Skip to main content
SpringerLink
Log in

Immunoglobulin Light Chain Systemic Amyloidosis

  • Chapter
  • First Online:
Plasma Cell Dyscrasias

Part of the book series: Cancer Treatment and Research ((CTAR,volume 169))

Abstract

Immunoglobulin light chain amyloidosis (AL) is a rare, complex disease caused by misfolded free light chains produced by a usually small, indolent plasma cell clone. Effective treatments exist that can alter the natural history, provided that they are started before irreversible organ damage has occurred. The cornerstones of the management of AL amyloidosis are early diagnosis, accurate typing, appropriate risk-adapted therapy, tight follow-up, and effective supportive treatment. The suppression of the amyloidogenic light chains using the cardiac biomarkers as guide to choose chemotherapy is still the mainstay of therapy. There are exciting possibilities ahead, including the study of oral proteasome inhibitors, antibodies directed at plasma cell clone, and finally antibodies attacking the amyloid deposits are entering the clinic, offering unprecedented opportunities for radically improving the care of this disease.

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

Access this chapter

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 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
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

Institutional subscriptions

References

  1. Merlini G, Bellotti V (2003) Molecular mechanisms of amyloidosis. N Engl J Med 349(6):583–596. doi:10.1056/NEJMra023144349/6/583

    Article  CAS  PubMed  Google Scholar 

  2. Merlini G, Palladini G (2008) Amyloidosis: is a cure possible? Ann Oncol 19 Suppl 4:iv63–66

    Google Scholar 

  3. Merlini G, Wechalekar AD, Palladini G (2013) Systemic light chain amyloidosis: an update for treating physicians. Blood 121(26):5124–5130. doi:10.1182/blood-2013-01-453001

    Article  CAS  PubMed  Google Scholar 

  4. Merlini G, Palladini G (2012) Differential diagnosis of monoclonal gammopathy of undetermined significance. Hematol Am Soc Hematol Educ Program 2012:595–603. doi:10.1182/asheducation-2012.1.595

    Google Scholar 

  5. Sipe JD, Benson MD, Buxbaum JN, Ikeda S, Merlini G, Saraiva MJ, Westermark P (2014) Nomenclature 2014: amyloid fibril proteins and clinical classification of the amyloidosis. Amyloid 21(4):221–224. doi:10.3109/13506129.2014.964858

    Article  PubMed  Google Scholar 

  6. Kyle RA, Linos A, Beard CM, Linke RP, Gertz MA, O’Fallon WM, Kurland LT (1992) Incidence and natural history of primary systemic amyloidosis in Olmsted County, Minnesota, 1950 through 1989. Blood 79(7):1817–1822

    CAS  PubMed  Google Scholar 

  7. Pinney JH, Smith CJ, Taube JB, Lachmann HJ, Venner CP, Gibbs SD, Dungu J, Banypersad SM, Wechalekar AD, Whelan CJ, Hawkins PN, Gillmore JD (2013) Systemic amyloidosis in England: an epidemiological study. Br J Haematol 161(4):525–532. doi:10.1111/bjh.12286

    Article  PubMed  PubMed Central  Google Scholar 

  8. Benson MD, Liepnieks JJ, Kluve-Beckerman B (2015) Hereditary systemic immunoglobulin light-chain amyloidosis. Blood 125(21):3281–3286. doi:10.1182/blood-2014-12-618108

    Article  CAS  PubMed  Google Scholar 

  9. Merlini G, Stone MJ (2006) Dangerous small B-cell clones. Blood 108(8):2520–2530

    Article  CAS  PubMed  Google Scholar 

  10. Dispenzieri A, Gertz MA, Buadi F (2012) What do I need to know about immunoglobulin light chain (AL) amyloidosis? Blood Rev 26(4):137–154. doi:10.1016/j.blre.2012.03.001

    Article  PubMed  Google Scholar 

  11. Biewend ML, Menke DM, Calamia KT (2006) The spectrum of localized amyloidosis: a case series of 20 patients and review of the literature. Amyloid 13(3):135–142. doi:10.1080/13506120600876773

    Article  PubMed  Google Scholar 

  12. Gertz MA, Kyle RA, Greipp PR (1989) The plasma cell labeling index: a valuable tool in primary systemic amyloidosis. Blood 74(3):1108–1111

    CAS  PubMed  Google Scholar 

  13. Rajkumar SV, Gertz MA, Kyle RA (1998) Primary systemic amyloidosis with delayed progression to multiple myeloma. Cancer 82(8):1501–1505. doi:10.1002/(SICI)1097-0142(19980415)82:8<1501:AID-CNCR11>3.0.CO;2-8

    Article  CAS  PubMed  Google Scholar 

  14. Perfetti V, Colli Vignarelli M, Anesi E, Garini P, Quaglini S, Ascari E, Merlini G (1999) The degrees of plasma cell clonality and marrow infiltration adversely influence the prognosis of AL amyloidosis patients. Haematologica 84(3):218–221

    CAS  PubMed  Google Scholar 

  15. Paiva B, Vidriales MB, Perez JJ, Lopez-Berges MC, Garcia-Sanz R, Ocio EM, de Las Heras N, Cuello R, de Coca AG, Pardal E, Alonso J, Sierra M, Barez A, Hernandez J, Suarez L, Galende J, Mateos MV, San Miguel JF (2011) The clinical utility and prognostic value of multiparameter flow cytometry immunophenotyping in light-chain amyloidosis. Blood 117(13):3613–3616. doi:10.1182/blood-2010-12-324665

    Article  CAS  PubMed  Google Scholar 

  16. Kourelis TV, Kumar SK, Gertz MA, Lacy MQ, Buadi FK, Hayman SR, Zeldenrust S, Leung N, Kyle RA, Russell S, Dingli D, Lust JA, Lin Y, Kapoor P, Rajkumar SV, McCurdy A, Dispenzieri A (2013) Coexistent multiple myeloma or increased bone marrow plasma cells define equally high-risk populations in patients with immunoglobulin light chain amyloidosis. J Clin Oncol 31(34):4319–4324. doi:10.1200/JCO.2013.50.8499

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Pardanani A, Witzig TE, Schroeder G, McElroy EA, Fonseca R, Dispenzieri A, Lacy MQ, Lust JA, Kyle RA, Greipp PR, Gertz MA, Rajkumar SV (2003) Circulating peripheral blood plasma cells as a prognostic indicator in patients with primary systemic amyloidosis. Blood 101(3):827–830. doi:10.1182/blood-2002-06-16982002-06-1698

    Article  CAS  PubMed  Google Scholar 

  18. Dispenzieri A, Lacy MQ, Katzmann JA, Rajkumar SV, Abraham RS, Hayman SR, Kumar SK, Clark R, Kyle RA, Litzow MR, Inwards DJ, Ansell SM, Micallef IM, Porrata LF, Elliott MA, Johnston PB, Greipp PR, Witzig TE, Zeldenrust SR, Russell SJ, Gastineau D, Gertz MA (2006) Absolute values of immunoglobulin free light chains are prognostic in patients with primary systemic amyloidosis undergoing peripheral blood stem cell transplantation. Blood 107(8):3378–3383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Wechalekar A (2009) A new staging system for AL amyloidosis incorporating serum free light chains, cardiac troponin-T and NT-proBNP. Blood 114:abstr. 2796

    Google Scholar 

  20. Kumar S (2009) A novel prognostic staging system for light chain amyloidosis (AL) incorporating markers of plasma cell burden and organ involvement. Blood 114:abstr. 2797

    Google Scholar 

  21. Merlini G, Seldin DC, Gertz MA (2011) Amyloidosis: pathogenesis and new therapeutic options. J Clin Oncol 29(14):1924–1933

    Article  PubMed  PubMed Central  Google Scholar 

  22. Fonseca R, Ahmann GJ, Jalal SM, Dewald GW, Larson DR, Therneau TM, Gertz MA, Kyle RA, Greipp PR (1998) Chromosomal abnormalities in systemic amyloidosis. Br J Haematol 103(3):704–710

    Article  CAS  PubMed  Google Scholar 

  23. Hayman SR, Bailey RJ, Jalal SM, Ahmann GJ, Dispenzieri A, Gertz MA, Greipp PR, Kyle RA, Lacy MQ, Rajkumar SV, Witzig TE, Lust JA, Fonseca R (2001) Translocations involving the immunoglobulin heavy-chain locus are possible early genetic events in patients with primary systemic amyloidosis. Blood 98(7):2266–2268

    Article  CAS  PubMed  Google Scholar 

  24. Perfetti V, Coluccia AM, Intini D, Malgeri U, Vignarelli MC, Casarini S, Merlini G, Neri A (2001) Translocation T(4;14)(p16.3;q32) is a recurrent genetic lesion in primary amyloidosis. Am J Pathol 158(5):1599–1603

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Bochtler T, Hegenbart U, Heiss C, Benner A, Moos M, Seckinger A, Pschowski-Zuck S, Kirn D, Neben K, Bartram CR, Ho AD, Goldschmidt H, Hose D, Jauch A, Schonland SO (2011) Hyperdiploidy is less frequent in AL amyloidosis compared with monoclonal gammopathy of undetermined significance and inversely associated with translocation t(11;14). Blood 117(14):3809–3815. doi:10.1182/blood-2010-02-268987

    Article  CAS  PubMed  Google Scholar 

  26. Bochtler T, Hegenbart U, Kunz C, Benner A, Seckinger A, Dietrich S, Granzow M, Neben K, Goldschmidt H, Ho AD, Hose D, Jauch A, Schonland SO (2014) Gain of chromosome 1q21 is an independent adverse prognostic factor in light chain amyloidosis patients treated with melphalan/dexamethasone. Amyloid 21(1):9–17. doi:10.3109/13506129.2013.854766

    Article  CAS  PubMed  Google Scholar 

  27. Kumar S, Dispenzieri A, Katzmann JA, Larson DR, Colby CL, Lacy MQ, Hayman SR, Buadi FK, Leung N, Zeldenrust SR, Ramirez-Alvarado M, Clark RJ, Kyle RA, Rajkumar SV, Gertz MA (2010) Serum immunoglobulin free light-chain measurement in primary amyloidosis: prognostic value and correlations with clinical features. Blood 116(24):5126–5129. doi:10.1182/blood-2010-06-290668

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Weinhold N, Forsti A, da Silva Filho MI, Nickel J, Campo C, Hoffmann P, Nothen MM, Hose D, Goldschmidt H, Jauch A, Langer C, Hegenbart U, Schonland SO, Hemminki K (2014) Immunoglobulin light-chain amyloidosis shares genetic susceptibility with multiple myeloma. Leukemia. doi:10.1038/leu.2014.208

    Google Scholar 

  29. Boyle EM, Walker BA, Rowczienio D, Wardell CP, Murison A, Mikulasova A, Sachchithanantham S, Baginska A, Mahmood S, Gillmore JD, Lachmann HJ, Hawkins PN, Leleu X, Davies FE, Morgan GJ, Wechalekar A (2014) Exome sequencing to define a genetic signature of plasma cells in systemic AL amyloidosis. Blood 124(21)

    Google Scholar 

  30. Blancas-Mejia LM, Tischer A, Thompson JR, Tai J, Wang L, Auton M, Ramirez-Alvarado M (2014) Kinetic control in protein folding for light chain amyloidosis and the differential effects of somatic mutations. J Mol Biol 426(2):347–361. doi:10.1016/j.jmb.2013.10.016

