Skip to main content
SpringerLink
Log in

Antibodies in the Treatment of Aplastic Anemia

  • Review
  • Published:
Archivum Immunologiae et Therapiae Experimentalis Aims and scope

Abstract

Antibodies have been the cornerstone of treatment of acquired aplastic anemia for more than 25 years. Treatment with antithymocyte globulin (ATG) is considered pivotal and the addition of cyclosporine improves the overall response rate. This antibody is heterogeneous and horse ATG is apparently more effective than rabbit ATG. Several issues remain unsolved in relation to the combination of ATG and cyclosporine: cost, toxicity and late clonal disorders. In recent years, alternative immunosuppressive therapy has been proposed and new antibodies have emerged: porcine ATG, alemtuzumab, daclizumab, and rituximab. Experience with these antibodies is limited to a few studies with alemtuzumab being the most promising, but the results are interesting and provocative. More studies are needed to find the perfect antibody.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Atta EH, Dias DS, Marra VL et al (2010) Comparison between horse and rabbit antithymocyte globulin as first-line treatment for patients with severe aplastic anemia: a single center retrospective study. Ann Hematol 89:851–859

    Article  PubMed  CAS  Google Scholar 

  • Bacigalupo A, Broccia G, Corda G et al (1995) Antilymphocyte globulin, cyclosporin and granulocyte colony-stimulating factor in patients with acquired severe aplastic anemia (SAA): a pilot study of the EBMT SAA Working Party. Blood 85:1348–1353

    PubMed  CAS  Google Scholar 

  • Bing H, Siyi Y, Weg Z et al (2010) The use of anti-human T lymphocyte porcine immunoglobulin and cyclosporine A to treat patients with acquired severe aplastic anemia. Acta Haematol 124:245–250

    Article  PubMed  Google Scholar 

  • Castiglione MG, Scatena P, Pandolfo C et al (2006) Rituximab therapy of severe aplastic anemia induced by fludarabine and cyclophosphamide in a patient affected by B-cell chronic lymphocytic leukemia. Leuk Lymphoma 47:1985–1986

    Article  Google Scholar 

  • Champlin R, Ho W, Gale RP (1983) Antithymocyte globulin treatment in patients with aplastic anemia: a prospective randomized trial. N Engl J Med 308:113–118

    Article  PubMed  CAS  Google Scholar 

  • Delgado-Lamas JL, López-Karpovitch X, Marín-López A et al (1989) Low-doses of high-potency antithymocyte globulin (ATG) in severe aplastic anemia: experience with the Mexican ATG. Acta Haematol 81:70–74

    Article  PubMed  CAS  Google Scholar 

  • Di Bona E, Rodeghiero F, Bruno B et al (1999) Rabbit antithymocyte globulin (r-ATG) plus cyclosporine and granulocyte colony stimulating factor is an effective treatment for aplastic anaemia patients unresponsive to a first course of intensive immunosuppressive therapy. Gruppo Italiano Trapianto di Midollo Osseo (GITMO). Br J Haematol 107:330–334

    Article  PubMed  Google Scholar 

  • Dufour C, Ferretti E, Bagnasco F et al (2009) Changes in cytokine profile pre and post immunosuppression in acquired aplastic anemia. Haematologica 94:1743–1747

    Article  PubMed  CAS  Google Scholar 

  • Frickhofen N, Kaltwasser JP, Schrezenmeier H et al (1991) Treatment of aplastic anemia with antilymphocyte globulin and methylprednisolone with or without cyclosporine. The German Aplastic Anemia Study Group. N Engl J Med 324:1297–1304

    Article  PubMed  CAS  Google Scholar 

  • Frickhofen N, Heimpel H, Kaltwasser JP et al (2003) Antithymocyte globulin with or without cyclosporine A: 11-year follow-up of a randomised trial comparing treatments of aplastic anemia. Blood 101:1236–1242

    Article  PubMed  CAS  Google Scholar 

  • Fuijiwara S, Miyake H, Nosaka K (2009) Hairy cell leukemia responsive to anti-thymocyte globulin used as immunosuppressive therapy for aplastic anemia. Int J Hematol 90:471–475

    Article  Google Scholar 

  • Gómez-Almaguer D, Vela-Ojeda J, Jaime-Pérez JC et al (2006) Allografting in patients with severe aplastic anemia using peripheral blood stem cells and a fludarabine-based conditoning regimen: the Mexican Experience. Am J Hematol 81:157–161

