Vol 9, No 3 (2018)
Review paper
Published online: 2018-10-17

open access

Page views 1090
Article views/downloads 5272
Get Citation

Connect on Social Media

Connect on Social Media

Diagnostics and treatment of AL amyloidosis

Krzysztof Jamroziak1, Paolo Milani2, Bartosz Puła1, Sonia Dębek1, Giovanni Palladini2
Hematologia 2018;9(3):181-195.

Abstract

Light chain amyloidosis (AL amyloidosis) is a disease in which monoclonal immunoglobulin light chains, produced by clonal plasma cells are deposited extracellularly in the form of misfolded, insoluble protein complexes known as amyloid. This disease is a heterogeneous condition, due to the organ tropism, which varies among patients. Heart involvement prevails (80% of patients), whereas kidneys, liver and nervous system may be also involved. To diagnose AL amyloidosis, amyloid should be detected by staining tissue samples with Congo red, and the amyloid typing should reveal the immunoglobulin light chain character of the amyloid fibrils. The therapy usually focuses on the elimination of clonal plasma cells. Assigning the patient to the proper risk group (low, intermediate, high) is crucial. For younger patients of the low-risk group, high-dose melphalan with autologous hematopoietic stem cell transplantation (auto-HSCT) with optional bortezomib-based consolidation treatment should be considered. For the most numerous (70% of patients), intermediate-risk group, MDex (melphalan, dexamethasone), as well as bortezomib-based therapies should be given. Patients in the high-risk group should undergo a chemotherapy with reduced intensity. Refractory disease can be treated with IMIDs (immunomodulatory drugs), as well as new-generation proteasome inhibitors, bendamustine and monoclonal antibodies.

