Summary
Intravenous immune globulin (IGIV) was introduced a decade ago as a therapy for primary immunodeficiency diseases. It proved to be a valuable therapeutic substance for this purpose and is now considered to be the treatment of choice. The intent was to supply ubiquitous anti-infectious agent antibodies through passive immunisation to replace deficient circulating antibody content. During such therapy, unexpected benefits were noted in thrombocytopenic patients. Since that time, the therapeutic indications for IGIV infusions have greatly increased, with a particular interest in infectious, haematological and autoimmune diseases. This review summarises the status of IGIV therapy in haematological diseases within the categories of primary immunodeficiency diseases, secondary immunodeficiency states and autoimmune syndromes.
The majority of firm data have been gathered on the treatment of patients with primary immunodeficiency disease. These data are reviewed from the aspect of anticipated therapeutic response and side effects. Emphasis should be placed on the IgG circulating blood levels as there is a need for individualising therapy because of marked interindividual patient variation. The use of IGIV therapy in primary and secondary immunodeficiency states should consider the potential benefits to be attained in haematological malignancies and related complications which may be magnified by chemotherapy and radiation therapy. The mode of action of IGIV in autoimmune diseases, although not yet precisely determined, may involve establishing reticuloen- dothelial blockade or immunomodulation by supplying anti-idiotype antibodies.
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Ammann AJ, Ashman RF, Buckley RH, Hardie WR, Kratmann HJ, et al. Use of intravenous gammaglobulin in antibody deficiency: results of a multicenter controlled trial. Clinical Immunology and Immunopathology 22: 60–67, 1982
Arsura EL, Bick A, Brumner NG, Namba T, Grob D. High dose intravenous immunoglobulin in the management of myasthenia gravis. Archives of Internal Medicine 146: 1365–1368, 1986
Ashida ER, Saxon A. Home intravenous immunoglobulin therapy by self-administration. Journal of Clinical Immunology 6: 306–309, 1986
Barandum S, Kisthler P, Jeunet F, Isliker H. Intravenous administration of human gammaglobulin. Vox Sanguinis 7: 157–174, 1962
Becton DL, Kinney TR, Chaffee S, Kurtzberg J, Friedman HS, et al. High dose intravenous immunoglobulin for severe platelet alloimmunization. Pediatrics 74: 1120–1122, 1984
Berkman SA, Lee ML, Gale RP. Clinical uses of intravenous immunoglobulins. Annals of Internal Medicine 112: 278–293, 1990
Bernatowska E, Medalinski K, Janowicz, Weremowicz R, Gutkowski P, et al. Results of a prospective controlled two-dose crossover study with intravenous immunoglobulin and comparison (retrospective) with plasma treatment. Clinical Immunology and Immunopathology 43: 153–162, 1987
Besa EC. Use of intravenous immunoglobulin in chronic lymphocytic leukemia. American Journal of Medicine 76 (Suppl. 3A): 209–218, 1984
Blacklock HA, Griffiths P, Stork P, Prentice HG. Specific hyperimmune globulin for cytomegalovirus pneumonitis. Lancet 2: 152–153, 1985
Bruton OC. Agammaglobulinemias. Pediatrics 9: 722–727, 1952
Buckley RH. Long term use of intravenous immune globulin in patients with primary immunodeficiency diseases: inadequacy of current dosage practices and approaches to the problem. Journal of Clinical Immunology 2 (Suppl.): 15s–21s, 1982
Burks W, Sampson HA, Buckley RH. Anaphylactic reactions after gammaglobulin administration in patients with hypogammaglobulinemia: detection of IgE antibodies to IgA. New England Journal of Medicine 314: 560–564, 1986
Bussel JB, Hilgartner M. The use and mechanism of action of high dose intravenous immunoglobulin in the treatment of immune haematologic disease. British Journal of Haematology 56: 1–7, 1984
