Summary
In haematological diseases, insufficient data has been accumulated to evaluate the efficacy of immunosuppressive drug treatment in patients with erythroid aplasia or sideroblastic anaemia. Cyclophosphamide may be efficacious in inhibiting circulating anticoagulants in patients who need continued replacement of clotting factors.
Azathioprine, 6-mercaptopurine, cyclophosphamide and vincristine have been used successfully in treating patients with idiopathic thrombocytopenic purpura, and some patients with auto-immune haemolytic anaemia may benefit from the addition of purine analogues. However, the use of immunosuppressive therapy seems to accelerate the presence of haematological malignancies in patients with macroglobulinaemia.
In gastro-intestinal diseases, uncontrolled studies have shown nitrogen mustard, 6-mercaptopurine and azathioprine to be of modest benefit to patients with ulcerative colitis and Crohn’s disease. In a controlled trial azathioprine plus prednisone proved more effective than prednisone alone in sustaining remission in patients with Crohn’s disease. In patients with either chronic active hepatitis or primary biliary cirrhosis, however, there seems to be no benefit from immunosuppressive therapy for primary treatment of these diseases.
Cyclophosphamide, azathioprine and methotrexate have all been used with some success in treating patients with uveitis, and in a controlled trial cytarabine has been shown to be beneficial to patients with herpes ophthalmicus. However, no benefit has been shown to patients with the eye changes of Graves* disease with either azathioprine or methotrexate.
Patients with Paget’s disease appear to be helped by mithramycin.
Cyclophosphamide, chlorambucil and azathioprine are ineffective in treating patients with multiple sclerosis. 6-Mercaptopurine, azathioprine, methotrexate and cyclophosphamide have all produced some benefit in patients with myasthenia gravis, and some patients with idiopathic pulmonary haemosiderosis have responded to azathioprine, 6-mercaptopurine and cyclophosphamide.
Alkylating agents have proved useful in treating some patients with asthma and in treating frequent relapsers among children with the nephrotic syndrome. In adults with membrano-proliferative glomerulonephritis some patients have responded to combination therapy with cyclophosphamide, azathioprine and corticosteroids. Immunosuppressive therapy is also indicated in prolonging graft survivals in patients receiving organ transplants.
Drug toxicities of immunosuppressive agents are discussed. Their long-term effects, including mutagenic potential, have as yet not been fully elucidated.
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Abramowicz, M.; Arneil, G.C.; Barnett, H.L.; Barron, B.A.; Edelmann, CM.; Gordillo, G.; Greifer, I.; Hallman, N.; Kobayashi, O. and Tiddens, H.A.: Controlled trial of azathioprine in children with nephrotic syndrome. Lancet 1: 959 (1970).
Ahn, Y.S.; Harrington, W.J.; Seelman, R.C. and Eytel, C.S.: Vincristine therapy of idiopathic and secondary thrombocytopenias. New England Journal of Medicine 291: 376 (1974).
Arustamova, R.G.; Serov, V.V.; Mukhin, N.A. et al.: Effect of Immuran on the course of experimental amyloidosis. Bulletin of Experimental Biology and Medicine 77: 153(1974).
Barnard, C.N.: The present status of heart transplantation. South African Medical Journal 49: 213 (1975).
Barratt, T.M. and Soothill, J.F.: Controlled trial of cyclophosphamide in steroid sensitive relapsing nephrotic syndrome of childhood. Lancet 2: 479 (1970).
Bayard, E.D.: Continuous chlorambucil therapy in primary macroglobulinemia of Waidenstrom. Mayo Clinic Proceedings 36: 135 (1961).
Beall, Jr., A.C.; Jenkins, D.E.; Weg, J.G. et al.: Human lung allotransplantation. American Journal of Surgery 119: 300 (1970).
Bean, R.H.: Treatment of ulcerative colitis with antimetabolites. British Medical Journal 2: 1081 (1966).
Bidwell, E.: Acquired inhibitors of coagulants. Annual Review of Medicine 20: 63 (1969).
Bishop, G.; Cosimi, A.B.; Voynow, N.K. et al.: Effect of immunosuppressive therapy for renal allografts on the number of circulating sheep red blood cell rosetting cells. Transplantation 20: 123 (1975).
Blumenstock, D.A.; Otte, H.P.; Grosjean, O.B. et al.: Transplantation of the lung. Transplantation Proceedings 1: 223 (1969).
