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Immunotherapy and chemoimmunotherapy of malignant disease with BCG and nonviable mycobacterial fractions

World Journal of Surgery volume 1, pages 555–579 (1977)Cite this article

Abstract

The administration of Bacillus Calmette-Guérin (BCG) has been associated with restoration of general immunocompetence, augmentation of specific tumor immunity, activation of local and regional host defense mechanisms, and stimulation of the reticuloendothelial system. There is evidence that antigens from a variety of unrelated tumors are shared with, or are similar to, antigens in BCG. However, it is uncertain whether this cross-reactivity is the basis for the antitumor activity of BCG. Numerous studies emphasize the importance of regional effects of immunotherapy. They suggest a two-step mechanism for antitumor activity that involves recognition of BCG by host defense mechanisms, followed by activation and mobilization of macrophages by specifically produced lymphokines. The several nonviable derivatives of BCG have activity comparable to BCG without many of the problems associated with viable BCG. An optimal, completely standardized BCG preparation has not yet been produced.

Clinical studies on the immunotherapeutic effects of BCG and its derivatives in cancer patients indicate that in cutaneous malignant melanoma, intralesional injection of BCG causes complete regression of tumor in 65–90% of instances, with long-term remission in patients with purely cutaneous metastatic disease. In patients with disseminated malignant melanoma, studies show prolongation of remission duration and overall survival in patients undergoing chemoimmunotherapy (with BCG + imidazole carboxamide) over those receiving chemotherapy alone. In acute lymphoblastic leukemia, one study has found a greater than 90% probability of survival in patients with the microlymphoblastic type undergoing immunotherapy after 5 years, yet other studies fail to show any therapeutic advantage. In most studies in acute myeloblastic leukemia, immunochemotherapy has given both qualitative and quantitative improvements in remission duration and particularly survival. Increased survival, particularly in stage I patients, has been reported in a trial of adjuvant BCG immunotherapy in lung cancer. Other studies on carcinoma of the colon, breast, and the head and neck, soft tissue sarcomas, and genitourinary cancers, utilizing various combinations of BCG and its derivatives, and chemotherapy, surgery, or radiation therapy indicate enhanced remission duration and survival. However, more research is needed to determine the optimum therapy combination in each case, to make refinements in dose, route, and schedule of administration, to improve product characteristics, and to overcome the complications of BCG immunotherapy.

Résumé

L'administration de BCG s'accompagne d'une restauration de l'immunocompétence générale, d'une augmentation de l'immunité antitumorale, d'une activation des mécanismes de défense locaux et régionaux et d'une stimulation du système réticuloendothélial. Il semble bien que les antigènes de divers types de tumeurs sont comparables, ou mÊme identiques, aux antigènes du BCG. Cependant, il n'est pas certain que cette réactivité croisée soit la base de l'activité antitumorale du BCG. De nombreuses études ont souligné l'importance des effets régionaux de l'immunothérapie. Ces travaux suggèrent que l'activité antitumorale du BCG agit sur deux mécanismes: la reconnaissance du BCG par les mécanismes de défense de l'hÔte suivie d'une activation et d'une mobilisation des macrophages par des lymphokines spécifiques. Les dérivés non viables du BCG ont un effet comparable, sans poser les problèmes du BCG viable. Il n'existe cependant pas encore de préparation complètement standardisée du BCG.

Les études cliniques d'immunothérapie par le BCG ont montré que, dans les mélanomes cutanés malins, l'injection intralésionelle de BCG entraÎne une régression complète de la tumeur dans 65–90% des cas, avec des rémissions à long terme chez les malades ayant uniquement des metastases cutanées. Dans les mélanomes malins disséminés, la chimioimmunothérapie (BCG + imidazole carboxamide) est plus efficace que la chimiothérapie seule. La durée des rémissions est allongée et la survie également. Dans la leucémie lymphoblastique aiquË de forme microlymphoblastique, une étude a obtenu par immunothérapie plus de 90% de survies de 5 ans; mais d'autres travaux n'ont observé aucun effet thérapeutique. Dans la plupart des études sur la leucémie myéloblastique aiguË, l'immunochimiothérapie améliore quantitativement et qualitativement la rémission et la survie. Dans un essai d'immunothérapie adjuvante au BCG dans le cancer pulmonaire, une prolongation de la survie a été observée, surtout dans les cas au stade I.

D'autres travaux sur les cancers du colon, du sein, de la tÊte et du cou, de l'appareil génito-urinaire et sur les sarcomes des tissus mous, ont utilisé des combinaisons variées de BCG et de ses dérivés, de chimiothérapie, de chirurgie et d'irradiation: elles montrent un allongement des rémissions et des survies. Il faudra cependant encore d'autres recherches pour trouver dans chaque cas la combinaison thérapeutique optimale, pour préciser les doses, modes et schémas d'administration, pour perfectionner les caractères du produit et pour prévenir les complications de l'immunothérapie au BCG.

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References

  1. Baldwin, R.W., Price, M.R.: Neoantigen expression in chemical carcinogenesis. In Cancer, a Comprehensive Treatise, F.F. Becker, editor, Vol. 4. New York, Plenum Press, 1975, pp. 353–383

    Google Scholar 

  2. Herberman, R.B., Hollinshead, A.C., Char, D., Oldham, R., McCoy, J., Cohen, M.: In vivo and in vitro studies of cell mediated immune response to antigens associated with malignant melanoma. Behring Inst. Mitt.56:131, 1975

    Google Scholar 

  3. Hersh, E.M., Gutterman, J.U., Mavligit, G.M.: Cancer and host defense mechanisms. In Pathobiology Annual, H.L. Ioachin, editor. New York, Appleton-Century-Crofts, 1975, pp. 133–159

    Google Scholar 

  4. Guerin, C.: The history of BCG. In BCG Vaccination against Tuberculosis, S.R. Rosenthal, editor. Boston, Little, Brown and Co., 1975, pp. 48–53

    Google Scholar 

  5. Sher, N.A., Chaparas, S.D., Pearson, J., Chirigos, M.: The virulence of six strains ofMycobacterium bovis (BCG) in the mouse. Infect. Immun.8:736, 1973

    Google Scholar 

  6. Mackaness, G.B., Auclair, D.J., Lagrange, P.H.: Immunopotentiation with BCG. I. Immune response to different strains and preparations. J. Natl. Cancer Inst.51:1655, 1973

    Google Scholar 

  7. Miller, T.E., Mackaness, G.B., Lagrange, P.H.: Immunopotentiation with BCG. II. Modulation of the response to sheep red blood cells. J. Natl. Cancer Inst.51:1669, 1973

    Google Scholar 

  8. Hawrylko, E., Mackaness, G.B.: Immunopotentiation with BCG. III. Modulation of the response to a tumor-specific antigen. J. Natl. Cancer Inst.51:1677, 1973

    Google Scholar 

  9. Hawrylko, R., Mackaness, G.B.: Immunopotentiation with BCG. IV. Factors affecting the magnitude of an antitumor response. J. Natl. Cancer Inst.51:1683, 1973

    Google Scholar 

  10. Fortner, G.W., Hanna, M.G., Jr., Coggin, J.H., Jr.: Differential effects of two strains of BCG on transplantation immunity to SV40-induced tumors in hamsters. Proc. Soc. Exp. Biol. Med.147:62, 1974

    Google Scholar 

  11. Halle-Pannenko, O., Bourut, C., Kamel, M: Comparison of various BCG preparations in the E.O.R.T.C.-I.C.I.G. experimental screening for systemic immunity adjuvants applicable to cancer immunotherapy. Cancer Immunol. Immunother.1:17, 1976

