Multiple Myeloma

Article1 February 1964Multiple MyelomaStudies of Mouse Plasma Cell Tumor and Human Myeloma Responsiveness to Cyclophosphamide (Cytoxan)DONALD R. KORST, M.D., F.A.C.P., EUGENE P. FRENKEL, M.D., JOHN C. NIXON, M.D.DONALD R. KORST, M.D., F.A.C.P.Search for more papers by this author, EUGENE P. FRENKEL, M.D.Search for more papers by this author, JOHN C. NIXON, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-60-2-217 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptMultiple myeloma, a neoplasm of plasma cell origin represents a difficult therapeutic problem. Preliminary clinical trials with a new alkylating agent cyclophosphamide*(1) suggested that palliative responses in human multiple myeloma could be obtained. Investigations of myeloma have been limited by the lack of a suitable animal prototype; however, in 1957, Potter, Fahey, and Pilgrim (2) observed a plasma cell tumor in the iliocecum of C3H mice and successfully transferred the tumor subcutaneously through many generations. The tumor in mice produces bone marrow, liver, and spleen plasma cell invasion. Changes in the serum proteins are similar to the human disease....References1. KORSTJOHNSONFRENKELCHALLENER DRFDEPWL: Preliminary evaluation of the effect of cyclophosphamide on the course of human neoplasm. Cancer Chemother. Rep. 7: 1, 1960. Google Scholar2. POTTERFAHEYPILGRIM MJLHI: Abnormal serum protein and bone destruction in transmissible mouse plasma cell neoplasm (multiple myeloma). Proc. Soc. Exp. Biol. Med. 94: 327, 1957. CrossrefMedlineGoogle Scholar3. COBAUKORST CDDR: Alterations of gamma globulin with plasma cell neoplasm in mice. Proc. Soc. Exp. Biol. Med. 101: 356, 1959. CrossrefMedlineGoogle Scholar4. FRENKELKORSTRACCUGLIA EPDRG: Effects of heterologous transplantation of a mouse plasmacytoma. I. Runting syndrome secondary to malignant tumors. J. Lab. Clin. Med. 59: 81, 1962. MedlineGoogle Scholar5. WALDENSTRÖM J: Abnormal proteins in myeloma, in Advances in Internal Medicine, Vol. 5 Year Book Publishers, Inc., Chicago, 1952, p. 398. Google Scholar6. WALL RL: The use of serum protein electrophoresis in clinical medicine. Arch. Intern. Med. (Chicago) 102: 618, 1958. CrossrefGoogle Scholar7. ADAMSALLINGLAWRENCE WSELJS: Multiple myeloma. It's clinical and laboratory diagnosis with emphasis on electrophoretic abnormalities. Amer. J. Med. 6: 141, 1949. CrossrefMedlineGoogle Scholar8. SNAPPERTURNERMOSCOVITY ILBHL: Multiple Myeloma, Grune and Stratton, Inc., New York, 1953. Google Scholar9. CARSONACKERMANMALTBY CPLVJD: Plasma cell myeloma: a clinical, pathologic, and roentgen review of 90 cases. Amer. J. Clin. Path. 25: 849, 1955. CrossrefMedlineGoogle Scholar10. BAYRDHECK EDFJ: Multiple myeloma: a review of 83 proven cases. JAMA 133: 147, 1947. CrossrefMedlineGoogle Scholar11. NATHANSFAHEYPOTTER DJLM: The formation of myeloma protein by a mouse plasma cell tumor. J. Exp. Med. 108: 121, 1958. CrossrefMedlineGoogle Scholar12. HENSONLEADERGORHAM JBRWJR: Hypergammaglobulinemia in mink. Proc. Soc. Exp. Biol. Med. 107: 919, 1961. CrossrefMedlineGoogle Scholar13. RUNDLESDILLONDILLON RWMLES: Multiple myeloma. III. Effect of urethane therapy of plasma cell growth, abnormal serum, protein components, and Bence Jones proteinuria. J. Clin. Invest. 