Bouroncle, B.A. and Doan, C.A.: Treatment of refractory idiopathic thrombocytopenic purpura. Journal of the American Medical Association 207: 2049 (1969).
Bowen, G.E.; Irons, G.V.; Rhodes, J.B. and Kirsner, J.B.: Early experiences with azathioprine in ulcerative colitis. Journal of the American Medical Association 195: 460 (1966).
Brooke, B.N.; Hoffman, D.C. and Swarbrick, E.T.: Azathioprine for Crohn’s disease. Lancet 2: 612 (1969).
Brooke, B.N.; Javett, S.L. and Davison, O.W.: Further experience with azathioprine for Crohn’s disease. Lancet 2: 1050 (1970).
Brown, C.H. and Achkar, E.: Azathioprine therapy for inflammatory bowel disease — a preliminary report. American Journal of Gastroenterology 54: 363 (1970).
Buckley, C.E. and Gills, J.P.: Cyclophosphamide therapy of uveitis. Archives of Internal Medicine 124: 29 (1969b).
Burrow, G.N.; Mitchell, M.S.; Howard, R.O. et al.: Immunosuppressive therapy for the eye changes of Graves’ disease. Journal of Clinical Endocrinology 31: 307(1970).
Buroton, I. and Korelitz, J.: Long-term immunosuppressive treatment of ulcerative colitis. American Journal of Digestive Diseases 18: 317 (1973).
Callerame, M.L.; Condemi, J.J.; Bohrind, M.G. et al.: Immunologic reaction of bronchial tissues in asthma. New England Journal of Medicine 284: 459 (1971).
Calne, R.Y.: Observations on experimental and clinical liver transplantation. Transplantation Proceedings 4: 773 (1972).
Cameron, J.S.; Chantier, C.; Ogg, C.S. and White, R.H.R.: Long-term stability of remission in nephrotic syndrome after treatment with cyclophosphamide. British Medical Journal 4: 7 (1974).
Camitta, B.M.; Rappeport, J.M.; Parkman, R. et al.: Selection of patients for bone marrow transplantation in severe aplastic anemia. Blood 45: 355 (1975).
Caprilli, R.; Canatu, R. and Babbini, M.: A double-blind comparison of the effect of azathioprine and sulfasalazine in idiopathic proctocolitis. American Journal of Digestive Diseases 20: 115 (1975).
Caves, P.K.; Stinson, G.B.; Griepp, R.B. et al: Results of 54 cardiac transplants. Surgery 74: 307 (1973).
Cendrowski, W.S.: Combined therapeutic trial in multiple sclerosis comparing hydrocortisone hemisuccinate with cyclophosphamide or Cytosar. Acta Neurologica Belgica 73: 209 (1973).
Cendrowski, W.S.: Multiple sclerosis: Pilot therapeutic trial of immunosuppresive. Schweizer Archiv fur Neurologie, Neurochimie and Psychologie 105: 241 (1969).
Chiu, J.; McLane, P.N. and Drummond, K.N.: A controlled prospective study of cyclophosphamide in relapsing, corticosteroid-responsive minimal-lesion nephrotic syndrome in childhood. Journal of Paediatrics 82: 607 (1973).
Cohen, E.P.; Petty, T.L.; Szentivanyi, A. et al.: Clinical and pathological observations in fatal bronchial asthma. Annals of Internal Medicine 62: 103 (1965).
Condon, J.R.; Reith, S.B.M.; Nassim, J.R.; Millard, F.J.C.; Hilb, A. and Stainthorpe, E.M.: Treatment of Paget’s disease of bone with mithramycin. British Medical Journal 1: 421 (1971).
Cook, G.C.; Mulligan, R. and Sherlock, S.: Controlled perspective trial of corticosteroid therapy in active chronic hepatitis. Quarterly Journal of Medicine 40: 159 (1971).
Corley, C.C.; Lessner, H.E. and Larsen, W.E.: Azathioprine therapy of autoimmune diseases. American Journal of Medicine 41: 404 (1966).
Dau, P. and Peterson, R.: Transformation of lymphocytes from patients with multiple sclerosis. Archives of Neurology 23: 32 (1970).
Dave, V.K. and Vickers, C.F.H.: Azathioprine in treatment of mucocutaneous pemphigoid. British Journal of Dermatology 90: 183 (1974).
