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Five decades of therapy for multiple myeloma: a paradigm for therapeutic models

Leukemia volume 19, pages 910–912 (2005)Cite this article

The past 50 years have seen significant therapeutic advances in the treatment of multiple myeloma. However, important observations about the disease were made over 150 years ago, in particular, in the case of a 45-year-old London tradesman, Thomas Alexander McBean.1 One day while walking, he stumbled, fell, and was seized with a severe pain in his chest. Over the course of 2 years, he was treated for recurrent severe pain with a variety of treatments: a strengthening plaster to the chest, removal of a pound of blood, maintenance therapy consisting of the application of leeches, and later, cupping, and steel and quinine. Remission from this last treatment, as was the case with all the others, did not last long. McBean's consulting physician, William Macintyre, MD, recognized the features of Bence Jones proteinuria, and when McBean's pain recurred, Dr Macintyre consulted Henry Bence Jones, MD, the leading chemical pathologist of London of the day. Bence Jones erroneously concluded that the protein that precipitated when McBean's urine sample was heated and cooled was a hydrated deuteroxide of albumen. However, he did make the statement that any patient with mollities ossium (softening of the bone) should be examined for this peculiar protein. Bence Jones prescribed alum in order to reduce the excretion of animal matter in McBean's urine. This was of no avail and on January 1, 1846, McBean died of ‘atrophy from albuminuria.’ At autopsy, his bones cut like butter and in a drawing the marrow appeared to contain malignant plasma cells. However, McBean was not the first case on record of multiple myeloma. In 1844, Sarah Newbury was described by her physician, Samuel Solly, MD, as having multiple fractures. He made an interesting statement about the role of blood vessels in the disease, ‘in which the earthy matter of the bone marrow is absorbed and thrown out by the kidneys in the urine’.

The topic of proteinuria lay dormant for many years until 1922, when Stanhope Bayne-Jones, MD, a professor at Johns Hopkins University, injected a number of Bence Jones proteins into rabbits and concluded that there were two or possibly three types of Bence Jones protein.2 In 1956, Korngold and Lipari3, 4 demonstrated that there were two main classes of light-chain proteins, at that time known as Bence Jones protein. In a remarkable report in 1962, Edelman and Gally5 demonstrated that the Bence Jones protein was identical to the light chains of the intact serum immunoglobulin in the same multiple myeloma patient.

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References

  1. Kyle RA . Multiple myeloma: how did it begin? Mayo Clin Proc 1994; 69: 680–683.

    Article  CAS  Google Scholar 

  2. Paul JR . Stanhope Bayne-Jones (1888–1970). Medical dean, military hero, microbiologist and epidemiologist, and medical historian. Yale J Biol Med 1972; 45: 22–32.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Korngold L, Lipari R . Multiple-myeloma proteins. III. The antigenic relationship of Bence Jones proteins to normal gammaglobulin and multiple-myeloma serum proteins. Cancer 1956; 9: 262–272.

    Article  CAS  Google Scholar 

  4. Korngold L, Lipari R . Multiple-myeloma proteins. I. Immunological studies. Cancer 1956; 9: 183–192.

    Article  CAS  Google Scholar 

  5. Edelman GM, Gally JA . The nature of Bence Jones proteins. Chemical similarities to polypetide chains of myeloma globulins and normal gamma-globulins. J Exp Med 1962; 116: 207–227.

    Article  CAS  Google Scholar 

  6. Alwall N . Urethane and stilbamidine in multiple myeloma: Report on two cases. Lancet 1947; 2: 388–389.

    Article  CAS  Google Scholar 

  7. Alwall N . Urethane in multiple myeloma. I. Final report of a case treated more than four years with urethane. Acta Med Scand 1952; 144: 114–118.

    Article  CAS  Google Scholar 

  8. Holland JR, Hosley H, Scharlau C, Carbone PP, Frei E III, Brindley CO et al. A controlled trial of urethane treatment in multiple myeloma. Blood 1966; 27: 328–342.

    CAS  PubMed  Google Scholar 

  9. Blokhin N, Larionov L, Perevodchikova N, Chebotareva L, Merkulova N . Clinical experiences with sarcolysin in neoplastic diseases. Ann NY Acad Sci 1958; 68: 1128–1132.