    Google Scholar 

  12. Mathé, G.: Surviving in the company of BCG (Editorial). Cancer Immunol. Immunother.1:3, 1976

    Google Scholar 

  13. Adam, A., Ciorbaru, R., Petit, J.F., Lederer, E.: Isolation and properties of a macromolecular, water soluble, immuno-adjuvant fraction from the cell wall ofMycobacterium smegmatis. Proc. Natl. Acad. Sci. USA69:851, 1972

    Google Scholar 

  14. Hiu, I.J.: Water soluble and lipid free fraction from BCG with adjuvant and antitumor activity. Nature [New Biol.]238:241, 1972

    Google Scholar 

  15. Ribi, E., Meyer, T.J., Azuma, I., Berton, Z.: Mycobacterial cell wall components in tumor suppression and regression. Natl. Cancer Inst. Monogr.39:115, 1973

    Google Scholar 

  16. Mathé, G., Halle-Pannenko, O., Bourut, C.: BCG in cancer immunotherapy: results obtained with various BCG preparations in a screening study for systemic adjuvants applicable to cancer immunoprophylaxis or immunotherapy. Natl. Cancer Inst. Monogr.39:107, 1973

    Google Scholar 

  17. Gheorghiu, M., Chambon, L.: Preservation of fresh BCG scarification vaccine at 4, −25, and −70‡C. Cancer Immunol. Immunother.1:11, 1976

    Google Scholar 

  18. Edwards, L.B., Palmer, C.E., Magnus, K.: BCG vaccination. WHO Monogr.12:71, 1953

    Google Scholar 

  19. Mackaness, G.B., Smith, N., Wells, A.Q.: The growth of intracellular tubercle bacilli in relation to their virulence. Am. Rev. Tuberc.69:479, 1954

    Google Scholar 

  20. Obayashi, Y.: Dried BCG vaccine. WHO Monogr.28:77, 1955

    Google Scholar 

  21. Halpern, B.N., Biozzi, G., Stiffel, C., Mouton, D.: Correlation entre l'activite phagocytaire du systeme reticuloendothelial et la Production d'anticorps antibacteriens. C.R. Soc. Biol. (Paris)152:758, 1958

    Google Scholar 

  22. Howard, J.G., Biozzi, G., Halpern, B.N., Stiffel, C., Mouton, D.: The effect ofMycobacterium tuberculosis (BCG) infection on the resistance of mice to endotoxin andSalmonella enteriditis infection. Br. J. Exp. Pathol.40:281, 1959

    Google Scholar 

  23. Stjernsward, J.: Effect of Bacillus Calmette-Guérin and/or methylcholanthrene on the antibody-forming cells measured at the cellular level of a hemolytic plaque test. Cancer Res.26:1591, 1966

    Google Scholar 

  24. Hibbs, J.B., Jr.: Discrimination between neoplastic and non-neoplastic cells in vitro by activated macrophages. J. Natl. Cancer Inst.53:1487, 1974

    Google Scholar 

  25. Evans, R., Alexander, P.: Mechanism of immunologically specific killing of tumour cells by macrophages. Nature236:168, 1972

    Google Scholar 

  26. Campbell, P.: Immunocompetent cells in resistance to bacterial infections. Bacteriol. Rev.40:284, 1976

    Google Scholar 

  27. Salvin, S.B., Younger, J.S., Lederer, W.H.: Migration inhibitory factor and interferon in the circulation of mice with delayed hypersensitivity. Infect. Immun.7:68, 1973

    Google Scholar 

  28. Hibbs, J.B., Jr.: Role of activated macrophages in non-specific resistance to neoplasia. J. Reticuloendothel. Soc.20:223, 1976

    Google Scholar 

  29. Borsos, T., Rapp, H.J.: Brief communication: Antigenic relationship betweenMycobacterium bovis (BCG) and a guinea pig hepatoma. J. Natl. Cancer Inst.51:1085, 1973

    Google Scholar 

  30. Bucana, C., Hanna, M.G., Jr.: Immunoelectron microscopic analysis of surface antigens common toMycobacterium bovis (BCG) and tumor cells. J. Natl. Cancer Inst.53:1313, 1974

    Google Scholar 

  31. Minden, P., McClatchy, J.K., Wainberg, M., Weiss, D.W.: Shared antigens betweenMycobacterium bovis (BCG) and neoplastic cells. J. Natl. Cancer Inst.53:1325, 1974

    Google Scholar 

  32. Minden, P., Sharpton, T.R., McClatchy, J.K.: Shared antigens between human malignant melanoma cells andMycobacterium bovis (BCG). J. Immunol.116:1407, 1976

    Google Scholar 

  33. Minden, P.: Shared antigens between animal and human tumors and microorganisms. In BCG in Cancer Immunotherapy, G. Lamoureaux, R. Turcotte, V. Portelance editors. New York, Grune and Stratton, 1976, pp. 73–81

    Google Scholar 

  34. Kaplan, M., Armstrong, D., Rosen, P.: Tuberculosis complicating neoplastic disease. Cancer33:850, 1974

    Google Scholar 

  35. Oster, M.W.: Tuberculosis in malignant melanoma. Med. Pediatr. Oncol.2:439, 1976

    Google Scholar 

  36. Florentin, I., Huchet, R., Bruley-Rosset, M., Halle-Pannenko, O., Mathé, G.: Studies on the mechanisms of action of BCG. Cancer Immunol. Immunother.1:31, 1976

    Google Scholar 

  37. Geffard, M., Orbach-Arbouys, S.: Enhancement of T suppressor activity in mice by high doses of BCG. Cancer Immunol. Immunother.1:41, 1976

    Google Scholar 

  38. Suter, E., Ullman, G.E., Hoffman, R.G.: Sensitivity of mice to endotoxin after vaccination with BCG (Bacillus Calmette-Guérin) (24282). Proc. Soc. Exp. Biol. Med.99:167, 1963

    Google Scholar 

  39. Carswell, E.A., Old, L.J., Dassel, R.L., Green, S., Fiore, N., Williamson, B.: An endotoxin-induced serum factor that causes necrosis of tumors. Proc. Natl. Acad. Sci. USA72:3666, 1975

    Google Scholar 

  40. Hersh, E.M. Gutterman, J.U., Mavligit, G.M., Mountain, C.W., McBride, C.M., Burgess, M.A., Lurie, P.M., Zelen, M., Takita, H., Vincent, R.G.: Immunocompetence, immunodeficiency, and prognosis in cancer. Ann. N.Y. Acad. Sci.276:386, 1976

    Google Scholar 

  41. Mavligit, G.M., Gutterman, J.U., Hersh, E.M.: Effect of BCG (Tice strain) on primary sensitization to 2, 4-dinitrochlorobenzene and on established delayed hypersensitivity in human malignant melanoma. J. Natl. Cancer Inst.57:749, 1976

    Google Scholar 

  42. Wybran, J., Spitler, L.W., Lieberman, R., Fudenberg, H.H.: “Active” T-cell rosettes and total T-rosettes in patients with melanoma following intratumoral inoculation of BCG: a clue to the mechanism of action of Bacillus Calmette-Guérin? Cancer Immunol. Immunother.1:153, 1976

    Google Scholar 

  43. Wybran, J., Fudenberg, H.H.: Thymus-derived rosette-forming cells. (Editorial) N. Engl. J. Med.288:1072, 1973

    Google Scholar 

  44. Belpomme, D., Joseph, R., Lelarge, N.: Increase of null cells in patients submitted to long-term active immunotherapy. Cancer Immunol. Immunother.1:113, 1976