Delobel, J.; Softic, N. and Caen, J.P.: in Bernard Actualities Hematologiques, Vol. 4, p.30 (Masson, Paris 1970).
Diaz, C.J.: Treatment of dysreaction diseases with nitrogen mustards. Annals of the Rheumatic Diseases 10: 144 (1952).
Donadio, J.V.; Holley, KE.; Anderson, C.F. et al.: Controlled trial of cyclophosphamide in idiopathic membranous nephritis. Kidney International 6: 431 (1976).
Doniarch, D.; Roitt, I.M.; Walker, J.G. et al.: Tissue antibodies in primary biliary cirrhosis active chronic hepatitis, cryptogenic cirrhosis and other liver diseases and their clinical implications. Clinical and Experimental Immunology 1: 237 (1966).
Dormandy, K.M.; Hawkey, C.; Churchill, W. et al.: Immuno suppression of inhibitors to human factor VIII. Thrombosis et Diathesis Haemorrhagica 43 (Suppl.): 355 (1971).
Drucker, W.R. and Jeejeebhoy, K.N.: Azathioprine: An adjunct to surgical therapy of granulomatous colitis. Annals of Surgery 172: 618 (1970).
Dubois de Montreynaud, J.M.; Doco, S.; Kochman, J. et al.: IntérÊt dans le traitement de certains asthmes d’une médication à effet immunodépresseur, le chlorambucil. Presse Médicale 76: 1786 (1968).
Engel, W.K.; Festoff, B.W.; Patter, B.M.; Swerdlow, M.L.; Newball, H.H. and Thompson, M.D.: Myasthenia Gravis. Annals of Internal Medicine 81: 225 (1974).
Everett, D.; Newcomer, K.; Anderson, J.; Bergin, J. and Overholt, E.L.: Goodpasture’s syndrome: Response to mercaptopurine and prednisone. Journal of the American Medical Association 213: 1849 (1970).
Fazio, M.; Minetto, E.; Sartoris, S. et al.: Le traitement de l’asthme bronchique chronique par la methylhydrazine. Presse Médicale 77: 1996 (1969).
Fefer, A.; Thomas, E.D.; Buckner, CD. et al.: Marrow transplantation in aplastic anemia and leukemia. Seminars in Hematology 11: 353 (1974).
Finch, S.C.; Castro, O.; Cooper, M. et al: Immunosuppressive therapy of chronic idiopathic thrombocytopenic purpura. American Journal of Medicine 56: 4 (1974).
Gelfand, M.; Steinberg, A.D.; Nagle, R. et al.: Therapeutic studies in NZB-W mice. I. Synergy of azathioprine and methylprednisolone. Arthritis and Rheumatism 15: 247 (1972).
Gills, J.P.: Combined medical and surgical therapy for complicated cases of peripheral uveitis. Archives of Ophthalmology 79: 723 (1968).
Gjone, E.; Boye, N. and Biomhoff, J.: Azathioprine in chronic active hepatitis. Acta Medica Scandinavica 193: 109 (1973).
Goebel, K.M.; Goebel, F.D.; Gassel, W.D. et al.: Immune response in patients with autoimmune thrombocytopenia and autoimmune hemolytic anemia receiving azathioprine. Klinische Wochenschrift 52: 916 (1974).
Graw, Jr., R.G.; Yankee, R.A.; Leventhal, B.G. et al.: Bone marrow transplantation in acute leukemia employing cyclophosphamide. Experimental Haematology 22: 118(1972).
Green, D.: Spontaneous inhibitors of factor VIII. British Journal of Haematology 15: 57 (1968).
Grupe, W.E.: Chlorambucil in steroid-dependent nephrotic syndrome. Journal of Pediatrics 82: 598 (1973a).
Grupe, W.E.: Chlorambucil in a controlled study of steroid-dependent nephrotic syndrome. Pediatric Research 7: 413 (1973b).
Hamburger, J.: in Nephrology, Chapter 6 (Saunders, Philadelphia 1966).
Hardt, F.: Immunosuppressive treatment of amyloid. Acta Pathologica et Microbiologica Scandinavica 79: 61 (1971).
Hayslett, J.P.; Kashgarian, M.; Bensch, K.G. et al: Clinicopathological correlations in the nephrotic syndrome due to primary renal disease. Medicine 52: 93 (1973).