Bussel JB, Lalezari P, Fikrig S. Intravenous treatment with gammaglobulin of autoimmune neutropenia of infancy. Journal of Pediatrics 112: 298–301, 1988
Bussel JB, Lalezari P, Hilgartner M, et al. Reversal of neutropenia with intravenous gammaglobulin in autoimmune neutropenia of infancy. Blood 62: 398–400, 1983
Bussel JB, Pham LC. Intravenous treatment with gammaglobulin in adults with immune thrombocytopenic purpura: review of the literature. Vox Sanguinis 52: 1228–1231, 1987
Clarkson SB, Bussel JB, Kimberly RP, Valinsky JE, Nachman RL, et al. Treatment of refractory immune thrombocytopenia purpura with an anti-FCR receptor antibody. New England Journal of Medicine 314: 1236–1239, 1986
Clauvel JP, Vainchekker W, Herrera A, et al. Treatment of pure red cell aplasia by high doses of intravenous immune globulin. British Journal of Haematology 55: 380–382, 1983
Condie RM, O’Reilly RJ. Prevention of cytomegalovirus infection by prophylaxis with an intravenous, hyperimmune, native, unmodified cytomgegalovirus globulin. American Journal of Medicine 76 (Suppl. 3A): 134–141, 1984
Cooperative Group for the Study of Immunoglobulin in Chronic Lymphocytic Leukemia. Intravenous immunoglobulin for the prevention of infection in chronic lymphocytic leukemia. New England Journal of Medicine 319: 902–907, 1988
Cunningham-Rundles C, Siegal FP, Smithwick EM, Lion-Boule A, Cunningham-Rundles S, et al. Efficacy of intravenous immunoglobulin in primary humoral immunodeficiency disease. Annals of Internal Medicine 101: 435–439, 1984
Dammacco F, Iodice G, Campobasso N. Treatment of adult patients with ITP with intravenous immunoglobulin: effects of T cell subsets and PWM induced antibody synthesis in vivo. British Journal of Haematology 62: 125–135, 1986
Dwyer JM. Thirty years of supplying the missing link. History of gammaglobulin therapy for immunodeficient states. American Journal of Medicine 76 (Suppl. 3A): 46–52, 1984
Emanuel D, Cunningham I, Jules-Elysec K, et al. Cytomegalovirus pneumonia after bone marrow transplantation successfully treated with the combination of ganciclovir and high-dose intravenous immune globulin. Annals of Internal Medicine 109: 777–782, 1988
Good RA. Proceedings of a symposium intravenous immune globulin and the compromised host. American Journal of Medicine 76 (Suppl. 3A): 1–231, 1984
Gordon DS, Hearn EB, Spira TJ, Reimer CB, Phillips DJ, et al. Phase I study of intravenous gammaglobulin in multiple myeloma. American Journal of Medicine 76 (Suppl, 3A): 111–116, 1984
Green D, Kwaan HC. An acquired factor VIII inhibitor responsive to high-dose gammaglobulin. Thrombosis and Haemostasis 58: 1005–1007, 1987
Griffiths H, Brennan V, Lea J, Bunch C, Lee M, et al. Crossover study of immunoglobulin replacement therapy in patients with low-grade B-cell tumors. Blood 73: 366–368, 1989
Hanada T, Saito K, Nagasawa T, Kabashima T, Nakahara S, et al. Intravenous gammaglobulin therapy for the thromboneutropenic neonates of mothers with systemic lupus erythematosus. European Journal of Haematology 38: 400–404, 1987
Hill H. Counterpoint: gammaglobulin therapy for children with recurrent respiratory infections. Again! Why not? Pediatric Infectious Disease Journal 5: 395–398, 1986
Imbach P, Bertold W, Hirt A, Mueller-Eckhardt C, Rossi E, et al. Intravenous use of immunoglobulin in acute immune thrombocytopenic purpura in childhood. Lancet 2: 464–468, 1985
Imbach P, d’Apuzzo V, Hirt A, Rossi E, Vest M, et al. High-dose intravenous gammaglobulin for idiopathic thrombocytopenic purpura in childhood. Lancet 2: 1228–1231, 1981
Imbach P, Jungi TW. Possible mechanisms of IV immunoglobulin treatment in childhood ITP. Blut 46: 117–124, 1983
Imbach P, Morell A. Idiopathic thrombocytopenic purpura (ITP): immunomodulation by intravenous immunoglobulin (IVIG). International Reviews of Immunology 5: 181–188, 1989
Janeway CA. The development of clinical uses of immunoglobulins: a review. In Merler E (Ed.) Immunoglobulins, pp. 3–14, National Academy of Sciences, Washington, 1970