    Google Scholar 

  45. MacLennan, I.C.M.: Immunosuppression and immunostimulation in acute leukemia. Proc. R. Soc. Med.68:216, 1975

    Google Scholar 

  46. Golub, S.H., O'Connell, T.X., Morton, D.L.: Correlation of in vivo and in vitro assays of immunocompetence in cancer patients. Cancer Res.34:1833, 1974

    Google Scholar 

  47. Simmler, M.C., Rameau, G., Chou, M.J., Mathé, G.: Monitoring of non-specific cell-mediated immunity in cancer patients. Isr. J. Med. Sci.12:472, 1976

    Google Scholar 

  48. Pouillart, P., Palangie, T., Schwarzenberg, L., Brugerie, H., Lheritier, J., Mathé, G.: Effect of BCG on hematopoietic stem cells: experimental and clinical study. Cancer Immunol. Immunother.1:163, 1976

    Google Scholar 

  49. Farquhar, D., Loo, T.L., Gutterman, J.U., Hersh, E.M., Luna, M.A.: Inhibition of drug-metabolizing enzymes in the rat after Bacillus-Calmette-Guérin treatment. Biochem. Pharmacol.25:1529, 1976

    Google Scholar 

  50. Biozzi, G., Stiffel, C., Halpern, B.N., Mouton, D.: Etude de la fonction phagocytaire du développement de tumeurs mignes expérimentales chez le rat et la souris. Ann. Inst. Pasteur94:681, 1958

    Google Scholar 

  51. Halpern, B.N., Biozzi, G., Stiffel, C., Mouton, D.: Effet de la stimulation du système réticulo-endothélial par l'inoculation du Bacille de Calmette-Guérin sur le développement de l'épithelioma atypique T-8 de Guérin chez le rat. C.R. Soc. Biol. (Paris)153:919, 1959

    Google Scholar 

  52. Old, L.J., Clark, D.A., Benacerraf, B.: Effect of Bacillus Calmette-Guérin infection on transplanted tumours in the mouse. Nature184:291, 1959

    Google Scholar 

  53. Weiss, D.W., Bonhag, R.S., Deome, K.B.: Protective activity of fractions of tubercle bacilli against isologous tumours in mice. Nature190:889, 1961

    Google Scholar 

  54. Bast, R.C., Jr., Zbar, B., Borsos, T., Rapp, H.J.: BCG and cancer. N. Engl. J. Med.290:1413, 1974

    Google Scholar 

  55. Bast, R.C., Jr., Bast, B.S., Rapp, H.J.: Critical review of previously reported animal studies of tumor immunotherapy with non-specific immunostimulants. Ann. N.Y. Acad. Sci.277:60, 1976

    Google Scholar 

  56. Chassoux, D., Salomon, J.C.: Therapeutic effect of intratumoral injection of BCG and other substances in rats and mice. Int. J. Cancer16:515, 1975

    Google Scholar 

  57. Zbar, B., Ribi, E., Rapp, H.J.: An experimental model for immunotherapy of cancer. Natl. Cancer Inst. Monogr.39:3, 1973

    Google Scholar 

  58. Sparks, F.C., O'Connell, T.X., Lee, Y.T.N.: Adjuvant pre-operative and post-operative immunochemotherapy for mammary adenocarcinoma in rats. Surg. Forum24:118, 1973

    Google Scholar 

  59. Baldwin, R.W., Pimm, M.V.: BCG immunotherapy or rat tumors of defined immunogenicity. Natl. Cancer Inst. Monogr.39:11, 1973

    Google Scholar 

  60. Baldwin, R.W., Pimm, M.V.: BCG immunotherapy of pulmonary growths from intravenously transferred rat tumor cells. Br. J. Cancer27:48, 1973

    Google Scholar 

  61. Baldwin, R.W., Pimm, M.V.: BCG immunotherapy of local subcutaneous growths and postsurgical pulmonary metastases of a transplanted rat epithelioma of spontaneous origin. Int. J. Cancer12:420, 1973

    Google Scholar 

  62. Zbar, B., Bernstein, I.D., Bartlett, G.L., Hanna, M.G., Jr., Rapp, H.J.: Immunotherapy of cancer: regression of intradermal tumors and prevention of growth of lymph node metastases after intralesional injection of livingMycobacterium bovis. J. Natl. Cancer Inst.49:119, 1972

    Google Scholar 

  63. Zbar, B., Ribi, E., Kelly, M., Granger, D., Evans, C., Rapp, H.J.: Immunologic approaches to the treatment of human cancer based on a guinea pig model. Cancer Immunol. Immunother.1:127, 1976

    Google Scholar 

  64. Amiel, J.L., Berardet, M.: Factor time for active immunotherapy after cytoreductive chemotherapy. Eur. J. Cancer10:89, 1974

    Google Scholar 

  65. Simmons, R.L., Rios, A.: Immunotherapy of cancer: immunospecific rejection of tumors in recipients of neuraminidase-treated tumor cells plus BCG. Science174:591, 1971

    Google Scholar 

  66. Piessens, W.F., LaChapelle, F.L., Legros, N., Heuson, J.C.: Facilitation of rat mammary tumour growth by BCG. Nature228:1210, 1970

    Google Scholar 

  67. Evans, R., Alexander, P.: Mechanism of immunologically specific killing of tumour cells by macrophages. Nature236:168, 1972

    Google Scholar 

  68. Piessens, W.F., Churchill, W.H., Jr., David, J.R.: Macrophages activated in vitro with lymphocyte mediators kill neoplastic but not normal cells. J. Immunol.114:293, 1975

    Google Scholar 

  69. Hanna, M.G., Jr.: Immunologic aspects of BCG-mediated regression of established tumors and metastases in guinea pigs. Semin. Oncol.1:319, 1974

    Google Scholar 

  70. Fidler, I.J., Budmen, M.B., Hanna, M.G., Jr.: Characterization of in vitro reactivity by BCG-treated guinea pigs to syngeneic line-10 hepatocarcinoma. Cancer Immunol. Immunother.1:179, 1976

    Google Scholar 

  71. Baldwin, R.W.: Relevant animal models for tumor immunotherapy (Editorial). Cancer Immunol. Immunother.1:197, 1976

    Google Scholar 

  72. Rapp, H.J., Kleinschuster, S.J., Lueker, D.C., Kramer, R.A.: Immunotherapy of experimental cancer as a guide to the treatment of human cancer. Ann. N.Y. Acad. Sci.276:550, 1976

    Google Scholar 

  73. Zbar, B., Ribi, E., Meyer, T., Azuma, I., Rapp, H.J.: Immunotherapy of cancer: regression of established intradermal tumors after intralesional injection of mycobacterial cell walls attached to oil droplets. J. Natl. Cancer Inst.52:1571, 1974

    Google Scholar 

  74. Freund, J.: The mode of action of immunological adjuvants. Adv. Tuberc. Res.7:130, 1956

    Google Scholar 

  75. Weiss, D.W.: MER and other mycobacterial fractions in the immunotherapy of cancer. Med. Clin. North Am.60:473, 1976

    Google Scholar 

  76. Wainberg, M.A., Margolese, R.G., Weiss, D.W.: Tumor immunoprophylaxis and immunotherapy in guinea pigs treated with the methanol extraction residue (MER) of BCG. In BCG in Cancer Immunotherapy, G. Lamoureaux, R. Turcotte, V. Portelance, editors. New York, Grune and Stratton, 1976, pp. 39–50

    Google Scholar 

  77. Cohen, D., Yron, L., Haber, M., Robinson, E., Weiss, D.W.: Effect of treatment with the MER tubercule bacilli fraction on the survival of mice carrying mammary tumor isografts: injection of MER at the tumor site or at a distal location. Br. J. Cancer32:483, 1975