Hetzel, B.S.; Mason, E.K. and Wang, H.K.: Studies of serum LATS in relation to exophthalmos. Australian Annals of Medicine 17: 307 (1968).
Hilgartner, M.W.; Lanzkowsky, P. and Smith, C.H.: The use of azathioprine in refractory idiopathic thrombocytopenic purpura in children. Acta Pediatrica Scandinavica 59: 409 (1970).
Hitzig, W.H. and Massimo, L.: Treatment of autoimmune hemolytic anemia in children with azathioprine. Blood 28: 841 (1966).
Hodges, N.G.; Brewis, R.A.L. and Howell, J.B.L.: An evaluation of azathioprine in severe chronic asthma. Thorax 26: 734 (1971).
Hume, D.H.; Magee, J.H.; Kauffman, H.M. et al: Renal homotransplantation in man in modified recipients. American Journal of Surgery 158: 608 (1963).
Hume, D.H.; Wolff, J.S.; Lee, H.M. et al.: Liver transplantation. Transplantation Proceedings 4: 781 (1972).
Hyndiuk, R.A. and Kaufman, H.E.: Newer compounds in therapy of herpes simplex and keratitis. Archives of Ophthalmology 78: 600 (1967).
Jeannet, I.; Bossia, G. and Wagner, H.P.: Autoimmune hemolytic anemia and cytomegalovirus infection in a 6 month old child treated with azathioprine. Helvetica Pediatrica Acta 27: 155 (1972).
Jewell, D.P. and Truelove, S.C.: Azathioprine in ulcerative colitis. British Medical Journal 1: 709 (1972).
Jewell, D.P. and Truelove, S.C.: Azathioprine in ulcerative colitis. Final report on controlled therapeutic trial. British Medical Journal 4: 627 (1974).
Jones, F.A.; Lennard-Jones, J.H.; Hinton, J.M. et al.: Dangers of immunosuppressive drugs in ulcerative colitis. British Medical Journal 1: 1418 (1966).
Jones, N.F.; Hilton, P.J.; Tighe, J.R. and Hobbs, J.R.: Treatment of primary renal amyloidosis with melphalan. Lancet 2: 616 (1972).
Jones, R.A.: Immunosuppressive therapy in ulcerative colitis. Proceedings of the Royal Society of Medicine 62: 499 (1969).
Jones, R.A.: Immunosuppressive therapy in Crohn’s disease. Proceedings of the Royal Society of Medicine 64: 171 (1971).
Kaiser, H.B. and Beall, G.N.: Azathioprine in chronic asthma. Annals of Allergy 24: 369 (1966).
Kasper, H.; Zimmermann, H.D. and Nagele, T.: Azathioprinbehandlung bei Einteritis regionalis. Deutsche medizinische Wochenschrift 95: 1261 (1970).
Kaufman, H.E.; Martola, E.L. and Dohlan, C.H.: Use of 5-iodo-2-deoxyuridine (IDU) in the treatment of herpes simplex keratitis. Archives of Ophthalmology 68: 235 (1962a).
Kaufman, H.E.; Nesburn, A.B. and Maloney, E.D.: Idoxuridine therapy of herpes simplex. Archives of Ophthalmology 67: 583 (1962b).
Kersey, J.; Roloff, J.; Hokeness, J. et al.: Retransplantation of human marrow. Transplantation 19: 475 (1975).
Kirsner, J.B.: Ulcerative colitis: 1970 recent developments. Scandinavian Journal of Gastroenterology 6 (Suppl.): (1970).
Klein, M.; Binder, H.J.; Mitchell, M.; Aaronson, R. and Spiro, H.: Treatment of Crohn’s disease with azathioprine: A controlled evaluation. Gastroenterology 66: 916 (1974).
Kott, E.; Genkins, G. and Rule, A.H.: Leukocyte response to muscle antigens in myasthenia gravis. Neurology 23: 374 (1972).
Krantz, S.B.: Studies on red cell aplasia. III. Blood 39: 347 (1972).
Krantz, S.B.: Pure red cell aplasia. New England Journal of Medicine 291: 345 (1974).
Krantz, S.B. and Kao, V.: Studies on red cell aplasia. I. Proceedings of the National Academy of Sciences 58: 493 (1967).
Krantz, S.B. and Kao, V.: Studies on red cell aplasia. II. Blood 34: 1 (1969).
