Skip to main content
SpringerLink
Log in
Book cover

Amyloidosis pp 155–164Cite as

Conventional Treatment of Amyloidosis

  • Chapter
  • First Online:

  • 1055 Accesses

Part of the book series: Contemporary Hematology ((CH))

Abstract

All patients with proven light chain amyloidosis deserve a trial of therapy. Although high dose therapy has been shown to be highly effective, only a quarter of patients are actually eligible for this technique. Lower intensity treatments are required for the majority of patients. We review the history of treatment of amyloidosis beginning with the use of conventional alkylating agent chemotherapy, the role of the novel agents bortezomib, lenalidomide, and thalidomide in the treatment of amyloidosis. A suggested treatment algorithm is given to help guide decisions regarding therapy.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Comenzo RL. Managing systemic light-chain amyloidosis. J Natl Compr Canc Netw. 2007;5:179–87.

    PubMed  CAS  Google Scholar 

  2. Miyazaki D, Yazaki M, Gono T, et al. AH amyloidosis associated with an immunoglobulin heavy chain variable region (VH1) fragment: a case report. Amyloid. 2008;15:125–28.

    Article  PubMed  CAS  Google Scholar 

  3. Obici L, Perfetti V, Palladini G, Moratti R, Merlini G. Clinical aspects of systemic amyloid diseases. Biochim Biophys Acta. 2005;1753:11–22.

    Article  PubMed  CAS  Google Scholar 

  4. Ionescu-Zanetti C, Khurana R, Gillespie JR, et al. Monitoring the assembly of Ig light-chain amyloid fibrils by atomic force microscopy. Proc Natl Acad Sci USA. 1999;96:13175–79.

    Article  PubMed  CAS  Google Scholar 

  5. Brenner DA, Jain M, Pimentel DR, et al. Human amyloidogenic light chains directly impair cardiomyocyte function through an increase in cellular oxidant stress. Circ Res. 2004;94:1008–10.

    Article  PubMed  CAS  Google Scholar 

  6. Kingsbury JS, Laue TM, Klimtchuk ES, Theberge R, Costello CE, Connors LH. The modulation of transthyretin tetramer stability by cysteine 10 adducts and the drug diflunisal. Direct analysis by fluorescence-detected analytical ultracentrifugation. J Biol Chem. 2008;283:11887–96.

    Article  PubMed  CAS  Google Scholar 

  7. Hazenberg BP, van Rijswijk MH, Lub-de Hooge MN, et al. Diagnostic performance and prognostic value of extravascular retention of 123I-labeled serum amyloid P component in systemic amyloidosis. J Nucl Med. 2007;48:865–72.

    Article  PubMed  CAS  Google Scholar 

  8. Buxbaum J. Aberrant immunoglobulin synthesis in light chain amyloidosis. Free light chain and light chain fragment production by human bone marrow cells in short-term tissue culture. J Clin Invest. 1986;78:798–806.

    Article  PubMed  CAS  Google Scholar 

  9. Cohen AS, Rubinow A, Anderson JJ, et al. Survival of patients with primary (AL) amyloidosis. Colchicine-treated cases from 1976 to 1983 compared with cases seen in previous years (1961 to 1973). Am J Med. 1987;82:1182–90.

    Article  PubMed  CAS  Google Scholar 

  10. Brandwein SR, Sipe JD, Skinner M, Cohen AS. Effect of colchicine on experimental amyloidosis in two CBA/J mouse models. Chronic inflammatory stimulation and administration of amyloid-enhancing factor during acute inflammation. Lab Invest. 1985;52: 319–25.

    PubMed  CAS  Google Scholar 

  11. Schwartz RS, Cohen JR, Schrier SL. Therapy of primary amyloidosis with melphalan and prednisone. Arch Intern Med. 1979;139:1144–47.

    Article  PubMed  CAS  Google Scholar 

  12. Gertz MA, Lacy MQ, Dispenzieri A, et al. Effect of hematologic response on outcome of patients undergoing transplantation for primary amyloidosis: importance of achieving a complete response. Haematologica. 2007;92:1415–18.

    Article  PubMed  Google Scholar 

  13. Gertz MA, Lacy MQ, Dispenzieri A, et al. Impact of age and serum creatinine value on outcome after autologous blood stem cell transplantation for patients with multiple myeloma. Bone Marrow Transplant. 2007;39:605–11.