    Article  PubMed  Google Scholar 

  • Gómez-Almaguer D, Ruiz-Argüelles GJ, Tarín-Arzaga LC et al (2008) Alemtuzumab for the treatment of steroid-refractory acute graft-versus-host disease. Biol Blood Marrow Transplant 14:10–15

    Article  PubMed  Google Scholar 

  • Gómez-Almaguer D, Jaime-Perez JC, Garza-Rodriguez V et al (2010a) Subcutaneous alemtuzumab plus cyclosporine for the treatment of aplastic anemia. Ann Hematol 89:299–303

    Article  PubMed  Google Scholar 

  • Gómez-Almaguer D, Solano-Genesta M, Tarín-Arzaga L et al (2010b) Low dose rituximab and alemtuzumab combination therapy for patients with steroid-refractory autoinmune cytopenias. Blood 116:4783–4785

    Article  PubMed  Google Scholar 

  • Grupta V, Ball SE, Sage D et al (2005) Marrow transplants from matched unrelated donors for aplastic anemia using alemtuzumab, fludarabine and cyclophosphamide based conditioning. Bone Marrow Transplant 35:467–471

    Article  Google Scholar 

  • Hansen PB, Lauritzen AM (2005) Aplastic anemia successfully treated with rituximab. Am J Hematol 80:292–294

    Article  PubMed  Google Scholar 

  • Jaime-Perez JC, Colunga-Pedraza PR, Gomez-Ramirez CD et al (2011) Danazol as first-line therapy for aplastic anemia. Ann Hematol 90:523–527

    Article  PubMed  CAS  Google Scholar 

  • Jaime-Pérez JC, Ruiz-Argüelles GJ, Gómez-Almaguer D (2005) Haematopoietic stem cell transplantation to treat aplastic anemia. Expert Opin Biol Ther 5:617–626

    Article  PubMed  Google Scholar 

  • Kamio T, Ito E, Ohara A et al (2011) Relapse of aplastic anemia in children after immunossuppresive therapy: a report from the Japan Childhood Aplastic Anemia Study Group. Haematologica 96:814–819

    Article  PubMed  Google Scholar 

  • Kim H, Min YJ, Baeck JH et al (2009) A pilot dose-escalating study of alemtuzumab plus cyclosporine for patients with bone marrow failure syndrome. Leuk Res 33:222–231

    Article  PubMed  CAS  Google Scholar 

  • Kojima S, Nakao S, Young N et al (2011) The Third Consensus Conference on the treatment of aplastic anemia. Int J Hematol 93:832–837

    Article  PubMed  Google Scholar 

  • Linton PJ, Harbertson J, Bradley LM (2000) A critical role for B cells in the development of memory CD4 cells. J Immunol 165:5558–5565

    PubMed  CAS  Google Scholar 

  • Maciejewski JP, Risitano AM (2005) Aplastic anemia: management of adult patients. Hematology Am Soc Hematol Educ Program 2005:110–117

    Article  Google Scholar 

  • Maciejewski JP, Selleri C, Sato T et al (1995) Increased expression of Fas antigen on bone marrow CD34+ cells of patients with aplastic anaemia. Br J Haematol 91:245–252

    Article  PubMed  CAS  Google Scholar 

  • Maciejewski JP, Sloand EM, Nuñez O et al (2003) Recombinant humanized anti-IL-2 receptor antibody (daclizumab) produces responses in patients with moderate aplastic anemia. Blood 102:3584–3586

    Article  PubMed  CAS  Google Scholar 

  • Marsh JC, Ball SE, Darbyshire P et al (2003) Guidelines for the diagnosis and management of acquired aplastic anaemia. Br J Haematol 123:782–801

    Article  PubMed  CAS  Google Scholar 

  • Nissen C, Schubert J (2002) Seeing the good and bad in aplastic anemia: is autoimmunity in AA dysregulated or antineoplastic? Hematol J 3:169–175

    Article  PubMed  Google Scholar 

  • Passweg J, Tichelli A (2009) Immunosuppressive treatment for aplastic anemia: are we hitting the ceiling? Haematologica 94:310–312

    Article  PubMed  Google Scholar 

  • Qi Z, Takamatsu H, Espinoza JL et al (2010) Autoantibodies specific to hnRNP K: a new diagnostic marker for immune pathophysiology in aplastic anemia. Ann Hematol 89:1255–1263