Kyle, R A.; Pierce, R.V. and Bayard, E.D.: Multiple myeloma and acute myelomonocytic leukemia. New England Journal of Medicine 283: 1121 (1970).
Laebson, P.R. and Leopold, I.H.: An evaluation of double-blind idoxuridine therapy in 100 cases of herpes keratitis. Transactions of the American Academy of Ophthalmology and Otolaryngology 68: 22 (1964).
Laros, R.K. and Penner, J.A.: ‘Refractory’ thrombocytopenic purpura treated successfully with cyclophosphamide. Journal of the American Medical Association 215: 445 (1971).
Lawson, R.K.; Talwalkar, Y.B.; Musgrave, J.E. et al: Renal transplantation in pediatric patients. Journal of Urology 113: 225 (1975).
Lebbin, D.; Ryan, W.G. and Schwartz, T.P.: Outpatient treatment of Paget’s disease of bone with mithramycin. Annals of Internal Medicine 81: 635 (1974).
Lechner, K.; Ludwig, E.; Nissner, H. et al.: Immunosuppressive treatment of patients with inhibitors of blood coagulation. International Society of Thrombosis and Hemostasis, p. 118 (Aug. 1972).
Lennard-Jones, E. and Williams, C.B.: Azathioprine in the treatment of Crohn’s disease. Proceedings of the Royal Society of Medicine 65: 291 (1972).
Lerner, R.A.; Glassock, R.J. and Dixon, F.J.: The role of anti-glomerular basement membrane antibodies in the pathogenesis of human glomerulonephritis. Journal of the Experimental Medicine 126: 989 (1967).
Levin, B.; Rosenberg, J.L.; Wall, A.J. et al.: A controlled trial of azathioprine in the treatment of Crohn’s disease. Clinical Research 21: 868 (1973).
Lillehei, R.C.; Idezoki, Y.; Kelly, W.D. et al.: Transplantation of the intestine and pancreas. Transplantation Proceedings 1: 230(1969).
Urn, V.S.; Sibley, R. and Scarzo, B.: Adult lipoid nephrosis: Clinicopathological correlations. Annals of Internal Medicine 81: 314 (1974).
Lorenzen, I. and Videbaek, A.: Treatment of collagen diseases with cytostatics. Lancet 2: 558 (1965).
McCallister, B.D.; Bayard, G.D.; Harrison, E.G. et al.: Primary macroglobulinemia. American Journal of Medicine 43: 394 (1967).
McCrory, W.W.; Shibuya, M.; Lu, W.H. et al.: Therapeutic and toxic effects observed with different dosage programs of cyclophosphamide in treatment of steroid responsive but frequently relapsing nephrotic syndrome. Journal of Paediatrics 82: 614 (1973).
McDonald, J.; Murphy, A.V. and Arneil, G.C.: Long term assessment of cyclophosphamide therapy for nephrosis in children. Lancet 2: 980 (1974).
McFarlin, D.E. and Johnson, J.S.: Studies of anti-muscle antibodies in myasthenia gravis. Journal of Immunology 106: 292 (1971).
Mackay, I.R.: Chronic hepatitis effect of prolonged suppressive treatment and comparison of azathioprine with prednisone. Quarterly Journal of Medicine 87: 379 (1968).
Mackay, I.R.; Wall, A.J. and Goldstein, G.: Response to azathioprine in ulcerative colitis. American Journal of Digestive Diseases 11: 536 (1966).
McPhail, J.J. and Dixon, F.J.: The presence of glomerular basement membrane antibodies in peripheral blood. Journal of Immunology 103: 1168 (1969).
Maimont, A.M. and Damasio, E.E.: Clinical experiences with cytotoxic immunosuppressive treatment of idiopathic thrombocytopenic purpura. Acta Haematologica 46: 74 (1971).
Marmont, A.; Peschle, C.; Sanguineti, M. et al.: Pure red cell aplasia. Blood 45: 247 (1975).
Massimo, L.; Cottafava, F. and Mori, P.G.: Sperimentazione terapeutica del Pazathioprine in alcune malattie immunologiche vel bambino. Minerva Pediatrica 18: 2010 (1966).
Melnick, S.C.: Thirty-eight cases of Guillian-Barre syndrome. An immunological study. British Medical Journal 7: 368(1963).
Mertens, H.G.; Balzereit, F. and Leipert, M.: Treatment of severe myasthenia gravis with immunosuppressive agents. Neurology 2: 321 (1969).