    Google Scholar 

  78. Weiss, D.W., Stupp, R., Manny, N., Izak, G.: Treatment of acute myelocytic leukemia (AML) patients with the MER tubercle bacillus fraction. A preliminary report. Transplant. Proc.7:545, 1975

    Google Scholar 

  79. Hopper, D.G., Pimm, M.V., Baldwin, R.W.: Methanol extraction residue of BCG in the treatment of transplanted rat tumors. Br. J. Cancer31:176, 1975

    Google Scholar 

  80. Ribi, E., Milner, K.C., Granger, D.L., Kelly, M.T., Yamamoto, K., Brehmer, W., Parker, R. Smith, R.F., Strain, S.M.: Immunotherapy with non-viable microbial components. Proc. N.Y. Acad. Sci.277:228, 1976

    Google Scholar 

  81. Granger, D.L., Yamamoto, K., Ribi, E.: Delayed hypersensitivity and granulomatous response following immunization with protein antigens associated with a mycobacterial glycolipid and oil droplets. J. Immunol.116:482, 1976

    Google Scholar 

  82. Kelly, M.T., Granger, D.L., Ribi, E., Milner, K.C., Strain, S.M., Stoenner, H.G.: Tumor regression with Q fever rickettsiae and a mycobacterial glycolipid. Cancer Immunol. Immunother.1:187, 1976

    Google Scholar 

  83. Lederer, E., Adam, A., Ciorbaru, R., Petit, J.F., Wietzerbin, J.: Cell walls of mycobacteria and related organisms: chemistry and immunostimulant properties. Mol. Cell Biochem.7:87, 1975

    Google Scholar 

  84. Juy, D., Chedid, L.: Comparison between macrophage activation and enhancement of non-specific resistance to tumors by mycobacterial immuno-adjuvants. Proc. Natl. Acad. Sci. USA72:4105, 1975

    Google Scholar 

  85. Lamesans, A., Chedid, L., Lederer, E., Rosselet, J.P., Gustafson, R.H., Spencer, H.J., Ludwig, B., Berger, F.M.: Enhancement of immunity against murine syngeneic tumors by a fraction extracted from nonpathogenic mycobacteria. Proc. Natl. Acad. Sci. USA72:3656, 1975

    Google Scholar 

  86. Davignon, L., Lemonde, P., Robillard, P., Frappier, A.: BCG vaccination and leukemia mortality. Lancet2:638, 1970

    Google Scholar 

  87. Rosenthal, S.R., Crispen, R.G., Thorne, M.G., Piekarski, N., Raisys, N., Rettig, P.G.: BCG vaccination and leukemia mortality. J.A.M.A.222:1543, 1972

    Google Scholar 

  88. Hoover, R.N.: Bacillus Calmette-Guérin vaccination and cancer prevention: a critical review of the human experience. Cancer Res.36:652, 1976

    Google Scholar 

  89. Kinlen, L.J., Pike, M.C.: BCG vaccination and leukemia. Evidence of vital statistics. Lancet1:398, 1971

    Google Scholar 

  90. Waaler, H.T.: BCG and leukemia mortality. Lancet2:1314, 1971

    Google Scholar 

  91. Coley, W.B.: A report of recent cases of inoperable sarcomas successfully treated with mixed toxins of erysipelas andBacillus prodigiosus. Surg. Gynecol. Obstet.13:179, 1911

    Google Scholar 

  92. Klein, E., Holtermann, O.A., Papermaster, B.W., Milgrom, H., Rosner, D., Klein, L., Walker, M.J., Zbar, B.: Immunologic approaches to various types of cancer with the use of BCG and purified protein derivatives. J. Natl. Cancer Inst. Monogr.39:229, 1973

    Google Scholar 

  93. Klein, E., Holterman, O., Milgrom, H., Case, R.W., Klein, D., Rosner, D., Djerassi, I.: Immunotherapy for accessible tumors utilizing delayed hypersensitivity reactions and separated components of the immune system. Med. Clin. North Am.60:389, 1976

    Google Scholar 

  94. Morton, D.L., Eilber, F.R., Malmgren, R.A., Wood, W.C.: Immunological factors which influence response to immunotherapy in malignant melanoma. Surgery68:158, 1970

    Google Scholar 

  95. Mathé, G., Amiel, J.L., Schwarzenberg, L., Schneider, M., Cattan, A., Schlumberger, J.R., Hayat, M., Devassal, F.: Active immunotherapy for acute lymphoblastic leukemia. Lancet1:697, 1969

    Google Scholar 

  96. Mathé, G., Pouillart, P., Lapeyraque, F.: Active immunotherapy of L1210 leukemia applied after the graft of tumour cells, Br. J. Cancer23:814, 1969

    Google Scholar 

  97. Rosenberg, S.A., Rapp, H.J.: Intralesional immunotherapy of melanoma with BCG. Med. Clin. North Am.60:419, 1976

    Google Scholar 

  98. Mastrangelo, M.J., Berd, D., Bellet, R.E.: Critical review of previously reported clinical trials of cancer immunotherapy with non-specific immunostimulants. Ann. N.Y. Acad. Sci.277:94, 1976

    Google Scholar 

  99. Cohen, M.H., Felix, E., Jessup, J., Rosenberg, S.: Treatment of metastatic melanoma by intralesional injection of BCG, organic chemicals andC. Parvum. In Neoplasm Immunity: Mechanisms, R.G. Crispen, editor. Chicago, Institute for Tuberculosis Research, 1976, pp. 121–131

    Google Scholar 

  100. Mastrangelo, M.J., Bellet, R.E., Berkelhammer, J., Clark, W.H., Jr.: Regression of pulmonary metastatic disease associated with intralesional BCG therapy of dermal melanoma metastases. Cancer36:1305, 1975

    Google Scholar 

  101. Morton, D.L., Eilber, F.R., Holmes, E.C., Hunt, J.S., Ketcham, A.S., Silverstein, M.S., Sparks, F.C.: BCG immunotherapy of malignant melanoma: summary of a seven-year experience. Ann. Surg.180:635, 1974

    Google Scholar 

  102. Mastrangelo, M.J., Sulit, H.L., Prehn, L.M., Bornstein, R.X., Yarbro, J.W., Prehn, R.T.: Intralesional BCG in the treatment of metastatic malignant melanoma. Cancer37:684, 1976

    Google Scholar 

  103. Nathanson, L.: Regression of intradermal malignant melanoma after intralesional injection ofMycobacterium bovis strain BCG. Cancer Chemother. Rep.56:659, 1972

    Google Scholar 

  104. Pinsky, C.M., El Domeiri, A., Caron, A.S., Knapper, W.H., Oettgen, H.F.: Delayed hypersensitivity reaction in patients with cancer. In Investigation and Stimulation of Immunity in Cancer Patients. Proceedings of CNRS Colloquium, Paris, June 21–22, 1972. G. Mathé, R. Weiner, editors. Recent Results in Cancer Research, Vol. 47, Berlin-Heidelberg-New York, Springer-Verlag, 1974, pp. 37–41

    Google Scholar 

  105. Lieberman, R., Wybran, J., Epstein, W.: The immunologic and histopathologic changes of BCG in cell mediated tumor regression in patients with malignant melanoma. Cancer35:756, 1975

    Google Scholar 

  106. Khalil, A., Rappaport, H., Misset, J.L.: Kinetics of histologic changes in human melanoma after local immunotherapy with BCG. Cancer Immunol. Immunother.1:193, 1976

