Immunoglobulin-Related Amyloidosis Follow-up

  • Author: Slavomir Urbancek, MD, PhD; Chief Editor: Emmanuel C Besa, MD  more...
 
Updated: Jan 29, 2015
 

Further Outpatient Care

A hematologist with experience in administering chemotherapy should care for patients with L chain–type amyloidosis on an ongoing basis.

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Complications

Complications of L chain–type amyloidosis reflect the organ systems involved. The most severe complication of systemic L chain–type amyloidosis is extensive cardiac deposition, with consequent congestive heart failure, arrhythmias, or both. Cardiac involvement eventually occurs in most patients and appears to be the cause of death in more than 50% of patients with L chain–type amyloidosis.

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Prognosis

The prognosis for patients with L chain–type amyloidosis depends largely on the specificity of the tissue deposition. Any organ can be involved, with symptoms and physical findings reflecting the pattern of anatomic compromise.

Patients with clinical cardiac involvement have the worst prognosis, with a median survival rate of 6 months. In these patients, increased troponin is associated with worse left ventricular and left atrial functions. Increased troponin at baseline strongly predicts all-cause mortality.[25]

Median overall survival was 29 months in a retrospective study of 63 patients with L chain–type amyloidosis, of which 32 (51%) presented with cardiac amyloid involvement. Overall survival did not differ between patients with or without cardiac involvement. During a median follow-up of 12.7 months, 38 (60%) patients died.[26]

Patients with involvement limited to the peripheral nerves have the longest survival. Other favorable prognostic features include a small number of clonal plasma cells in the bone marrow and normal renal function.

In the absence of chemotherapy, systemic L chain–type amyloidosis is always progressive. A subgroup of cases respond to chemotherapy with temporary resorption of amyloid fibrils and improvement of end-organ function.

In a retrospective study of 146 patients with L chain–type amyloidosis who relapsed after treatment wih chemotherapy and autologous stem cell transplant, median overall survival and 5-year overall survival from the time of post-transplant relapse were 51.7 months and 39%, respectively.[27]

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Contributor Information and Disclosures
Author

Slavomir Urbancek, MD, PhD Head, Department of Dermatology, FD Roosevelt Hospital, Slovakia; Member of executive commitee - Slovak Dermatovenereological Society

Slavomir Urbancek, MD, PhD is a member of the following medical societies: American Academy of Dermatology, European Academy of Dermatology and Venereology, Slovakian Dermatovenerological Society, Slovak Society of Allergology and Clinical Immunology

Disclosure: Received honoraria from Abbott for speaking and teaching; Received honoraria from Pfizer for none; Received honoraria from Janssen for speaking and teaching; Received honoraria from MSD for speaking and teaching; Received consulting fee from Roche for speaking and teaching.

Coauthor(s)

Daniel R Jacobson, MD Professor of Medicine, Boston University School of Medicine; Chief of Oncology, Veterans Affairs Boston Healthcare System

Disclosure: Nothing to disclose.

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, Rutgers New Jersey Medical School; Visiting Professor, Rutgers University School of Public Affairs and Administration

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, New York Academy of Medicine, American Academy of Dermatology, American College of Physicians, Sigma Xi

Disclosure: Nothing to disclose.

Carol A Bogdan, MD Consultant in Hematology-Oncology, Myrtle Beach, SC

Disclosure: Nothing to disclose.

Joel N Buxbaum, MD Professor, Department of Molecular and Experimental Medicine, The Scripps Research Institute

Joel N Buxbaum, MD is a member of the following medical societies: American Association for the Advancement of Science, American Society for Clinical Investigation, American Society of Human Genetics, Association of American Physicians, Association of Black Cardiologists, Henry Kunkel Society

Disclosure: Received consulting fee from Foldrx pharmaceuticals for consulting; Received consulting fee from Isis pharmaceuticals for consulting; Received consulting fee from alnylam pharmaceutical for consulting; Received consulting fee from Pfizer Pharmaceuticals for consulting.

Pere Gascon, MD, PhD Professor and Director, Division of Medical Oncology, Institute of Hematology and Medical Oncology, IDIBAPS, University of Barcelona Faculty of Medicine, Spain

Pere Gascon, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, New York Academy of Medicine, New York Academy of Sciences, Sigma Xi

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Lawrence H Brent, MD Associate Professor of Medicine, Jefferson Medical College of Thomas Jefferson University; Chair, Program Director, Department of Medicine, Division of Rheumatology, Albert Einstein Medical Center

Lawrence H Brent, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association of Immunologists, American College of Physicians, American College of Rheumatology

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Janssen<br/>Serve(d) as a speaker or a member of a speakers bureau for: Genentech; Pfizer; Mallinckrodt.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Additional Contributors

Robert E Wolf, MD, PhD Professor Emeritus, Department of Medicine, Louisiana State University School of Medicine in Shreveport; Chief, Rheumatology Section, Medical Service, Overton Brooks Veterans Affairs Medical Center

Robert E Wolf, MD, PhD is a member of the following medical societies: American College of Rheumatology, Arthritis Foundation, Society for Leukocyte Biology

Disclosure: Nothing to disclose.

References
  1. Shaughnessy JD Jr, Zhan F, Burington BE, Huang Y, Colla S, Hanamura I, et al. A validated gene expression model of high-risk multiple myeloma is defined by deregulated expression of genes mapping to chromosome 1. Blood. 2007 Mar 15. 109(6):2276-84. [Medline]. [Full Text].

  2. Kyle RA, Gertz MA. Primary systemic amyloidosis: clinical and laboratory features in 474 cases. Semin Hematol. 1995 Jan. 32(1):45-59. [Medline].

  3. Leibovitch I, Selva D, Goldberg RA, et al. Periocular and orbital amyloidosis: clinical characteristics, management, and outcome. Ophthalmology. 2006 Sep. 113(9):1657-64. [Medline].

  4. Cross TJ, Wendon JA, Quaglia A, et al. Myeloma associated amyloidosis presenting as subacute liver failure. Postgrad Med J. 2006 Jul. 82(969):e13. [Medline].

  5. Kumar S, Dispenzieri A, Katzmann JA, et al. Serum immunoglobulin free light-chain measurement in primary amyloidosis: prognostic value and correlations with clinical features. Blood. 2010 Dec 9. 116(24):5126-9. [Medline]. [Full Text].

  6. 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 Apr 15. 107(8):3378-83. [Medline]. [Full Text].

  7. Porrata LF, Gertz MA, Litzow MR, et al. Early lymphocyte recovery predicts superior survival after autologous hematopoietic stem cell transplantation for patients with primary systemic amyloidosis. Clin Cancer Res. 2005 Feb 1. 11(3):1210-8. [Medline]. [Full Text].

  8. Paiva B, Vídriales MB, Pérez JJ, López-Berges MC, García-Sanz R, Ocio EM, et al. The clinical utility and prognostic value of multiparameter flow cytometry immunophenotyping in light-chain amyloidosis. Blood. 2011 Mar 31. 117(13):3613-6. [Medline].

  9. Chopra A. 125I-Labeled single-chain monoclonal antibody, NS4F5, that targets the GlcNS6S-IdoA2S motif of heparan sulfate proteoglycans for the in vivo imaging of peripheral amyloidosis. 2004. [Medline].

  10. Wall JS, Richey T, Williams A, Stuckey A, Osborne D, Martin E, et al. Comparative analysis of peptide p5 and serum amyloid P component for imaging AA amyloid in mice using dual-isotope SPECT. Mol Imaging Biol. 2012 Aug. 14(4):402-7. [Medline]. [Full Text].

  11. Wall JS, Kennel SJ, Stuckey AC, Long MJ, Townsend DW, Smith GT. Radioimmunodetection of amyloid deposits in patients with AL amyloidosis. Blood. 2010 Sep 30. 116(13):2241-4. [Medline].

  12. Pan WH, Li NP. Clinical pathological feature of early tongue amyloidosis. Chin Med Sci J. 2006 Jun. 21(2):104-6. [Medline].

  13. 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 Apr 24. 336(17):1202-7. [Medline]. [Full Text].

  14. 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 Mar. 100(3):290-8. [Medline].

  15. Gertz MA, Lacy MQ, Lust JA, et al. Prospective randomized trial of melphalan and prednisone versus vincristine, carmustine, melphalan, cyclophosphamide, and prednisone in the treatment of primary systemic amyloidosis. J Clin Oncol. 1999 Jan. 17(1):262-7. [Medline]. [Full Text].

  16. Anderson K, Richardson P, Chanan-Khan A, et al. Single-agent bortezomib in previously untreated multiple myeloma (MM): results of a phase II multicenter study [abstract 7504]. J Clin Oncol. 2006. 24:423s.

  17. Dispenzieri A, Zhang L, Fonseca R, et al. Single agent bortezomib is associated with a high response rate in patients with high risk myeloma. A phase II study from the Eastern Cooperative Oncology Group (E2A02) [abstract 3527]. Blood. 2006. 108(11):1006s. [Full Text].

  18. Mateos MV, Richardson PG, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, et al. Bortezomib plus melphalan and prednisone compared with melphalan and prednisone in previously untreated multiple myeloma: updated follow-up and impact of subsequent therapy in the phase III VISTA trial. J Clin Oncol. 2010 May 1. 28(13):2259-66. [Medline].

  19. Harousseau JL, Palumbo A, Richardson PG, Schlag R, Dimopoulos MA, Shpilberg O, et al. Superior outcomes associated with complete response in newly diagnosed multiple myeloma patients treated with nonintensive therapy: analysis of the phase 3 VISTA study of bortezomib plus melphalan-prednisone versus melphalan-prednisone. Blood. 2010 Nov 11. 116(19):3743-50. [Medline].

  20. Harousseau JL, Attal M, Leleu X, et al. Bortezomib plus dexamethasone as induction treatment prior to autologous stem cell transplantation in patients with newly diagnosed multiple myeloma: results of an IFM phase II study. Haematologica. 2006 Nov. 91(11):1498-505. [Medline]. [Full Text].

  21. San Miguel J, Weisel K, Moreau P, Lacy M, Song K, Delforge M, et al. Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013 Oct. 14(11):1055-66. [Medline].

  22. Gianni L, Bellotti V, Gianni AM, Merlini G. New drug therapy of amyloidoses: resorption of AL-type deposits with 4'-iodo-4'-deoxydoxorubicin. Blood. 1995 Aug 1. 86(3):855-61. [Medline]. [Full Text].

  23. Gertz MA, Lacy MQ, Dispenzieri A, Cheson BD, Barlogie B, Kyle RA, et al. A multicenter phase II trial of 4'-iodo-4'deoxydoxorubicin (IDOX) in primary amyloidosis (AL). Amyloid. 2002 Mar. 9(1):24-30. [Medline].

  24. Tran Thang NN, Abdo G, Martin JB, et al. Percutaneous cementoplasty in multiple myeloma: a valuable adjunct for pain control and ambulation maintenance. Support Care Cancer. 2008 Aug. 16(8):891-6. [Medline].

  25. Apridonidze T, Steingart RM, Comenzo RL, Hoffman J, Goldsmith Y, Bella JN, et al. Clinical and Echocardiographic Correlates of Elevated Troponin in Amyloid Light-Chain Cardiac Amyloidosis. Am J Cardiol. 2012 Jul 5. [Medline].

  26. Nelson LM, Gustafsson F, Gimsing P. Characteristics and Long-Term Outcome of Patients with Systemic Immunoglobulin Light-Chain Amyloidosis. Acta Haematol. 2014 Dec 16. 133(4):336-346. [Medline].

  27. Warsame R, Bang SM, Kumar SK, Gertz MA, Lacy MQ, Buadi F, et al. Outcomes and treatments of patients with immunoglobulin light chain amyloidosis who progress or relapse postautologous stem cell transplant. Eur J Haematol. 2014 Jun. 92(6):485-90. [Medline].

  28. Biehn SE, Moore DT, Voorhees PM, et al. Extended follow-up of outcome measures in multiple myeloma patients treated on a phase I study with bortezomib and pegylated liposomal doxorubicin. Ann Hematol. 2007 Mar. 86(3):211-6. [Medline].

  29. Browning MJ, Banks RA, Tribe CR, et al. Ten years' experience of an amyloid clinic--a clinicopathological survey. Q J Med. 1985 Mar. 54(215):213-27. [Medline].

  30. Buxbaum J, Gallo G. Nonamyloidotic monoclonal immunoglobulin deposition disease. Light-chain, heavy-chain, and light- and heavy-chain deposition diseases. Hematol Oncol Clin North Am. 1999 Dec. 13(6):1235-48. [Medline].

  31. Camoriano JK, Greipp PR, Bayer GK, Bowie EJ. Resolution of acquired factor X deficiency and amyloidosis with melphalan and prednisone therapy. N Engl J Med. 1987 Apr 30. 316(18):1133-5. [Medline].

  32. Davern S, Tang LX, Williams TK, et al. Immunodiagnostic capabilities of anti-free immunoglobulin light chain monoclonal antibodies. Am J Clin Pathol. 2008 Nov. 130(5):702-11. [Medline]. [Full Text].

  33. [Guideline] Dimopoulos MA., Weise K, Song KW, Delforge M, Karlin L, Goldschmidt H, et al. Final Analysis, Cytogenetics, Long-Term Treatment, and Long-Term Survival In MM-003, A Phase 3 Study Comparing Pomalidomide + Low-Dose Dexamethasone (POM + LoDEX) Vs High-Dose Dexamethasone (HiDEX) In Relapsed/Refractory Multiple Myeloma (RRMM). www.myelomabeacon.com. Available at http://www.myelomabeacon.com/resources/mtgs/ash2013/abs/408/. Accessed: May, 18, 2014.

  34. Dispenzieri A, Kyle R, Merlini G, et al. International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders. Leukemia. 2008 Nov 20. epub ahead of print. [Medline].

  35. Gertz MA, Kyle RA, Greipp PR. Response rates and survival in primary systemic amyloidosis. Blood. 1991 Jan 15. 77(2):257-62. [Medline]. [Full Text].

  36. Harousseau JL. The allogeneic dilemma. Bone Marrow Transplant. 2007 Dec. 40(12):1123-8. [Medline]. [Full Text].

  37. Jagannath S, Durie BG, Wolf J, et al. Bortezomib therapy alone and in combination with dexamethasone for previously untreated symptomatic multiple myeloma. Br J Haematol. 2005 Jun. 129(6):776-83. [Medline].

  38. Jagannath S, Durie BGM, Wolf JL, et al. Long-term follow-up of patients treated with bortezomib alone and in combination with dexamethasone as frontline therapy for multiple myeloma [abstract 796]. Blood. Nov 2006. 108:238a. [Full Text].

  39. Jakubowiak AJ, Al-Zoubi A, Kendall T, et al. High rate of complete and near complete responses (CR/nCR) after initial therapy with bortezomib (Velcade®), Doxil®, and dexamethasone (VDD) is further increased after autologous stem cell transplantation (ASCT) [abstract 3093]. Blood. 2006. 108:882a. [Full Text].

  40. Kyle RA. High-dose therapy in multiple myeloma and primary amyloidosis: an overview. Semin Oncol. 1999 Feb. 26(1):74-83. [Medline].

  41. Lee AI, Munshi NC. Integration of novel agents into treatment of myeloma. Clin Lymphoma Myeloma. 2007 Aug. 7(suppl 5):S215-21. [Medline].

  42. Oakervee HE, Popat R, Curry N, et al. PAD combination therapy (PS-341/bortezomib, doxorubicin and dexamethasone) for previously untreated patients with multiple myeloma. Br J Haematol. 2005 Jun. 129(6):755-62. [Medline].

  43. Pelosi F Jr, Capehart J, Roberts WC. Effectiveness of cardiac transplantation for primary (AL) cardiac amyloidosis. Am J Cardiol. 1997 Feb 15. 79(4):532-5. [Medline].

  44. Popat R, Oakervee HE, Curry N, et al. Reduced dose PAD combination therapy (PS-341/bortezomib, Adriamycin and dexamethasone) for previously untreated patients with multiple myeloma [abstract 2554]. Blood. 2005. 106:171a-718a. [Full Text].

  45. Richardson PG, Barlogie B, Berenson J, et al. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med. 2003 Jun 26. 348(26):2609-17. [Medline]. [Full Text].

  46. Richardson PG1, Siegel DS, Vij R, Hofmeister CC, Baz R, Jagannath S, et al. Pomalidomide alone or in combination with low-dose dexamethasone in relapsed and refractory multiple myeloma: a randomized phase 2 study. Blood. 2014. 123:1826-32. [Full Text].

  47. Rubinow A, Skinner M, Cohen AS. Digoxin sensitivity in amyloid cardiomyopathy. Circulation. 1981 Jun. 63(6):1285-8. [Medline].

  48. Simons M, Isner JM. Assessment of relative sensitivities of noninvasive tests for cardiac amyloidosis in documented cardiac amyloidosis. Am J Cardiol. 1992 Feb 1. 69(4):425-7. [Medline].

  49. Solomon A, Weiss DT, Murphy C. Primary amyloidosis associated with a novel heavy-chain fragment (AH amyloidosis). Am J Hematol. 1994 Feb. 45(2):171-6. [Medline].

  50. van Gameren II, Hazenberg BP, Bijzet J, van Rijswijk MH. Diagnostic accuracy of subcutaneous abdominal fat tissue aspiration for detecting systemic amyloidosis and its utility in clinical practice. Arthritis Rheum. 2006 Jun. 54(6):2015-21. [Medline]. [Full Text].

  51. Yood RA, Skinner M, Rubinow A, Talarico L, Cohen AS. Bleeding manifestations in 100 patients with amyloidosis. JAMA. 1983 Mar 11. 249(10):1322-4. [Medline].

 
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The relationship among light chain–type amyloidosis (AL), the other monoclonal plasma cell disorders, and the other amyloidoses. Ig = immunoglobulin; MGUS = monoclonal gammopathy of undetermined significance.
 
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