    Article  PubMed  CAS  Google Scholar 

  14. Comenzo RL. Systemic immunoglobulin light-chain amyloidosis. Clin Lymphoma Myeloma. 2006;7:182–85.

    Article  PubMed  CAS  Google Scholar 

  15. Gertz MA, Lacy MQ, Dispenzieri A, Hayman SR, Kumar S. Transplantation for amyloidosis. Curr Opin Oncol. 2007;19:136–41.

    Article  PubMed  CAS  Google Scholar 

  16. Jaccard A, Moreau P, Leblond V, et al. High-dose melphalan versus melphalan plus dexamethasone for AL amyloidosis. N Engl J Med. 2007;357:1083–93.

    Article  PubMed  CAS  Google Scholar 

  17. Kumar S, Dispenzieri A, Gertz MA. High-dose melphalan versus melphalan plus dexamethasone for AL amyloidosis. N Engl J Med. 2008;358:91, author reply 92–93.

    Article  PubMed  CAS  Google Scholar 

  18. Horne MK III.. Letter: improvement in amyloidosis. Ann Intern Med. 1975;83:281–282.

    PubMed  Google Scholar 

  19. Corkery J, Bern MM, Tullis JL. Resolution of amyloidosis and plasma-cell dyscrasia with combination chemotherapy. Lancet. 1978;2:425–426.

    Article  PubMed  CAS  Google Scholar 

  20. Gertz MA, Kyle RA. Acute leukemia and cytogenetic abnormalities complicating melphalan treatment of primary systemic amyloidosis. Arch Intern Med. 1990;150:629–33.

    Article  PubMed  CAS  Google Scholar 

  21. Gertz MA, Lacy MQ, Lust JA, Greipp PR, Witzig TE, Kyle RA. Long-term risk of myelodysplasia in melphalan-treated patients with immunoglobulin light-chain amyloidosis. Haematologica. 2008;93:1402–6.

    Article  PubMed  CAS  Google Scholar 

  22. Kyle RA, Greipp PR. Primary systemic amyloidosis: comparison of melphalan and prednisone versus placebo. Blood. 1978;52:818–27.

    PubMed  CAS  Google Scholar 

  23. Kyle RA, Greipp PR. Amyloidosis (AL). Clinical and laboratory features in 229 cases. Mayo Clin Proc. 1983;58:665–83.

    PubMed  CAS  Google Scholar 

  24. Gertz MA, Kyle RA, Greipp PR. Response rates and survival in primary systemic amyloidosis. Blood. 1991;77:257–62.

    PubMed  CAS  Google Scholar 

  25. Grogan M, Gertz MA, Kyle RA, Tajik AJ. Five or more years of survival in patients with primary systemic amyloidosis and biopsy-proven cardiac involvement. Am J Cardiol. 2000;85(664–665):A611.

    Google Scholar 

  26. Kyle RA, Gertz MA, Greipp PR, et al. Long-term survival (10 years or more) in 30 patients with primary amyloidosis. Blood. 1999;93:1062–66.

    PubMed  CAS  Google Scholar 

  27. Kyle RA, Gertz MA, Greipp PR, et al. A trial of three regimens for primary amyloidosis: colchicine alone, melphalan and prednisone, and melphalan, prednisone, and colchicine. N Engl J Med. 1997;336:1202–07.

    Article  PubMed  CAS  Google Scholar 

  28. Skinner M, Anderson J, Simms R, et al. Treatment of 100 patients with primary amyloidosis: a randomized trial of melphalan, prednisone, and colchicine versus colchicine only. Am J Med. 1996;100:290–98.

    Article  PubMed  CAS  Google Scholar 

  29. Sanchorawala V, Wright DG, Seldin DC, et al. Low-dose continuous oral melphalan for the treatment of primary systemic (AL) amyloidosis. Br J Haematol. 2002;117:886–89.

    Article  PubMed  CAS  Google Scholar 

  30. Tazawa K, Matsuda M, Yoshida T, et al. Therapeutic outcome of cyclic VAD (vincristine, doxorubicin and dexamethasone) therapy in primary systemic AL amyloidosis patients. Intern Med. 2008;47:1517–22.

    Article  PubMed  Google Scholar 

  31. Sezer O, Schmid P, Shweigert M, et al. Rapid reversal of nephrotic syndrome due to primary systemic AL amyloidosis after VAD and subsequent high-dose chemotherapy with autologous stem cell support. Bone Marrow Transplant. 1999;23:967–69.