Article available in PDF format

View PDF (Polish) Download PDF file

References

  1. Gillmore JD, Wechalekar A, Bird J, et al. BCSH Committee. Guidelines on the management of AL amyloidosis. Br J Haematol. 2015; 168(2): 186–206.
  2. Buxbaum JN, Chuba JV, Hellman GC, et al. Monoclonal immunoglobulin deposition disease: light chain and light and heavy chain deposition diseases and their relation to light chain amyloidosis. Clinical features, immunopathology, and molecular analysis. Ann Intern Med. 1990; 112(6): 455–464.
  3. Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016; 127(20): 2375–2390.
  4. Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014; 15(12): e538–e548.
  5. da Silva Filho MI, Försti A, Weinhold N, et al. Genome-wide association study of immunoglobulin light chain amyloidosis in three patient cohorts: comparison with myeloma. Leukemia. 2017; 31(8): 1735–1742.
  6. Milani P, Merlini G, Palladini G. Light Chain Amyloidosis. Mediterr J Hematol Infect Dis. 2018; 10(1): e2018022.
  7. Bochtler T, Hegenbart U, Kunz C, et al. Translocation t(11;14) is associated with adverse outcome in patients with newly diagnosed AL amyloidosis when treated with bortezomib-based regimens. J Clin Oncol. 2015; 33(12): 1371–1378.
  8. Muchtar E, Dispenzieri A, Kumar SK, et al. Interphase fluorescence in situ hybridization in untreated AL amyloidosis has an independent prognostic impact by abnormality type and treatment category. Leukemia. 2017; 31(7): 1562–1569.
  9. Yu W, Guo R, Qu X, et al. The amplification of 1q21 is an adverse prognostic factor in patients with multiple myeloma in a Chinese population. Onco Targets Ther. 2016; 9: 295–302.
  10. Perfetti V, Casarini S, Palladini G, et al. 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. 2002; 100(3): 948–953.
  11. Kourelis TV, Dasari S, Theis JD, et al. Clarifying immunoglobulin gene usage in systemic and localized immunoglobulin light-chain amyloidosis by mass spectrometry. Blood. 2017; 129(3): 299–306.
  12. Perfetti V, Palladini G, Casarini S, et al. The repertoire of λ light chains causing predominant amyloid heart involvement and identification of a preferentially involved germline gene, IGLV1-44. Blood. 2012; 119(1): 144–150.
  13. 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(19): 2440–2445.
  14. Palladini G, Lavatelli F, Russo P, et al. Circulating amyloidogenic free light chains and serum N-terminal natriuretic peptide type B decrease simultaneously in association with improvement of survival in AL. Blood. 2006; 107(10): 3854–3858.
  15. Palladini G, Barassi A, Klersy C, et al. The combination of high-sensitivity cardiac troponin T (hs-cTnT) at presentation and changes in N-terminal natriuretic peptide type B (NT-proBNP) after chemotherapy best predicts survival in AL amyloidosis. Blood. 2010; 116(18): 3426–3430.
  16. Liao R, Jain M, Teller P, et al. Infusion of light chains from patients with cardiac amyloidosis causes diastolic dysfunction in isolated mouse hearts. Circulation. 2001; 104(14): 1594–1597.
  17. Diomede L, Rognoni P, Lavatelli F, et al. A Caenorhabditis elegans-based assay recognizes immunoglobulin light chains causing heart amyloidosis. Blood. 2014; 123(23): 3543–3552.
  18. Mishra S, Guan J, Plovie E, et al. Human amyloidogenic light chain proteins result in cardiac dysfunction, cell death, and early mortality in zebrafish. Am J Physiol Heart Circ Physiol. 2013; 305(1): H95–H103.
  19. Lousada I, Comenzo RL, Landau H, et al. Light Chain Amyloidosis: Patient Experience Survey from the Amyloidosis Research Consortium. Adv Ther. 2015; 32(10): 920–928.
  20. Grzybowski J. SERCA. In: Offermanns S, Rosenthal W. ed. Encyclopedia of Molecular Pharmacology. Springer-Verlag, Berlin, Heidelberg 2008: 1119.
  21. Merlini G, Palladini G. Differential diagnosis of monoclonal gammopathy of undetermined significance. Hematology Am Soc Hematol Educ Program. 2012; 2012: 595–603.
