Abstract
Numerous laboratory and clinical investigations have suggested that immunological mechanisms may be responsible for the hemopoietic suppression in a large number of patients with aplastic anemia. Bone marrow culture studies incubating T-lymphocytes from these patients with normal allogeneic bone marrow have resulted in a decrease in the number of erythroids and myeloid colony formation in cultures.1–3 Conversely, bone marrow T cell depletion has resulted in an increase in the number of colonies.4 More recently, it has been demonstrated that the majority of patients with aplastic anemia exhibit a large number of circulating activated T-lymphocytes, producing γ interferon.5–7 Since various studies have shown an inhibitory effect of this lymphokine on hematopoiesis in vitro 8–10 and in vivo,11 it has been postulated that γ interferon may play an important role in the pathogenesis of acquired aplastic anemia.12 On clinical grounds, it has been found that prior immunosuppressive conditioning is necessary for successful bone marrow transplantation in identical twins in approximately half of the cases.13,14 In addition, some patients conditioned by immunosuppressive agents including antilymphocyte globulin (ALG) for bone marrow transplantation have achieved autologous bone marrow regeneration.15–18 The above observations have led to several therapeutic trials with antilymphocyte globulin (ALG) and antithymocyte globulin (ATG) in patients with acquired aplastic anemia with variable rates of response ranging from 17 to 85%.19,20 Most studies, including a recent multicenter trial, however, have reported a hematologic response in 40–60% of the patients.21
Keywords
- Aplastic Anemia
- Antithymocyte Globulin
- Hematologic Response
- Severe Aplastic Anemia
- Antilymphocyte Globulin
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Ascensao J, Kagan W, Moore MAS, et al. Aplastic anaemia: Evidence for an immunological mechanism. Lancet 1976; 1:669–671.
Kagan W, Ascensao J, Pahwa R, et al. Aplastic anemia: Presence in human bone marrow of cells that suppress myelopoiesis. Proc Natl Acad Sei USA 1976; 73:2890–2894.
Hoffman R, Zanjani ED, Lutton J, et al. Suppression of erythroid-colony formation by lymphocytes from patients with aplastic anemia. N Engl J Med 1977; 296:10–13.
Haak HL, Goselink HM. Evidence that certain human aplastic anemia may be caused by cell-mediated immune mechanism. Lancet 1977; 1:194.
Zoumbos NC, Gascon P, Djeu JY, et al. Circulating activated suppressor T lymphocytes in aplastic anemia. N Engl J Med 1985; 312:257–265.
Hinterberger W, Adolf G, Aichinger G, et al. Further evidence for lymphokine overproduction in severe aplastic anemia. Blood 1988; 72:266–272.
Laver J, Castro-Malaspina, Kernan NA, et al. In vitro interferon-gamma production by cultured T-cells in severe aplastic anaemia: Correlation with granulomonopoietic inhibition in patients who respond to anti-thymocyte globulin. Br J Haematol 1988; 69:545–550.
Verma DS, Spitzer G, Gutterman JU. Human leukocyte interferon preparation blocks granulopoietic differential. Blood 1979; 54:1423.
Kumpel GR, Fleischmann WR, Kumpel KD. Gamma interferon (IFN) and IFN a/ß suppress murine myeloid colony formation (CFU-C): Magnitude of suppression is dependent upon level of colony-stimulating factor (CSF). J Immunol 1982; 129:76–80.
Toretsky JA, Shahidi NT, Finlay JL. Effects of recombinant human interferon gamma on hematopoietic progenitor cell growth. Exp Hematol 1986; 14:182–186.
Mangan KF, Zidar B, Shadduck RK, et al. Interferon-induced aplasia: Evidence for T-cell mediated suppression of hematopoiesis and recovery after treatment with horse antihuman thymocyte globulin. Am J Hematol 1985; 19:401–413.
Zoumbos NC, Gascon P, Djeu JY, et al. Interferon is a mediator of hematopoietic suppression in aplastic anemia in vitro and possibly in vivo. Proc Natl Acad Sei USA, 1985; 82:188–192.
Appelbaum FR, Fefer A, Cheever MA, et al. Treatment of aplastic anemia by bone marrow transplantation in identical twins. Blood 1980; 55:1033–1039.
Lu D-P. Syngeneic bone marrow transplantation for treatment of aplastic anaemia: Report of a case and review of the literature. Exp Hematol 1981; 9:257–263.
Speck B, Cornu P, Jeannet M, et al. Autologous marrow recovery following allogeneic marrow transplantation in a patient with severe aplastic anemia. Exp Hematol 1976; 4:131–137.
Jeannet M, Speck B, Rubinstein A, et al. Autologous marrow reconstitution in severe aplastic anemia after ALG pretreatment and HLA semi compatible bone marrow cell transfusion. Acta Hematol 1976; 55:129–139.
Sensenbrenner LL, Steele AA, Santos GW. Recovery of hematologic competence without engraftment following attempted bone marrow transplantation for aplastic anemia: A report of a case with diffusion chamber studies. Exp Hematol 1977; 5:51–58.
Territo MC, et al. Autologous bone marrow repopulation following high dose cyclophosphamide and allogeneic marrow transplantation in aplastic anaemia. Br J Haematol 1977; 36:305–312.
Hunter RF, Huang AT. Antithymocyte globulin: A realistic approach to therapy for severe aplastic anemia. South Med J 1986; 79:1121–1125.