    Google Scholar 

  107. Hanna, M.G., Jr., Snodgrass, M.J., Zbar, B., Rapp, H.J.: Histologic and ultrastructural studies of tumor regression in inbred guinea pigs after intralesional injection ofMycobacterium bovis (BCG). Natl. Cancer Inst. Mongr.39:71, 1973

    Google Scholar 

  108. Everall, J.D., O'Doherty, E.J., Wand, J., Dowd, P.M.: Treatment of primary melanoma by intralesional vaccinia before excision. Lancet2:583, 1975

    Google Scholar 

  109. Yamamura, Y., Yoshizaki, K., Azuma, I., Yagura, T., Watanabe, T.: Immunotherapy of human malignant melanoma with oil-attached BCG cell wall skeleton. Gann66:355, 1975

    Google Scholar 

  110. Bluming, A.Z., Vogel, C.L., Ziegler, J.L.. Mody, N., Kamya, G.: Immunological effects of BCG in malignant melanoma: two modes of administration compared. Ann. Intern. Med.76:405, 1972

    Google Scholar 

  111. Gutterman, J.U., Mavligit, G.M., McBride, C.M., Frei, E., Freireich, E.J., Hersh, E.M.: Active immunotherapy with BCG for recurrent malignant melanoma. Lancet1:1208, 1973

    Google Scholar 

  112. Gutterman, J.U., Mavligit, G.M., Burgess, M.A., Cardenas, J.O., Blumenschein, G.R., Gottlieb, J.A., McBride, C.M., McCredie, K.B., Bodey, G.P., Rodriguez, V., Freireich, E.J., Hersh, E.M.: Immunotherapy of human solid tumors and acute leukemia with BCG: prolongation of disease-free interval and survival. Cancer Immunol. Immunother.1:99, 1976

    Google Scholar 

  113. Eilber, F.R., Morton, D.L., Holmes, E.C., Sparks, F.C., Ramming, K.P.: Adjuvant immunotherapy with BCG in treatment of regional lymph node metastases from malignant melanoma. N. Engl. J. Med.294:237, 1976

    Google Scholar 

  114. Ikanopisov, R.L.: The use of BCG in the combined treatment of malignant melanoma. In International Symposium on Immunological Reactions to Melanoma Antigens, E. Heide, editor. Behring-Werke, 1975, pp. 206–214

  115. Beretta, G.: Controlled study for prolonged chemotherapy, immunotherapy and chemotherapy plus immunotherapy as an adjuvant to surgery. In Immunotherapy of Cancer. Present Status of Trials in Man, D. Windhorst, R. Terry, editors. New York, Raven Press (in press)

  116. Pinsky, C.M., Hirshant, Y., Wanebo, J.H., Fortner, J.G., Mike, V., Schottenfeld, D., Oettgen, H.F.: Randomized trial of Bacillus Calmette-Guérin (percutaneous administration) as surgical adjuvant immunotherapy for patients with stage II melanoma. Ann. N.Y. Acad. Sci.277:187, 1976

    Google Scholar 

  117. Gutterman, J.U., Mavligit, G.M., McBride, C.M., Richman, S.P., Burgess, M.A., Hersh, E.M.: Post-operative immunotherapy for recurrent malignant melanoma: an updated report. In Immunotherapy of Cancer. Present Status of Trials in Man, D. Windhorst, R. Terry, editors. New York, Raven Press (in press)

  118. Gutterman, J.U., Mavligit, G.M., Gottlieb, J.A., Burgess, M.A., McBride, C.M., Einhorn, L., Freireich, E.J., Hersh, E.M.: Chemoimmunotherapy of disseminated malignant melanoma with dimethyl triazeno imidazole carboxamide and Bacillus Calmette-Guérin. N. Engl. J. Med.291:592, 1974

    Google Scholar 

  119. Gutterman, J.U., Hersh, E.M., Mavligit, G.M., Burgess, M.A., Richman, S.P., Schwarz, M.A., Rodriguez, G., Valdivieso, M.: Chemoimmunotherapy of disseminated malignant melanoma with Bacillus Calmette-Guérin: follow-up report. In Immunotherapy of Cancer. Present Status of Trials in Man, D. Windhorst, R. Terry, editors. New York, Raven Press (in press)

  120. Costanzi, J.J.: Chemotherapy and BCG in the treatment of disseminated malignant melanoma—a Southwest Oncology Group study. In Immunotherapy of Cancer. Present Status of Trials in Man, D. Windhorst, R. Terry, editors. New York, Raven Press (in press)

  121. Laucius, J.F., Bodurtha, A.J., Berkelhammer, J., Prehn, L.M., Prehn, R.T., Mastrangelo, M.J.: Intradermal injection of autochthonous irradiated tumor cells plus BCG in the treatment of metastatic malignant melanoma. Proc. Am. Assoc. Cancer Res.15:849, 1974

    Google Scholar 

  122. Currie, G.A., McElwain, T.J.: Active immunotherapy as an adjuvant to chemotherapy in the treatment of disseminated malignant melanoma. A pilot study. Br. J. Cancer31:143, 1975

    Google Scholar 

  123. Mastrangelo, M.J., Bellet, R.W., Berd, D.: A randomized prospective trial comparing MeCCNU + vincristine to MeCCNU + vincristine + BCG + allogeneic tumor cells in patients with metastatic malignant melanoma. In Immunotherapy of Cancer. Present Status of Trials in Man, D. Windhorst, R. Terry, editors. New York, Raven Press (in press)

  124. Simmons, R.L.: Comparison of chemotherapy plus VCN-treated autologous tumor cells in stages II and III melanoma. In Immunotherapy of Cancer. Present Status of Trials in Man, D. Windhorst, R. Terry, editors. New York, Raven Press (in press)

  125. Mathe, G.L., Schwarzenberg, L., Amiel, J.L., Pouillart, P., Hayat, M., DeVassal, F., Rosenfeld, C., Jasmin, E.: New experimental and clinical data on leukemia immunotherapy. Proc. R. Soc. Med.68:211, 1975

    Google Scholar 

  126. Mathé, G., DeVassal, F., Delgado, M., Pouillart, P., Belpomme, D., Joseph, R., Schwarzenberg, L., Amiel, J.L., Schneider, M., Cattan, A., Musset, M., Misset, J.L., Jasmin, C.: 1975 current results of the first 100 cytologically typed acute lymphoid leukemia submitted to BCG active immunotherapy. Cancer Immunol. Immunother.1:77, 1976

    Google Scholar 

  127. Mathé, G., Schwarzenberg, L., DeVassal, G., Delgado, M., Pena-Angulo, J., Belpomme, D., Pouillart, P., Machover, D., Misset, J.L., Pico, J.L., Jasmin, C., Hayat, M., Schneider, M., Cattan, A., Amiel, J.L., Musset, M., Rosenfeld, C.: Chemotherapy followed by active immunotherapy in the treatment of acute lymphoid leukemias for patients for all ages. In Immunotherapy of Cancer. Present Status of Trials in Man, D. Windhorst, R. Terry, editors. New York, Raven Press (in press)

  128. Medical Research Council: Treatment of acute lymphoblastic leukemia. Comparison of immunotherapy (BCG), intermittent methotrexate and no therapy after a five month intensive cytotoxic regimen (Concord Trial). Preliminary report to the Medical Research Council by the Leukemia Committee and the Working Party on Leukemia in Childhood. Br. Med. J.4:189, 1971

    Google Scholar 

  129. Leventhal, B.G., LePourhiet, A., Halterman, R.H., Henderson, E.S., Herberman, R.B.: Immunotherapy in previously treated acute lymphatic leukemia. Natl. Cancer Inst. Monogr.39:177, 1973

