Present possibilities of diagnosis and treatment of systemic AL-amyloidosis


Authors: V. Ščudla;  T. Pika
Authors‘ workplace: III. interní klinika Lékařské fakulty UP a FN Olomouc, přednosta prof. MUDr. Vlastimil Ščudla, CSc.
Published in: Vnitř Lék 2009; 55(Suppl 1)(Supplementum 1): 77-87

Overview

The aim of presented communication is summary of actual knowledge in pathogenesis, diagnosis and treatment of primary systemic AL-amyloidosis. Great attention is devoted to contribution of assessment of serum levels of free light chains including κ/λ ratio, measurement of cardiac biomarkers NT-proBNP and troponin, and also 132I-SAP immunoscintigraphy for treatment response monitoring. The necessity of standardized evaluation of treatment results according to International Society for Amyloidosis recommended criteria are discussed. And also current possibilities of conventional chemotherapy, contribution of high‑dose chemotherapy with autologous stem cell transplantation support (HDT-ASCT), inclusively individual “risk adapted” HDT-ASCT considering prognostic factors of the disease were discussed. Present possibility of immunomodulatory therapy with incorporation of thalidomide, bortezomib and lenalidomide, used in case of treatment failure or disease progression, and also supporting care, including organ transplantation are mentioned. The important role of general practitioners and expert internists in diagnosis of early stages of the disease is highlighted – circumstances chiefly determining treatment strategy and prognosis of this severe, formerly difficult to treat and devastating disease.

Key words:
systemic AL-amyloidosis – diagnosis and classification – conventional chemotherapy – autologous stem cell transplantation – prognosis


Sources

1. Adam Z, Ščudla V. Klinické projevy a diagnostika AL-amyloidózy a některých dalších typů amyloidóz. Vnitř Lék 2001; 47: 36–45.

2. Falk RH, Skinner M. The systemic amyloidoses: an overview. Adv Intern Med 2000; 45: 107–137.

3. Guidelines on the diagnosis and management of AL amyloidosis. Br J Haematol 2004; 125: 681–700.

4. Gertz MA, Hayman SR. Imunoglobulin light chain amyloidosis. In: Rajkumar SV, Kyle RA. Treatment of multiple myeloma and related disorders. Cambridge: Cambridge University Press 2009: 112–128.

5. Sanchorawala V. Light‑chain (AL) amyloidosis, diagnosis and treatment. Clin J Am Soc Nephrol 2006; 1: 1331–1341.

6. Merlini G. AL amyloidosis: diagnosis and prognosis. Haematologica 2007; 92 (Suppl 2): 58–59.

7. Rajkumar SV, Glassock RJ, Kyle RA et al. Diagnosis of primary (AL) amyloidosis. Available from: www.uptodate.com.

8. Kyle RA, Gertz MA. Primary systemic amyloidosis: clinical and laboratory features in 474 cases. Semin Hematol 1995; 32: 45–59.

9. Palladini G, Perfetti V, Merlini G. Therapy and management of systemic AL (primary) amyloidosis. Swiss Med Wkly 2006; 136: 715–720.

10. Kyle RA, Linos A, Beard CM et al. Incidence and natural history of primary systemic amyloidosis in Olmsted County, Minnesota, 1950 through 1989. Blood 1992; 79: 1817–1822.

11. Gorevic PD, Schur PH, Greene JM. An overview of amyloidosis. Available from: www.uptodate.com.

12. Rajkumar SV, Glassock RJ, Kyle RA et al. Pathogenesis and clinical features of primary (AL) amyloidosis and light and heavy chain deposition diseases. Available from: www.uptodate.com.

13. Kaplan B, Livneh A, Gallo G. Charge differences between in vivo deposits in immunoglobulin light chain amyloidosis and non‑amyloid light chain deposition disease. Br J Haematol 2007; 136: 723–728.

14. Comenzo RL, Wally J, Kica G et al. Clonal immunoglobulin light chain variable region germline gene use in AL amyloidosis: association with dominant amyloid‑related organ involvement and survival after stem cell transplantation. Br J Haematol 1999; 106: 744–751.

15. Kisilevsky R. The relation of proteoglycans, serum amyloid P and apo E to amyloidosis current status. Amyloid 2000; 7: 23–25.