    Article  PubMed  CAS  Google Scholar 

  • Risitano AM (2011) Immunosuppresive therapies in the management of immune-mediated marrow failures in adults: where we stand and where we are going. Br J Haematol 152:127–140

    Article  PubMed  CAS  Google Scholar 

  • Risitano AM, Maciejewski J, Green S et al (2004) In-vivo dominant immune responses in aplastic anaemia: molecular tracking of putatively pathogenetic T-cell clones by TCR beta-CDR3 sequencing. Lancet 364:355–364

    Article  PubMed  CAS  Google Scholar 

  • Risitano AM, Selleri C, Serio B et al (2010) Alemtuzumab is safe and effective as immunosuppressive treatment for aplastic anemia and single-lineage bone marrow failure: a pilot study and a survey from the EBMT WPSSAA. Br J Haematol 148:791–796

    Article  PubMed  CAS  Google Scholar 

  • Rosenfeld S, Follmann D, Nunez O et al (2003) Antithymocyte globulin and cyclosporine for severe aplastic anemia: association between hematopoietic response and long term outcome. JAMA 289:1130–1135

    Article  PubMed  CAS  Google Scholar 

  • Ruiz-Argüelles GJ (2009) Hipoplasias y displasias medulares. In: Ruiz-Argüelles GJ (ed) Fundamentos de Hematología, 4th edn. Editorial Médica Panamericana, México, pp 117–127

    Google Scholar 

  • Ruiz-Argüelles GJ, Díaz-Jouanen E (1979) Existen formas autoinmunes de aplasia medular? Rev Invest Clin Méx 32:195–196

    Google Scholar 

  • Ruiz-Argüelles GJ, Gómez-Almaguer D (2008) Making allogeneic bone marrow transplantation available to patients in developing countries: the Mexican Experience. Open Hematol J 2:30–36

    Article  Google Scholar 

  • Ruiz-Argüelles GJ, Gómez-Rangel D (2003) Long term results of the immunosuppressive treatment of patients with severe, acquired aplastic anemia: a single institution study. Acta Haematol 110:184–187

    Article  PubMed  Google Scholar 

  • Ruiz-Argüelles GJ, Katzmann JA, Greipp PR et al (1984) Lymphocyte subsets in patients with aplastic anemia. Am J Hematol 16:267–275

    Article  PubMed  Google Scholar 

  • Ruiz-Argüelles A, Salvador Ruiz-González JD, Miguel Presno-Bernal J (1986) Preparation and characteristics of an equine anti-human thymocyte gamma globulin produced in Mexico (in Spanish). Rev Invest Clin 38:273–278

    PubMed  Google Scholar 

  • Saracco P, Quarelli P, Iori AP et al (2008) Cyclosporin A response and dependence in children with acquired aplastic anemia: a multicentre retrospective study with long-term observation follow-up. Br J Haematol 140:197–205

    Article  PubMed  CAS  Google Scholar 

  • Scheinberg P, Nuñez O, Wu C et al (2006) Treatment of severe aplastic anaemia with combined immunosuppression: anthytimocyte globulin, cyclosporine and mycophenolate mofetil. Br J Haematol 133:606–611

    Article  PubMed  CAS  Google Scholar 

  • Scheinberg P, Wu CO, Nuñez O et al (2009a) Treatment of severe aplastic anemia with a combination of horse antithymocyte globulin and cyclosporine, with and without sirolimus, a prospective randomized study. Haematologica 94:348–354

    Article  PubMed  CAS  Google Scholar 

  • Scheinberg P, Wu CO, Nuñez O et al (2009b) Predicting response to immunosuppressive therapy and survival in severe aplastic anaemia. Br J Haematol 144:206–216

    Article  PubMed  CAS  Google Scholar 

  • Scheinberg P, Wu CO, Scheinberg P et al (2010a) A randomized trial of horse versus rabbit antithymocyte globulin in severe acquired aplastic anemia. Blood 116:a4

    Article  Google Scholar 

  • Scheinberg P, Wu CO, Scheinberg P et al (2010b) Alemtuzumab (Campath) monotherapy for severe aplastic anemia. Blood 116:a1167

    Google Scholar 

  • Selleri C, Serio B, Risitano AM (2011) Novel immunosuppressive strategies for bone marrow failure syndromes: a focus on Alemtuzumab. Mini Rev Med Chem 11:536–543