Janeway CA, Rosen FS. The gammaglobulins. IV. Therapeutic uses of gammaglobulin. New England Journal of Medicine 275: 826–831, 1966
Jungi TW, Eicholzer J, Lerch PG, Barandun S. The capacity of various types of immunoglobulin for intravenous use to interact with Fc receptors of human monocytes and macrophages. Blut 53: 321–322, 1986
Kazatchkine MD, Rossi F, Sultan Y, Nydegger U. Anti-idiotypes against autoantibodies to procoagulant factor VIII (VII:C) in intravenous immunoglobulins. International Reviews of Immunology 5: 157–164, 1989
Kekomaki R, Elfenbein G, Gardner R, Graham-Pole J, Mehta P, et al. Improved response of patients refractory to random-donor platelet transfusions by intravenous gammaglobulin. American Journal of Medicine 76 (Suppl. 3A): 199–203, 1984
Kurtzberg J, Friedman HS, Kinney TR, Chaffee S, Falletta JM. Treatment of platelet alloimmunization with intravenous immunoglobulin. American Journal of Medicine 83 (Suppl. 4A): 30–33, 1987
Leung DYM. The immunologic effects of IGIV in Kawasaki disease. International Reviews of Immunology 5: 197–202, 1989
Lundblad JL, Londerce N, Mitra G. Characterization of various intravenous immunoglobulin preparations. Journal of Infection 15 (Suppl. 1): 3–12, 1987
Mannhalter JW, Eibl MM. Down regulation of Fc receptors by IVIG. International Review of Immunology 5: 173–180, 1989
Montanaro A, Pirofsky B. High dose prolonged interval intravenous immunoglobulin in patients with primary immunodeficiency. American Journal of Medicine 76 (Suppl. 3A): 67–72, 1984
Morell A and Nydegger UE (Eds) Clinical use of intravenous immunoglobulins, Academic Press, London, 1986
Mueller-Eckhardt C, Salama A, Mahn I, Kiefel V, Neuzner J, et al. Lack of efficacy of high-dose intravenous immunoglobulin in autoimmune haemolytic anaemia: a clue to its mechanism. Scandinavican Journal of Haematology 34: 394–400, 1985
Meyers JD, Leszczynski J, Zaia JA, Flournoy N, Newton B, et al. Prevention of cytomegalovirus infection by cytomegalovirus immune globulin after marrow transplantation. Annals of Internal Medicine 98: 442–446, 1983
Newland AC. Idiopathic thrombocytopenic purpura and IgG: a review. Journal of Infection 15 (Suppl. 1): 41–50, 1987
Nicholls AJ, Brown CB, Edward N, Cuthbertson B, Yap PL, et al. Hyperimmune immunoglobulin for cytomegalovirus infections. Lancet 1: 532–533, 1983
Nilsson IM, Berntorp E, Zettervall O. Induction of immune tolerance in patients with hemophilia and antibodies to factor VIII by combined treatment with intravenous IgG, cyclophosphamide, and factor VIII. New England Journal of Medicine 319: 947–950, 1988
Nolte MT, Pirofsky B, Gerritz GA, Golding B. Intravenous immunoglobulin therapy for antibody deficiency. Clinical and Experimental Immunology 36: 237–243, 1979
Ochs HD, Fischer SH, Lee ML, Delson ES, Kingdon HS, et al. Intravenous immunoglobulin home treatment for patients with primary immunodeficiency diseases. Lancet 1: 610–611, 1986
Ochs HD, Fischer SH, Wedgwood RJ, Wara DW, Cowan MJ, et al. Comparison of high-dose and low-dose intravenous immunoglobulin therapy in patients with primary immunodeficiency diseases. American Journal of Medicine 76 (Suppl. 3A): 78–82, 1984
Ochs HD, Morell A, Skvaril F, Fischer SH, Wedgwood RJ. Survival of IgG subclasses following administration of intravenous gammaglobulin in patients with primary immunodeficiency diseases. In Morell A and Nydegger UE (Eds) Clinical use of intravenous immunoglobulins, pp. 77–86, Academic Press, London, 1986
Painter RH, Walcroft MJ, Weber JCW. The efficacy of fragmented immune serum globulin in passive immunization. Canadian Journal of Biochemistry 44: 381, 1965
Pennington JE (Ed.) Symposium properties and characteristics of a new immunoglobulin G intravenous preparation. Reviews of Infectious Diseases 8 (Suppl. 4), 1986
Pirofsky B. Intravenous immune globulin therapy in hypogammaglobulinemia: a review. American Journal of Medicine 76 (Suppl. 3A): 53–60, 1984