    Google Scholar 

  130. Heyn, R., Borges, W., Joo, P., Karon, M., Nesbit, M., Shore, N., Breslow, N., Weiner, J., Reid, A., Hammond, D.: BCG in the treatment of acute lymphatic leukemia. Blood46:431, 1975

    Google Scholar 

  131. Poplack, D.G., Graw, R.G., Pomeroy, T.C., Henderson, E.S., Leventhal, B.G.: Chemotherapy versus chemotherapy and immunotherapy in childhood acute lymphatic leukemia. Proc. Am. Assoc. Cancer Res.16:230, 1975

    Google Scholar 

  132. Gutterman, J.U., Hersh, E.M., Rodriguez, V., McCredie, K.B., Mavligit, G.M., Reed, R., Burgess, M.A., Smith, T., Gehan, E., Bodey, G.P., Freireich, E.J.: Chemoimmunotherapy of adult acute leukemia. Prolongation of remission in myeloblastic leukemia with BCG. Lancet2:1405, 1974

    Google Scholar 

  133. Ekert, H., Jose, D.G., Waters, K.D., Smith, P.J., Mathews, R.N.: Intermittent chemotherapy and BCG in continuation therapy of children with acute lymphocytic leukemia. In Immunotherapy of Cancer. Present Status of Trials in Man, D. Windhorst, R. Terry, editors. New York, Raven Press (in press)

  134. European Organization for Research on Treatment of Cancer Hemopathies Working Party: Immunotherapy versus chemotherapy as maintenance treatment of acute lymphoblastic leukemia. In Immunotherapy of Cancer. Present Status of Trials in Man, D. Windhorst, R. Terry, editors. New York, Raven Press (in press)

  135. Simone, J.: Acute lymphocytic leukemia in childhood. Semin. Hematol.11:25, 1974

    Google Scholar 

  136. Aur, R.J., Simone, J., Hustu, H.O., Verzosa, M.S., Pinkel, D.: Cessation of therapy during complete remission of childhood acute lymphacytic leukemia. N. Engl. J. Med.291:1230, 1974

    Google Scholar 

  137. Aur, R., Verzosa, M., Hustu, O., Simone, J., Barker, L.: Leucoencephalopathy (LEP) during initial complete remission (CR) in children with acute lymphocytic leukemia (ALL) receiving methotrexate (MTX). Pros. Am. Assoc. Cancer Res.16:92, 1975

    Google Scholar 

  138. Canellos, G.P., DeVita, V.T., Arseneau, J.C., Johnson, R.C.: Carcinogenesis by cancer chemotherapeutic agents: second malignancies complicating Hodgkin's disease in remission. In Complications of Cancer Chemotherapy, G. Mathé, R.K. Oldham, editors. Recent Results in Cancer Research, Vol. 49, Berlin-Heidelberg-New York, Springer-Verlag, 1974, pp. 108–114

    Google Scholar 

  139. Freeman, C.B., Harris, R., Geary, C.G., Leyland, M.H., MacIver, J.E., Delamore, I.W.: Active immunotherapy used alone for maintenance of patients with acute myeloid leukemia. Br. Med. J.4:571, 1973

    Google Scholar 

  140. Powles, R.: Immunotherapy for acute myelogenous leukemia. Br. J. Cancer28 [Suppl. 1]:262, 1973

    Google Scholar 

  141. Gutterman, J.U., Rossen, R.D., Butler, W.T., McCredie, K.B., Bodey, G.P., Sr., Freireich, E.J., Hersh, E.M.: Immunoglobulin on tumor cells and tumor-induced lymphocyte blastogenesis in human acute leukemia. N. Engl. J. Med.288:169, 1973

    Google Scholar 

  142. Powles, R., Russell, J., Lister, T.A., Oliver, T., Whitehouse, J.M.A., Malpas, J., Chapuis, B., Crowther, D., Alexander, P.: Immunotherapy for acute myelogenous leukemia: analysis of a controlled clinical study 2 1/2 years after entry of the last patient. In Immunotherapy of Cancer. Present Status of Trials in Man, D. Windhorst, R. Terry, editors. New York, Raven Press (in press)

  143. Gutterman, J.U., Rodriguez, V., McCredie, K.B., Hester, J.P., Bodey, G.P., Freireich, E.J., Hersh, E.M.: Chemoimmunotherapy of acute myeloblastic leukemia: four-year follow-up with BCG. In Immunotherapy of Cancer. Present Status of Trials in Man, D. Windhorst, R. Terry, editors. New York, Raven Press (in press)

  144. Sokal, J.E., Aungst, C.W., Grace, J.T.: Immunotherapy in well controlled chronic myelocytic leukemia. N.Y. State J. Med.73:1180, 1973

    Google Scholar 

  145. Sokal, J.E., Aungst, C.W., Snyderman, M., Gomez, G.: Immunotherapy of chronic myelocytic leukemia: effects of different vaccination schedules. Ann. N.Y. Acad. Sci.277:367, 1976

    Google Scholar 

  146. Schwarzenberg, L., Simmler, M.C., Pico, J.L.: Human toxicology of BCG applied in cancer immunotherapy. Cancer Immunol. Immunother.1:69, 1976

    Google Scholar 

  147. Sokal, J.E., Aungst, C.W., Snyderman, M.: Delay in progression of malignant lymphoma after BCG vaccination. N. Engl. J. Med.291:1226, 1974

    Google Scholar 

  148. Bakemeier, R.F., Costello, W., Horton, J., DeVita, V.T.: BCG immunotherapy following chemotherapy-induced remissions of stage III and IV Hodgkin's disease. In Immunotherapy of Cancer. Present Status of Trials in Man, D. Windhorst, R. Terry, editors. New York, Raven Press (in press)

  149. Jones, S.E., Salmon, S.E., Moon, T.E., Butler, J.J.: Chemoimmunotherapy of non-Hodgkin's lymphoma with BCG: a preliminary report. In Immunotherapy of Cancer. Present Status of Trials in Man, D. Windhorst, R. Terry, editors. New York, Raven Press (in press)

  150. Hoerni, B., Chauvergne, J., Hoerni-Simon, G., Durand, M., Lagarde, C.: The utility of BCG in the immunotherapy of malignant lymphomas. Cancer Immunol. Immunother. (in press)

  151. Mathé, G., Belpomme, D., Pouillart, P., Schwarzenberg, L., Misset, J.L., Jasmin, C., Musset, M., Cattan, A., Amiel, J.L., Schneider, M.: Preliminary results of an immunotherapy trial of terminal leukaemic lymphosarcoma. Biomedicine23:465, 1975

    Google Scholar 

  152. Magrath, I.T., Ziegler, J.L.: Failure of BCG immunostimulation to affect the clinical course of Burkitt's Lymphoma. Br. Med. J.1:615, 1976

    Google Scholar 

  153. Edwards, F.R., Whitwell, F.: Use of BCG as an immunostimulant in the surgical treatment of carcinoma of the lung. Thorax,29:654, 1974

    Google Scholar 

  154. Ruckdeschel, J., Codish, S.D., Stranahan, A., McKneally, M.G.: Postoperative empyema improves survival in lung cancer. N. Engl. J. Med.287:1013, 1972

    Google Scholar 

  155. McKneally, M.F., Maver, C., Kausel, H.W.: Regional immunotherapy of lung cancer using intrapleural BCG. Lancet1:377, 1976

    Google Scholar 

  156. McKneally, M.F., Maver, C., Kausel, H.W.: Regional immunotherapy of lung cancer using intrapleural BCG. In Immunotherapy of Cancer. Present Status of Trials in Man, D. Windhorst, R. Terry, editors. New York, Raven Press (in press)