    Article  PubMed  CAS  Google Scholar 

  32. van G II, Hazenberg BP, Jager PL, Smit JW, Vellenga E. AL amyloidosis treated with induction chemotherapy with VAD followed by high dose melphalan and autologous stem cell transplantation. Amyloid. 2002;9:165–74.

    Article  Google Scholar 

  33. Lachmann HJ, Gallimore R, Gillmore JD, et al. Outcome in systemic AL amyloidosis in relation to changes in concentration of circulating free immunoglobulin light chains following chemotherapy. Br J Haematol. 2003;122:78–84.

    Article  PubMed  CAS  Google Scholar 

  34. Dhodapkar MV, Jagannath S, Vesole D, et al. Treatment of AL-amyloidosis with dexamethasone plus alpha interferon. Leuk Lymphoma. 1997;27:351–56.

    PubMed  CAS  Google Scholar 

  35. Gertz MA, Lacy MQ, Lust JA, Greipp PR, Witzig TE, Kyle RA. Phase II trial of high-dose dexamethasone for untreated patients with primary systemic amyloidosis. Med Oncol. 1999;16:104–09.

    Article  PubMed  CAS  Google Scholar 

  36. Gertz MA, Lacy MQ, Lust JA, Greipp PR, Witzig TE, Kyle RA. Phase II trial of high-dose dexamethasone for previously treated immunoglobulin light-chain amyloidosis. Am J Hematol. 1999;61:115–19.

    Article  PubMed  CAS  Google Scholar 

  37. Palladini G, Anesi E, Perfetti V, et al. A modified high-dose dexamethasone regimen for primary systemic (AL) amyloidosis. Br J Haematol. 2001;113:1044–46.

    Article  PubMed  CAS  Google Scholar 

  38. Dhodapkar MV, Hussein MA, Rasmussen E, et al. Clinical efficacy of high-dose dexamethasone with maintenance dexamethasone/alpha interferon in patients with primary systemic amyloidosis: results of United States Intergroup Trial Southwest Oncology Group (SWOG) S9628. Blood. 2004;104:3520–26.

    Article  PubMed  CAS  Google Scholar 

  39. Palladini G, Perfetti V, Obici L, et al. Association of melphalan and high-dose dexamethasone is effective and well tolerated in patients with AL (primary) amyloidosis who are ineligible for stem cell transplantation. Blood. 2004;103:2936–38.

    Article  PubMed  CAS  Google Scholar 

  40. Palladini G, Russo P, Nuvolone M, et al. Treatment with oral melphalan plus dexamethasone produces long-term remissions in AL amyloidosis. Blood. 2007;110:787–788.

    Article  PubMed  CAS  Google Scholar 

  41. Goodman HJB, Lachmann HJ, Bradwell AR, Hawkins PN. Intermediate dose intravenous melphalan and dexamethasone treatment in 144 patients with systemic AL amyloidosis (abstract 755). Blood. 2004;104:755.

    Article  Google Scholar 

  42. Seldin DC, Choufani EB, Dember LM, et al. Tolerability and efficacy of thalidomide for the treatment of patients with light chain-associated (AL) amyloidosis. Clin Lymphoma. 2003;3:241–46.

    Article  PubMed  CAS  Google Scholar 

  43. Dispenzieri A, Lacy MQ, Rajkumar SV, et al. Poor tolerance to high doses of thalidomide in patients with primary systemic amyloidosis. Amyloid. 2003;10:257–61.

    Article  PubMed  CAS  Google Scholar 

  44. Palladini G, Perfetti V, Perlini S, et al. The combination of thalidomide and intermediate-dose dexamethasone is an effective but toxic treatment for patients with primary amyloidosis (AL). Blood. 2005;105:2949–51.

    Article  PubMed  CAS  Google Scholar 

  45. Wechalekar AD, Goodman HJ, Lachmann HJ, Offer M, Hawkins PN, Gillmore JD. Safety and efficacy of risk-adapted cyclophosphamide, thalidomide, and dexamethasone in systemic AL amyloidosis. Blood. 2007;109:457–64.

    Article  PubMed  CAS  Google Scholar 

  46. Palladini G, Russo P, Lavatelli F, et al. Treatment of patients with advanced cardiac AL amyloidosis with oral melphalan, dexamethasone, and thalidomide. Ann Hematol. 2009 Apr; 88(4):347–50.