16. McLaurin J, Yang D, Yip CM et al. Review: modulating factors in amyloid‑beta fibril formation. J Struct Biol 2000; 130: 259–270.

17. Seldin DC, Sanchorawala V. Adapting to AL amyloidosis. Haematologica 2006; 91: 1591–1595.

18. Palladini G, Lavatelli F, Russo P et al. Circulating amyloidogenic free light chains and serum N‑terminal natriuretic peptide type B decrease simultaneously in association with improvement of survival in AL. Blood 2006; 107: 3854–3858.

19. Harrison CJ, Mazzullo H, Ross FM et al. Translocations of 14q32 and deletions of 13q14 are common chromosomal abnormalities in systemic amyloidosis. Br J Haematol 2002; 117: 427–435.

20. Kyriakides T, Marquez B, Panousopoulos A et al. Amyloid myopathy: evidence for mechanical injury to the sarcolemma. Clin Neuropathol 2002; 21: 145–148.

21. Fautrel B, Fermand JP, Sibilia J et al. Amyloid arthropathy in the course of multiple myeloma. J Rheumatol 2002; 29: 1473–1481.

22. Mumford AD, O’Donnell J, Gillmore JD. Bleeding symptoms and coagulation abnormalities in 337 patients with AL-amyloidosis. Br J Haematol 2000; 110: 454–460.

23. Kyle RA, Gertz MA. Primary systemic amyloidosis: Clinical and laboratory features in 474 cases. Semin Hematol 1995; 32: 45–59.

24. Gertz MA, Greipp PR, Kyle RA. Classification of amyloidosis by the detection of clonal excess of plasma cells in the bone marrow. J Lab Clin Med 1991; 118: 33–39.

25. Westermark P, Benson L, Juul J et al. Use of subcutaneous abdominal fat biopsy specimen for detailed typing of amyloid fibril protein‑AL by amino acid sequence analysis. J Clin Pathol 1989; 42: 817–819.

26. Bradwell AR. Serum free light chain analysis. 4th ed. Birmingham: The Binding Site Ltd 2006.

27. Katzmann JA, Abraham RS, Dispenzieri A et al. Diagnostic performance of quantitative kappa and lambda free light chain assays in clinical practice. Clin Chem 2005; 51: 878–881.

28. 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.

29. Bochtler T, Hegenbart U, Cremer FW et al. Evaluation of the cytogenetic aberration pattern in amyloid light chain amyloidosis as compared with monoclonal gammopathy of undetermined significance reveals common pathways of karyotypic instability. Blood 2008; 111: 4700–4705.

30. Gertz MA, Comenzo R, Falk RH et al. Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL): a consensus opinion from the 10th International symposium on amyloid and amyloidosis, Tours, France, 18–22 April 2004. Am J Hematol 2005; 79: 319–328.

31. Palladini G, Campana C, Klersy C et al. Serum N‑terminal pro‑brain natriuretic peptide is a sensitive marker of myocardial dysfunction in AL amyloidosis. Circulation 2003; 107: 2440–2445.

32. Dispenzieri A, Kyle RA, Gertz MA et al. Survival in patients with primary systemic amyloidosis and raised serum cardiac troponins. Lancet 2003; 361: 1787–1789.

33. Hawkins PN. Serum amyloid P component scintigraphy for diagnosis and monitoring amyloidosis. Curr Opin Nephrol Hypertens 2002; 11: 649–655.

34. Hazenberg BP, van Rijswijk MH, Piers DA et al. Diagnostic performance of 123-I-labeled serum amyloid P component scintigraphy in patients with amyloidosis. Am J Med 2006; 119: 355–365.

35. Dispenzieri A, Lacy MQ, Katzmann JA et al. Absolute values of immunoglobulin free light chains are prognostic in patients with primary systemic amyloidosis undergoing peripheral blood stem cell transplantation. Blood 2006; 107: 3378–3383.

36. 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: 1202–1207.

37. Pardanani A, Witzig TE, Schroeder G et al. Circulating peripheral blood plasma cells as a prognostic indicator in patients with primary systemic amyloidosis. Blood 2003; 101: 827–830.

38. Dominguez W, Weinberg P, Claros P et al. Primary localized nasopharyngeal amyloidosis. A case report. Int J Pediatr Otorhinolaryngol 1996; 36: 61–67.

39. Glenner GG. Amyloid deposits and amyloidosis. The b-fibrilloses (first of two parts). N Engl J Med 1980; 302: 1283–1292.

40. Lachmann HJ, Booth DR, Booth SE et al. Misdiagnosis of hereditary amyloidosis as AL (primary) amyloidosis. N Engl J Med 2002; 346: 1786–1791.

41. Adam Z, Ščudla V, Tomíška M. Léčba AL-amyloidózy a některých dalších typů amyloidóz. Vnitř Lék 2001; 47: 46–52.

42. Schey SA, Kazmi M, Ireland R et al. The use of intravenous intermediate dose melphalan and dexamethasone as induction treatment in the management of de novo multiple myeloma. Eur J Haematol 1998; 61: 306–310.

43. 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: 2936–2938.

44. 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.

45. Dispenzieri A, Kyle RA, Lacy MQ et al. Superior survival in primary systemic amyloidosis patients undergoing peripheral blood stem cell transplantation: a case-control study. Blood 2004; 103: 3960–3963.

46. Skinner M, Sanchorawala V, Seldin DC et al. High‑dose melphalan and autologous stem-cell transplantation in patients with AL amyloidosis: An 8-year study. Ann Intern Med 2004; 140: 85–93.

47. Comenzo RL, Gertz MA. Autologous stem cell transplantation for primary systemic amyloidosis. Blood 2002; 99: 4276–4282.

48. Gertz MA, Lacy MQ, Dispenzieri A et al. Risk‑adjusted manipulation of melphalan dose before stem cell transplantation in patients with amyloidosis is associated with a lower response rate. Bone Marrow Transplant 2004; 34: 1025–1031.

49. Dispenzieri A, Lacy MQ, Kyle RA et al. Eligibility for hematopoietic stem-cell transplantation for primary systemic amyloidosis is a favorable prognostic factor for survival. J Clin Oncol 2001; 19: 3350–3356.

50. Moreau P, Leblond V, Bourquelot P et al. Prognostic factors for survival and response after high‑dose therapy and autologous stem cell transplantation in systemic AL amyloidosis: A report on 21 patients. Br J Haematol 1998; 101: 766–769.

51. Perfetti V, Siena S, Palladini G et al. Long‑term results of a risk‑adapted approach to melphalan conditioning in autologous peripheral blood stem cell transplantation for primary (AL) amyloidosis. Haematologica 2006; 91: 1635–1643.

52. Cohen AD, Zhou P, Chou J et al. Risk‑adapted autologous stem cell transplantation with adjuvant dexamethasone ± thalidomide for systemic light‑chain amyloidosis: results of a phase II trial. Br J Haematol 2007; 139: 224–233.

53. Jaccard A, Moreau P, Leblond V et al. High‑dose melphalan versus melphalan plus dexametasone for AL amyloidosis. N Engl J Med 2007; 357: 1083–1093.

54. Rajkumar SV, Glassock RJ, Kyle RA et al. Prognosis and treatment of primary (AL) amyloidosis and light and heavy chain deposition disease. Available from: www.uptodate.com.

55. 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: 3520–3526.

56. 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: 2949–2951.

57. Wechalekar AD, Goodman HJ, Lachmann HJ et al. Safety and efficacy of risk‑adapted cyclophosphamide, thalidomide, and dexamethasone in systemic AL amyloidosis. Blood 2007; 109: 457–464.

58. 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: 465–470.

59. 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: 492–496.

60. Gertz MA, Lacy MQ, Dispenzieri A et al. A multicenter phase II trial of 4’-  iodo-4’-deoxydoxorubicin (IDOX) in primary amyloidosis (AL). Amyloid 2002; 9: 24–30.

61. Gillmore JD, Goodman HJ, Lachmann HJ et al. Sequential heart and autologous stem cell transplantation for systemic AL amyloidosis. Blood 2006; 107: 1227–1229.

Labels
Diabetology Endocrinology Internal medicine

Article was published in

Internal Medicine

Issue Supplementum 1

2009 Issue Supplementum 1

Most read in this issue

This topic is also in:


Login
Forgotten password

Don‘t have an account?  Create new account

Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account