29: 1243, 1950. CrossrefMedlineGoogle Scholar14. THIERY JP: Microcinematographic contributions to study of plasma cells, in Ciba Foundation Symposium on Cellular Aspects of Immunity , edited by WOLSTENHOLME, G. E. W., and O'CONNOR, C. M., Little, Brown and Company, Boston, 1961, p. 59. (See also EDITORIAL, JAMA 179: 285, 1962.) Google Scholar15. LANE SL: Plasmocytoma of the mandible. Oral Surg. 5: 434, 1952. CrossrefMedlineGoogle Scholar16. LANE SL: Personnel communication: March 29, 1962. Google Scholar17. MILLERBROWNMILLEREITELMAN GLCEEEES: An electrophoretic study on the origin of the abnormal plasma proteins in multiple myeloma. Cancer Res. 12: 716, 1952. MedlineGoogle Scholar18. FAGRAEUS A: Antibody formation in relation to the development of plasma cells. Acta Med. Scand. Supp. 204: 1, 1948. Google Scholar19. WHITE RG: Observations on the formation and nature of Russell bodies. Brit. J. Exp. Path. 35: 365, 1954. MedlineGoogle Scholar20. VAZQUEZ JJ: Immunocytochemical study of plasma cells in multiple myeloma. J. Lab. Clin. Med. 51: 271, 1958. MedlineGoogle Scholar21. TRUAXBRAYPERRY WEJJE: A method for demonstrating probable synthesis of protein by bone marrow cells. J. Lab. Clin. Med. 17: 54, 1961. Google Scholar22. FAHEY JL: Comparison of serum myeloma proteins in mouse and man (abstract). Proc. Amer. Ass. Cancer Res. 3: 223, 1961. Google Scholar23. ASKONAS BA: A study on globulin formation by plasma-cell neoplasm (5563). Biochem. J. 79: 33, 1961. CrossrefMedlineGoogle Scholar24. DALTONPOTTERMERWIN AJMRM: Some ultrastructural characteristics of a series of primary and transplanted plasma-cell tumors of the mouse. J. Nat. Cancer Inst. 26: 1221, 1961. MedlineGoogle Scholar25. LANE M: Preliminary report of animal studies with Cytoxan (cyclophosphamide). Cancer Chemother. Rep. 3: 1, 1959. Google Scholar26. LANE M: Some effects of cyclophosphamide (Cytoxan) on normal mice and mice with L1210 leukemia. J. Nat. Cancer Inst. 23: 1347, 1959. MedlineGoogle Scholar27. POTTERLOW MLW: Studies of a plasma cell neoplasm of the mouse. J. Nat. Cancer Inst. 18: 413, 1957. MedlineGoogle Scholar28. KORSTFRENKELJOHNSONCOBAUKNORPP DREPFDCDCT: Experimental studies of the biologic and tumorigenic behavior of cyclophosphamide. Proc. VIII Int. Cong. Hematology, Tokyo, Japan, September, 1960. Google Scholar29. FOLEYFRIENDMANDROLET GEOMBP: Studies on the mechanism of action of Cytoxan. Evidence of activation in vivo and in vitro. Cancer Res. 21: 57, 1961. MedlineGoogle Scholar30. GROSSLAMBERS RK: Erste Erfahrungen in der Behandlung maligner Tumoren mit einen neuen N-lost-phosphamid-ester. Deutsch. Med. Wschr. 83: 458, 1958. CrossrefMedlineGoogle Scholar31. FAYECHAPMANWILLETTADAMS LVCGFMWS: Cyclophosphamide: a preliminary study of a new alkylating agent. Cancer Chemother. Rep. 6: 39, 1960. MedlineGoogle Scholar32. CORONBOALPERT VLK: Cancer chemotherapy with cyclophosphamide (abstract). Clin. Res. 8: 250, 1960. Google Scholar33. BERGSAGELLEVIN DEWC: A prelusive clinical trial of cyclophosphamide. Cancer Chemother. Rep. 8: 120, 1960. MedlineGoogle Scholar34. MATTHIASMISIEWICZSCOTT JQJJRB: Cyclosphosphamide in Hodgkin's disease and related disorders. Brit. Med. J. 1: 1837, 1960. CrossrefMedlineGoogle Scholar35. WALLCONRAD RLFG: Cyclophosphamide therapy. Arch. Intern. Med. (Chicago) 108: 178, 1961. CrossrefGoogle Scholar36. BAYRD ED: Continuous chlorambucil therapy in primary macroglobulinemia of Waldenström: report of 4 cases. Proc. Mayo Clin. 36: 135, 1961. MedlineGoogle Scholar37. GARLANDKENNEDY LHRB: Roentgen treatment of multiple myeloma. Radiology 50: 297, 1948. CrossrefMedlineGoogle Scholar38. BETHELL FH: Discussion remarks, in Proceedings of the Second Clinical ACTH Conference, Vol. 