  157. Pouillart, P., Mathé, G., Palangie, T., Schwarzenberg, L., Huguenin, P., Morin, P., Gautier, M., Parrot, R.: Trial of BCG immunotherapy in the treatment of resectable squamous cell carcinoma of the bronchus (stages I and II). Cancer Immunol. Immunother.1:271, 1976

    Google Scholar 

  158. Pines, A.: A 5-year controlled study of BCG and radiotherapy for inoperable lung cancer. Lancet1:380, 1976

    Google Scholar 

  159. Yamamura, Y., Azuma, I., Taniyama, T., Sugimura, K., Hirao, F., Tokuzen, R., Okabe, M., Nakahara, W., Yasumoto, K., Ohta, M.: Immunotherapy of cancer with cell wall skeleton ofMycobacterium bovis—Bacillus Calmette-Guérin: experimental and clinical results. Ann. N.Y. Acad. Sci.277:209, 1976

    Google Scholar 

  160. Yamamura, Y.: Immunotherapy of lung cancer with oil-attached cell wall skeleton of BCG. In Immunotherapy of Cancer. Present Status of Trials in Man, D. Windhorst, R. Terry, editors. New York, Raven Press (in press)

  161. Garner, F.B., Meyer, C.A., White, D.S., Lipton, A.: Aerosol BCG treatment of carcinoma metastatic to the lung: a phase I study. Cancer35:1088, 1975

    Google Scholar 

  162. Stewart, T.H.M., Hollinshead, A.C., Harris, J.E., Belanger, R., Crepeau, A., Hooper, G.D., Sachs, H.J., Klaassen, D.J., Hirte, W., Rapp, E., Crook, A.F., Orizaga, M., Sengar, D.P.S., Raman, S.: Immunochemotherapy of lung cancer. Ann. N.Y., Acad. Sci.277:436, 1976

    Google Scholar 

  163. Takita, H., Takada, N., Minowada, J., Han, T., Edgerton, F.: Adjuvant immunotherapy of stage III lung carcinoma. In Immunotherapy of Cancer. Present Status of Trials in Man, D. Windhorst, R. Terry, editors. New York, Raven Press (in press)

  164. Mavligit, G.M., Gutterman, J.U., Burgess, M.A., Khankhanian, N., Seibert, G.B., Speer, J.F., Jubert, A.V., Martin, R.C., McBride, C.M., Copeland, E.M., Gehan, E.A., Hersh, E.M.: Prolongation of postoperative disease-free interval and survival in human colorectal cancer by Bacillus Calmette-Guérin (BCG) or BCG plus 5-fluorouracil. Lancet1:871, 1976

    Google Scholar 

  165. Mavligit, G.M., Gutterman, J.U., Malahy, M.A., Burgess, M.A., McBride, C.M., Jubert, A., Hersh, E.M.: Systemic adjuvant immunotherapy and chemoimmunotherapy in patients with colorectal cancer (Dukes' C class): prolongation of disease-free interval and survival. In Immunotherapy of Cancer. Present Status of Trials in Man, D. Windhorst, R. Terry, editors. New York, Raven Press (in press)

  166. Moertel, C.G., Ritts, R.E., Schutt, A.J., Hahn, R.G.:Clinical studies of methanol extraction fraction of Bacillus Calmette-Guérin as an immunostimulant in patients with advanced cancer. Cancer Res.35:3075, 1975

    Google Scholar 

  167. Moertel, C.G., O'Connell, M.J., Ritts, R.E., Jr., Schutt, A.J., Reitemeier, R.J., Hahn, R.G., Frytak, S.K.: A controlled evaluation of combined immunotherapy (MER-BCG) and chemotherapy for advanced colorectal cancer. In Immunotherapy of Cancer. Present Status of Trials in Man, D. Windhorst, R. Terry, editors. New York, Raven Press (in press)

  168. Weiss, D.: Discussion on “A controlled evaluation of combined immunotherapy (MER-BCG) and chemotherapy for advanced colorectal cancer”. In Immunotherapy of Cancer. Present Status of Trials in Man, D. Windhorst, R. Terry, editors. New York, Raven Press (in press)

  169. Engstrom, P.F., Paul, A.R., Catalano, R.B., Mastrangelo, M.J., Creech, R.H.: Fluorouracil versus fluorouracil + Bacillus Calmette-Guérin in colorectal adenocarcinoma. In Immunotherapy of Cancer. Present Status of Trials in Man, D. Windhorst, R. Terry, editors. New York, Raven Press (in press)

  170. Falk, R.E., Macgregor, A.B., Landi, S., Ambus, U., Langer, B.: Immunostimulation with intraperitoneally administered Bacillus Calmette-Guérin for advanced malignant tumors of the gastrointestinal tract. Surg. Gynecol. Obstet.142:363, 1976

    Google Scholar 

  171. Gutterman, J.U., Cardenas, J.O., Blumenschein, G.R., Hortobagyi, G., Livingston, R.B., Mavligit, G.M., Freireich, E.J., Gottlieb, J.A., Hersh, E.M.: Chemoimmunotherapy of disseminated breast cancer: prolongation of remission and survival. Br. Med. J.2:1222, 1976

    Google Scholar 

  172. Tashima, C.K., Blumenschein, G.R., Gutterman, J.U.: Comparison of adriamycin combination drug program with BCG immunotherapy versus MER immunotherapy for metastatic breast cancer. Proc. Am. Soc. Clin. Oncol.17:288, 1976

    Google Scholar 

  173. Donaldson, R.C.: Methotrexate plus Bacillus Calmette-Guérin (BCG) and isoniazid in the treatment of cancer of the head and neck. Am. J. Surg.124:527, 1972

    Google Scholar 

  174. Richman, S.P., Livingston, R.B., Gutterman, J.U., Suen, J.Y., Hersh, E.M.: Chemotherapy versus chemoimmunotherapy of head and neck cancer: report of a randomized study. Cancer Treat. Rep.60:535, 1976

    Google Scholar 

  175. Eilber, F.R., Morton, D.L.: Adjuvant chemoimmunotherapy in advanced lesions of the head and neck. Am. J. Roentgenol. Radium Ther. Nucl. Med.126:1082, 1976

    Google Scholar 

  176. Townsend, C.M., Eilber, F.R., Morton, D.L.: Skeletal and soft tissue sarcomas. Treatment with adjuvant immunotherapy. J.A.M.A.236:2187, 1976

    Google Scholar 

  177. Eilber, F.R., Morton, D.L.: Adjuvant treatment of osteosarcoma with BCG and allogeneic cells. In Immunotherapy of Cancer. Present Status of Trials in Man, D. Windhorst, R. Terry, editors. New York, Raven Press (in press)

  178. Morales, A., Eidinger, D., Bruce, A.W.: Intracavitary Bacillus Calmette-Guérin in the treatment of superficial bladder tumors. J. Urol.116:180, 1976

    Google Scholar 

  179. Morales, A., Eidinger, D., Bruce, A.W.: Adjuvant BCG immunotherapy in recurrent superficial bladder cancer. In Immunotherapy of Cancer. Present Status of Trials in Man, D. Windhorst, R. Terry, editors. New York, Raven Press (in press)

  180. Morales, A., Eidinger, D.: Bacillus Calmette-Guérin in the treatment of adenocarcinoma of the kidney. J. Urol.115:377, 1976

    Google Scholar 

  181. Merrin, C., Han, T., Klein, E., Wajsman, Z., Murphy, G.P.: Immunotherapy of prostatic carcinoma with Bacillus Calmette-Guérin. Cancer Chemother. Rep.59:157, 1975