    Article  CAS  PubMed  Google Scholar 

  31. Bellotti V, Mangione P, Merlini G (2000) Review: Immunoglobulin light chain amyloidosis - The archetype of structural and pathogenic variability. J Struct Biol 130(2–3):280–289

    Article  CAS  PubMed  Google Scholar 

  32. Prokaeva T, Spencer B, et al (2010) Contribution of light chain variable region genes to organ tropism and survival in AL amyloidosis. Amyloid 17(S1):62, Abstract OP-046

    Google Scholar 

  33. Comenzo RL, Zhang Y, Martinez C, Osman K, Herrera GA (2001) The tropism of organ involvement in primary systemic amyloidosis: contributions of Ig V-L germ line gene use and clonal plasma cell burden. Blood 98(3):714–720

    Article  CAS  PubMed  Google Scholar 

  34. Perfetti V, Casarini S, Palladini G, Vignarelli MC, Klersy C, Diegoli M, Ascari E, Merlini G (2002) Analysis of V lambda-J lambda expression in plasma cells from primary (AL) amyloidosis and normal bone marrow identifies 3r (lambda III) as a new amyloid-associated germline gene segment. Blood 100(3):948–953

    Article  CAS  PubMed  Google Scholar 

  35. Abraham RS, Geyer SM, Price-Troska TL, Allmer C, Kyle RA, Gertz MA, Fonseca R (2003) Immunoglobulin light chain variable (V) region genes influence clinical presentation and outcome in light chain-associated amyloidosis (AL). Blood 101(10):3801–3808

    Article  CAS  PubMed  Google Scholar 

  36. Perfetti V, Palladini G, Casarini S, Navazza V, Rognoni P, Obici L, Invernizzi R, Perlini S, Klersy C, Merlini G (2012) The repertoire of lambda light chains causing predominant amyloid heart involvement and identification of a preferentially involved germline gene, IGLV1-44. Blood 119(1):144–150. doi:10.1182/blood-2011-05-355784

    Article  CAS  PubMed  Google Scholar 

  37. Poshusta TL, Sikkink LA, Leung N, Clark RJ, Dispenzieri A, Ramirez-Alvarado M (2009) Mutations in specific structural regions of immunoglobulin light chains are associated with free light chain levels in patients with Al amyloidosis. PLoS ONE 4(4):e5169

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Grogg KL, Aubry MC, Vrana JA, Theis JD, Dogan A (2013) Nodular pulmonary amyloidosis is characterized by localized immunoglobulin deposition and is frequently associated with an indolent B-cell lymphoproliferative disorder. Am J Surg Pathol 37(3):406–412. doi:10.1097/PAS.0b013e318272fe19

    Article  PubMed  Google Scholar 

  39. Nasr SH, Said SM, Valeri AM, Sethi S, Fidler ME, Cornell LD, Gertz MA, Dispenzieri A, Buadi FK, Vrana JA, Theis JD, Dogan A, Leung N (2013) The diagnosis and characteristics of renal heavy-chain and heavy/light-chain amyloidosis and their comparison with renal light-chain amyloidosis. Kidney Int 83(3):463–470. doi:10.1038/ki.2012.414

    Article  CAS  PubMed  Google Scholar 

  40. Picken MM (2013) Non-light-chain immunoglobulin amyloidosis: time to expand or refine the spectrum to include light + heavy chain amyloidosis? Kidney Int 83(3):353–356. doi:10.1038/ki.2012.433

    Article  CAS  PubMed  Google Scholar 

  41. Shi J, Guan J, Jiang B, Brenner DA, Del Monte F, Ward JE, Connors LH, Sawyer DB, Semigran MJ, Macgillivray TE, Seldin DC, Falk R, Liao R (2010) Amyloidogenic light chains induce cardiomyocyte contractile dysfunction and apoptosis via a non-canonical p38alpha MAPK pathway. Proc Natl Acad Sci USA 107(9):4188–4193. doi:10.1073/pnas.0912263107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Mishra S, Guan J, Plovie E, Seldin DC, Connors LH, Merlini G, Falk RH, MacRae CA, Liao R (2013) Human amyloidogenic light chain proteins result in cardiac dysfunction, cell death, and early mortality in zebrafish. Am J Physiol Heart Circ Physiol 305(1):H95–103. doi:10.1152/ajpheart.00186.2013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Liao R, Jain M, Teller P, Connors LH, Ngoy S, Skinner M, Falk RH, Apstein CS (2001) Infusion of light chains from patients with cardiac amyloidosis causes diastolic dysfunction in isolated mouse hearts. Circulation 104(14):1594–1597

    CAS  PubMed  Google Scholar 

  44. Guan J, Mishra S, Shi J, Plovie E, Qiu Y, Cao X, Gianni D, Jiang B, Del Monte F, Connors LH, Seldin DC, Lavatelli F, Rognoni P, Palladini G, Merlini G, Falk RH, Semigran MJ, Dec GW, Macrae CA, Liao R (2013) Stanniocalcin1 is a key mediator of amyloidogenic light chain induced cardiotoxicity. Basic Res Cardiol 108(5):378. doi:10.1007/s00395-013-0378-5

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Brenner DA, Jain M, Pimentel DR, Wang B, Connors LH, Skinner M, Apstein CS, Liao R (2004) Human amyloidogenic light chains directly impair cardiomyocyte function through an increase in cellular oxidant stress. Circ Res 94(8):1008–1010

    Article  CAS  PubMed  Google Scholar 

  46. Walsh DM, Klyubin I, Fadeeva JV, Cullen WK, Anwyl R, Wolfe MS, Rowan MJ, Selkoe DJ (2002) Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature 416(6880):535–539. doi:10.1038/416535a

    Article  CAS  PubMed  Google Scholar 

  47. Reixach N, Deechongkit S, Jiang X, Kelly JW, Buxbaum JN (2004) Tissue damage in the amyloidoses: Transthyretin monomers and nonnative oligomers are the major cytotoxic species in tissue culture. Proc Natl Acad Sci USA 101(9):2817–2822. doi:10.1073/pnas.04000621010400062101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Laurén J, Gimbel DA, Nygaard HB, Gilbert JW, Strittmatter SM (2009) Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers. Nature 457(7233):1128–1132. doi:10.1038/nature07761

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Ren R, Hong Z, Gong H, Laporte K, Skinner M, Seldin DC, Costello CE, Connors LH, Trinkaus-Randall V (2010) Role of glycosaminoglycan sulfation in the formation of immunoglobulin light chain amyloid oligomers and fibrils. J Biol Chem 285(48):37672–37682. doi:10.1074/jbc.M110.149575

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Laganowsky A, Liu C, Sawaya MR, Whitelegge JP, Park J, Zhao M, Pensalfini A, Soriaga AB, Landau M, Teng PK, Cascio D, Glabe C, Eisenberg D (2012) Atomic view of a toxic amyloid small oligomer. Science 335(6073):1228–1231. doi:10.1126/science.1213151

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Walsh DM, Selkoe DJ (2007) A beta oligomers—a decade of discovery. J Neurochem 101(5):1172–1184. doi:10.1111/j.1471-4159.2006.04426.x

    Article  CAS  PubMed  Google Scholar 

  52. Palladini G, Lavatelli F, Russo P, Perlini S, Perfetti V, Bosoni T, Obici L, Bradwell AR, D’Eril GM, Fogari R, Moratti R, Merlini G (2006) Circulating amyloidogenic free light chains and serum N-terminal natriuretic peptide type B decrease simultaneously in association with improvement of survival in AL. Blood 107(10):3854–3858

    Article  CAS  PubMed  Google Scholar 

  53. Palladini G, Campana C, Klersy C, Balduini A, Vadacca G, Perfetti V, Perlini S, Obici L, Ascari E, d’Eril GM, Moratti R, Merlini G (2003) Serum N-terminal pro-brain natriuretic peptide is a sensitive marker of myocardial dysfunction in AL amyloidosis. Circulation 107(19):2440–2445

    Article  CAS  PubMed  Google Scholar 

  54. Sousa MM, Cardoso I, Fernandes R, Guimaraes A, Saraiva MJ (2001) Deposition of transthyretin in early stages of familial amyloidotic polyneuropathy: evidence for toxicity of nonfibrillar aggregates. Am J Pathol 159(6):1993–2000

    Article  CAS  PubMed  Google Scholar 

  55. Diomede L, Rognoni P, Lavatelli F, Romeo M, del Favero E, Cantu L, Ghibaudi E, di Fonzo A, Corbelli A, Fiordaliso F, Palladini G, Valentini V, Perfetti V, Salmona M, Merlini G (2014) A Caenorhabditis elegans-based assay recognizes immunoglobulin light chains causing heart amyloidosis. Blood 123(23):3543–3552. doi:10.1182/blood-2013-10-525634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Comenzo RL, Vosburgh E, Simms RW, Bergethon P, Sarnacki D, Finn K, Dubrey S, Faller DV, Wright DG, Falk RH, Skinner M (1996) Dose-intensive melphalan with blood stem cell support for the treatment of AL amyloidosis: one-year follow-up in five patients. Blood 88(7):2801–2806

    CAS  PubMed  Google Scholar 

  57. Dember LM, Sanchorawala V, Seldin DC, Wright DG, LaValley M, Berk JL, Falk RH, Skinner M (2001) Effect of dose-intensive intravenous melphalan and autologous blood stem-cell transplantation on al amyloidosis-associated renal disease. Ann Intern Med 134(9 Pt 1):746–753. doi:200105010-00011

    Article  CAS  PubMed  Google Scholar 

  58. Caccialanza R, Palladini G, Klersy C, Cena H, Vagia C, Cameletti B, Russo P, Lavatelli F, Merlini G (2006) Nutritional status of outpatients with systemic immunoglobulin light-chain amyloidosis 1. Am J Clin Nutr 83(2):350–354

    CAS  PubMed  Google Scholar 

  59. Caccialanza R, Palladini G, Klersy C, Cereda E, Bonardi C, Cameletti B, Montagna E, Russo P, Foli A, Milani P, Lavatelli F, Merlini G (2011) Nutritional status independently affects quality of life of patients with systemic immunoglobulin light-chain (AL) amyloidosis. Ann Hematol. doi:10.1007/s00277-011-1309-x

    PubMed  Google Scholar 

  60. Obici L, Perfetti V, Palladini G, Moratti R, Merlini G (2005) Clinical aspects of systemic amyloid diseases. Biochim Biophys Acta 1753(1):11–22

    Article  CAS  PubMed  Google Scholar 

  61. Cowan AJ, Skinner M, Berk JL, Sloan JM, O’Hara C, Seldin DC, Sanchorawala V (2011) Macroglossia - not always AL amyloidosis. Amyloid 18(2):83–86. doi:10.3109/13506129.2011.560217

    Article  PubMed  Google Scholar 

  62. Prokaeva T, Spencer B, Kaut M, Ozonoff A, Doros G, Connors LH, Skinner M, Seldin DC (2007) Soft tissue, joint, and bone manifestations of AL amyloidosis: clinical presentation, molecular features, and survival. Arthritis Rheum 56(11):3858–3868. doi:10.1002/art.22959

    Article  PubMed  Google Scholar 

  63. Gertz MA, Lacy MQ, Dispenzieri A (2002) Immunoglobulin light chain amyloidosis and the kidney. Kidney Int 61(1):1–9. doi:10.1046/j.1523-1755.2002.00085.x

