    Jose Luis Díez-Martin

  4. Hospital Vall D´Hebron, Barcelona, Spain

    Laura Gallur

  5. Hospital La Fe, Valencia, Spain

    Isidro Jarque

  6. Hospital Clínico de Salamanca, Salamanca, Spain

    Dolores Caballero

  7. Hospital Clínico de Madrid, Madrid, Spain

    Joaquín Díaz-Mediavilla

  8. Hospital Universitario 12 de Octubre, Madrid, Spain

    Rosalía Bustelos

  9. Fundación Jiménez Díaz, Biostatistics, Madrid, Spain

    María Jesús Fernández-Aceñero

  10. Hospital Universitario Puerta de Hierro, Madrid, Spain

    José Rafael Cabrera

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  1. Francisco Javier Peñalver
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  2. Alberto Alvarez-Larrán
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  3. Jose Luis Díez-Martin
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  4. Laura Gallur
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  5. Isidro Jarque
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  6. Dolores Caballero
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  7. Joaquín Díaz-Mediavilla
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  8. Rosalía Bustelos
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  9. María Jesús Fernández-Aceñero
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  10. José Rafael Cabrera
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on behalf of the Multi-institutional Retrospective Study on the use of rituximab in refractory AIHA

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Correspondence to Francisco Javier Peñalver.

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Peñalver, F.J., Alvarez-Larrán, A., Díez-Martin, J.L. et al. Rituximab is an effective and safe therapeutic alternative in adults with refractory and severe autoimmune hemolytic anemia. Ann Hematol 89, 1073–1080 (2010). https://doi.org/10.1007/s00277-010-0997-y

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  • DOI: https://doi.org/10.1007/s00277-010-0997-y

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