Miller, P. and Miller, H.: Cyclophosphamide in multiple sclerosis. Lancet 1: 783 (1969).
Mistilis, S.P. and Blackburn, C.R.B.: The treatment of active chronic hepatitis with 6-mercaptopurine and azathioprine. Australasian Annals of Medicine 16: 305 (1967).
Moncrieff, M.W.; White, R.H.R.; Ogg, C.S. and Cameron, J.S.: Cyclophosphamide therapy in the nephrotic syndrome of childhood. British Medical Journal 1: 666(1969).
Mukherjee, A.P.: Combined prednisolone, azathioprine and cyclophosphamide treatment for persistent proliferative glomerulonephritis in adults. Lancet 2: 1350 (1971).
Murray, J.E.; Merrill, J.P.; Harrison, J.H. et al.: Prolonged survival of human kidney homografts by immunosuppressive drug therapy. New England Journal of Medicine 268: 1315 (1963).
Murray-Lyon, L.M.; Stern, R.B. and Williams, R.: Controlled trial of prednisone and azathioprine in chronic active hepatitis. Lancet 1: 735 (1973).
Neumann, J. and Ziegler, D.: Trial of immunosuppressive agents in multiple sclerosis. Neurology 22: 1268 (1972).
Newell, F.W.: Treatment of uveitis with azathioprine. Transactions of the Ophthalmological Society of the United Kingdom 87: 449 (1967).
Newell, F.W. and Krill, A.E.: The treatment of uveitis with 6-mercaptopurine. American Journal of Ophthalmology 61: 1250(1966).
Nilsson, I.; Hedner, U. and Bjorlin, G.: Suppression of factor IX antibody in hemophilia B by factor IX and cyclophosphamide. Annals of Internal Medicine 78: 91 (1973).
Nilsson, I.; Hedner, U.; Ekberg, M. et al.: Circulating anticoagulants against factor V. Acta Medica Scandinavica 195: 69 (1974a).
Nilsson, I.; Hedner, U. and Holmber, L.: Suppression of factor VIII antibody by combined factor VIII and cyclophosphamide. Acta Medica Scandinavica 195: 65 (1974b).
Nouza, K. and Smart, V.: The favorable effect of cyclophosphamide in myasthenia gravis. Revue Europeene d’Etudes Cliniques et Biologiques 13: 161 (1968).
O’Donohue, W.J.: Idiopathic pulmonary hemosiderosis with manifestations of multiple connective tissue and immune disorders. Annual Review of Respiratory Diseases 109: 473 (1974).
Oetliker, O.; Kaiser, G.; Kineta, A. et al.: Hemodialysis and renal transplantation in childhood. Journal of Pédiatric Surgery 10: 77 (1975).
Osterberg, R. and Raisin, A.: Reticulum cell sarcoma in Waldenstrom’s macroglobulinemia after chlorambucil. Acta Medica Scandinavica 188: 497 (1970).
Page, A.R.; Condie, R.M. and Good, R.A.: Suppression of plasma cell hepatitis with 6-mercaptopurine. American Journal of Medicine 36: 200 (1964).
Palmer, K.N.V.: Polyradiculopathy treated with 6-mercaptopurine. Lancet 1: 733 (1965).
Papp, J.P.; Brill, F.E. and Watson, D.W.: An evaluation of azathioprine in the management of Crohn’s disease. Gastroenterology 60: 705 (1971).
Patterson, J.F.; Norton, R.A. and Schwartz, R.S.: Azathioprine treatment of ulcerative colitis, granulomatous colitis and regional enteritis. American Journal of Digestive Diseases 16: 327 (1971).
Paven-Langston, D.; Dohlman, C.H. and Geary, P.: Intraocular penetration of ARA-A and idoxuridine — therapeutic implications in clinical herpetic uveitis. Transactions of the American Academy of Ophthalmology and Otolaryngology 77: 455 (1973).
Perlmann, P. and Broberger, O.: In vitro studies of ulcerative colitis. Journal of Experimental Medicine 117: 717 (1963).
Peterson, H.S.: Erythroleukemia in a melphalan treated patient with primary macroglobulinemia. Scandinavian Journal of Haematology 10: 5 (1973).
Pickering, J.G.: Wegener’s granulomatosis treated with azathioprine. Proceedings of the Royal Society of Medicine 65: 592 (1972).