    Article  PubMed  CAS  Google Scholar 

  • Shereck EB, Deyell RJ, Kurre P (2011) Costs and consequences of immunosuppressive therapy in children with aplastic anemia. Haematologica 96:793–795

    Article  PubMed  Google Scholar 

  • Shlomchik MJ, Craft JE, Mamula MJ (2001) From T to B and back again: positive feedback in systemic autoimmune disease. Nat Rev Immunol 1:147–153

    Article  PubMed  CAS  Google Scholar 

  • Sloand EM, Olnes MJ, Shenoy A et al (2010a) Alemtuzumab treatment of intermediate-1 myelodysplasia patients is associated with sustained improvement in blood counts and cytogenetic remission. J Clin Oncol 28:5166–5173

    Article  PubMed  CAS  Google Scholar 

  • Sloand EM, Olnes MJ, Weinstein B et al (2010b) Long-term follow-up of patients with moderate aplastic anemia and pure red cell aplasia treated with daclizumab. Haematologica 95:382–387

    Article  PubMed  CAS  Google Scholar 

  • Speck B, Gluckman E, Haak HL et al (1977) Treatment of aplastic anaemia by antilymphocyte globulin with and without allogeneic bone-marrow infusions. Lancet 2:1145–1148

    Article  PubMed  CAS  Google Scholar 

  • Stasi R (2010) Rituximab in autoimmune hematologic diseases: not just a matter of B cells. Semin Hematol 47:170–179

    Article  PubMed  CAS  Google Scholar 

  • Sugimori C, Kaito K, Nakao S (2003) Persistent remission after immunosuppressive therapy of hairy cell leukemia mimicking aplastic anemia: two case reports. Int J Hematol 77:391–394

    Article  PubMed  Google Scholar 

  • Takamatsu H, Yagasaki H, Takahashi Y et al (2011) Aplastic anemia successfully treated with rituximab: the possible role of aplastic anemia-associated autoantibodies as a marker for response. Eur J Haematol 86:541–545

    Article  PubMed  CAS  Google Scholar 

  • Thomas ED, Storb R, Fefer A et al (1972) Aplastic anemia treated by marrow transplantation. Lancet 1:284–289

    Article  PubMed  CAS  Google Scholar 

  • Vallejo C, Montesinos P, Rosell A et al (2009) Comparison between lymphoglobulin- and thymoglobulin-based immunosuppressive therapy as first-line treatment for patients with aplastic anemia. Blood 114:a3194

    Google Scholar 

  • Willis F, Marsh JC, Bevan DH et al (2001) The effect of treatment with Campath-1H in patients with autoimmune cytopenias. Br J Haematol 114:891–898

    Article  PubMed  CAS  Google Scholar 

  • Young NS (2000) Acquired aplastic anemia. In: Schechter GP, Berliner N, Telen MJ (eds) Hematology 2000. The American Society of Hematology Education Program Book, Washington, pp 18–38

    Google Scholar 

  • Young NS, Maciejewski JP (1997) The pathophysiology of acquired aplastic anemia. N Engl J Med 336:1365–1372

    Article  PubMed  CAS  Google Scholar 

  • Zheng Y, Liu Y, Chu Y et al (2006) Immunosuppressive therapy for acquired severe aplastic anemia (SAA): a prospective comparison of four different regimens. Exp Hematol 34:826–831

    Article  PubMed  CAS  Google Scholar 

  • Zoumbos NC, Gascón P, Djeu JY et al (1985) Circulating activated suppressor T lymphocytes in Aplastic anemia. N Engl J Med 312:257–265

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Hematology Service, Hospital Universitario, UANL, Paris 3029 Col. Cumbres, 64610, Monterrey, N.L., Mexico

    David Gómez-Almaguer & Jose Carlos Jaime-Pérez

  2. Centro de Hematología y Medicina Interna de Puebla, Puebla, Mexico

    Guillermo J. Ruiz-Arguelles

Authors
  1. David Gómez-Almaguer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jose Carlos Jaime-Pérez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Guillermo J. Ruiz-Arguelles
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David Gómez-Almaguer.

About this article

Cite this article

Gómez-Almaguer, D., Jaime-Pérez, J.C. & Ruiz-Arguelles, G.J. Antibodies in the Treatment of Aplastic Anemia. Arch. Immunol. Ther. Exp. 60, 99–106 (2012). https://doi.org/10.1007/s00005-012-0164-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00005-012-0164-3

Keywords

Search

Navigation