  22. 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(4): 319–328.
  23. Wołyniec W. Amyloidoza nerek. : Hematologia.
  24. Comenzo R. Managing Systemic Light-Chain Amyloidosis. J Natl Compr Canc Netw. 2007; 5(2): 179–187.
  25. Kumar S, Dispenzieri A, Katzmann JA, et al. Serum immunoglobulin free light-chain measurement in primary amyloidosis: prognostic value and correlations with clinical features. Blood. 2010; 116(24): 5126–5129.
  26. Puła B, Dębek S, Jamroziak K. Nazewnictwo amyloidoz. : Hematologia.
  27. Vrana JA, Gamez JD, Madden BJ, et al. Classification of amyloidosis by laser microdissection and mass spectrometry-based proteomic analysis in clinical biopsy specimens. Blood. 2009; 114(24): 4957–4959.
  28. Brambilla F, Lavatelli F, Di Silvestre D, et al. Reliable typing of systemic amyloidoses through proteomic analysis of subcutaneous adipose tissue. Blood. 2012; 119(8): 1844–1847.
  29. 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(9): 989–995.
  30. 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(10): 1302–1307.
  31. 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(6): 1881–1887.
  32. Palladini G, Merlini G. What is new in diagnosis and management of light chain amyloidosis? Blood. 2016; 128(2): 159–168.
  33. D'Souza A, Dispenzieri A, Wirk B, et al. Improved Outcomes After Autologous Hematopoietic Cell Transplantation for Light Chain Amyloidosis: A Center for International Blood and Marrow Transplant Research Study. J Clin Oncol. 2015; 33(32): 3741–3749.
  34. Dittrich T, Bochtler T, Kimmich C, et al. AL amyloidosis patients with low amyloidogenic free light chain levels at first diagnosis have an excellent prognosis. Blood. 2017; 130(5): 632–642.
  35. Milani P, Basset M, Russo F, et al. Patients with light-chain amyloidosis and low free light-chain burden have distinct clinical features and outcome. Blood. 2017; 130(5): 625–631.
  36. 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(36): 4541–4549.
  37. Palladini G, Hegenbart U, Milani P, et al. A staging system for renal outcome and early markers of renal response to chemotherapy in AL amyloidosis. Blood. 2014; 124(15): 2325–2332.
  38. Merlini G, Lousada I, Ando Y, et al. Rationale, application and clinical qualification for NT-proBNP as a surrogate end point in pivotal clinical trials in patients with AL amyloidosis. Leukemia. 2016; 30(10): 1979–1986.
  39. Sher T, Gertz MA, Sher T, et al. Evolution of Hematopoietic Cell Transplantation for Immunoglobulin Light Chain Amyloidosis. Biol Blood Marrow Transplant. 2016; 22(5): 796–801.
  40. Jaccard A, Moreau P, Leblond V, et al. Myélome Autogreffe (MAG) and Intergroupe Francophone du Myélome (IFM) Intergroup. High-dose melphalan versus melphalan plus dexamethasone for AL amyloidosis. N Engl J Med. 2007; 357(11): 1083–1093.
  41. Muchtar E, Gertz MA, Kumar SK, et al. Improved outcomes for newly diagnosed AL amyloidosis between 2000 and 2014: cracking the glass ceiling of early death. Blood. 2017; 129(15): 2111–2119.
  42. Migrino RQ, Mareedu RK, Eastwood D, et al. Left ventricular ejection time on echocardiography predicts long-term mortality in light chain amyloidosis. J Am Soc Echocardiogr. 2009; 22(12): 1396–1402.
  43. Gertz MA, Lacy MQ, Dispenzieri A, et al. Refinement in patient selection to reduce treatment-related mortality from autologous stem cell transplantation in amyloidosis. Bone Marrow Transpl. 2013; 48(4): 557–561.
  44. Dispenzieri A, Buadi F, Kumar SK, et al. Treatment of Immunoglobulin Light Chain Amyloidosis: Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) Consensus Statement. Mayo Clin Proc. 2015; 90(8): 1054–1081.
  45. 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(16): 4346–4352.
  46. 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(22): 4445–4446.
  47. Nguyen VP, Landau H, Quillen K, et al. Modified High-Dose Melphalan and Autologous Stem Cell Transplantation for Immunoglobulin Light Chain Amyloidosis. Biol Blood Marrow Transplant. 2018 [Epub ahead of print]; 53(3): 371–373.
  48. Sanchorawala V, Sun F, Quillen K, et al. Long-term outcome of patients with AL amyloidosis treated with high-dose melphalan and stem cell transplantation: 20-year experience. Blood. 2015; 126(20): 2345–2347.
  49. Landau H, Smith M, Landry C, et al. Long-term event-free and overall survival after risk-adapted melphalan and SCT for systemic light chain amyloidosis. Leukemia. 2017; 31(1): 136–142.
  50. Hwa YiL, Kumar SK, Gertz MA, et al. Induction therapy pre-autologous stem cell transplantation in immunoglobulin light chain amyloidosis: a retrospective evaluation. Am J Hematol. 2016; 91(10): 984–988.
  51. 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(8): 2936–2938.
  52. Palladini G, Russo P, Nuvolone M, et al. Treatment with oral melphalan plus dexamethasone produces long-term remissions in AL amyloidosis. Blood. 2007; 110(2): 787–788.
  53. 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(4): 743–750.
  54. Kastritis E, Gavriatopoulou M, Roussou M, et al. Addition of cyclophosphamide and higher doses of dexamethasone do not improve outcomes of patients with AL amyloidosis treated with bortezomib. Blood Cancer J. 2017; 7(6): e570.
  55. Kastritis E, Wechalekar AD, Dimopoulos MA, et al. Bortezomib with or without dexamethasone in primary systemic (light chain) amyloidosis. J Clin Oncol. 2010; 28(6): 1031–1037.
  56. Reece DE, Hegenbart U, Sanchorawala V, et al. Long-term follow-up from a phase 1/2 study of single-agent bortezomib in relapsed systemic AL amyloidosis. Blood. 2014; 124(16): 2498–2506.
  57. 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(4): 865–873.
  58. 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(8): 1489–1497.
  59. Palladini G, Milani P, Foli A, et al. Melphalan and dexamethasone with or without bortezomib in newly diagnosed AL amyloidosis: a matched case-control study on 174 patients. Leukemia. 2014; 28(12): 2311–2316.
  60. Palladini G, Sachchithanantham S, Milani P, et al. A European collaborative study of cyclophosphamide, bortezomib, and dexamethasone in upfront treatment of systemic AL amyloidosis. Blood. 2015; 126(5): 612–615.
  61. Venner CP, Gillmore JD, Sachchithanantham S, et al. A matched comparison of cyclophosphamide, bortezomib and dexamethasone (CVD) versus risk-adapted cyclophosphamide, thalidomide and dexamethasone (CTD) in AL amyloidosis. Leukemia. 2014; 28(12): 2304–2310.
  62. Bochtler T, Hegenbart U, Kunz C, et al. Prognostic impact of cytogenetic aberrations in AL amyloidosis patients after high-dose melphalan: a long-term follow-up study. Blood. 2016; 128(4): 594–602.
  63. Bochtler T, Hegenbart U, Kunz C, et al. Gain of chromosome 1q21 is an independent adverse prognostic factor in light chain amyloidosis patients treated with melphalan/dexamethasone. Amyloid. 2014; 21(1): 9–17.
  64. Manwani R, Hegenbart U, Foard D, et al. Safety and Efficacy of Deferred Autologous Stem Cell Transplantation in Patients with Systemic AL Amyloidosis with Significant Cardiac Involvement at Presentation. Blood. 2017; 130(Suppl 1): 1815.
  65. Sidana S, Tandon N, Gertz MA, et al. Impact of prior melphalan exposure on stem cell collection in light chain amyloidosis. Bone Marrow Transplant. 2018; 53(3): 326–333.
  66. Palladini G, Milani P, Merlini G. Novel strategies for the diagnosis and treatment of cardiac amyloidosis. Expert Rev Cardiovasc Ther. 2015; 13(11): 1195–1211.
  67. 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(17): 3420–3427.
  68. Manwani R, Foard D, Mahmood S, et al. Rapid hematologic responses improve outcomes in patients with very advanced (stage IIIb) cardiac immunoglobulin light chain amyloidosis. Haematologica. 2018; 103(4): e165–e168.
  69. Milani P, Gertz MA, Merlini G, et al. Attitudes about when and how to treat patients with AL amyloidosis: an international survey. Amyloid. 2017; 24(4): 213–216.
  70. Palladini G, Milani P, Foli A, et al. Presentation and outcome with second-line treatment in AL amyloidosis previously sensitive to nontransplant therapies. Blood. 2018; 131(5): 525–532.
  71. Tandon N, Sidana S, Rajkumar SV, et al. Treatment patterns and outcome following initial relapse or refractory disease in patients with systemic light chain amyloidosis. Am J Hematol. 2017; 92(6): 549–554.
  72. Warsame R, Laplant B, Laumann K, et al. Long-Term Outcomes of IMiD Based Trials in Patients with Immunoglobulin Light Chain Amyloidosis (AL): A Pooled Analysis. Blood. 2017; 130(Suppl 1): 1833.
  73. Chanan-Khan AA, Swaika A, Paulus A, et al. The activity of lenalidomide with or without dexamethasone in patients with primary systemic amyloidosis. Blood. 2007; 109(2): 465–470.
  74. 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(2): 492–496.
  75. Palladini G, Russo P, Foli A, et al. Salvage therapy with lenalidomide and dexamethasone in patients with advanced AL amyloidosis refractory to melphalan, bortezomib, and thalidomide. Ann Hematol. 2012; 91(1): 89–92.
  76. 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(23): 5384–5390.
  77. 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(21): 4860–4867.
  78. Mahmood S, Venner CP, Sachchithanantham S, et al. Lenalidomide and dexamethasone for systemic AL amyloidosis following prior treatment with thalidomide or bortezomib regimens. Br J Haematol. 2014; 166(6): 842–848.
  79. Specter R, Sanchorawala V, Seldin DC, et al. Kidney dysfunction during lenalidomide treatment for AL amyloidosis. Nephrol Dial Transplant. 2011; 26(3): 881–886.
  80. 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(23): 4777–4782.
  81. Sanchorawala V, Patel JM, Sloan JM, et al. Melphalan, lenalidomide and dexamethasone for the treatment of immunoglobulin light chain amyloidosis: results of a phase II trial. Haematologica. 2013; 98(5): 789–792.
  82. Cibeira MT, Oriol A, Lahuerta JJ, et al. PETHEMA cooperative study group. A phase II trial of lenalidomide, dexamethasone and cyclophosphamide for newly diagnosed patients with systemic immunoglobulin light chain amyloidosis. Br J Haematol. 2015; 170(6): 804–813.
  83. Hegenbart U, Bochtler T, Benner A, et al. Lenalidomide/melphalan/dexamethasone in newly diagnosed patients with immunoglobulin light chain amyloidosis: results of a prospective phase 2 study with long-term follow up. Haematologica. 2017; 102(8): 1424–1431.
  84. Dispenzieri A, Buadi F, Laumann K, et al. Activity of pomalidomide in patients with immunoglobulin light-chain amyloidosis. Blood. 2012; 119(23): 5397–5404.
  85. Sanchorawala V, Shelton AC, Lo S, et al. Pomalidomide and dexamethasone in the treatment of AL amyloidosis: results of a phase 1 and 2 trial. Blood. 2016; 128(8): 1059–1062.
  86. Palladini G, Milani P, Foli A, et al. A phase 2 trial of pomalidomide and dexamethasone rescue treatment in patients with AL amyloidosis. Blood. 2017; 129(15): 2120–2123.
  87. Cohen AD, Liedtke M, Scott EC, et al. Safety and efficacy of carfilzomib (CFZ) in previously-treated systemic light-chain (AL) amyloidosis. Clinical Lymphoma Myeloma and Leukemia. 2015; 15: e58–e59.
  88. Sanchorawala V, Palladini G, Kukreti V, et al. A phase 1/2 study of the oral proteasome inhibitor ixazomib in relapsed or refractory AL amyloidosis. Blood. 2017; 130(5): 597–605.
  89. Salomon-Perzyński A, Jamroziak K. The role of daratumumab in the treatment of relapsed/refractory plasma cell myeloma. Hematologia. 2017; 8(4): 255–264.
  90. Kaufman GP, Schrier SL, Lafayette RA, et al. Daratumumab yields rapid and deep hematologic responses in patients with heavily pretreated AL amyloidosis. Blood. 2017; 130(7): 900–902.
  91. Khouri J, Kin A, Thapa B, et al. Daratumumab proves safe and highly effective in AL amyloidosis. Br J Haematol. 2018 [Epub ahead of print]: 1–3.
  92. Roussel M, Stoppa A, Perrot AA, et al. Prospective Phase II of Daratumumab in Previously-Treated Systemic Light-Chain (AL) Amyloidosis. Blood. 2017; 130(Suppl 1): 508.
  93. Sanchorawala V, Sarosiek S, Sloan JM, et al. Safety and Tolerability of Daratumumab in Patients with Relapsed Light Chain (AL) Amyloidosis: Preliminary Results of a Phase II Study. Blood. 2017; 130(Suppl 1): 507.
  94. Gran C, Gahrton G, Alici E, et al. Case Report: Treatment of light-chain amyloidosis with daratumumab monotherapy in two patients. Eur J Haematol. 2018; 100(4): 386–388.
  95. Puła B, Jamroziak K. Rola wenetoklaksu w leczeniu chorych na przewlekłą białaczkę limfocytową. Hematologia. 2017; 8(1): 20–32.
  96. Gertz MA. Immunoglobulin light chain amyloidosis diagnosis and treatment algorithm 2018. Blood Cancer J. 2018; 8(5): 44.
  97. Gertz MA, Landau H, Comenzo RL, et al. First-in-Human Phase I/II Study of NEOD001 in Patients With Light Chain Amyloidosis and Persistent Organ Dysfunction. J Clin Oncol. 2016; 34(10): 1097–1103.
  98. Edwards CV, Gould J, Langer AL, et al. Interim analysis of the phase 1a/b study of chimeric fibril-reactive monoclonal antibody 11-1F4 in patients with AL amyloidosis. Amyloid. 2017; 24(Suppl 1): 58–59.
  99. Richards DB, Cookson LM, Berges AC, et al. Therapeutic Clearance of Amyloid by Antibodies to Serum Amyloid P Component. N Engl J Med. 2015; 373(12): 1106–1114.
  100. Ward JE, Ren R, Toraldo G, et al. Doxycycline reduces fibril formation in a transgenic mouse model of AL amyloidosis. Blood. 2011; 118(25): 6610–6617.
  101. Kumar SK, Dispenzieri A, Lacy MQ, et al. Doxycycline Used As Post Transplant Antibacterial Prophylaxis Improves Survival in Patients with Light Chain Amyloidosis Undergoing Autologous Stem Cell Transplantation. Blood. 2012; 120(21): 3138–3138.
  102. Scully MS, Wessman DE, McKee JM, et al. Total Artificial Heart Implantation as a Bridge to Heart Transplantation in an Active Duty Service Member With Amyloid Cardiomyopathy. Mil Med. 2017; 182(3): e1858–e1860.
  103. Kristen AV, Kreusser MM, Blum P, et al. Improved outcomes after heart transplantation for cardiac amyloidosis in the modern era. J Heart Lung Transplant. 2018; 37(5): 611–618.
  104. Sousa M, Monohan G, Rajagopalan N, et al. Heart transplantation in cardiac amyloidosis. Heart Fail Rev. 2017; 22(3): 317–327.
  105. Grogan M, Gertz M, McCurdy A, et al. Long term outcomes of cardiac transplant for immunoglobulin light chain amyloidosis: The Mayo Clinic experience. World J Transplant. 2016; 6(2): 380–388.
  106. Meyers DE, Adu-Gyamfi B, Segura AM, et al. Fatal cardiac and renal allograft rejection with lenalidomide therapy for light-chain amyloidosis. Am J Transplant. 2013; 13(10): 2730–2733.
  107. Caccialanza R, Palladini G, Klersy C, et al. Nutritional status of outpatients with systemic immunoglobulin light-chain amyloidosis 1. Am J Clin Nutr. 2006; 83(2): 350–354.
  108. Caccialanza R, Palladini G, Klersy C, et al. Nutritional status independently affects quality of life of patients with systemic immunoglobulin light-chain (AL) amyloidosis. Ann Hematol. 2012; 91(3): 399–406.
  109. Caccialanza R, Palladini G, Klersy C, et al. Malnutrition at diagnosis predicts mortality in patients with systemic immunoglobulin light-chain amyloidosis independently of cardiac stage and response to treatment. JPEN J Parenter Enteral Nutr. 2014; 38(7): 891–894.
  110. Caccialanza R, Palladini G, Cereda E, et al. Nutritional counseling improves quality of life and preserves body weight in systemic immunoglobulin light-chain (AL) amyloidosis. Nutrition. 2015; 31(10): 1228–1234.
  111. 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(6): 1881–1887.
  112. 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(9): 989–995.
  113. Palladini G, Hegenbart U, Milani P, et al. A staging system for renal outcome and early markers of renal response to chemotherapy in AL amyloidosis. Blood. 2014; 124(15): 2325–2332.



Hematology in Clinical Practice