Pierce, L.G. and Jenkins, R.B.: Herpes zoster ophthalmicus treated with cytosine arabinoside. Archives of Ophthalmology 89: 21 (1973).
Reynolds, T.B.; Denison, E.K.; Frankl, H.D. et al.: Primary biliary cirrhosis with scleroderma, Raynaud’s phenomenon and telangiectasias. American Journal of Medicine 50: 302 (1971).
Rhodes, J.; Bainton, D. and Beck, P,: Azathioprine in Crohn’s disease. Lancet 2: 1142 (1970).
Rhodes, J.; Bainton, D.; Beck, P. and Campbell, H.: Controlled trial of azathioprine in Crohn’s disease. Lancet 2: 1273(1971).
Ring, J.; Lob, G.; Angstwurm, H.; Brass, R.; Backmund, H.; Seifert, J.; Coulin, K.; Frick, E.; Mertin, J. and Brendel, W.: Intensive immunosuppression in the treatment of multiple sclerosis. Lancet 4: 1093 (1974).
Rosenberg, J.L.; Wall, A.J.; Levin, B. et al.: A controlled trial of azathioprine in management of chronic ulcerative colitis. Gastroenterology 69: 96 (1975).
Ross, A. and Sherlock, S.: A trial of azathioprine in primary biliary cirrhosis. Gut 11: 1058 (1970).
Safdar, S.; Krantz, S. and Brown, E.: Successful immunosuppressive treatment of erythroid aplasia appearing after thymectomy. British Journal of Haematology 19: 435 (1970).
Santos, G.W.: Immunosuppression for clinical marrow transplantation. Seminars in Hematology 11: 341 (1974).
Schwartz, R.S. and Dameshk, W.: The treatment of autoimmune hemolytic anemia with 6-mercaptopurine and thioguanine. Blood 19: 483 (1962).
Seitzer, A.: The effect of cyclophosphamide in childhood nephrotic syndrome: A report from the international study of kidney disease in children. Pediatric Research 6: 330 (1970).
Sharpstone, P.; Ogg, C.S. and Cameron, J.S.: Nephrotic syndrome due to primary renal disease in adults: A controlled trial of prednisolone and azathioprine. British Medical Journal 2: 535 (1969).
Silberberg, D.; Lisak, R. and Zweiman, B.: Multiple sclerosis unaffected by azathioprine in pilot study. Archives of Neurology 28: 210 (1975).
Soergel, K.H. and Sommers, S.C.: Idiopathic pulmonary hemosiderosis and related syndromes. American Journal of Medicine 32: 499 (1962).
Soloway, R.D.; Baggenstoss, A.H.; Elveback, L.R. et al.: The treatment of chronic active liver disease. Gastroenterology 60: 168 (1971).
Soloway, R.D.; Summerskill, W.H.; Baggenstoss, A.H. et al.: Clinical, biochemical and histological remission of severe chronic active liver disease. Gastroenterology 63: 820 (1972).
Starzl, T.; Corman, J.; Growth, C.G. et al.: Personal experience with orthoptic liver transplantation. Transplantation Proceedings 4: 759 (1972a).
Starzl, T.; Marchiono, T.L.; Porter, K.A. et al.: The use of heterologous anti-lymphoid agents in canine renal and liver homotransplantation and in human renal homotransplantation. Surgery, Gynecology and Obstetrics 124: 301 (1967).
Starzl, T.; Marchiono, T.L. and Waddell, W.R.: The reversal of rejection in human renal homografts with subsequent development of homograft tolerance. Surgery, Gynecology and Obstetrics 117: 385 (1963).
Starzl, T.; Penn, L.; Schroter, G.; Putnam, C.W.; Halgrimson, C.G.; Martineau, G.; Amemiya, H. and Groth, C.G.: Cyclophosphamide and human organ transplantation. Lancet 2: 70 (1971).
Starzl, T.; Putnam, C.W.; Halgrimson, C.G. et al.: Renal transplantation under cyclophosphamide. Transplantation Proceedings 4: 461 (1972b).
Steiner, B.: Idiopathic autoimmune lung purpura treated with azathioprine and with splenectomy and azathioprine. Helvetica Pediatrica Acta 24: 413 (1969).
Steiner, B. and Nabradis, T.: Idiopathic autoimmune lung purpura treated with azathioprine. Lancet 1: 140 (1965).
Storb, R.; Floersheim, G.L.; Weiden, P.L. et al.: Effect of prior blood transplant on marrow grafts. Journal of Immunology 112: 1508 (1974).
Summerskill, W.H.J.; Korman, M.G.; Ammon, H.V. et al.: Prednisone for chronic active liver disease. Gastroenterology 67: 830(1974).
Sussman, L.N.: Azathioprine in refractory idiopathic thrombocytopenic purpura. Journal of the American Medical Association 202: 259 (1967).
Swinburn, W.R. and Liversedge, L.M.: Long-term treatment of multiple sclerosis with azathioprine. Journal of Neurology, Neurosurgery and Psychiatry 36: 124 (1973).
Theodor, E.; Gilon, E. and Waks, U.: Treatment of ulcerative colitis with azathioprine. British Medical Journal 4: 741 (1968).
Thomas, E.; Storb, R.; Clift, R.A.; Fefer, A.; Johnson, F.L.; Neiman, P.E.; Lerner, K.G.; Glucksberg, H. and Buckner, C.D.: Bone marrow transplantation. New England Journal of Medicine 292: 832 (1975).
Tucker, W.G. and Kapphahn, K.H.: A preliminary evaluation of azathioprine in the treatment of multiple sclerosis. Henry Ford Hospital Medical Journal 17: 89 (1969).
Udall, P.R.; Morley, A.R.; Feest, T.G.; Tomlinson, B.E. and Kerr, D.N.S.: Cyclophosphamide therapy in adults with minimal change nephrotic syndrome. Lancet 1: 1250 (1972).
Vanselow, N.A.; Kelly, Jr.; Meyers, J.C. et al.: The effect of 6-MP on antibody production in atopic individuals. Journal of Allergy 37: 145 (1966).
Veith, F.J.; Koerner, S.K.; Attai, L.A.; Bardfeld, P.; Boley, S.J.; Bloomberg, A.; Everhard, M.; Anderson, J.; Pollara, B.; Steckler, R.; Nagashima, H.; Siegelman, S.; Lalezari, P. and Gliedman, M.L.: Single lung transplantation in emphysema. Lancet 1: 1138 (1972).
Veith, F.J. and Koerner, S.K.: Problems in the management of human lung transplant patients. Vascular Surgery 8: 273 (1974a).
Veith, F.J. and Koerner, S.K.: The present status of lung transplantation. Archives of Surgery. 109: 734 (1974b).
Waldbott, G.L.: Nitrogen mustard in the treatment of bronchial asthma. Annals of Allergy. 10: 428 (1952).
Werner, S.C.: in Irvine (Ed.) Thyrotoxicosis, p.238 (William and Wilkins, Baltimore 1967).
White, R.H.R.; Glasgow, E.F. and Mills, R.J.: Clinico-pathological study of nephrotic syndrome in childhood. Lancet 1: 1353(1970).
Willoughby, J.M.T.; Kumar, P.J.; Beckett, J. and Dawson, A.M.: Controlled trial of azathioprine in Crohn’s disease. Lancet 2: 944 (1971).
Winkelman, E.I. and Brown, C.H.: Nitrogen mustard in the treatment of chronic ulcerative colitis and regional enteritis: A preliminary report. Cleveland Clinical Quarterly 32: 165 (1965).
Wong, V.G. and Hersh, E.M.: Methotrexate in the therapy of cyclitis. Transactions of American Academy of Ophthalmology and Otolaryngology 69: 279 (1965).
Woodruff, M.F.; Nolan, B.; Wilson, T.I. Lambie, A. and Clark, J.G.: Homotransplantation of kidney in patients treated by preoperative local irradiation and postoperative administration of an anti-metabolite (IMMURAN). Report of 6 cases. Lancet 2: 675 (1963).
Wright, R. and Truelove, S.C.: Autoimmune reactions in ulcerative colitis. Gut 7: 32 (1966).
Zervas, J.; Geary, C.G. and Oleesky, S.: Sideroblastic anemia treated with immunosuppressive therapy. Blood 44: 117(1974).
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Second of a 2-part review. Part I appeared in previous issue
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Gerber, N.L., Steinberg, A.D. Clinical Use of Immunosuppressive Drugs: Part II. Drugs 11, 90–112 (1976). https://doi.org/10.2165/00003495-197611020-00002
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DOI: https://doi.org/10.2165/00003495-197611020-00002