    Google Scholar 

  182. Hudson, C.N., McHardy, J.E., Curling, O.M., English, P.E., Levin, L., Poulton, T.Z., Crowther, M., Leighton, M.: Active specific immunotherapy for ovarian cancer. Lancet2:877, 1976

    Google Scholar 

  183. Sparks, F.C.: Hazards and complications of BCG immunotherapy. Med. Clin. North Am.60:499, 1976

    Google Scholar 

  184. Aranha, C.B., McKhann, C.F.: Disseminated BCG infections and systemic BCG toxicity. In BCG in Cancer Immunotherapy, G. Lamoureux, R. Turcotte, V. Portelance, editors. New York, Grune and Stratton, 1976, pp. 141–147

    Google Scholar 

  185. Richman, S.P., Mavligit, G.M., Wolk, R., Gutterman, J.U., Hersh, E.M.: Epilesional scarification: preliminary report of a new approach to local immunotherapy with BCG. J.A.M.A.234:1233, 1975

    Google Scholar 

  186. Whittaker, J.A., Slater, A.J.: The immunotherapy of acute myelogenous leukemia using intravenous BCG. In Immunotherapy of Cancer. Present Status of Trials in Man, D. Windhorst, R. Terry, editors. New York, Raven Press (in press)

  187. Old, L.J., Benacerraf, B., Clarke, D.A., Carswell, E.A., Stockert, E.: The role of the reticuloendothelial system in the host reaction to neoplasia. Cancer Res.21:1281, 1961

    Google Scholar 

  188. Stjernsward, J.: Immune status of the primary host toward its own methyl-cholanthrene-induced sarcomas. J. Natl. Cancer Inst.40:13, 1968

    Google Scholar 

  189. Sparks, F.C., Albert, N.E.: Does isoniazid decrease the effect of BCG on local tumor growth? Surg. Forum26:162, 1975

    Google Scholar 

  190. Bornstein, R.S., Mastrangelo, M.J., Sulit, H., Chee, D., Yarbro, J.W., Prehn, L.; Prehn, R.T.: Immunotherapy of melanoma with intralesional BCG. Natl. Cancer Inst. Monogr.39:213, 1973

    Google Scholar 

  191. Meltzer, M.D., Leonard, E.J.: Enhanced tumor growth in animals pretreated with complete Freund's adjuvant. J. Natl. Cancer Inst.50:209, 1973

    Google Scholar 

  192. Rook, G.A.W.: The immunological consequences of antigen overload in experimental mycobacterial infection of mice. Clin. Exp. Immunol.19:167, 1975

    Google Scholar 

  193. Hester, J.P., McCredie, K.B., Freireich, E.J.: Immunological evaluation in patients with chronic myelogenous leukemia. Proc. Am. Soc. Clin. Oncol.15:180, 1974

    Google Scholar 

  194. Vogler, W.R., Chan, Y.K.: Prolonging remission in myeloblastic leukemia by Tice-strain Bacillus Calmette-Guérin. Lancet2:128, 1974

    Google Scholar 

  195. Mathé, G., Musset, M., Schwarzenberg, L., Hayat, M., DeVassal, G., Amiel, J.L., Pouillart, P., Misset, J.L.: Phase II trial of active immunotherapy on acute myeloid leukemia. Biomedicine23:291, 1975

    Google Scholar 

  196. Bodey, G.P., Sr., Freireich, E.J., Gehan, E.A., McCredie, K.B., Rodriguez, V., Gutterman, J.U., Burgess, M.A.: Late intensification therapy for acute leukemia in remission. J.A.M.A.235:1021, 1976

    Google Scholar 

  197. Crowther, D., Powles, R.L., Bateman, C.J.T., Beard, M.E.J., Gauci, C.J., Wrigley, P.F.M., Malpas, J.S., Hamilton-Fairley, G., Scott, R.B.: Management of adult acute myelogenous leukemia. Br. Med. J.1:131, 1973

    Google Scholar 

  198. Powles, R.L., Crowther, D., Bateman, C.J.T., Beard, M.E.J., McElwain, T.J., Russell, J., Lister, T.A., Whitehouse, J.M.A., Wrigley, P.F.M., Pike, M., Alexander, P., Hamilton-Fairley, G.: Immunotherapy for acute myelogenous leukemia. Br. J. Cancer28:365, 1973

    Google Scholar 

  199. Whiteside, M.G., Cauchi, M.N., Paton, C., Stone, J.: Chemoimmunotherapy for maintenance in acute myeloblastic leukemia. Cancer38:1581, 1976

    Google Scholar 

  200. Reizenstein, P., Brenning, G., Engstedt, L., et al.: Leukemia Group of Central Sweden: effect of immunotherapy on survival and remission duration in acute, non-lymphatic leukemia. In Immunotherapy of Cancer. Present Status of Trials in Man, D. Windhorst, R. Terry, editors. New York, Raven Press (in press)

  201. Cuttner, J., Bekesi, J.G., Holland, J.F.: Chemoimmunotherapy of acute leukemia using MER. Proc. Am. Assoc. Cancer Res.17:196, 1976

    Google Scholar 

  202. Bekesi, J.G., Holland, J.F., Cuttner, J., Silver, R., Coleman, M., Javowski, C., Vincequerra, V.: Immunotherapy in acute myelocytic leukemia (AML) with neuramindase (N'ase) treated myeloblasts with or without MER. Proc. Am. Assoc. Cancer Res.17:184, 1976

    Google Scholar 

  203. Hewlett, J.S., Balcerzak, S., Gutterman, J.U.: Remission induction in adult leukemia by 10-day continuous infusion of ARA-C, plus oncovin and prednisone. Maintenance with and without BCG. In Immunotherapy of Cancer. Present Status of Trials in Man, D. Windhorst, R. Terry, editors. New York, Raven Press (in press)

  204. Fiere, D., Doillon, M., Martin, C.I., Vuvan, T., Revol, L.: Chemoimmunotherapy versus chemotherapy in acute myeloid leukemia. Preliminary results. Biomedicine25:318, 1976

    Google Scholar 

  205. Peto, R.: Immunotherapy of acute myeloid leukemia. In Immunotherapy of Cancer. Present Status of Trials in Man, D. Windhorst, R. Terry, editors. New York, Raven Press (in press)

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Author notes

  1. Max A. Schwarz M.B., B.S., F.R.A.C.P.

    Present address: Hematology-Oncology Unit, Alfred Hospital, Victoria, Australia

Affiliations

  1. Department of Developmental Therapeutics, The University of Texas System Cancer Center, M.D. Anderson Hospital and Tumor Institute, Houston, Texas, USA

    Max A. Schwarz M.B., B.S., F.R.A.C.P., Jordan U. Gutterman M.D., Evan M. Hersh M.D., Stephen P. Richman M.D. & Giora M. Mavligit M.D.

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Supported by Contract NO1-CB-33888 and Grant 05831 from the National Cancer Institute, Bethesda, Maryland. Drs. Gutterman and Mavligit are the recipients of Career Development Awards (CA 71001-03 and CA 00130-02, respectively) from the National Cancer Institute, Bethesda, Dr. Schwarz is the recipient of a Fulbright-Hays Scholarship.

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Schwarz, M.A., Gutterman, J.U., Hersh, E.M. et al. Immunotherapy and chemoimmunotherapy of malignant disease with BCG and nonviable mycobacterial fractions. World J. Surg. 1, 555–579 (1977). https://doi.org/10.1007/BF01556181

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Keywords

  • Cutaneous Malignant Melanoma
  • Acute Myeloblastic Leukemia
  • Remission Duration
  • Intralesional Injection
  • Genitourinary Cancer