2, 1951, p. 216. Google Scholar39. ADAMSSKOOG WSWA: The management of multiple myeloma. J. Chron. Dis. 6: 446, 1957. CrossrefMedlineGoogle Scholar40. ALWALL N: Urethane and stilbamidine in multiple myeloma: a report on two cases. Lancet 2: 388, 1947. CrossrefMedlineGoogle Scholar41. HARRINGTONMOLONEY JW: Treatment of multiple myeloma with urethane. Cancer 3: 253, 1950. CrossrefGoogle Scholar42. LUTTGENSBAYRD WFED: Treatment of multiple myeloma with urethane. JAMA 147: 824, 1951. CrossrefMedlineGoogle Scholar43. OSSERMAN EF: Plasma cell myeloma. New Eng. J. Med. 261: 952, 1959. CrossrefMedlineGoogle Scholar44. ALWALL N: Urethane in multiple myeloma. Acta Med. Scand. 144: 114, 1952. CrossrefMedlineGoogle Scholar45. REINHARDMOOREBIERBAUMMOORE EHCVOSS: Radioactive phosphorus as a therapeutic agent. J. Lab. Clin. Med. 31: 107, 1946. MedlineGoogle Scholar46. LAWRENCEWASSERMAN JHLR: Multiple myeloma: study of 24 patients treated with radioactive isotopes (P32 and Sr89). Ann. Intern. Med. 33: 41, 1950. LinkGoogle Scholar47. LINDGRENBERGSTROMWIHMAN EIG: The treatment of multiple myelomata with radioactive phosphorus. Acta Radiol. (Stockholm) 36: 49, 1951. CrossrefMedlineGoogle Scholar48. KRISSBIERMANTHOMASNEWELL JPHRSFRR: Treatment of multiple myeloma with radioactive iodine and radioactive iodinated serum albumin. Radiology 65: 241, 1955. CrossrefMedlineGoogle Scholar49. ANDERSONEMERYMCALISTEROSBORN JEWJMSB: The metabolism of a therapeutic dose of 45ca in a case of multiple myeloma. Clin. Sci. 15: 267, 1956. Google Scholar50. BENEFIELHELSPERSHARP WWJRGG: Apparent control of multiple myeloma by 1-amino-cyclopentane-1-carboxylic acid (NSC-1026). Cancer Chemother. Rep. 9: 21, 1960. Google Scholar51. HAYESSPURR DMCL: The effect of 1-Aminocyclopentane-carboxylic acid (NSC-1026) on mouse plasmacytoma. Cancer Chemother. Rep. 14: 91, 1961. MedlineGoogle Scholar52. HOLLAND JF: Eastern solid tumor group: a comparative study of optimal medical care with and without azaserine in multiple myeloma. Clinical Pharmacol. Ther. 2: 22, 1961. CrossrefMedlineGoogle Scholar53. BAYRDHALL EDBE: Unusual remission after radiophosphorus therapy in a case of acute plasma cell leukemia. Blood 3: 1019, 1948. CrossrefMedlineGoogle Scholar54. BAYRD ED: Personal communication. March 23, 1962. Google Scholar55. GESCHICTERCOPELAND CFMM: Multiple myeloma. Arch. Surg. (Chicago) 16: 807, 1928. CrossrefGoogle Scholar56. ANDA L: Multiple myeloma. Acta Radiol. (Stockholm) 33: 515, 1950. CrossrefMedlineGoogle Scholar57. OSGOOD EE: The survival time of patients with plasmocytic myeloma. Cancer Chemother. Rep. 9: 1, 1960. MedlineGoogle Scholar58. FEINLEIBMACMAHON MB:. Duration of survival in multiple myeloma. J. Nat. Cancer Inst. 24: 1259, 1960. MedlineGoogle Scholar59. KENNYMALONEY JJWC: Long term survival in multiple myeloma. Ann. Intern. Med. 45: 950, 1956. LinkGoogle Scholar60. OWENPITNEYO'DEA JAWRJF: "Myeloma" serum electrophoretic patterns in conditions other than myelomatosis. J. Clin. Path. 12: 344, 1959. CrossrefMedlineGoogle Scholar61. KYLEBAYRD RAED: "Primary" systemic amyloidosis and myeloma. Arch Intern. Med. (Chicago) 107: 344, 1961. CrossrefMedlineGoogle Scholar62. WALDENSTRÖM J: Disturbances of gamma globulin synthesis (abstract). Ann. Intern. Med. 56: 695, 1962. LinkGoogle Scholar63. BAYRDHECK EFJ: Myeloma, a review of 469 cases. Proc. VI Congr. European Soc. Hematology, Copenhagen, Basel. S. Karger, New York, 1957. Google Scholar64. MASS RE: A comparison of the effect of