    Article  PubMed  Google Scholar 

  47. Sanchorawala V, Wright DG, Rosenzweig M, et al. Lenalidomide and dexamethasone in the treatment of AL amyloidosis: results of a phase 2 trial. Blood. 2007;109:492–96.

    Article  PubMed  CAS  Google Scholar 

  48. Dispenzieri A, Lacy MQ, Zeldenrust SR, et al. The activity of lenalidomide with or without dexamethasone in patients with primary systemic amyloidosis. Blood. 2007;109: 465–70.

    Article  PubMed  CAS  Google Scholar 

  49. Sviggum HP, Davis MD, Rajkumar SV, Dispenzieri A. Dermatologic adverse effects of lenalidomide therapy for amyloidosis and multiple myeloma. Arch Dermatol. 2006;142:1298–302.

    Article  PubMed  CAS  Google Scholar 

  50. Batts ED, Sanchorawala V, Hegerfeldt Y, Lazarus HM. Azotemia associated with use of lenalidomide in plasma cell dyscrasias. Leuk Lymphoma. 2008;49:1108–15.

    Article  PubMed  CAS  Google Scholar 

  51. Sterz J, von Metzler I, Hahne JC, et al. The potential of proteasome inhibitors in cancer therapy. Expert Opin Invest Drugs. 2008;17:879–95.

    Article  CAS  Google Scholar 

  52. Dimopoulos MA, Kastritis E, Rosinol L, Blade J, Ludwig H. Pathogenesis and treatment of renal failure in multiple myeloma. Leukemia. 2008;22:1485–93.

    Article  PubMed  CAS  Google Scholar 

  53. Sitia R, Palladini G, Merlini G. Bortezomib in the treatment of AL amyloidosis: targeted therapy? Haematologica. 2007;92:1302–7.

    Article  PubMed  CAS  Google Scholar 

  54. Fauble VS, Shah-Reddy I. Primary amyloidosis treated with bortezomib with a clinical and radiological response (abstract 5111). Blood. 2006;108:5111.

    Google Scholar 

  55. Wechalekar AD, Gillmore JD, Lachmann HJ, Offer M, Hawkins PN. Efficacy and safety of bortezomib in systemic AL amyloidosis – a preliminary report (abstract 129). Blood. 2006;108:129.

    Google Scholar 

  56. Wechalekar AD, Lachmann HJ, Offer M, Hawkins PN, Gillmore JD. Efficacy of bortezomib in systemic AL amyloidosis with relapsed/refractory clonal disease. Haematologica. 2008;93:295–98.

    Article  PubMed  CAS  Google Scholar 

  57. Reece DESV, Hegenbart U, Merlini G, et al. Phase I/II study of bortezomib (B) in patients with systemic AL-amyloidosis (AL). J Clin Oncol. 2007;25:453s.

    Google Scholar 

  58. Kastritis E, Anagnostopoulos A, Roussou M, et al. Treatment of light chain (AL) amyloidosis with the combination of bortezomib and dexamethasone. Haematologica. 2007;92:1351–58.

    Article  PubMed  CAS  Google Scholar 

  59. Wall JS, Kennel SJ, Paulus M, et al. Radioimaging of light chain amyloid with a fibril-reactive monoclonal antibody. J Nucl Med. 2006;47:2016–24.

    PubMed  CAS  Google Scholar 

  60. Solomon A, Weiss DT, Wall JS. Immunotherapy in systemic primary (AL) amyloidosis using amyloid-reactive monoclonal antibodies. Cancer Biother Radiopharm. 2003;18:853–60.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, Mayo Clinic, Rochester, MN, USA

    Morie A. Gertz MD

  2. Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA

    Francis Buadi MB, ChB

Authors
  1. Morie A. Gertz MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Francis Buadi MB, ChB
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Mayo Clinic, First Street SW. 200, Rochester, 55905, Minnesota, USA

    Morie A. Gertz

  2. Mayo Clinic, First Street SW. 200, Rochester, 55905, Minnesota, USA

    S. Vincent Rajkumar

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Gertz, M.A., Buadi, F. (2010). Conventional Treatment of Amyloidosis. In: Gertz, M., Rajkumar, S. (eds) Amyloidosis. Contemporary Hematology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-631-3_11

Download citation

  • DOI: https://doi.org/10.1007/978-1-60761-631-3_11

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60761-630-6

  • Online ISBN: 978-1-60761-631-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation