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Prognosis and treatment of immunoglobulin light chain (AL) amyloidosis and light and heavy chain deposition diseases

INTRODUCTION

Immunoglobulin light chain (AL) amyloidosis (previously referred to as primary amyloidosis), light chain deposition disease (LCDD), and heavy chain deposition disease (HCDD) are monoclonal plasma cell proliferative disorders that are characterized by tissue deposits of light chain or heavy chain fragments, leading to organ dysfunction. The incidence of AL amyloidosis is approximately one-tenth that of multiple myeloma. In approximately 10 percent of patients with AL amyloidosis, multiple myeloma is also present at the time of initial diagnosis; the clinical course and treatment of these patients is dependent on which of the two diseases is dominant in terms of end-organ damage and symptoms. Less than 1 percent of patients with isolated AL amyloidosis at diagnosis develop multiple myeloma at a future time point.

The prognosis and treatment of AL amyloidosis will be reviewed in detail here. The treatment of LCDD and HCDD is also reviewed briefly. The pathogenesis, clinical features, and diagnosis of these disorders and the diagnosis of primary amyloidosis are discussed in detail separately. (See "Pathogenesis of immunoglobulin light chain (AL) amyloidosis and light and heavy chain deposition diseases" and "Clinical presentation, laboratory manifestations, and diagnosis of immunoglobulin light chain (AL) amyloidosis (primary amyloidosis)".)

PRE-TREATMENT EVALUATION

Assessment — To best treat patients with AL amyloidosis, the initial evaluation must confirm the diagnosis, establish the extent and sites of disease, and evaluate for comorbidities that are likely to have an impact on treatment options. The diagnosis of AL amyloidosis is presented separately. (See "Clinical presentation, laboratory manifestations, and diagnosis of immunoglobulin light chain (AL) amyloidosis (primary amyloidosis)".)

In addition to a history and physical examination, it is our practice to perform the following pre-treatment studies in patients with AL amyloidosis:

Laboratory studies include a complete blood count with differential, chemistries with liver and renal function and electrolytes, prothrombin time (PT), partial thromboplastin time (PTT), electrophoresis of the serum and urine, immunoelectrophoresis of the serum and urine, serum free light chain assay, 24-hour urinary protein and creatinine clearance, brain natriuretic peptide (BNP), troponin, NT-proBNP, thyroid stimulating hormone (TSH), and cortisol level. Factor X levels should be included for patients with abnormal bleeding or abnormal PT/PTT testing.

                           

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Literature review current through: Sep 2014. | This topic last updated: May 29, 2014.
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References
Top
  1. Bryce AH, Ketterling RP, Gertz MA, et al. Translocation t(11;14) and survival of patients with light chain (AL) amyloidosis. Haematologica 2009; 94:380.
  2. 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.
  3. Merlini G, Seldin DC, Gertz MA. Amyloidosis: pathogenesis and new therapeutic options. J Clin Oncol 2011; 29:1924.
  4. http://msmart.org/amyloid.pdf (Accessed on June 21, 2012).
  5. Gertz MA. How to manage primary amyloidosis. Leukemia 2012; 26:191.
  6. Choufani EB, Sanchorawala V, Ernst T, et al. Acquired factor X deficiency in patients with amyloid light-chain amyloidosis: incidence, bleeding manifestations, and response to high-dose chemotherapy. Blood 2001; 97:1885.
  7. Comenzo RL. How I treat amyloidosis. Blood 2009; 114:3147.
  8. 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.
  9. Comenzo RL, Vosburgh E, Falk RH, et al. Dose-intensive melphalan with blood stem-cell support for the treatment of AL (amyloid light-chain) amyloidosis: survival and responses in 25 patients. Blood 1998; 91:3662.
  10. Goodman HJ, Gillmore JD, Lachmann HJ, et al. Outcome of autologous stem cell transplantation for AL amyloidosis in the UK. Br J Haematol 2006; 134:417.
  11. 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; 11:1210.
  12. Leung N, Slezak JM, Bergstralh EJ, et al. Acute renal insufficiency after high-dose melphalan in patients with primary systemic amyloidosis during stem cell transplantation. Am J Kidney Dis 2005; 45:102.
  13. Cordes S, Dispenzieri A, Lacy MQ, et al. Ten-year survival after autologous stem cell transplantation for immunoglobulin light chain amyloidosis. Cancer 2012; 118:6105.
  14. Schönland SO, Lokhorst H, Buzyn A, et al. Allogeneic and syngeneic hematopoietic cell transplantation in patients with amyloid light-chain amyloidosis: a report from the European Group for Blood and Marrow Transplantation. Blood 2006; 107:2578.
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. 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.
  20. Gertz MA, Lacy MQ, Dispenzieri A, et al. Stem cell transplantation for the management of primary systemic amyloidosis. Am J Med 2002; 113:549.
  21. Comenzo RL, Gertz MA. Autologous stem cell transplantation for primary systemic amyloidosis. Blood 2002; 99:4276.
  22. Gertz MA, Lacy MQ, Dispenzieri A, et al. Trends in day 100 and 2-year survival after auto-SCT for AL amyloidosis: outcomes before and after 2006. Bone Marrow Transplant 2011; 46:970.
  23. Gertz MA, Lacy MQ, Dispenzieri A, et al. Autologous stem cell transplant for immunoglobulin light chain amyloidosis: a status report. Leuk Lymphoma 2010; 51:2181.
  24. Gertz MA, Blood E, Vesole DH, et al. A multicenter phase 2 trial of stem cell transplantation for immunoglobulin light-chain amyloidosis (E4A97): an Eastern Cooperative Oncology Group Study. Bone Marrow Transplant 2004; 34:149.
  25. Comenzo RL, Sanchorawala V, Fisher C, et al. Intermediate-dose intravenous melphalan and blood stem cells mobilized with sequential GM+G-CSF or G-CSF alone to treat AL (amyloid light chain) amyloidosis. Br J Haematol 1999; 104:553.
  26. Casserly LF, Fadia A, Sanchorawala V, et al. High-dose intravenous melphalan with autologous stem cell transplantation in AL amyloidosis-associated end-stage renal disease. Kidney Int 2003; 63:1051.
  27. 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.
  28. Seldin DC, Anderson JJ, Sanchorawala V, et al. Improvement in quality of life of patients with AL amyloidosis treated with high-dose melphalan and autologous stem cell transplantation. Blood 2004; 104:1888.
  29. Cibeira MT, Sanchorawala V, Seldin DC, et al. Outcome of AL amyloidosis after high-dose melphalan and autologous stem cell transplantation: long-term results in a series of 421 patients. Blood 2011; 118:4346.
  30. Tsai SB, Seldin DC, Quillen K, et al. High-dose melphalan and stem cell transplantation for patients with AL amyloidosis: trends in treatment-related mortality over the past 17 years at a single referral center. Blood 2012; 120:4445.
  31. Seldin DC, Anderson JJ, Skinner M, et al. Successful treatment of AL amyloidosis with high-dose melphalan and autologous stem cell transplantation in patients over age 65. Blood 2006; 108:3945.
  32. Dispenzieri A, Seenithamby K, Lacy MQ, et al. Patients with immunoglobulin light chain amyloidosis undergoing autologous stem cell transplantation have superior outcomes compared with patients with multiple myeloma: a retrospective review from a tertiary referral center. Bone Marrow Transplant 2013; 48:1302.
  33. Wechalekar AD, Hawkins PN, Gillmore JD. Perspectives in treatment of AL amyloidosis. Br J Haematol 2008; 140:365.
  34. 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.
  35. 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.
  36. Tan SY, Pepys MB, Hawkins PN. Treatment of amyloidosis. Am J Kidney Dis 1995; 26:267.
  37. 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.
  38. 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.
  39. Kyle RA, Wagoner RD, Holley KE. Primary systemic amyloidosis: resolution of the nephrotic syndrome with melphalan and prednisone. Arch Intern Med 1982; 142:1445.
  40. Gertz MA, Kyle RA. Acute leukemia and cytogenetic abnormalities complicating melphalan treatment of primary systemic amyloidosis. Arch Intern Med 1990; 150:629.
  41. Wechalekar AD, Schonland SO, Kastritis E, et al. A European collaborative study of treatment outcomes in 346 patients with cardiac stage III AL amyloidosis. Blood 2013; 121:3420.
  42. Palladini G, Milani P, Foli A, et al. Oral melphalan and dexamethasone grants extended survival with minimal toxicity in AL amyloidosis: long-term results of a risk-adapted approach. Haematologica 2014; 99:743.
  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.
  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.
  45. Lebovic D, Hoffman J, Levine BM, et al. Predictors of survival in patients with systemic light-chain amyloidosis and cardiac involvement initially ineligible for stem cell transplantation and treated with oral melphalan and dexamethasone. Br J Haematol 2008; 143:369.
  46. Dietrich S, Schönland SO, Benner A, et al. Treatment with intravenous melphalan and dexamethasone is not able to overcome the poor prognosis of patients with newly diagnosed systemic light chain amyloidosis and severe cardiac involvement. Blood 2010; 116:522.
  47. Reece DE, Hegenbart U, Sanchorawala V, et al. Efficacy and safety of once-weekly and twice-weekly bortezomib in patients with relapsed systemic AL amyloidosis: results of a phase 1/2 study. Blood 2011; 118:865.
  48. Reece DE, Sanchorawala V, Hegenbart U, et al. Weekly and twice-weekly bortezomib in patients with systemic AL amyloidosis: results of a phase 1 dose-escalation study. Blood 2009; 114:1489.
  49. Venner CP, Lane T, Foard D, et al. Cyclophosphamide, bortezomib, and dexamethasone therapy in AL amyloidosis is associated with high clonal response rates and prolonged progression-free survival. Blood 2012; 119:4387.
  50. Mikhael JR, Schuster SR, Jimenez-Zepeda VH, et al. Cyclophosphamide-bortezomib-dexamethasone (CyBorD) produces rapid and complete hematologic response in patients with AL amyloidosis. Blood 2012; 119:4391.
  51. Comenzo RL, Reece D, Palladini G, et al. Consensus guidelines for the conduct and reporting of clinical trials in systemic light-chain amyloidosis. Leukemia 2012; 26:2317.
  52. Palladini G, Dispenzieri A, Gertz MA, et al. New criteria for response to treatment in immunoglobulin light chain amyloidosis based on free light chain measurement and cardiac biomarkers: impact on survival outcomes. J Clin Oncol 2012; 30:4541.
  53. Leung N, Glavey SV, Kumar S, et al. A detailed evaluation of the current renal response criteria in AL amyloidosis: is it time for a revision? Haematologica 2013; 98:988.
  54. Kumar SK, Dispenzieri A, Lacy MQ, et al. Changes in serum-free light chain rather than intact monoclonal immunoglobulin levels predicts outcome following therapy in primary amyloidosis. Am J Hematol 2011; 86:251.
  55. Landau H, Hassoun H, Rosenzweig MA, et al. Bortezomib and dexamethasone consolidation following risk-adapted melphalan and stem cell transplantation for patients with newly diagnosed light-chain amyloidosis. Leukemia 2013; 27:823.
  56. Kastritis E, Wechalekar AD, Dimopoulos MA, et al. Bortezomib with or without dexamethasone in primary systemic (light chain) amyloidosis. J Clin Oncol 2010; 28:1031.
  57. Wechalekar AD, Lachmann HJ, Offer M, et al. Efficacy of bortezomib in systemic AL amyloidosis with relapsed/refractory clonal disease. Haematologica 2008; 93:295.
  58. Landau HJ, Hassoun H, Elizabeth H, et al. Adjuvant bortezomib and dexamethasone following risk-adapted melphalan and stem cell transplant in patients with light-chain amyloidosis (abstract). J Clin Oncol 2009; 27:443S(abstract 8540).
  59. Lamm W, Willenbacher W, Lang A, et al. Efficacy of the combination of bortezomib and dexamethasone in systemic AL amyloidosis. Ann Hematol 2011; 90:201.
  60. Sanchorawala V, Finn KT, Fennessey S, et al. Durable hematologic complete responses can be achieved with lenalidomide in AL amyloidosis. Blood 2010; 116:1990.