Marsh JWC, Hows JM, Bryett KA, et al. Survival after antilymphocyte globulin therapy for aplastic anemia depends on disease severity. Blood 1987; 70:1046–1052.
Young N, Griffith P, Brittain E, et al. A multicenter trial of antithymocyte globulin in aplastic anemia and related diseases. Blood 1988; 72:1861–1869.
Finlay JL, Toretsky J, Hoffman R, et al. Cyclosporine A (CyA) in refractory aplastic anemia (AA). Presented at the Twenty-Sixth Annual Meeting of the American Society of Hematology, Miami Beach, December 1–4, 1984. Blood 1984; 64: abstract #326.
Stryckmans P, Debusscher L, Paridaens R, et al. Cyclosporin (Cs) for therapy of severe aplastic anemia (SAA) and pure red cell anemia (PRCA). Presented at the Twenty-Sixth Annual Meeting of the American Society of Hematology, Miami Beach, December 1–4, 1984, Blood 1984; 64: abstract #344.
Holt DW, White DIG. How to measure cyclosporin, letter. Lancet 1984; 2:228.
Frickhofen N, Kaltwasser JP. Immunosuppressive treatment of aplastic anemia: A prospective, randomized multicenter trial evaluating antilymphocyte globulin (ALG) versus ALG and cyclosporin A. Blut 1988; 56:191–192.
Gluckman E, Esperou H, Devergie A. Comparison of cyclosporine A (CyA) and horse antithymocyte globulin (H.ATG) for treatment of severe aplastic anemia (SAA): A multicenter prospective randomized study. Presented at the Thirtieth Annual Meeting of the American Society of Hematology, San Antonio, December 3–6, 1988, Blood 1988; 72: abstract #78.
Cohen DJ, Loertscher R, Rubin MF, et al. Cyclosporine: A new immunosuppressive agent for organ transplantation. Ann Intern Med 1984; 101:667–682.
Wish JB. Immunologic effects of cyclosporine. Transplant Proc 1986; 18:(3, suppl 2): 15–18.
In: Schindler R ed. Ciclosporin in Autoimmune Diseases. Berlin, Heidelberg, New York, Tokyo, Springer-Verlag, 1985.
Muller W, Hermann B. Die therapie der chronischen polyarthritis mit cyclosporin A, einem neuen immunsuppressivum. Acta Rheumatol 1979; 4:173–186.
Bougneres PF, Carel JC, Castano L, et al. Factors associated with early remission of Type I diabetes in children treated with cyclosporine. N Engl J Med 1988; 318:663–670.
Totterman TH, Nissell J, Killander A, et al. Successful treatment of pure red cell aplasia with cyclosporin. Lancet 1984; 2:693.
Baker BL, Hendricks SA, Shahidi NT, et al. Hormonal and cellular immunosuppression of granulopoiesis in a patient with neutropenia. Am J Med 1988; 85:264–267.
Hendricks JB, Schultz JC, Norback DH, Shahidi NT. The effect of cyclosporine in T-cell proliferation and erythropoiesis in vitro. In: Zanjani ED, Tavassoli M, Ascensao JL, eds. Regulation of Erythropoesis. New York, PMA Publishing Group, 1988: pp. 537–543.
Jacobs P, Wood L, Martell RW. Cyclosporin A in the treatment of severe aplastic anaemia. Br J Haematol 1985; 61:267–272.
Speck B, Gluckman E, Haak HL, et al. Treatment of aplastic anemia by anti-lymphocyte globulin with and without allogeneic bone marrow infusion. Lancet 1977; 2:1145–1148.
Speck B, Gratwohl A, Nissen C, et al. Treatment of severe aplastic anemia with antilymphocyte globulin in bone-marrow transplantation. Br Med J 1981; 282:860–863.
Gluckman E, Devergie A, Faille A, et al. Treatment of severe aplastic anemia with antilymphocyte globulin and androgens. Exp Hematol 1978; 6:679–687.
Champlin RE, Ho WG, Feig SA, et al. Do androgens enhance the response to antithymocyte globulin in patients with aplastic anemia? A prospective randomized trial. Blood 1985; 66:184–188.
Means RT, Krantz SB, Dessypris EN, et al. Re-treatment of aplastic anemia with antithymocyte globulin or antilymphocyte serum. Am J Med 1988; 84:678–682.
Shahidi NT. Androgens and erythropoiesis. N Engl J Med 1973; 189:72–80.
Alter BP. Bone marrow failure syndromes In: Nathan DG, Oski FA, eds. In Hematology of Infancy and Childhood. Philadelphia, W.B. Saunders, 1987: p. 183.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1990 Springer-Verlag Inc.
About this chapter
Cite this chapter
Shahidi, N.T., Wang, W., Shurin, S., Finlay, J., Sondel, P., Dinndorf, P. (1990). Treatment of Acquired Aplastic Anemia with Cyclosporine and Androgens. In: Shahidi, N.T. (eds) Aplastic Anemia and Other Bone Marrow Failure Syndromes. Springer, New York, NY. https://doi.org/10.1007/978-1-4612-3254-4_14
Download citation
DOI: https://doi.org/10.1007/978-1-4612-3254-4_14
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4612-7935-8
Online ISBN: 978-1-4612-3254-4
eBook Packages: Springer Book Archive