Pirofsky B. Safety and toxicity of a new serum immunoglobulin G intravenous preparation, IGIV pH 4.25. Reviews of Infectious Diseases 9 (Suppl. 4): s457–s463, 1986
Pirofsky B. Clinical use of a new pH 4.25 intravenous immunoglobulin preparation (Gammimune-N). Journal of Infection 15 (Suppl. 1): 29–38, 1987
Pirofsky B, Campbell SM, Montanaro A. Individual patient variations in the kinetics of intravenous immune globulin administration. Journal of Clinical Immunology 2 (Suppl.): 7s–14s, 1982
Pollack S, Cunningham-Rundles C, Smithwick EM, et al. High-dose intravenous gammaglobulin in autoimmune neutropenia. New England Journal of Medicine 307: 253–255, 1982
Reed EC, Bowden RA, Dandliker PS, Lilleby KE, Meyers JD. Treatment of cytomegalovirus pneumonia with ganciclovir and intravenous cytomegalovirus immunoglobulin in patients with bone marrow transplants. Annals of Internal Medicine 109: 783–788, 1988
Richmond GW, Ray I, Korenbitt A. Initial stabilization proceeding enhanced hemolysis in autoimmune hemolytic anemia treated with intravenous gammaglobulin. Journal of Pediatrics 110: 917–919, 1987
Roifman CM, Levison H, Gelfand EW. High-dose versus low-dose intravenous immune globulin in hypogammaglobulinemia and chronic lung disease. Lancet 1: 1075–1077, 1987
Rosen FS, Wedgwood RJ (Eds) Immunomodulation: role of intravenous immunoglobulins. International Reviews of Immunology 5: 97–202, 1989
Salama A, Mahn I, Neuzmer J, Graubner M, Mueller-Eckhard TC. IgG therapy in autoimmune haemolytic anaemia of warm type. Blut 48: 391–392, 1987
Schede I. Application of immunoglobulin preparations in multiple myeloma. In Morell A and Nydegger UE (Eds) Clinical use of intravenous immunoglobulins, pp. 123–132, Academic Press, London, 1986
Schiff RI. Half-life and clearance of pH 6.8 and pH 4.25 immunoglobulin G intravenous preparations in patients with primary disorders of humoral immunity. Reviews of Infectious Diseases 8 (Suppl. 4): s456–s463, 1986
Schiffer CA, Hogge DE, Aisner J, Dutcher JP, Lee EJ, et al. High-dose intravenous gammaglobulin in alloimmunized platelet transfusion recipients. Blood 64: 937–940, 1984
Schreiber A. The use of intravenous immune globulin in immunological neutropenia and anemias. In New directions in the clinical use of intravenous immune globulin, Vol. II, pp. 3–11, Health Dimensions New Jersey, Fort Lee, 1990
Schwartz RS. Properties of a system of public idiotypes of lupus autoantibodies. International Reviews of Immunology 5: 153–155, 1989
Stiehm ER (moderator). Intravenous immunoglobulins as therapeutic agents. Annals of Internal Medicine 107: 367–382, 1987
Sullivan-KM, Kopecky K, Jocum J, Buckner CD, Counts G, et al. Antimicrobial and immunomodulatory effects of intravenous immunoglobulin in bone marrow transplantation. Blood 72: 410A, 1988
Sultan Y, Kazatchkine MD, Maisonneuve P, Nydegger UE. Anti-idiotypic suppression of autoantibodies to factor VIII (anti-haemophilic factor) by high-dose of intravenous gammaglobulin. Lancet 2: 765–768, 1984
Winston DC, Ho WG, Lin C-H, et al. Intravenous immune globulin for prevention of cytomegalovirus infection and interstitial pneumonia after bone marrow transplantation. Annals of Internal Medicine 106: 12–18, 1987
Winston DJ, Pollard RB, Ho WG, et al. Cytomegalovirus immune plasma in bone marrow transplant recipients. Annals of Internal Medicine 97: 11–18, 1982
Zeigler ZR, Shadduck RK, Rosenfeld CS, et al. High-dose intravenous gammaglobulin improves responses to single-donor platelets in patients refractory to platelet transfusion. Blood 70: 1433–1436, 1987
Zimmerman R, Kommerell B, Harenberg J, Eich W, Rother K, et al. Intravenous IgG for patients with spontaneous inhibitor to factor VIII. Lancet 1: 273–274, 1985
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Pirofsky, B., Kinzey, D.M. Intravenous Immune Globulins. Drugs 43, 6–14 (1992). https://doi.org/10.2165/00003495-199243010-00002
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DOI: https://doi.org/10.2165/00003495-199243010-00002