  61. 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.
  62. 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.
  63. Moreau P, Jaccard A, Benboubker L, et al. Lenalidomide in combination with melphalan and dexamethasone in patients with newly diagnosed AL amyloidosis: a multicenter phase 1/2 dose-escalation study. Blood 2010; 116:4777.
  64. Kastritis E, Terpos E, Roussou M, et al. A phase 1/2 study of lenalidomide with low-dose oral cyclophosphamide and low-dose dexamethasone (RdC) in AL amyloidosis. Blood 2012; 119:5384.
  65. Kumar SK, Hayman SR, Buadi FK, et al. Lenalidomide, cyclophosphamide, and dexamethasone (CRd) for light-chain amyloidosis: long-term results from a phase 2 trial. Blood 2012; 119:4860.
  66. 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.
  67. 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.
  68. 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.
  69. 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.
  70. 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.
  71. Kyle RA, Greipp PR. Amyloidosis (AL). Clinical and laboratory features in 229 cases. Mayo Clin Proc 1983; 58:665.
  72. 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.
  73. Dispenzieri A, Kyle RA, Gertz MA, et al. Survival in patients with primary systemic amyloidosis and raised serum cardiac troponins. Lancet 2003; 361:1787.
  74. 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.
  75. Dispenzieri A, Gertz MA, Kyle RA, et al. Serum cardiac troponins and N-terminal pro-brain natriuretic peptide: a staging system for primary systemic amyloidosis. J Clin Oncol 2004; 22:3751.
  76. Dispenzieri A, Gertz MA, Kyle RA, et al. Prognostication of survival using cardiac troponins and N-terminal pro-brain natriuretic peptide in patients with primary systemic amyloidosis undergoing peripheral blood stem cell transplantation. Blood 2004; 104:1881.
  77. Kumar S, Dispenzieri A, Lacy MQ, et al. Serum uric acid: novel prognostic factor in primary systemic amyloidosis. Mayo Clin Proc 2008; 83:297.
  78. Kumar SK, Gertz MA, Lacy MQ, et al. Recent improvements in survival in primary systemic amyloidosis and the importance of an early mortality risk score. Mayo Clin Proc 2011; 86:12.
  79. Kumar S, Dispenzieri A, Lacy MQ, et al. Revised prognostic staging system for light chain amyloidosis incorporating cardiac biomarkers and serum free light chain measurements. J Clin Oncol 2012; 30:989.
  80. Kourelis TV, Kumar SK, Gertz MA, et al. Coexistent multiple myeloma or increased bone marrow plasma cells define equally high-risk populations in patients with immunoglobulin light chain amyloidosis. J Clin Oncol 2013; 31:4319.
  81. Dispenzieri A, Buadi F, Laumann K, et al. Activity of pomalidomide in patients with immunoglobulin light-chain amyloidosis. Blood 2012; 119:5397.
  82. Lorenz EC, Gertz MA, Fervenza FC, et al. Long-term outcome of autologous stem cell transplantation in light chain deposition disease. Nephrol Dial Transplant 2008; 23:2052.
  83. Nasr SH, Valeri AM, Cornell LD, et al. Renal monoclonal immunoglobulin deposition disease: a report of 64 patients from a single institution. Clin J Am Soc Nephrol 2012; 7:231.
  84. Sanders PW. Management of paraproteinemic renal disease. Curr Opin Nephrol Hypertens 2005; 14:97.
  85. Royer B, Arnulf B, Martinez F, et al. High dose chemotherapy in light chain or light and heavy chain deposition disease. Kidney Int 2004; 65:642.
  86. Soma J, Sato K, Sakuma T, et al. Immunoglobulin gamma3-heavy-chain deposition disease: report of a case and relationship with hypocomplementemia. Am J Kidney Dis 2004; 43:E10.
  87. Lin J, Markowitz GS, Valeri AM, et al. Renal monoclonal immunoglobulin deposition disease: the disease spectrum. J Am Soc Nephrol 2001; 12:1482.
  88. Light chain deposition disease. In: Serum free light chain analysis, 3rd ed, Bradwell AR, Mead GP, Carr-Smith HD (Eds), The Binding Site, Birmingham 2005. p.149.
  89. Ganeval D, Noël LH, Preud'homme JL, et al. Light-chain deposition disease: its relation with AL-type amyloidosis. Kidney Int 1984; 26:1.
  90. Heilman RL, Velosa JA, Holley KE, et al. Long-term follow-up and response to chemotherapy in patients with light-chain deposition disease. Am J Kidney Dis 1992; 20:34.
  91. Leung N, Lager DJ, Gertz MA, et al. Long-term outcome of renal transplantation in light-chain deposition disease. Am J Kidney Dis 2004; 43:147.
  92. Pozzi C, D'Amico M, Fogazzi GB, et al. Light chain deposition disease with renal involvement: clinical characteristics and prognostic factors. Am J Kidney Dis 2003; 42:1154.