prednisone and a placebo in the treatment of multiple myeloma. Cancer Chemother. Rep. 16: 257, 1962. MedlineGoogle Scholar65. LIEBLINGGRIZZLEHAMMACKRUNDLES MEJWRW: Comparison of chlorambucil and prednisone with urethan and prednisone regimens in the treatment of multiple myeloma. Ibid., p. 253. Google Scholar66. BERGSAGEL DE: Phase II trials of Mitomycin C, AB-100, NSC-1026, L-Sarcolysin, and Meta-Sarcolysin, in the treatment of multiple myeloma. Ibid., p. 261. Google Scholar67. BERGSAGELSPRAGUEROSS DECCSW: Evaluation of new chemotherapeutic agents in the treatment of multiple myeloma. I. Plan of study. Cancer Chemother. Rep. 21: 69, 1962. MedlineGoogle Scholar68. BERGSAGELROSSDAVIS DESWP: Evaluation of new chemotherapeutic agents in the treatment of multiple myeloma. II. Mitomycin C (NSC-26980). Ibid., p. 75. Google Scholar69. BROWNBERGSAGELLEVIN CLDEWC: Evaluation of new chemotherapeutic agents in the treatment of multiple myeloma. III. AB-100 (NSC-37095). Ibid., p. 81. Google Scholar70. BERGSAGELSPRAGUEAUSTINGRIFFITH DECCCKM: Evaluation of new chemotherapeutic agents in the treatment of multiple myeloma. IV. L-Phenylalanine mustard (NSC-8806). Ibid., p. 87. Google Scholar71. BERGSAGELROSSBAKER DESWDT: Evaluation of new chemotherapeutic agents in the treatment of multiple myeloma. V. 1-Aminocyclopentanecarboxylic acid (NSC-1026). Ibid., p. 101. Google Scholar72. AUSTINBERGSAGELSPRAGUE CDECC: Evaluation of new chemotherapeutic agents in the treatment of multiple myeloma. VI. Meta-sarcolysin. Ibid., p. 107. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: DONALD R. KORST, M.D., F.A.C.P.; EUGENE P. FRENKEL, M.D.; JOHN C. NIXON, M.D.Affiliations: Ann Arbor, MichiganFrom the Department of Hematology and Cancer Chemotherapy of St. Joseph Mercy Hospital, and the Department of Internal Medicine, The University of Michigan Medical Center, Ann Arbor, Michigan.This is the Preliminary Report presented at the Forty-third Annual Meeting of the American College of Physicians, Philadelphia, Pennsylvania, April, 1962.Requests for reprints should be addressed to Donald R. Korst, M.D., 326 North Ingalls Street, Ann Arbor, Michigan.*Cyclophosphamide is an ester of phosphamide and the active alkylating group of nitrogen mustard. The drug is available in Europe as Endoxan, in Canada as Protoxan and in the U. S. as Cytoxan® (Meade-Johnson and Company). PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byCyclophosphamide immunosuppression does not permit successful myoblast allotransplantation in mouseA plasma clot culture system for growing and antiproliferative drug sensitivity testing of myeloma stem cellsLiteraturverzeichnisParaproteinämische HämoblastosenMelphalan and prednisone: An effective combination for the treatment of multiple myelomaSerum ribonuclease in multiple myelomaMonoclonal gammopathy with hyperlipidemiaCyclophosphamideDie therapie der ParaproteinämienZur Lebenserwartung unbehandelter und behandelter PlasmozytomkrankerClinical and metabolic investigations of eight cases of multiple myeloma during prolonged cyclophosphamide administrationAggregation of IgG globulin in vivoScientific Methodology in Clinical Medicine III. The Evaluation of Therapeutic ResponseALVAN R. FEINSTEIN, M.D. 1 February 1964Volume 60, Issue 2_Part_1Page: 217-230KeywordsCancer chemotherapyCyclophosphamideDrugsHospital medicineMultiple myelomaMyelomaPlasma cellsProteinsSpleenTumor resection ePublished: 1 December 2008 Issue Published: 1 February 1964 PDF downloadLoading ...