    Article  CAS  Google Scholar 

  10. Bergsagel DE . Phase II trials of mitomycin C, AB-100, NSC-1026, L-sarcolysin, and meta-sarcolysin, in the treatment of multiple myeloma. Cancer Chemother Rep 1962; 16: 261–266.

    CAS  PubMed  Google Scholar 

  11. Kyle RA, Pierre RV, Bayrd ED . Multiple myeloma and acute myelomonocytic leukemia. N Engl J Med 1970; 283: 1121–1125.

    Article  CAS  Google Scholar 

  12. Child JA, Morgan GJ, Davies FE, Owen RG, Bell SE, Hawkins K et al. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med 2003; 348: 1875–1883.

    Article  CAS  Google Scholar 

  13. Attal M, Harousseau JL, Facon T, Guilhot F, Doyen C, Fuzibet JG et al. Single vs double autologous stem-cell transplantation for multiple myeloma. N Engl J Med 2003; 349: 2495–2502.

    Article  CAS  Google Scholar 

  14. Badros A, Barlogie B, Siegel E, Cottler-Fox M, Zangari M, Fassas A et al. Improved outcome of allogeneic transplantation in high-risk multiple myeloma patients after nonmyeloablative conditioning. J Clin Oncol 2002; 20: 1295–1303.

    Article  Google Scholar 

  15. Maloney DG, Molina AJ, Sahebi F, Stockerl-Goldstein KE, Sandmaier BM, Bensinger W et al. Allografting with nonmyeloablative conditioning following cytoreductive autografts for the treatment of patients with multiple myeloma. Blood 2003; 102: 3447–3454.

    Article  CAS  Google Scholar 

  16. Singhal S, Mehta J, Desikan R, Ayers D, Roberson P, Eddlemon P et al. Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med 1999; 341: 1565–1571.

    Article  CAS  Google Scholar 

  17. Barlogie B, Desikan R, Eddlemon P, Spencer T, Zeldis J, Munshi N et al. Extended survival in advanced and refractory multiple myeloma after single-agent thalidomide: identification of prognostic factors in a phase 2 study of 169 patients. Blood 2001; 98: 492–494.

    Article  CAS  Google Scholar 

  18. Anagnostopoulos A, Weber D, Rankin K, Delasalle K, Alexanian R . Thalidomide and dexamethasone for resistant multiple myeloma. Br J Haematol 2003; 121: 768–771.

    Article  CAS  Google Scholar 

  19. Palumbo A, Giaccone L, Bertola A, Pregno P, Bringhen S, Rus C et al. Low-dose thalidomide plus dexamethasone is an effective salvage therapy for advanced myeloma. Haematologica 2001; 86: 399–403.

    CAS  PubMed  Google Scholar 

  20. Coleman M, Leonard J, Lyons L, Pekle K, Nahum K, Pearse R et al. BLT-D (clarithromycin [Biaxin], low-dose thalidomide, and dexamethasone) for the treatment of myeloma and Waldenstrom's macroglobulinemia. Leuk Lymphoma 2002; 43: 1777–1782.

    Article  CAS  Google Scholar 

  21. Richardson PG, Schlossman RL, Weller E, Hideshima T, Mitsiades C, Davies F et al. Immunomodulatory drug CC-5013 overcomes drug resistance and is well tolerated in patients with relapsed multiple myeloma. Blood 2002; 100: 3063–3067.

    Article  CAS  Google Scholar 

  22. Richardson PG, Barlogie B, Berenson J, Singhal S, Jagannath S, Irwin D et al. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med 2003; 348: 2609–2617.

    Article  CAS  Google Scholar 

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  1. Mayo Clinic, Rochester, MN, USA

    R A Kyle

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Correspondence to R A Kyle.

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This paper is part of a series of keynote addresses to be published in Leukemia. They were presented at the Acute Leukemia Forum, San Francisco, Friday April 16, 2004

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Kyle, R. Five decades of therapy for multiple myeloma: a paradigm for therapeutic models. Leukemia 19, 910–912 (2005). https://doi.org/10.1038/sj.leu.2403728

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