    Article  PubMed  Google Scholar 

  64. Gertz MA, Leung N, Lacy MQ, Dispenzieri A, Zeldenrust SR, Hayman SR, Buadi FK, Dingli D, Greipp PR, Kumar SK, Lust JA, Rajkumar SV, Russell SJ, Witzig TE (2009) Clinical outcome of immunoglobulin light chain amyloidosis affecting the kidney. Nephrol Dial Transplant 24(10):3132–3137. doi:10.1093/ndt/gfp201

    Article  CAS  PubMed  Google Scholar 

  65. Bergesio F, Ciciani AM, Manganaro M, Palladini G, Santostefano M, Brugnano R, Di Palma AM, Gallo M, Rosati A, Tosi PL, Salvadori M (2008) Renal involvement in systemic amyloidosis: an Italian collaborative study on survival and renal outcome. Nephrol Dial Transplant 23(3):941–951. doi:10.1093/ndt/gfm684

    Article  CAS  PubMed  Google Scholar 

  66. Palladini G, Hegenbart U, Milani P, Kimmich C, Foli A, Ho AD, Vidus Rosin M, Albertini R, Moratti R, Merlini G, Schonland S (2014) A staging system for renal outcome and early markers of renal response to chemotherapy in AL amyloidosis. Blood. doi:10.1182/blood-2014-04-570010

    Google Scholar 

  67. Leung N, Dispenzieri A, Lacy MQ, Kumar SK, Hayman SR, Fervenza FC, Cha SS, Gertz MA (2007) Severity of baseline proteinuria predicts renal response in immunoglobulin light chain-associated amyloidosis after autologous stem cell transplantation. Clin J Am Soc Nephrol 2(3):440–444. doi:10.2215/CJN.02450706

    Article  PubMed  Google Scholar 

  68. Palladini G, Hegenbart U, Milani P, Kimmich C, Foli A, Ho AD, Rosin MV, Albertini R, Moratti R, Merlini G, Schoenland S (2014) A staging system for renal outcome and early markers of renal response to chemotherapy in AL amyloidosis. Blood 124(15):2325–2332. doi:10.1182/blood-2014-04-570010

    Article  CAS  PubMed  Google Scholar 

  69. Park MA, Mueller PS, Kyle RA, Larson DR, Plevak MF, Gertz MA (2003) Primary (AL) hepatic amyloidosis: clinical features and natural history in 98 patients. Medicine (Baltimore) 82(5):291–298. doi:10.1097/01.md.0000091183.93122.c7

    Article  Google Scholar 

  70. Peters RA, Koukoulis G, Gimson A, Portmann B, Westaby D, Williams R (1994) Primary amyloidosis and severe intrahepatic cholestatic jaundice. Gut 35(9):1322–1325

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Rubinow A, Koff RS, Cohen AS (1978) Severe intrahepatic cholestasis in primary amyloidosis: a report of four cases and a review of the literature. Am J Med 64(6):937–946

    Article  CAS  PubMed  Google Scholar 

  72. Falk RH, Quarta CC (2015) Echocardiography in cardiac amyloidosis. Heart Fail Rev 20(2):125–131. doi:10.1007/s10741-014-9466-3

    Article  PubMed  Google Scholar 

  73. Buss SJ, Emami M, Mereles D, Korosoglou G, Kristen AV, Voss A, Schellberg D, Zugck C, Galuschky C, Giannitsis E, Hegenbart U, Ho AD, Katus HA, Schonland SO, Hardt SE (2012) Longitudinal left ventricular function for prediction of survival in systemic light-chain amyloidosis: incremental value compared with clinical and biochemical markers. J Am Coll Cardiol 60(12):1067–1076. doi:10.1016/j.jacc.2012.04.043

    Article  PubMed  Google Scholar 

  74. Nesbitt GC, Mankad S (2009) Strain and strain rate imaging in cardiomyopathy. Echocardiography 26(3):337–344. doi:10.1111/j.1540-8175.2008.00867.x

    Article  PubMed  Google Scholar 

  75. Rahman JE, Helou EF, Gelzer-Bell R, Thompson RE, Kuo C, Rodriguez ER, Hare JM, Baughman KL, Kasper EK (2004) Noninvasive diagnosis of biopsy-proven cardiac amyloidosis. J Am Coll Cardiol 43(3):410–415

    Article  PubMed  Google Scholar 

  76. Rapezzi C, Merlini G, Quarta CC, Riva L, Longhi S, Leone O, Salvi F, Ciliberti P, Pastorelli F, Biagini E, Coccolo F, Cooke RM, Bacchi-Reggiani L, Sangiorgi D, Ferlini A, Cavo M, Zamagni E, Fonte ML, Palladini G, Salinaro F, Musca F, Obici L, Branzi A, Perlini S (2009) Systemic cardiac amyloidoses: disease profiles and clinical courses of the 3 main types. Circulation 120(13):1203–1212. doi:10.1161/CIRCULATIONAHA.108.843334

    Article  CAS  PubMed  Google Scholar 

  77. Maceira AM, Joshi J, Prasad SK, Moon JC, Perugini E, Harding I, Sheppard MN, Poole-Wilson PA, Hawkins PN, Pennell DJ (2005) Cardiovascular magnetic resonance in cardiac amyloidosis. Circulation 111(2):186–193. doi:10.1161/01.CIR.0000152819.97857.9D

    Article  PubMed  Google Scholar 

  78. Banypersad SM, Sado DM, Flett AS, Gibbs SD, Pinney JH, Maestrini V, Cox AT, Fontana M, Whelan CJ, Wechalekar AD, Hawkins PN, Moon JC (2013) Quantification of myocardial extracellular volume fraction in systemic Al amyloidosis: an equilibrium contrast cardiovascular magnetic resonance study. Circ Cardiovasc Imaging 6(1):34–39. doi:10.1161/CIRCIMAGING.112.978627

    Article  PubMed  Google Scholar 

  79. Fontana M, Chung R, Hawkins PN, Moon JC (2015) Cardiovascular magnetic resonance for amyloidosis. Heart Fail Rev 20(2):133–144. doi:10.1007/s10741-014-9470-7

    Article  CAS  PubMed  Google Scholar 

  80. Antoni G, Lubberink M, Estrada S, Axelsson J, Carlson K, Lindsjo L, Kero T, Langstrom B, Granstam SO, Rosengren S, Vedin O, Wassberg C, Wikstrom G, Westermark P, Sorensen J (2013) In vivo visualization of amyloid deposits in the heart with 11C-PIB and PET. J Nucl Med 54(2):213–220. doi:10.2967/jnumed.111.102053

    Article  CAS  PubMed  Google Scholar 

  81. Dorbala S, Vangala D, Semer J, Strader C, Bruyere JR Jr, Di Carli MF, Moore SC, Falk RH (2014) Imaging cardiac amyloidosis: a pilot study using F-florbetapir positron emission tomography. Eur J Nucl Med Mol Imaging. doi:10.1007/s00259-014-2787-6

    PubMed  Google Scholar 

  82. Merlini G, Narula J, Arbustini E (2014) Molecular imaging of misfolded protein pathology for early clues to involvement of the heart. Eur J Nucl Med Mol Imaging. doi:10.1007/s00259-014-2832-5

    PubMed  Google Scholar 

  83. Russo P, Palladini G, Foli A, Zenone Bragotti L, Milani P, Nuvolone M, Obici L, Perfetti V, Brugnatelli S, Invernizzi R, Merlini G (2011) Liver involvement as the hallmark of aggressive disease in light chain amyloidosis: distinctive clinical features and role of light chain type in 225 patients. Amyloid 18(Suppl 1):92–93. doi:10.3109/13506129.2011.574354033

    Article  PubMed  Google Scholar 

  84. Mosconi G, Scolari MP, Feliciangeli G, Zanetti A, Zanelli P, Buscaroli A, Piccari M, Faenza S, Ercolani G, Faenza A, Pinna AD, Stefoni S (2006) Combined liver-kidney transplantation with preformed anti-HLA antibodies: a case report. Transplant Proc 38(4):1125–1126. doi:10.1016/j.transproceed.2006.03.045

    Article  CAS  PubMed  Google Scholar 

  85. Di Sabatino A, Carsetti R, Corazza GR (2011) Post-splenectomy and hyposplenic states. Lancet. doi:10.1016/S0140-6736(10)61493-6

    PubMed  Google Scholar 

  86. Renzulli P, Schoepfer A, Mueller E, Candinas D (2009) Atraumatic splenic rupture in amyloidosis. Amyloid 16(1):47–53. doi:10.1080/13506120802676922

    Article  PubMed  Google Scholar 

  87. Matsuda M, Gono T, Morita H, Katoh N, Kodaira M, Ikeda S (2011) Peripheral nerve involvement in primary systemic AL amyloidosis: a clinical and electrophysiological study. Eur J Neurol 18(4):604–610. doi:10.1111/j.1468-1331.2010.03215.x

    Article  CAS  PubMed  Google Scholar 

  88. Gertz M, Comenzo R, Falk R, Fermand J, Hazenberg B, Hawkins P, Merlini G, Moreau P, Ronco P, Sanchorawala V, Sezer O, Solomon A, Grateau G (2005) 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 79(4):319–328

    Article  PubMed  Google Scholar 

  89. Palladini G, Dispenzieri A, Gertz MA, Kumar S, Wechalekar A, Hawkins PN, Schonland S, Hegenbart U, Comenzo R, Kastritis E, Dimopoulos MA, Jaccard A, Klersy C, Merlini G (2012) 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 30(36):4541–4549. doi:10.1200/JCO.2011.37.7614

    Article  CAS  PubMed  Google Scholar 

  90. Gertz MA, Merlini G (2010) Definition of organ involvement and response to treatment in AL amyloidosis: an updated consensus opinion. Amyloid 17(S1):48–49

    Google Scholar 

  91. Palladini G, Verga L, Corona S, Obici L, Morbini P, Lavatelli F, Donadei S, Sarais G, Roggeri L, Foli A, Russo P, Bragotti LZ, Paulli M, Minoli L, Magrini U, Merlini G (2010) Diagnostic performance of immuno-electron microscopy of abdominal fat in systemic amyloidoses. Amyloid 17:59–60

    Google Scholar 

  92. Fernandez de Larrea C, Verga L, Morbini P, Klersy C, Lavatelli F, Foli A, Obici L, Milani P, Capello GL, Paulli M, Palladini G, Merlini G (2015) A practical approach to the diagnosis of systemic amyloidoses. Blood. doi:10.1182/blood-2014-11-609883

    Google Scholar 

  93. Foli A, Palladini G, Caporali R, Verga L, Morbini P, Obici L, Russo P, Sarais G, Donadei S, Montecucco C, Merlini G (2011) The role of minor salivary gland biopsy in the diagnosis of systemic amyloidosis: results of a prospective study in 62 patients. Amyloid 18:80–82

    Article  PubMed  Google Scholar 

  94. Yilmaz M, Unsal A, Sokmen M, Harmankaya O, Alkim C, Kabukcuoglu F, Ozagari A (2012) Duodenal biopsy for diagnosis of renal involvement in amyloidosis. Clin Nephrol 77(2):114–118. doi:10.5414/CN107139

    Article  PubMed  Google Scholar 

  95. Soares SM, Fervenza FC, Lager DJ, Gertz MA, Cosio FG, Leung N (2008) Bleeding complications after transcutaneous kidney biopsy in patients with systemic amyloidosis: single-center experience in 101 patients. Am J Kidney Dis 52(6):1079–1083. doi:10.1053/j.ajkd.2008.05.022

    Article  PubMed  Google Scholar 

  96. Arbustini E, Merlini G, Gavazzi A, Grasso M, Diegoli M, Fasani R, Bellotti V, Marinone G, Morbini P, Dal Bello B (1995) Cardiac immunocyte-derived (AL) amyloidosis: an endomyocardial biopsy study in 11 patients. 130(3 Pt 1):528–536

    Google Scholar 

  97. Pellikka PA, Holmes DR Jr, Edwards WD, Nishimura RA, Tajik AJ, Kyle RA (1988) Endomyocardial biopsy in 30 patients with primary amyloidosis and suspected cardiac involvement. Arch Intern Med 148(3):662–666

    Article  CAS  PubMed  Google Scholar 

  98. Park MA, Mueller PS, Kyle RA, Larson DR, Plevak MF, Gertz MA (2003) Primary (AL) hepatic amyloidosis—clinical features and natural history in 98 patients. Medicine 82(5):291–298

    Article  PubMed  Google Scholar 

  99. Lavatelli F, Perlman DH, McComb ME, Theberge R, Seldin DC, Connors LH, Merlini G, Skinner M, Costello CE (2006) A proteomic approach to the study of systemic amyloidoses. Amyloid 13(Suppl. 1):13

    Google Scholar 

  100. Vrana JA, Gamez JD, Madden BJ, Theis JD, Bergen HR 3rd, Dogan A (2009) Classification of amyloidosis by laser microdissection and mass spectrometry-based proteomic analysis in clinical biopsy specimens. Blood 114(24):4957–4959

    Article  CAS  PubMed  Google Scholar 

  101. Theis JD, Dasari S, Vrana JA, Kurtin PJ, Dogan A (2013) Shotgun-proteomics-based clinical testing for diagnosis and classification of amyloidosis. J Mass Spectrom 48(10):1067–1077. doi:10.1002/jms.3264

    Article  CAS  PubMed  Google Scholar 

  102. Arbustini E, Morbini P, Verga L, Concardi M, Porcu E, Pilotto A, Zorzoli I, Garini P, Anesi E, Merlini G (1997) Light and electron microscopy immunohistochemical characterization of amyloid deposits. Amyloid 4(3):157–170

    Article  CAS  Google Scholar 

  103. Schonland SO, Hegenbart U, Bochtler T, Mangatter A, Hansberg M, Ho AD, Lohse P, Rocken C (2012) Immunohistochemistry in the classification of systemic forms of amyloidosis: a systematic investigation of 117 patients. Blood 119(2):488–493. doi:10.1182/blood-2011-06-358507

    Article  PubMed  CAS  Google Scholar 

  104. Palladini G, Russo P, Bosoni T, Verga L, Sarais G, Lavatelli F, Nuvolone M, Obici L, Casarini S, Donadei S, Albertini R, Righetti G, Marini M, Graziani MS, Melzi D’Eril GV, Moratti R, Merlini G (2009) Identification of amyloidogenic light chains requires the combination of serum-free light chain assay with immunofixation of serum and urine. Clin Chem 55(3):499–504

    Article  CAS  PubMed  Google Scholar 

  105. Katzmann JA, Kyle RA, Benson J, Larson DR, Snyder MR, Lust JA, Rajkumar SV, Dispenzieri A (2009) Screening panels for detection of monoclonal gammopathies. Clin Chem 55(8):1517–1522

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Wechalekar AD, Schonland SO, Kastritis E, Gillmore JD, Dimopoulos MA, Lane T, Foli A, Foard D, Milani P, Rannigan L, Hegenbart U, Hawkins PN, Merlini G, Palladini G (2013) A European collaborative study of treatment outcomes in 346 patients with cardiac stage III AL amyloidosis. Blood 121(17):3420–3427. doi:10.1182/blood-2012-12-473066

    Article  CAS  PubMed  Google Scholar 

  107. Dispenzieri A, Gertz MA, Kyle RA, Lacy MQ, Burritt MF, Therneau TM, McConnell JP, Litzow MR, Gastineau DA, Tefferi A, Inwards DJ, Micallef IN, Ansell SM, Porrata LF, Elliott MA, Hogan WJ, Rajkumar SV, Fonseca R, Greipp PR, Witzig TE, Lust JA, Zeldenrust SR, Snow DS, Hayman SR, McGregor CG, Jaffe AS (2004) 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 104(6):1881–1887

    Article  CAS  PubMed  Google Scholar 

  108. Palladini G, Foli A, Milani P, Russo P, Albertini R, Lavatelli F, Obici L, Perlini S, Moratti R, Merlini G (2012) Best use of cardiac biomarkers in patients with AL amyloidosis and renal failure. Am J Hematol 87(5):465–471. doi:10.1002/ajh.23141

    Article  CAS  PubMed  Google Scholar 

  109. Dispenzieri A, Gertz MA, Kumar SK, Lacy MQ, Kyle RA, Saenger AK, Grogan M, Zeldenrust SR, Hayman SR, Buadi F, Greipp PR, Leung N, Russell SR, Dingli D, Lust JA, Rajkumar SV, Jaffe AS (2014) High sensitivity cardiac troponin T in patients with immunoglobulin light chain amyloidosis. Heart 100(5):383–388. doi:10.1136/heartjnl-2013-304957

    Article  CAS  PubMed  Google Scholar 

  110. Wechalekar A, Schonland SO, Kastritis E, Hawkins PN, Dimopoulos MA, Russo P, Lane T, Foli A, Foard D, Milani P, Rannigan L, Hegenbart U, Gillmore JD, Merlini G, Palladini G (2011) European collaborative study of treatment outcomes in 347 patients with systemic AL amyloidosis with Mayo stage III disease. Blood 118(21):454–455

    Google Scholar 

  111. Gertz M, Lacy M, Dispenzieri A, Hayman S, Kumar S, Buadi F, Leung N, Litzow M (2008) Troponin T level as an exclusion criterion for stem cell transplantation in light-chain amyloidosis. Leukemia & lymphoma 49(1):36–41

    Article  CAS  Google Scholar 

  112. Gertz MA, Lacy MQ, Dispenzieri A, Kumar SK, Dingli D, Leung N, Hogan WJ, Buadi FK, Hayman SR (2013) Refinement in patient selection to reduce treatment-related mortality from autologous stem cell transplantation in amyloidosis. Bone Marrow Transplant 48(4):557–561. doi:10.1038/bmt.2012.170

    Article  CAS  PubMed  Google Scholar 

  113. Warsame R, Kumar SK, Gertz MA, Lacy MQ, Buadi FK, Hayman SR, Leung N, Dingli D, Lust JA, Ketterling RP, Lin Y, Russell S, Hwa L, Kapoor P, Go RS, Zeldenrust SR, Kyle RA, Rajkumar SV, Dispenzieri A (2015) Abnormal FISH in patients with immunoglobulin light chain amyloidosis is a risk factor for cardiac involvement and for death. Blood Cancer J 5:e310. doi:10.1038/bcj.2015.34

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Bochtler T, Hegenbart U, Kunz C, Granzow M, Benner A, Seckinger A, Kimmich C, Goldschmidt H, Ho AD, Hose D, Jauch A, Schonland SO (2015) Translocation t(11;14) with is associated adverse outcome in patients with newly diagnosed AL amyloidosis when treated with bortezomib-based regimens. J Clin Oncol 33(12):1371–1378. doi:10.1200/JCO.2014.57.4947

    Article  CAS  PubMed  Google Scholar 

  115. Palladini G, Dispenzieri A, Gertz MA, Kumar S, Wechalekar A, Hawkins PN, Schonland S, Hegenbart U, Comenzo R, Kastritis E, Dimopoulos MA, Jaccard A, Klersy C, Merlini G (2012) 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 Clinical Oncol: Off J Amer Soc Clinical Oncol 30(36):4541–4549. doi:10.1200/JCO.2011.37.7614

    Article  CAS  Google Scholar 

  116. Gertz MA, Comenzo R, Falk RH, Fermand JP, Hazenberg BP, Hawkins PN, Merlini G, Moreau P, Ronco P, Sanchorawala V, Sezer O, Solomon A, Grateau G (2005) Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL): a consensus opinion from the 10(th) international symposium on amyloid and amyloidosis. Am J Hematol 79(4):319–328

    Article  PubMed  Google Scholar 

  117. Merlini G, Comenzo RL, Seldin DC, Wechalekar A, Gertz MA (2014) Immunoglobulin light chain amyloidosis. Expert Rev Hematol 7(1):143–156. doi:10.1586/17474086.2014.858594

    Article  CAS  PubMed  Google Scholar 

  118. Perfetti V, Casarini S, Palladini G, Vignarelli MC, Klersy C, Diegoli M, Ascari E, Merlini G (2002) Analysis of V(lambda)-J(lambda) expression in plasma cells from primary (AL) amyloidosis and normal bone marrow identifies 3r (lambdaIII) as a new amyloid-associated germline gene segment. Blood 100(3):948–953. doi:10.1182/blood-2002-01-0114

    Article  CAS  PubMed  Google Scholar 

  119. Stevens FJ, Weiss DT, Solomon A (1999) Structural bases of light chain related pathology. In: Zanetti M, Capra JD (eds) The Antibodies, vol 5. Harwood Academic Publishers, Amsterdam, pp 175–208

    Google Scholar 

  120. Hurle MR, Helms LR, Li L, Chan W, Wetzel R (1994) A role for destabilizing amino acid replacements in light-chain amyloidosis. Proc Natl Acad Sci USA 91(12):5446–5450

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Stevens PW, Raffen R, Hanson DK, Deng YL, Berrios-Hammond M, Westholm FA, Murphy C, Eulitz M, Wetzel R, Solomon A et al (1995) Recombinant immunoglobulin variable domains generated from synthetic genes provide a system for in vitro characterization of light-chain amyloid proteins. Protein Sci 4(3):421–432. doi:10.1002/pro.5560040309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Connors LH, Jiang Y, Budnik M, Theberge R, Prokaeva T, Bodi KL, Seldin DC, Costello CE, Skinner M (2007) Heterogeneity in primary structure, post-translational modifications, and germline gene usage of nine full-length amyloidogenic kappa1 immunoglobulin light chains. Biochemistry 46(49):14259–14271

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Randles EG, Thompson JR, Martin DJ, Ramirez-Alvarado M (2009) Structural alterations within native amyloidogenic immunoglobulin light chains. J Mol Biol 389(1):199–210

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Kaufman GP, Dispenzieri A, Gertz MA, Lacy MQ, Buadi FK, Hayman SR, Leung N, Dingli D, Lust JA, Lin Y, Kapoor P, Go RS, Zeldenrust SR, Kyle RA, Rajkumar SV, Kumar SK (2015) Kinetics of organ response and survival following normalization of the serum free light chain ratio in AL amyloidosis. Am J Hematol 90(3):181–186. doi:10.1002/ajh.23898

    Article  CAS  PubMed  Google Scholar 

  125. Trinkaus-Randall V, Walsh MT, Steeves S, Monis G, Connors LH, Skinner M (2005) Cellular response of cardiac fibroblasts to amyloidogenic light chains. Am J Pathol 166(1):197–208

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Mishra S, Guan J, Plovie E, Seldin DC, Connors LH, Merlini G, Falk RH, MacRae CA, Liao R (2013) Human amyloidogenic light chain proteins result in cardiac dysfunction, cell death, and early mortality in zebrafish. Am J Physiol Heart Circ Physiol 305(1):H95–103. doi:10.1152/ajpheart.00186.2013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Pepys MB, Herbert J, Hutchinson WL, Tennent GA, Lachmann HJ, Gallimore JR, Lovat LB, Bartfai T, Alanine A, Hertel C, Hoffmann T, Jakob-Roetne R, Norcross RD, Kemp JA, Yamamura K, Suzuki M, Taylor GW, Murray S, Thompson D, Purvis A, Kolstoe S, Wood SP, Hawkins PN (2002) Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis. Nature 417(6886):254–259

    Article  CAS  PubMed  Google Scholar 

  128. Bodin K, Ellmerich S, Kahan MC, Tennent GA, Loesch A, Gilbertson JA, Hutchinson WL, Mangione PP, Gallimore JR, Millar DJ, Minogue S, Dhillon AP, Taylor GW, Bradwell AR, Petrie A, Gillmore JD, Bellotti V, Botto M, Hawkins PN, Pepys MB (2010) Antibodies to human serum amyloid P component eliminate visceral amyloid deposits. Nature 468(7320):93–97

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Wall JS, Kennel SJ, Stuckey AC, Long MJ, Townsend DW, Smith GT, Wells KJ, Fu Y, Stabin MG, Weiss DT, Solomon A (2010) Radioimmunodetection of amyloid deposits in patients with AL amyloidosis. Blood 116(13):2241–2244. doi:10.1182/blood-2010-03-273797

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Jaccard A, Moreau P, Leblond V, Leleu X, Benboubker L, Hermine O, Recher C, Asli B, Lioure B, Royer B, Jardin F, Bridoux F, Grosbois B, Jaubert J, Piette JC, Ronco P, Quet F, Cogne M, Fermand JP (2007) High-dose melphalan versus melphalan plus dexamethasone for AL amyloidosis. New Engl J Med 357(11):1083–1093

    Article  CAS  PubMed  Google Scholar 

  131. Gertz MA, Lacy MQ, Dispenzieri A, Hayman SR, Kumar SK, Leung N, Gastineau DA (2007) Effect of hematologic response on outcome of patients undergoing transplantation for primary amyloidosis: importance of achieving a complete response. Haematologica 92(10):1415–1418

    Article  PubMed  Google Scholar 

  132. Sanchorawala V, Skinner M, Quillen K, Finn KT, Doros G, Seldin DC (2007) Long-term outcome of patients with AL amyloidosis treated with high-dose melphalan and stem-cell transplantation. Blood 110(10):3561–3563

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Palladini G, Russo P, Nuvolone M, Lavatelli F, Perfetti V, Obici L, Merlini G (2007) Treatment with oral melphalan plus dexamethasone produces long-term remissions in AL amyloidosis. Blood 110(2):787–788

    Article  CAS  PubMed  Google Scholar 

  134. Dispenzieri A, Buadi F, Kumar SK, Reeder C, etc. (2015) The treatment of AL amyloidosis: Mayo stratification of myeloma and risk-adapted Therapy (mSMART) Consensus Statement. Mayo Clin Proc 90(8):1054–1081

    Google Scholar 

  135. Kyle RA, Gertz MA, Greipp PR, Witzig TE, Lust JA, Lacy MQ, Therneau TM (1997) A trial of three regimens for primary amyloidosis: colchicine alone, melphalan and prednisone, and melphalan, prednisone, and colchicine. N Engl J Med 336(17):1202–1207

    Article  CAS  PubMed  Google Scholar 

  136. Skinner M, Anderson J, Simms R, Falk R, Wang M, Libbey C, Jones LA, Cohen AS (1996) Treatment of 100 patients with primary amyloidosis: a randomized trial of melphalan, prednisone, and colchicine versus colchicine only. Am J Med 100(3):290–298

    Article  CAS  PubMed  Google Scholar 

  137. Gertz MA, Kyle RA, Greipp PR (1991) Response rates and survival in primary systemic amyloidosis. Blood 77(2):257–262

    CAS  PubMed  Google Scholar 

  138. Gertz MA, Lacy MQ, Lust JA, Greipp PR, Witzig TE, Kyle RA (1999) Prospective randomized trial of melphalan and prednisone versus vincristine, carmustine, melphalan, cyclophosphamide, and prednisone in the treatment of primary systemic amyloidosis. J Clin Oncol 17(1):262–267

    CAS  PubMed  Google Scholar 

  139. Palladini G, Perfetti V, Obici L, Caccialanza R, Semino A, Adami F, Cavallero G, Rustichelli R, Virga G, Merlini G (2004) 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 103(8):2936–2938

    Article  CAS  PubMed  Google Scholar 

  140. Kyle RA, Greipp PR, Garton JP, Gertz MA (1985) Primary systemic amyloidosis. Comparison of melphalan/prednisone versus colchicine. Am J Med 79(6):708–716

    Article  CAS  PubMed  Google Scholar 

  141. Kyle RA, Greipp PR (1978) Primary systemic amyloidosis: comparison of melphalan and prednisone versus placebo. Blood 52(4):818–827

    CAS  PubMed  Google Scholar 

  142. Lachmann HJ, Gallimore R, Gillmore JD, Carr-Smith HD, Bradwell AR, Pepys MB, Hawkins PN (2003) Outcome in systemic AL amyloidosis in relation to changes in concentration of circulating free immunoglobulin light chains following chemotherapy. Br J Haematol 122(1):78–84

    Article  CAS  PubMed  Google Scholar 

  143. Gertz MA, Lacy MQ, Lust JA, Greipp PR, Witzig TE, Kyle RA (1999) Phase II trial of high-dose dexamethasone for previously treated immunoglobulin light-chain amyloidosis. Am J Hematol 61(2):115–119

    Article  CAS  PubMed  Google Scholar 

  144. Gertz MA, Lacy MQ, Lust JA, Greipp PR, Witzig TE, Kyle RA (1999) Phase II trial of high-dose dexamethasone for untreated patients with primary systemic amyloidosis. Med Oncol 16(2):104–109

    Article  CAS  PubMed  Google Scholar 

  145. Palladini G, Anesi E, Perfetti V, Obici L, Invernizzi R, Balduini C, Ascari E, Merlini G (2001) A modified high-dose dexamethasone regimen for primary systemic (AL) amyloidosis. Br J Haematol 113(4):1044–1046

    Article  CAS  PubMed  Google Scholar 

  146. Dhodapkar MV, Hussein MA, Rasmussen E, Solomon A, Larson RA, Crowley JJ, Barlogie B (2004) 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 104(12):3520–3526

    Article  CAS  PubMed  Google Scholar 

  147. Levy Y, Belghiti-Deprez D, Sobel A (1988) Treatment of AL amyloidosis without myeloma. Ann Med Interne 139(3):190–193

    CAS  Google Scholar 

  148. Wardley AM, Jayson GC, Goldsmith DJ, Venning MC, Ackrill P, Scarffe JH (1998) The treatment of nephrotic syndrome caused by primary (light chain) amyloid with vincristine, doxorubicin and dexamethasone. Br J Cancer 78(6):774–776

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. van Gameren I, Hazenberg BP, Jager PL, Smit JW, Vellenga E (2002) AL amyloidosis treated with induction chemotherapy with VAD followed by high dose melphalan and autologous stem cell transplantation. Amyloid 9(3):165–174

    Article  PubMed  Google Scholar 

  150. Ichida M, Imagawa S, Ohmine K, Komatsu N, Hatake K, Ozawa K, Miura Y (2000) Successful treatment of multiple myeloma–associated amyloidosis by interferon-alpha, dimethyl sulfoxide, and VAD (vincristine, adriamycin, and dexamethasone). Int J Hematol 72(4):491–493

    CAS  PubMed  Google Scholar 

  151. Gono T, Matsuda M, Shimojima Y, Ishii W, Koyama J, Sakashita K, Koike K, Hoshii Y, Ikeda S (2004) VAD with or without subsequent high-dose melphalan followed by autologous stem cell support in AL amyloidosis: Japanese experience and criteria for patient selection. Amyloid 11(4):245–256

    Article  PubMed  Google Scholar 

  152. Palladini G, Milani P, Foli A, Obici L, Lavatelli F, Nuvolone M, Caccialanza R, Perlini S, Merlini G (2014) Oral melphalan and dexamethasone grants extended survival with minimal toxicity in AL amyloidosis: long-term results of a risk-adapted approach. Haematologica 99(4):743–750. doi:10.3324/haematol.2013.095463

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Lebovic D, Hoffman J, Levine BM, Hassoun H, Landau H, Goldsmith Y, Maurer MS, Steingart RM, Cohen AD, Comenzo RL (2008) 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 143(3):369–373

    Article  CAS  PubMed  Google Scholar 

  154. Dietrich S, Schonland SO, Benner A, Bochtler T, Kristen AV, Beimler J, Hund E, Zorn M, Goldschmidt H, Ho AD, Hegenbart U (2010) 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 116(4):522–528. doi:10.1182/blood-2009-11-253237

    Article  CAS  PubMed  Google Scholar 

  155. Sanchorawala V, Seldin DC, Berk JL, Sloan JM, Doros G, Skinner M (2010) Oral cyclic melphalan and dexamethasone for patients with AL amyloidosis. Clin Lymphoma Myeloma Leuk 10(6):469–472. doi:10.3816/CLML.2010.n.081

    Article  CAS  PubMed  Google Scholar 

  156. Seldin DC, Choufani EB, Dember LM, Wiesman JF, Berk JL, Falk RH, O’Hara C, Fennessey S, Finn KT, Wright DG, Skinner M, Sanchorawala V (2003) Tolerability and efficacy of thalidomide for the treatment of patients with light cahin-associated (AL) amyloidosis. Clinical Lymphoma 3(4):241–246

    Article  CAS  PubMed  Google Scholar 

  157. Palladini G, Perfetti V, Perlini S, Obici L, Lavatelli F, Caccialanza R, Invernizzi R, Comotti B, Merlini G (2005) The combination of thalidomide and intermediate-dose dexamethasone is an effective but toxic treatment for patients with primary amyloidosis (AL). Blood 105(7):2949–2951

    Article  CAS  PubMed  Google Scholar 

  158. Dispenzieri A, Lacy MQ, Rajkumar SV, Geyer S, Witzig TE, Fonseca R, Lust JA, Greipp PR, Kyle RA, Gertz MA (2003) Poor tolerance to high doses of thalidomide in patients with primary systemic amyloidosis. Amyloid 10(4):257–261

    Article  CAS  PubMed  Google Scholar 

  159. Dispenzieri A, Lacy MQ, Geyer SM, Greipp PR, Witzig TE, Lust JA, Zeldenrust SR, Rajkumar SV, Kyle RA, Fonseca R, Gertz MA (2004) Low dose single agent thalidomide is tolerated in patients with primary systemic amyloidosis, but responses are limited. ASH Annual Meeting Abstracts 104(11):4920

    Google Scholar 

  160. Wechalekar AD, Goodman HJ, Lachmann HJ, Offer M, Hawkins PN, Gillmore JD (2007) Safety and efficacy of risk-adapted cyclophosphamide, thalidomide, and dexamethasone in systemic AL amyloidosis. Blood 109(2):457–464

    Article  CAS  PubMed  Google Scholar 

  161. Palladini G, Russo P, Lavatelli F, Nuvolone M, Albertini R, Bosoni T, Perfetti V, Obici L, Perlini S, Moratti R, Merlini G (2009) Treatment of patients with advanced cardiac AL amyloidosis with oral melphalan, dexamethasone, and thalidomide. Ann Hematol 88(4):347–350

    Article  CAS  PubMed  Google Scholar 

  162. Dispenzieri A, Lacy MQ, Zeldenrust SR, Hayman SR, Kumar SK, Geyer SM, Lust JA, Allred JB, Witzig TE, Rajkumar SV, Greipp PR, Russell SJ, Kabat B, Gertz MA (2007) The activity of lenalidomide with or without dexamethasone in patients with primary systemic amyloidosis. Blood 109(2):465–470

    Article  CAS  PubMed  Google Scholar 

  163. Sanchorawala V, Wright DG, Rosenzweig M, Finn KT, Fennessey S, Zeldis JB, Skinner M, Seldin DC (2007) Lenalidomide and dexamethasone in the treatment of AL amyloidosis: results of a phase 2 trial. Blood 109(2):492–496

    Article  CAS  PubMed  Google Scholar 

  164. Palladini G, Russo P, Foli A, Milani P, Lavatelli F, Obici L, Nuvolone M, Brugnatelli S, Invernizzi R, Merlini G (2012) Salvage therapy with lenalidomide and dexamethasone in patients with advanced AL amyloidosis refractory to melphalan, bortezomib, and thalidomide. Ann Hematol 91(1):89–92. doi:10.1007/s00277-011-1244-x

    Article  CAS  PubMed  Google Scholar 

  165. Moreau P, Jaccard A, Benboubker L, Royer B, Leleu X, Bridoux F, Salles G, Leblond V, Roussel M, Alakl M, Hermine O, Planche L, Harousseau JL, Fermand JP (2010) Lenalidomide in combination with melphalan and dexamethasone in patients with newly diagnosed AL amyloidosis: a multicenter phase 1/2 dose-escalation study. Blood 116(23):4777–4782

    Article  CAS  PubMed  Google Scholar 

  166. Dinner S, Witteles W, Afghahi A, Witteles R, Arai S, Lafayette R, Schrier S, Liedtke M (2013) Lenalidomide, melphalan and dexamethasone in an immunoglobulin light chain amyloidosis patient population with high rates of advanced cardiac involvement. Haematologica 98(10):1593–1599. doi:10.3324/haematol.2013.084574

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Sanchorawala V, Patel JM, Sloan JM, Shelton AC, Zeldis JB, Seldin DC (2013) Melphalan, lenalidomide and dexamethasone for the treatment of immunoglobulin light chain amyloidosis: results of a phase II trial. Haematologica 98(5):789–792. doi:10.3324/haematol.2012.075192

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Palladini G, Russo P, Milani P, Foli A, Lavatelli F, Nuvolone M, Perlini S, Merlini G (2013) A phase II trial of cyclophosphamide, lenalidomide and dexamethasone in previously treated patients with AL amyloidosis. Haematologica 98(3):433–436. doi:10.3324/haematol.2012.073593

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Kumar SK, Hayman SR, Buadi FK, Roy V, Lacy MQ, Gertz MA, Allred J, Laumann KM, Bergsagel LP, Dingli D, Mikhael JR, Reeder CB, Stewart AK, Zeldenrust SR, Greipp PR, Lust JA, Fonseca R, Russell SJ, Rajkumar SV, Dispenzieri A (2012) Lenalidomide, cyclophosphamide, and dexamethasone (CRd) for light-chain amyloidosis: long-term results from a phase 2 trial. Blood 119(21):4860–4867. doi:10.1182/blood-2012-01-407791

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Kastritis E, Terpos E, Roussou M, Gavriatopoulou M, Pamboukas C, Boletis I, Marinaki S, Apostolou T, Nikitas N, Gkortzolidis G, Michalis E, Delimpasi S, Dimopoulos MA (2012) A phase 1/2 study of lenalidomide with low-dose oral cyclophosphamide and low-dose dexamethasone (RdC) in AL amyloidosis. Blood 119(23):5384–5390. doi:10.1182/blood-2011-12-396903

    Article  CAS  PubMed  Google Scholar 

  171. Dispenzieri A, Buadi F, Laumann K, LaPlant B, Hayman SR, Kumar SK, Dingli D, Zeldenrust SR, Mikhael JR, Hall R, Rajkumar SV, Reeder C, Fonseca R, Bergsagel PL, Stewart AK, Roy V, Witzig TE, Lust JA, Russell SJ, Gertz MA, Lacy MQ (2012) Activity of pomalidomide in patients with immunoglobulin light-chain amyloidosis. Blood 119(23):5397–5404. doi:10.1182/blood-2012-02-413161

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Dispenzieri A, Lacy MQ, Kyle RA, Therneau TM, Larson DR, Rajkumar SV, Fonseca R, Greipp PR, Witzig TE, Lust JA, Gertz MA (2001) Eligibility for hematopoietic stem-cell transplantation for primary systemic amyloidosis is a favorable prognostic factor for survival. J Clinical Oncol: Off J Amer Soc Clinical Oncol 19(14):3350–3356

    CAS  Google Scholar 

  173. Gertz MA, Kyle RA (1990) Acute leukemia and cytogenetic abnormalities complicating melphalan treatment of primary systemic amyloidosis. Arch Intern Med 150(3):629–633

    Article  CAS  PubMed  Google Scholar 

  174. Gillmore J, Cocks K, Gibbs SDJ, Sattianayagam PT, Lane T, Lachmann H, Schey S, Cavenagh JD, Oakervee H, Morgan GJ, Mehta AB, Bourne S, Skinner E, Booth G, Hawkins PN, Wechalekar AD (2009) Cyclophosphamide, thalidomide and dexamethasone (CTD) versus melphalan plus dexamethasone (MD) for newly-diagnosed systemic AL amyloidosis—results from the UK amyloidosis treatment trial. ASH Annual Meeting Abstracts 114(22):2869

    Google Scholar 

  175. Kumar SK, Gertz MA, Lacy MQ, Dingli D, Hayman SR, Buadi FK, Short-Detweiler K, Zeldenrust SR, Leung N, Greipp PR, Lust JA, Russell SJ, Kyle RA, Rajkumar SV, Dispenzieri A (2011) Recent improvements in survival in primary systemic amyloidosis and the importance of an early mortality risk score. Mayo Clin Proc 86(1):12–18. doi:10.4065/mcp.2010.0480

    Article  PubMed  PubMed Central  Google Scholar 

  176. Dispenzieri A, Dingli D, Kumar SK, Rajkumar SV, Lacy MQ, Hayman S, Buadi F, Zeldenrust S, Leung N, Detweiler-Short K, Lust JA, Russell SJ, Kyle RA, Gertz MA (2010) Discordance between serum cardiac biomarker and immunoglobulin-free light-chain response in patients with immunoglobulin light-chain amyloidosis treated with immune modulatory drugs. Am J Hematol 85(10):757–759

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Tapan U, Seldin DC, Finn KT, Fennessey S, Shelton A, Zeldis JB, Sanchorawala V (2010) Increases in B-type natriuretic peptide (BNP) during treatment with lenalidomide in AL amyloidosis. Blood 116(23):5071–5072. doi:10.1182/blood-2010-09-305136

    Article  CAS  PubMed  Google Scholar 

  178. Specter R, Sanchorawala V, Seldin DC, Shelton A, Fennessey S, Finn KT, Zeldis JB, Dember LM (2011) Kidney dysfunction during lenalidomide treatment for AL amyloidosis. Nephrol Dial Transplant 26(3):881–886. doi:10.1093/ndt/gfq482

    Article  CAS  PubMed  Google Scholar 

  179. Huang X, Wang Q, Chen W, Zeng C, Chen Z, Gong D, Zhang H, Liu Z (2014) Induction therapy with bortezomib and dexamethasone followed by autologous stem cell transplantation versus autologous stem cell transplantation alone in the treatment of renal AL amyloidosis: a randomized controlled trial. BMC Med 12:2. doi:10.1186/1741-7015-12-2

    Article  PubMed  PubMed Central  Google Scholar 

  180. Kastritis E, Leleu X, Arrnulf B, Zamagni E, Mollee P, Cibeira MT, Schonland S, Moreau P, Hajek R, Jaccard A, Nicolas-Virelizier E, Filshie R, Augustson B, Mateos MV, Milani P, Dimopoulos M, Hachulla E, Fermand JP, Foli A, Palumbo A, Sonneveld P, Johnsen E, Merlini G, Palladini G (2014) A randomized phase III trial of melphalan and dexamethasone (MDex) versus bortezomib, melphalan and dexamethasone (BMDex) for untreated patients with AL amyloidosis. Blood 124(21):35

    Google Scholar 

  181. Reece DE, Hegenbart U, Sanchorawala V, Merlini G, Palladini G, Blade J, Fermand JP, Hassoun H, Heffner L, Vescio RA, Liu K, Enny C, Esseltine DL, van de Velde H, Cakana A, Comenzo RL (2011) 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 118(4):865–873. doi:10.1182/blood-2011-02-334227

    Article  CAS  PubMed  Google Scholar 

  182. Reece DE, Sanchorawala V, Hegenbart U, Merlini G, Palladini G, Fermand JP, Vescio RA, Liu X, Elsayed YA, Cakana A, Comenzo RL (2009) Weekly and twice-weekly bortezomib in patients with systemic AL amyloidosis: results of a phase 1 dose-escalation study. Blood 114(8):1489–1497

    Article  CAS  PubMed  Google Scholar 

  183. Reece DE, Hegenbart U, Sanchorawala V, Merlini G, Palladini G, Blade J, Fermand JP, Hassoun H, Heffner L, Kukreti V, Vescio RA, Pei L, Enny C, Esseltine DL, van de Velde H, Cakana A, Comenzo RL (2014) Long-term follow-up from a phase 1/2 study of single-agent bortezomib in relapsed systemic AL amyloidosis. Blood 124(16):2498–2506. doi:10.1182/blood-2014-04-568329

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Palladini G, Foli A, Russo P, Milani P, Obici L, Lavatelli F, Merlini G (2011) Treatment of IgM-associated AL amyloidosis with the combination of rituximab, bortezomib, and dexamethasone. Clin Lymphoma Myeloma Leuk 11(1):143–145. doi:10.3816/CLML.2011.n.033

    Article  CAS  PubMed  Google Scholar 

  185. Gasparetto C, Sanchorawala V, Snyder RM, Matous J, Terebelo HR, Janakiraman N, Mapara MY, Webb C, Abrams J, Zonder JA (2010) Use of melphalan (M)/dexamethasone (D)/bortezomib in AL amyloidosis. J Clin Oncol (Meeting Abstracts) 28 (15_suppl):8024-

    Google Scholar 

  186. Kastritis E, Wechalekar AD, Dimopoulos MA, Merlini G, Hawkins PN, Perfetti V, Gillmore JD, Palladini G (2010) Bortezomib with or without dexamethasone in primary systemic (light chain) amyloidosis. J Clin Oncol 28(6):1031–1037

    Article  CAS  PubMed  Google Scholar 

  187. Lamm W, Willenbacher W, Lang A, Zojer N, Muldur E, Ludwig H, Schauer-Stalzer B, Zielinski CC, Drach J (2011) Efficacy of the combination of bortezomib and dexamethasone in systemic AL amyloidosis. Ann Hematol 90(2):201–206. doi:10.1007/s00277-010-1062-6

    Article  CAS  PubMed  Google Scholar 

  188. Palladini G, Milani P, Foli A, Vidus Rosin M, Basset M, Lavatelli F, Nuvolone M, Obici L, Perlini S, Merlini G (2014) Melphalan and dexamethasone with or without bortezomib in newly diagnosed AL amyloidosis: a matched case-control study on 174 patients. Leukemia 28(12):2311–2316. doi:10.1038/leu.2014.227

    Article  CAS  PubMed  Google Scholar 

  189. Venner CP, Gillmore JD, Sachchithanantham S, Mahmood S, Lane T, Foard D, Rannigan L, Gibbs SD, Pinney JH, Whelan CJ, Lachmann HJ, Hawkins PN, Wechalekar AD (2014) A matched comparison of cyclophosphamide, bortezomib and dexamethasone (CVD) versus risk-adapted cyclophosphamide, thalidomide and dexamethasone (CTD) in AL amyloidosis. Leukemia 28(12):2304–2310. doi:10.1038/leu.2014.218

    Article  CAS  PubMed  Google Scholar 

  190. Mikhael JR, Schuster SR, Jimenez-Zepeda VH, Bello N, Spong J, Reeder CB, Stewart AK, Bergsagel PL, Fonseca R (2012) Cyclophosphamide-bortezomib-dexamethasone (CyBorD) produces rapid and complete hematologic response in patients with AL amyloidosis. Blood 119(19):4391–4394. doi:10.1182/blood-2011-11-390930

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  191. Venner CP, Lane T, Foard D, Rannigan L, Gibbs SD, Pinney JH, Whelan CJ, Lachmann HJ, Gillmore JD, Hawkins PN, Wechalekar AD (2012) Cyclophosphamide, bortezomib, and dexamethasone therapy in AL amyloidosis is associated with high clonal response rates and prolonged progression-free survival. Blood 119(19):4387–4390. doi:10.1182/blood-2011-10-388462

    Article  CAS  PubMed  Google Scholar 

  192. Jaccard A, Comenzo RL, Hari P, Hawkins PN, Roussel M, Morel P, Macro M, Pellegrin JL, Lazaro E, Mohty D, Mercie P, Decaux O, Gillmore J, Lavergne D, Bridoux F, Wechalekar AD, Venner CP (2014) Efficacy of bortezomib, cyclophosphamide and dexamethasone in treatment-naive patients with high-risk cardiac AL amyloidosis (Mayo Clinic stage III). Haematologica 99(9):1479–1485. doi:10.3324/haematol.2014.104109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  193. Lee JY, Lim SH, Kim SJ, Lee GY, Lee JE, Choi JO, Kim JS, Kim HJ, Lee SY, Min JH, Jeon ES, Kim K (2014) Bortezomib, melphalan, and prednisolone combination chemotherapy for newly diagnosed light chain (AL) amyloidosis. Amyloid: Int J Exp Clinical Investigation: Off J Int Soc Amyloidosis 21(4):261–266. doi:10.3109/13506129.2014.960560

    Article  CAS  Google Scholar 

  194. Wechalekar AD, Schonland SO, Kastritis E, Gillmore JD, Dimopoulos MA, Lane T, Foli A, Foard D, Milani P, Rannigan L, Hegenbart U, Hawkins PN, Merlini G, Palladini G (2013) A European collaborative study of treatment outcomes in 346 patients with cardiac stage III AL amyloidosis. Blood 121(17):3420–3427. doi:10.1182/blood-2012-12-473066

    Article  CAS  PubMed  Google Scholar 

  195. Gertz MA, Kyle RA (2003) Amyloidosis with IgM monoclonal gammopathies. Semin Oncol 30(2):325–328

    Article  PubMed  Google Scholar 

  196. Sanchorawala V, Blanchard E, Seldin DC, O’Hara C, Skinner M, Wright DG (2006) AL amyloidosis associated with B-cell lymphoproliferative disorders: frequency and treatment outcomes. Am J Hematol 81(9):692–695

    Article  CAS  PubMed  Google Scholar 

  197. Wechalekar AD, Lachmann HJ, Goodman HJ, Bradwell A, Hawkins PN, Gillmore JD (2008) AL amyloidosis associated with IgM paraproteinemia: clinical profile and treatment outcome. Blood 112(10):4009–4016. doi:10.1182/blood-2008-02-138156

    Article  CAS  PubMed  Google Scholar 

  198. Kikukawa Y, Yuki H, Hirata S, Ide K, Nakata H, Miyakawa T, Matsuno N, Nosaka K, Yonemura Y, Kawaguchi T, Hata H, Mitsuya H, Okuno Y (2015) Combined use of bortezomib, cyclophosphamide, and dexamethasone induces favorable hematological and organ responses in Japanese patients with amyloid light-chain amyloidosis: a single-institution retrospective study. Int J Hematol 101(2):133–139. doi:10.1007/s12185-014-1705-9

    Article  CAS  PubMed  Google Scholar 

  199. Comenzo RL, Vosburgh E, Falk RH, Sanchorawala V, Reisinger J, Dubrey S, Dember LM, Berk JL, Akpek G, LaValley M, O’Hara C, Arkin CF, Wright DG, Skinner M (1998) Dose-intensive melphalan with blood stem-cell support for the treatment of AL (amyloid light-chain) amyloidosis: survival and responses in 25 patients. Blood 91(10):3662–3670

    CAS  PubMed  Google Scholar 

  200. Dispenzieri A, Seenithamby K, Lacy MQ, Kumar SK, Buadi FK, Hayman SR, Dingli D, Litzow MR, Gastineau DA, Inwards DJ, Micallef IN, Ansell SM, Johnston PB, Porrata LF, Patnaik MM, Hogan WJ, Gertz MA (2013) 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 48(10):1302–1307. doi:10.1038/bmt.2013.53

    Article  CAS  PubMed  Google Scholar 

  201. Cibeira MT, Sanchorawala V, Seldin DC, Quillen K, Berk JL, Dember LM, Segal A, Ruberg F, Meier-Ewert H, Andrea NT, Sloan JM, Finn KT, Doros G, Blade J, Skinner M (2011) Outcome of AL amyloidosis after high-dose melphalan and autologous stem cell transplantation: long-term results in a series of 421 patients. Blood 118(16):4346–4352. doi:10.1182/blood-2011-01-330738

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  202. Moreau P, Milpied N, de Faucal P, Petit T, Herbouiller P, Bataille R, Harousseau JL (1996) High-dose melphalan and autologous bone marrow transplantation for systemic AL amyloidosis with cardiac involvement. Blood 87(7):3063–3064

    CAS  PubMed  Google Scholar 

  203. Skinner M, Sanchorawala V, Seldin DC, Dember LM, Falk RH, Berk JL, Anderson JJ, O’Hara C, Finn KT, Libbey CA, Wiesman J, Quillen K, Swan N, Wright DG (2004) High-dose melphalan and autologous stem-cell transplantation in patients with AL amyloidosis: an 8-year study. Ann Intern Med 140(2):85–93

    Article  CAS  PubMed  Google Scholar 

  204. Vesole DH, Perez WS, Akasheh M, Boudreau C, Reece DE, Bredeson CN (2006) High-dose therapy and autologous hematopoietic stem cell transplantation for patients with primary systemic amyloidosis: a Center for International Blood and Marrow Transplant Research Study. Mayo Clin Proc 81(7):880–888

    Article  PubMed  Google Scholar 

  205. Comenzo RL, Gertz MA (2002) Autologous stem cell transplantation for primary systemic amyloidosis. Blood 99(12):4276–4282

    Article  CAS  PubMed  Google Scholar 

  206. D’Souza A, Dispenzieri A, Wirk B, Zhang MJ, Huang J, Gertz MA, Kyle RA, Kumar SK, Comenzo R, Gale RP, Lazarus HM, Savani B, Cornell R, Weiss B, Vogl DT, Freytes CO, Scott EC, Landau H, Moreb J, Costa L, Ramathan M, Callander NS, Kamble RT, Olsson R, Ganguly S, Nishihori T, Kindwall-Keller T, Wood W, Mark T, Hari P (Submitted) Improved outcomes after autologous hematopoietic cell transplantation for light chain amyloidosis: a Center for International Blood and Marrow Transplant Research Study. J Clinical Oncol

    Google Scholar 

  207. Moreau P, Leblond V, Bourquelot P, Facon T, Huynh A, Caillot D, Hermine O, Attal M, Hamidou M, Nedellec G, Ferrant A, Audhuy B, Bataille R, Milpied N, Harousseau JL (1998) 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 101(4):766–769

    Article  CAS  PubMed  Google Scholar 

  208. Goodman HJ, Gillmore JD, Lachmann HJ, Wechalekar AD, Bradwell AR, Hawkins PN (2006) Outcome of autologous stem cell transplantation for AL amyloidosis in the UK. Br J Haematol 134(4):417–425

    Article  PubMed  Google Scholar 

  209. Gertz MA, Blood E, Vesole DH, Abonour R, Lazarus HM, Greipp PR (2004) A multicenter phase 2 trial of stem cell transplantation for immunoglobulin light-chain amyloidosis (E4A97): an Eastern Cooperative Oncology Group Study. Bone Marrow Transplant 34(2):149–154

    Article  CAS  PubMed  Google Scholar 

  210. Mollee PN, Wechalekar AD, Pereira DL, Franke N, Reece D, Chen C, Stewart AK (2004) Autologous stem cell transplantation in primary systemic amyloidosis: the impact of selection criteria on outcome. Bone Marrow Transplant 33(3):271–277. doi:10.1038/sj.bmt.1704344

    Article  CAS  PubMed  Google Scholar 

  211. Perz JB, Schonland SO, Hundemer M, Kristen AV, Dengler TJ, Zeier M, Linke RP, Ho AD, Goldschmidt H (2004) High-dose melphalan with autologous stem cell transplantation after VAD induction chemotherapy for treatment of amyloid light chain amyloidosis: a single centre prospective phase II study. Br J Haematol 127(5):543–551. doi:10.1111/j.1365-2141.2004.05232.x

    Article  CAS  PubMed  Google Scholar 

  212. Perfetti V, Siena S, Palladini G, Bregni M, Di Nicola M, Obici L, Magni M, Brunetti L, Gianni AM, Merlini G (2006) Long-term results of a risk-adapted approach to melphalan conditioning in autologous peripheral blood stem cell transplantation for primary (AL) amyloidosis. Haematologica 91(12):1635–1643

    CAS  PubMed  Google Scholar 

  213. Cohen AD, Zhou P, Chou J, Teruya-Feldstein J, Reich L, Hassoun H, Levine B, Filippa DA, Riedel E, Kewalramani T, Stubblefield MD, Fleisher M, Nimer S, Comenzo RL (2007) Risk-adapted autologous stem cell transplantation with adjuvant dexamethasone ± thalidomide for systemic light-chain amyloidosis: results of a phase II trial. Br J Haematol 139(2):224–233

    Article  CAS  PubMed  Google Scholar 

  214. Landau H, Hassoun H, Rosenzweig MA, Maurer M, Liu J, Flombaum C, Bello C, Hoover E, Riedel E, Giralt S, Comenzo RL (2013) Bortezomib and dexamethasone consolidation following risk-adapted melphalan and stem cell transplantation for patients with newly diagnosed light-chain amyloidosis. Leukemia 27(4):823–828. doi:10.1038/leu.2012.274

    Article  CAS  PubMed  Google Scholar 

  215. Kim SJ, Lee GY, Jang HR, Choi JO, Kim JS, Kim HJ, Lee SY, Min JH, Jeon ES, Kim K (2013) Autologous stem cell transplantation in light-chain amyloidosis patients: a single-center experience in Korea. Amyloid 20(4):204–211. doi:10.3109/13506129.2013.824417

    Article  PubMed  Google Scholar 

  216. D’Souza A, Wirk B, Zhang MJ, Huang J, Krishnan A, Mark T, Gasparetto CJ, Hari P (2014) Improved outcomes of autologous hematopoietic cell transplantation (AHCT) for light chain (AL) amyloidosis: a Center for International Blood and Marrow Transplant Registry (CIBMTR) Study. Blood 124(21):193

    Google Scholar 

  217. Fadia A, Casserly LF, Sanchorawala V, Seldin DC, Wright DG, Skinner M, Dember LM (2003) Incidence and outcome of acute renal failure complicating autologous stem cell transplantation for AL amyloidosis. Kidney Int 63(5):1868–1873

    Article  PubMed  Google Scholar 

  218. Mereuta OM, Theis JD, Vrana JA, Law ME, Grogg KL, Dasari S, Chandan VS, Wu TT, Jimenez-Zepeda VH, Fonseca R, Dispenzieri A, Kurtin PJ, Dogan A (2014) Leukocyte cell-derived chemotaxin 2 (LECT2)-associated amyloidosis is a frequent cause of hepatic amyloidosis in the United States. Blood 123(10):1479–1482. doi:10.1182/blood-2013-07-517938

    Article  CAS  PubMed  Google Scholar 

  219. Huang X, Wang Q, Jiang S, Chen W, Zeng C, Liu Z (2015) The clinical features and outcomes of systemic AL amyloidosis: a cohort of 231 Chinese patients. Clin Kidney J 8(1):120–126. doi:10.1093/ckj/sfu117

    Article  PubMed  Google Scholar 

  220. Sanchorawala V, Wright DG, Seldin DC, Falk RH, Finn KT, Dember LM, Berk JL, Quillen K, Anderson JJ, Comenzo RL, Skinner M (2004) High-dose intravenous melphalan and autologous stem cell transplantation as initial therapy or following two cycles of oral chemotherapy for the treatment of AL amyloidosis: results of a prospective randomized trial. Bone Marrow Transplant 33(4):381–388

    Article  CAS  PubMed  Google Scholar 

  221. Sanchorawala V, Brauneis D, Shelton AC, Lo S, Sun F, Sloan JM, Quillen K, Seldin DC (In press) Induction therapy with bortezomib followed by bortezomib-high dose melphalan and stem cell transplantation for AL amyloidosis: results of a prospective clinical trial. Biol Blood Marrow Transplant. doi:10.1016/j.bbmt.2015.04.001

    Google Scholar 

  222. Sanchorawala V, Wright DG, Quillen K, Finn KT, Dember LM, Berk JL, Doros G, Fisher C, Skinner M, Seldin DC (2007) Tandem cycles of high-dose melphalan and autologous stem cell transplantation increases the response rate in AL amyloidosis. Bone Marrow Transplant 40(6):557–562. doi:10.1038/sj.bmt.1705746

    Article  CAS  PubMed  Google Scholar 

  223. Sanchorawala V, Hoering A, Seldin DC, Finn KT, Fennessey SA, Sexton R, Mattar B, Safah HF, Holmberg LA, Dean RM, Orlowski RZ, Barlogie B (2013) Modified high-dose melphalan and autologous SCT for AL amyloidosis or high-risk myeloma: analysis of SWOG trial S0115. Bone Marrow Transplant 48(12):1537–1542. doi:10.1038/bmt.2013.98

    Article  CAS  PubMed  Google Scholar 

  224. Guillaume B, Straetmans N, Jadoul M, Cosyns JP, Ferrant A (1997) Allogeneic bone marrow transplantation for AL amyloidosis. Bone Marrow Transplant 20(10):907–908

    Article  CAS  PubMed  Google Scholar 

  225. Gillmore JD, Davies J, Iqbal A, Madhoo S, Russell NH, Hawkins PN (1998) Allogeneic bone marrow transplantation for systemic AL amyloidosis. Br J Haematol 100(1):226–228

    Article  CAS  PubMed  Google Scholar 

  226. Schonland SO, Lokhorst H, Buzyn A, Leblond V, Hegenbart U, Bandini G, Campbell A, Carreras E, Ferrant A, Grommisch L, Jacobs P, Kroger N, La Nasa G, Russell N, Zachee P, Goldschmidt H, Iacobelli S, Niederwieser D, Gahrton G (2006) 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 107(6):2578–2584

    Article  PubMed  CAS  Google Scholar 

  227. Dubrey S, Pollak A, Skinner M, Falk RH (1995) Atrial thrombi occurring during sinus rhythm in cardiac amyloidosis: evidence for atrial electromechanical dissociation. Br Heart J 74(5):541–544

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  228. Feng D, Syed IS, Martinez M, Oh JK, Jaffe AS, Grogan M, Edwards WD, Gertz MA, Klarich KW (2009) Intracardiac thrombosis and anticoagulation therapy in cardiac amyloidosis. Circulation 119(18):2490–2497

    Article  CAS  PubMed  Google Scholar 

  229. Rubinow A, Skinner M, Cohen AS (1981) Digoxin sensitivity in amyloid cardiomyopathy. Circulation 63(6):1285–1288

    Article  CAS  PubMed  Google Scholar 

  230. Gertz MA, Falk RH, Skinner M, Cohen AS, Kyle RA (1985) Worsening of congestive heart failure in amyloid heart disease treated by calcium channel-blocking agents. Am J Cardiol 55(13 Pt 1):1645

    Article  CAS  PubMed  Google Scholar 

  231. Palladini G, Malamani G, Co F, Pistorio A, Recusani F, Anesi E, Garini P, Merlini G (2001) Holter monitoring in AL amyloidosis: prognostic implications. Pacing Clin Electrophysiol 24(8 Pt 1):1228–1233

    Article  CAS  PubMed  Google Scholar 

  232. Kristen AV, Dengler TJ, Hegenbart U, Schonland SO, Goldschmidt H, Sack FU, Voss F, Becker R, Katus HA, Bauer A (2008) Prophylactic implantation of cardioverter-defibrillator in patients with severe cardiac amyloidosis and high risk for sudden cardiac death. Heart Rhythm 5(2):235–240

    Article  PubMed  Google Scholar 

  233. Dhoble A, Khasnis A, Olomu A, Thakur R (2009) Cardiac amyloidosis treated with an implantable cardioverter defibrillator and subcutaneous array lead system: report of a case and literature review. Clin Cardiol 32(8):E63–65. doi:10.1002/clc.20389

    Article  PubMed  Google Scholar 

  234. Yaoita H, Iwai-Takano M, Ogawa K, Suzuki H, Akutsu K, Noji H, Kamiyama Y, Kimura S, Ohtake H, Ishibashi T, Maruyama Y (2008) Attenuation of diastolic heart failure and life-threatening ventricular tachyarrhythmia after peripheral blood stem cell transplantation combined with cardioverter-defibrillator implantation in myeloma-associated cardiac amyloidosis. Circ J 72(2):331–334

    Article  PubMed  Google Scholar 

  235. Valleix S, Gillmore JD, Bridoux F, Mangione PP, Dogan A, Nedelec B, Boimard M, Touchard G, Goujon JM, Lacombe C, Lozeron P, Adams D, Lacroix C, Maisonobe T, Plante-Bordeneuve V, Vrana JA, Theis JD, Giorgetti S, Porcari R, Ricagno S, Bolognesi M, Stoppini M, Delpech M, Pepys MB, Hawkins PN, Bellotti V (2012) Hereditary systemic amyloidosis due to Asp76Asn variant beta2-microglobulin. N Engl J Med 366(24):2276–2283. doi:10.1056/NEJMoa1201356

    Article  CAS  PubMed  Google Scholar 

  236. Sayed RH, Rogers D, Khan F, Wechalekar AD, Lachmann HJ, Fontana M, Mahmood S, Sachchithanantham S, Patel K, Hawkins PN, Whelan CJ, Gillmore JD (2014) A study of implanted cardiac rhythm recorders in advanced cardiac AL amyloidosis. Eur Heart J. doi:10.1093/eurheartj/ehu506

    PubMed  Google Scholar 

  237. Pinney JH, Lachmann HJ, Bansi L, Wechalekar AD, Gilbertson JA, Rowczenio D, Sattianayagam PT, Gibbs SD, Orlandi E, Wassef NL, Bradwell AR, Hawkins PN, Gillmore JD (2011) Outcome in renal Al amyloidosis after chemotherapy. J Clinical Oncol: Off J Amer Soc Clinical Oncol 29(6):674–681. doi:10.1200/JCO.2010.30.5235

    Article  Google Scholar 

  238. Singer W, Sandroni P, Opfer-Gehrking TL, Suarez GA, Klein CM, Hines S, O’Brien PC, Slezak J, Low PA (2006) Pyridostigmine treatment trial in neurogenic orthostatic hypotension. Arch Neurol 63(4):513–518

    Article  PubMed  Google Scholar 

  239. Sattianayagam PT, Gibbs SD, Pinney JH, Wechalekar AD, Lachmann HJ, Whelan CJ, Gilbertson JA, Hawkins PN, Gillmore JD (2010) Solid organ transplantation in AL amyloidosis. Am J Transplant 10(9):2124–2131

    Article  CAS  PubMed  Google Scholar 

  240. Nowak G, Westermark P, Wernerson A, Herlenius G, Sletten K, Ericzon BG (2000) Liver transplantation as rescue treatment in a patient with primary AL kappa amyloidosis. Transpl Int 13(2):92–97

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Hematology, Mayo Clinic, Rochester, MN, USA

    Angela Dispenzieri

  2. Division of Laboratory Medicine, Mayo Clinic, Rochester, MN, USA

    Angela Dispenzieri

  3. Amyloidosis Research and Treatment Center, Foundation IRCCS Policlinico San Matteo and Department of Molecular Medicine, University of Pavia, Pavia, Italy

    Giampaolo Merlini

Authors
  1. Angela Dispenzieri
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Giampaolo Merlini
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Giampaolo Merlini .

Editor information

Editors and Affiliations

  1. Dept. of Medical Oncolgy/Hematology,, ASST-Spedali Civili di Brescia Dept. of Medical Oncolgy/Hematology,, Brescia, Brescia, Italy

    Aldo M. Roccaro

  2. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA

    Irene M. Ghobrial

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Dispenzieri, A., Merlini, G. (2016). Immunoglobulin Light Chain Systemic Amyloidosis. In: Roccaro, A., Ghobrial, I. (eds) Plasma Cell Dyscrasias. Cancer Treatment and Research, vol 169. Springer, Cham. https://doi.org/10.1007/978-3-319-40320-5_15

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-40320-5_15

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-40318-2

  • Online ISBN: 978-3-319-40320-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation