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Review

New concepts in the treatment and diagnosis of amyloidosis

, &
Pages 117-127 | Received 02 Nov 2017, Accepted 03 Jan 2018, Published online: 10 Jan 2018

References

  • Merlini G, Bellotti V. Molecular mechanisms of amyloidosis. N Engl J Med. 2003 Aug;349(6):583–596. PubMed PMID: 12904524; eng.
  • Sipe JD, Benson MD, Buxbaum JN, et al. Amyloid fibril proteins and amyloidosis: chemical identification and clinical classification International Society of Amyloidosis 2016 nomenclature guidelines. Amyloid. 2016 Dec;23(4):209–213. PubMed PMID: 27884064. DOI:10.1080/13506129.2016.1257986
  • Mahmood S, Bridoux F, Venner CP, et al. Natural history and outcomes in localised immunoglobulin light-chain amyloidosis: a long-term observational study. Lancet Haematol. 2015 Jun;2(6):e241–50. PubMed PMID: 26688234. DOI:10.1016/S2352-3026(15)00068-X
  • Kourelis T, Buadi F, Gertz MA, et al. Presentation and outcomes of localized amyloidosis: the Mayo Clinic experience. Blood. 2015;126:4197.
  • Milani P, Basset M, Russo F, et al. The lung in amyloidosis. Eur Respir Rev. 2017 Sep 30;26(145). PubMed PMID: 28877975.
  • Merlini G, Stone M. Dangerous small B-cell clones. Blood. 2006 Oct;108(8):2520–2530. PubMed PMID: 16794250; eng.
  • Kyle R, Linos A, Beard C, et al. Incidence and natural history of primary systemic amyloidosis in Olmsted County, Minnesota, 1950 through 1989. Blood. 1992 Apr;79(7):1817–1822. PubMed PMID: 1558973; eng.
  • Gertz M, Lacy M, Dispenzieri A. Amyloidosis. Hematol Oncol Clin North Am. 1999 Dec;13(6):1211–33, ix. PubMed PMID: 10626146; eng.
  • Lousada I, Comenzo RL, Landau H, et al. Light Chain amyloidosis: patient experience survey from the amyloidosis research consortium. Adv Ther. 2015 Oct. 10.1007/s12325-015-0250-0. PubMed PMID: 26498944; PubMed Central PMCID: PMCPMC4635176. ENG.
  • Palladini G, Merlini G. What is new in diagnosis and management of light chain amyloidosis? Blood. 2016 Jul 14;128(2):159–168. doi:10.1182/blood-2016-01-629790. PubMed PMID: 27053535.
  • 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 May;107(19):2440–2445. PubMed PMID: 12719281; eng.
  • Merlini G, Palladini G. Differential diagnosis of monoclonal gammopathy of undetermined significance. Hematology Am Soc Hematol Educ Program. 2012; 2012:595–603. PubMed PMID: 23233640. DOI:10.1182/asheducation-2012.1.595.
  • Merlini G, Wechalekar AD, Palladini G. Systemic light chain amyloidosis: an update for treating physicians. Blood. 2013 Jun 27;121(26):5124–5130. PubMed PMID: 23670179.
  • Fernandez De Larrea C, Verga L, Morbini P, et al. A practical approach to the diagnosis of systemic amyloidoses. Blood. 2015 Apr 2;125(14):2239–2244. PubMed PMID: 25636337. DOI:10.1182/blood-2014-11-609883
  • Quarta CC, Gonzalez-Lopez E, Gilbertson JA, et al. Diagnostic sensitivity of abdominal fat aspiration in cardiac amyloidosis. Eur Heart J. 2017 Jun 21;38(24):1905–1908. PubMed PMID: 28605421. DOI:10.1093/eurheartj/ehx047
  • Foli A, Palladini G, Caporali R, et al. The role of minor salivary gland biopsy in the diagnosis of systemic amyloidosis: results of a prospective study in 62 patients. Amyloid. 2011 Jun;18(Suppl 1):80–82. PubMed PMID: 21838441. DOI:10.3109/13506129.2011.574354029
  • Muchtar E, Dispenzieri A, Lacy MQ, et al. Overuse of organ biopsies in immunoglobulin light chain amyloidosis (AL): the consequence of failure of early recognition. Ann Med. 2017 Mar 27:1–7. PubMed PMID: 28271734. DOI: 10.1080/07853890.2017.1304649
  • Palladini G, Merlini G. Systemic amyloidoses: what an internist should know. Eur J Intern Med. 2013 Dec;24(8):729–739. DOI:10.1016/j.ejim.2013.10.007. PubMed PMID: 24262289.
  • Lachmann H, Booth D, Booth S, et al. Misdiagnosis of hereditary amyloidosis as AL (primary) amyloidosis. N Engl J Med. 2002 Jun;346(23):1786–1791. PubMed PMID: 12050338; eng.
  • Satoskar AA, Efebera Y, Hasan A, et al. Strong transthyretin immunostaining: potential pitfall in cardiac amyloid typing. Am J Surg Pathol. 2011 Nov;35(11):1685–1690. PubMed PMID: 21945954; PubMed Central PMCID: PMCPMC4061151. DOI:10.1097/PAS.0b013e3182263d74
  • Schonland SO, Hegenbart U, Bochtler T, et al. Immunohistochemistry in the classification of systemic forms of amyloidosis: a systematic investigation of 117 patients. Blood. 2012 Jan 12;119(2):488–493. PubMed PMID: 22106346.
  • Vrana J, Gamez J, Madden B, et al. Classification of amyloidosis by laser microdissection and mass spectrometry-based proteomic analysis in clinical biopsy specimens. Blood. 2009 Dec;114(24):4957–4959. PubMed PMID: 19797517; eng.
  • Brambilla F, Lavatelli F, Di Silvestre D, et al. Reliable typing of systemic amyloidoses through proteomic analysis of subcutaneous adipose tissue. Blood. 2012 Feb;119(8):1844–1847. PubMed PMID: 21917755; eng.
  • Gillmore JD, Maurer MS, Falk RH, et al. Non-biopsy diagnosis of cardiac transthyretin amyloidosis. Circulation. PubMed PMID: 27143678 Apr 22 2016. 10.1161/CIRCULATIONAHA.116.021612.
  • Park MA, Padera RF, Belanger A, et al. 18F-florbetapir binds specifically to myocardial light chain and transthyretin amyloid deposits: autoradiography study. Circ Cardiovasc Imaging. 2015 Aug;8(8). PubMed PMID: 26259579; PubMed Central PMCID: PMCPMC4535193. DOI:10.1161/CIRCIMAGING.114.002954.
  • Broski SM, Spinner RJ, Howe BM, et al. 18F-florbetapir and 18F-FDG PET/CT in systemic immunoglobulin light chain amyloidosis involving the peripheral nerves. Clin Nucl Med. 2016 Feb;41(2):e115–7. PubMed PMID: 26284768. DOI:10.1097/RLU.0000000000000947
  • Law WP, Wang W, Moore P, et al. Cardiac amyloid imaging with 18F-florbetaben positron emission tomography: a pilot study. Amyloid. 2017 Mar;24(sup1):162. PubMed PMID: 28434374. DOI:10.1080/13506129.2017.1281120
  • Bellavia D, Pellikka PA, Abraham TP, et al. Evidence of impaired left ventricular systolic function by Doppler myocardial imaging in patients with systemic amyloidosis and no evidence of cardiac involvement by standard two-dimensional and Doppler echocardiography. Am J Cardiol. 2008 Apr 01;101(7):1039–1045. PubMed PMID: 18359328. DOI:10.1016/j.amjcard.2007.11.047
  • Buss SJ, Emami M, Mereles D, et al. 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. 2012 Sep 18;60(12):1067–1076. PubMed PMID: 22883634. DOI:10.1016/j.jacc.2012.04.043
  • Perlini S, Salinaro F, Musca F, et al. Prognostic value of depressed midwall systolic function in cardiac light-chain amyloidosis. J Hypertens. 2014 May;32(5):1121-31; discussion 1131. PubMed PMID: 24509117. DOI:10.1097/HJH.0000000000000120
  • Fontana M, Chung R, Hawkins PN, et al. Cardiovascular magnetic resonance for amyloidosis. Heart Fail Rev. 2015 Mar;20(2):133–144. PubMed PMID: 25549885. DOI:10.1007/s10741-014-9470-7
  • Bochtler T, Hegenbart U, Heiss C, et al. Evaluation of the serum-free light chain test in untreated patients with AL amyloidosis. Haematologica. 2008 Mar;93(3):459–462. PubMed PMID: 18287137; eng.
  • Katzmann J, Kyle R, Benson J, et al. Screening panels for detection of monoclonal gammopathies. Clin Chem. 2009 Aug;55(8):1517–1522. PubMed PMID: 19520758; eng. DOI:10.1373/clinchem.2009.126664
  • Palladini G, Russo P, Bosoni T, et al. Identification of amyloidogenic light chains requires the combination of serum-free light chain assay with immunofixation of serum and urine. Clin Chem. 2009 Mar;55(3):499–504. PubMed PMID: 19131635; eng.
  • Palladini G, Jaccard A, Milani P, et al. Circulating free light chain measurement in the diagnosis, prognostic assessment and evaluation of response of AL amyloidosis: comparison of Freelite and N latex FLC assays. Clin Chem Lab Med. 2017 Mar 27 PubMed PMID: 28343171. DOI:10.1515/cclm-2016-1024.
  • Milani P, Murray DL, Barnidge DR, et al. The utility of MASS-FIX to detect and monitor monoclonal proteins in the clinic. Am J Hematol. 2017 Apr 25 PubMed PMID: 28439985. DOI:10.1002/ajh.24772.
  • Muchtar E, Jevremovic D, Dispenzieri A, et al. The prognostic value of multiparametric flow cytometry in AL amyloidosis at diagnosis and at the end of first-line treatment. Blood. 2017 Jan 05;129(1):82–87. PubMed PMID: 27729322. DOI:10.1182/blood-2016-06-721878
  • 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 Apr 20;33(12):1371–1378. PubMed PMID: 25779559. DOI:10.1200/JCO.2014.57.4947
  • 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 Mar;21(1):9–17. PubMed PMID: 24455967. DOI:10.3109/13506129.2013.854766
  • 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. 2016 Dec 16 PubMed PMID: 27904139. DOI:10.1038/leu.2016.369.
  • Da Silva Filho MI, Forsti A, Weinhold N, et al. Genome-wide association study of immunoglobulin light chain amyloidosis in three patient cohorts: comparison with myeloma. Leukemia. 2017 Aug;31(8):1735–1742. PubMed PMID: 28025584. DOI:10.1038/leu.2016.387
  • Meziane I, Huhn S, Da Silva Filho MI, et al. Genome-wide association study of clinical parameters in immunoglobulin light chain amyloidosis in three patient cohorts. Haematologica. 2017 Jul 04 PubMed PMID: 28679651. DOI:10.3324/haematol.2017.171108.
  • Oliva L, Orfanelli U, Resnati M, et al. The amyloidogenic light chain is a stressor that sensitizes plasma cells to proteasome inhibitor toxicity. Blood. PubMed PMID: 28130214 Jan 27 2017. 10.1182/blood-2016-08-730978.
  • Dispenzieri A, Gertz MA, Kyle RA, et al. Serum cardiac troponins and N-terminal pro-brain natriuretic peptide: a staging system for primary systemic amyloidosis. J Clin Oncol. 2004 Sep 15;22(18):3751–3757. PubMed PMID: 15365071.
  • Palladini G, Foli A, Milani P, et al. Best use of cardiac biomarkers in patients with AL amyloidosis and renal failure. Am J Hematol. 2012 May;87(5):465–471. PubMed PMID: 22389105; eng. DOI:10.1002/ajh.23141
  • 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 Mar 20;30(9):989–995. PubMed PMID: 22331953.
  • 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 Apr 25;121(17):3420–3427. PubMed PMID: 23479568. DOI:10.1182/blood-2012-12-473066
  • Dispenzieri A, Gertz MA, Saenger A, et al. Soluble suppression of tumorigenicity 2 (sST2), but not galactin-3, adds to prognostication in patients with systemic AL amyloidosis independent of NT-proBNP and troponin T. Am J Hematol. 2015 Jun;90(6):524–528. PubMed PMID: 25753178. DOI:10.1002/ajh.24001
  • Palladini G, Barassi A, Perlini S, et al. Midregional proadrenomedullin (MR-proADM) is a powerful predictor of early death in AL amyloidosis. Amyloid. 2011 Dec;18(4):216–221. PubMed PMID: 22070520. DOI:10.3109/13506129.2011.627069
  • Kastritis E, Merlini G, Papassotiriou I, et al. Growth Differentiation Factor-15 (GDF-15) Is a new biomarker with independent prognostic significance for survival and renal outcomes in different cohorts of patients with light chain (AL) amyloidosis. Blood. 2016;128(22):648. [Cited 2018 Jan 05]. Available from: http://www.bloodjournal.org/content/128/22/648.
  • 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 Oct 9;124(15):2325–2332. PubMed PMID: 25115890. DOI:10.1182/blood-2014-04-570010
  • Kastritis E, Gavriatopoulou M, Roussou M, et al. Renal outcomes in patients with al amyloidosis: prognostic factors, renal response and the impact of therapy. Am J Hematol. 2017 Mar 28 PubMed PMID: 28370245. DOI:10.1002/ajh.24738.
  • Milani P, Gertz MA, Merlini G, et al. Attitudes about when and how to treat patients with AL amyloidosis: an international survey. Amyloid. 2017 Aug 31:1–4. PubMed PMID: 28857614. DOI: 10.1080/13506129.2017.1370421
  • 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 Dec 20;30(36):4541–4549. PubMed PMID: 23091105.
  • 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. PubMed PMID: 28550043 May 26 2017. 10.1182/blood-2017-02-767475.
  • Milani P, Basset M, Russo F, et al. Patients with light chain (AL) amyloidosis and low free light chain burden have distinct clinical features and outcome. Blood. PubMed PMID: 28546143 May 25 2017. 10.1182/blood-2017-02-767467.
  • Sidana S, Tandon N, Dispenzieri A, et al. Clinical presentation and outcomes in light chain amyloidosis patients with non-evaluable serum free light chains. Leukemia. 2017 Sep 18 PubMed PMID: 28919633. DOI:10.1038/leu.2017.286.
  • Palladini G, Perfetti V, Merlini G. Therapy and management of systemic AL (primary) amyloidosis. Swiss Med Wkly. 2006 Nov 11;136(45–46):715–720. PubMed PMID: 17183435.
  • Caccialanza R, Palladini G, Klersy C, et al. Nutritional status of outpatients with systemic immunoglobulin light-chain amyloidosis 1. Am J Clin Nutr. 2006 Feb;83(2):350–354. PubMed PMID: 16469994.
  • 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 Sep;38(7):891–894. PubMed PMID: 24072737. DOI:10.1177/0148607113501328
  • 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 Oct;31(10):1228–1234. PubMed PMID: 26250487. DOI:10.1016/j.nut.2015.04.011
  • Kristen AV, Dengler TJ, Hegenbart U, et al. Prophylactic implantation of cardioverter-defibrillator in patients with severe cardiac amyloidosis and high risk for sudden cardiac death. Heart Rhythm. 2008 Feb;5(2):235–240. PubMed PMID: 18242546; eng. DOI:10.1016/j.hrthm.2007.10.016
  • Lin G, Dispenzieri A, Kyle R, et al. Implantable cardioverter defibrillators in patients with cardiac amyloidosis. J Cardiovasc Electrophysiol. 2013 Jul;24(7):793–798. PubMed PMID: 23489983; eng. DOI:10.1111/jce.12123
  • Rezk T, Whelan CJ, Lachmann HJ, et al. Role of implantable intracardiac defibrillators in patients with cardiac immunoglobulin light chain amyloidosis. Br J Haematol. 2017 May 09 PubMed PMID: 28485005. DOI:10.1111/bjh.14747.
  • Sousa M, Monohan G, Rajagopalan N, et al. Heart transplantation in cardiac amyloidosis. Heart Fail Rev. 2017 May;22(3):317–327. 10.1007/s10741-017-9601-z. PubMed PMID: 28281017.
  • Herrmann SM, Gertz MA, Stegall MD, et al. Long-term outcomes of patients with light chain amyloidosis (AL) after renal transplantation with or without stem cell transplantation. Nephrol Dial Transplant. 2011 Jun;26(6):2032–2036. PubMed PMID: 21543655. DOI:10.1093/ndt/gfr067
  • Pinney JH, Lachmann HJ, Sattianayagam PT, et al. Renal transplantation in systemic amyloidosis-importance of amyloid fibril type and precursor protein abundance. Am J Transplant. 2013 Feb;13(2):433–441. PubMed PMID: 23167457. DOI:10.1111/j.1600-6143.2012.04326.x
  • 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 Nov 10;33(32):3741–3749. PubMed PMID: 26371138; PubMed Central PMCID: PMCPMC4737858. DOI:10.1200/JCO.2015.62.4015
  • 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 Transplant. 2013 Apr;48(4):557–561. PubMed PMID: 22964596; eng. DOI:10.1038/bmt.2012.170
  • 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 Aug;90(8):1054–1081. PubMed PMID: 26250727. DOI:10.1016/j.mayocp.2015.06.009
  • 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 Oct;118(16):4346–4352. PubMed PMID: 21828140; eng. DOI:10.1182/blood-2011-01-330738
  • 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 Nov 12;126(20):2345–2347. PubMed PMID: 26443620. DOI:10.1182/blood-2015-08-662726
  • Tandon N, Muchtar E, Sidana S, et al. Revisiting conditioning dose in newly diagnosed light chain amyloidosis undergoing frontline autologous stem cell transplant: impact on response and survival. Bone Marrow Transplant. 2017 Aug;52(8):1126–1132. PubMed PMID: 28394369. DOI:10.1038/bmt.2017.68
  • Hwa YL, 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 Oct;91(10):984–988. PubMed PMID: 27341539; eng. DOI:10.1002/ajh.24453
  • 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 Jan;31(1):136–142. PubMed PMID: 27560108; PubMed Central PMCID: PMCPMC5220129. DOI:10.1038/leu.2016.229
  • Minnema M, Nasserinejad K, Hazenberg B, et al. Hovon 104; final results from a multicenter, prospective phase ii study of bortezomib based induction treatment followed by autologous stem cell transplantation in patients with de novo al amyloidosis [meeting abstract]. Haematologica. 2017 JUN 26;2017(102):144. PubMed PMID: WOS:000404127001305; English.
  • 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 Apr;103(8):2936–2938. PubMed PMID: 15070667; eng.
  • Palladini G, Russo P, Nuvolone M, et al. Treatment with oral melphalan plus dexamethasone produces long-term remissions in AL amyloidosis. Blood. 2007 Jul;110(2):787–788. PubMed PMID: 17606766; eng.
  • 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 Apr;99(4):743–750. PubMed PMID: 24213149; PubMed Central PMCID: PMCPMC3971085.
  • Jaccard A, Moreau P, Leblond V, et al. High-dose melphalan versus melphalan plus dexamethasone for AL amyloidosis. N Engl J Med. 2007 Sep;357(11):1083–1093. PubMed PMID: 17855669; eng.
  • Kastritis E, Wechalekar A, Dimopoulos M, et al. Bortezomib with or without dexamethasone in primary systemic (light chain) amyloidosis. J Clin Oncol. 2010 Feb;28(6):1031–1037. PubMed PMID: 20085941; eng. DOI:10.1200/JCO.2009.23.8220
  • Reece D, 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 Aug;114(8):1489–1497. PubMed PMID: 19498019; eng.
  • 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 Jul;118(4):865–873. PubMed PMID: 21562045; eng. DOI:10.1182/blood-2011-02-334227
  • 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 Oct 16;124(16):2498–2506. PubMed PMID: 25202139; PubMed Central PMCID: PMC4199951. DOI:10.1182/blood-2014-04-568329
  • Venner CP, Lane T, Foard D, et al. Cyclophosphamide, bortezomib, and dexamethasone therapy in AL amyloidosis is associated with high clonal response rates and prolonged progression-free survival. Blood. 2012 May;119(19):4387–4390. PubMed PMID: 22331187; eng. DOI:10.1182/blood-2011-10-388462
  • Mikhael JR, Schuster SR, Jimenez-Zepeda VH, et al. Cyclophosphamide-bortezomib-dexamethasone (CyBorD) produces rapid and complete hematologic response in patients with AL amyloidosis. Blood. 2012 May;119(19):4391–4394. PubMed PMID: 22331188; eng. DOI:10.1182/blood-2011-11-390930
  • 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 Jul 30;126(5):612–615. PubMed PMID: 25987656. DOI:10.1182/blood-2015-01-620302
  • 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 Dec;28(12):2311–2316. PubMed PMID: 25059496. DOI:10.1038/leu.2014.227
  • 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 Dec;28(12):2304–2310. PubMed PMID: 25027514. DOI:10.1038/leu.2014.218
  • 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 Jun;7(6):e570. PubMed PMID: 28622303; PubMed Central PMCID: PMCPMC5520394. eng. DOI:10.1038/bcj.2017.47
  • Kastritis E, Leleu X, Arnulf B, et al. A randomized phase III trial of melphalan and dexamethasone (MDex) versus bortezomib, melphalan and dexamethasone (BMDex) for untreated patients with Al amyloidosis. Blood. 2016; 128(22):646. 2016 DEC 2. PubMed PMID: WOS:000394446805139.
  • 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 Jul 28;128(4):594–602. PubMed PMID: 27257181. DOI:10.1182/blood-2015-10-676361
  • 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 Jul;31(7):1562–1569. PubMed PMID: 27904139; eng. DOI:10.1038/leu.2016.369
  • Palladini G, Milani P, Merlini G. Novel strategies for the diagnosis and treatment of cardiac amyloidosis. Exp Rev Cardiovasc Ther. 2015;13(11):1195–1211. 2015-Nov. DOI:10.1586/14779072.2015.1093936
  • Merlini G, Palladini G. Light chain amyloidosis: the heart of the problem. Haematologica. 2013 Oct;98(10):1492–1495. DOI:10.3324/haematol.2013.094482. PubMed PMID: 24091927; PubMed Central PMCID: PMCPMC3789451.
  • Dispenzieri A, Lacy M, Zeldenrust S, et al. The activity of lenalidomide with or without dexamethasone in patients with primary systemic amyloidosis. Blood. 2007 Jan;109(2):465–470. PubMed PMID: 17008538; eng.
  • Sanchorawala V, Wright D, Rosenzweig M, et al. Lenalidomide and dexamethasone in the treatment of AL amyloidosis: results of a phase 2 trial. Blood. 2007 Jan;109(2):492–496. PubMed PMID: 16960148; eng.
  • 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. Apr 2011. PubMed PMID: 21533608; ENG. Doi: 10.1007/s00277-011-1244-x
  • 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 Jun;119(23):5384–5390. PubMed PMID: 22517904; eng. DOI:10.1182/blood-2011-12-396903
  • 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 May;119(21):4860–4867. PubMed PMID: 22504925; eng. DOI:10.1182/blood-2012-01-407791
  • 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 Sep;166(6):842–848. PubMed PMID: 24930361; eng. DOI:10.1111/bjh.12973
  • Dispenzieri A, Buadi F, Laumann K, et al. Activity of pomalidomide in patients with immunoglobulin light-chain amyloidosis. Blood. 2012 Jun 07;119(23):5397–5404. PubMed PMID: 22493299; PubMed Central PMCID: PMCPMC3369677. DOI:10.1182/blood-2012-02-413161
  • 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 Aug 25;128(8):1059–1062. PubMed PMID: 27381904. DOI:10.1182/blood-2016-04-710822
  • 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 Apr;129(15):2120–2123. PubMed PMID: 28130212; eng. DOI:10.1182/blood-2016-12-756528
  • Milani P, Schonland S, Palladini G, et al. Response to bendamustine is associated with a survival advantage in a heavily pretreated patients with AL amyloidosis. Amyloid. 2017 Mar;24(sup1):56–57. PubMed PMID: 28434298. DOI:10.1080/13506129.2017.1292240
  • Cohen A, Landau H, Scott E, et al. Safety and efficacy of carfilzomib (CFZ) in previously-treated systemic light-chain (AL) amyloidosis [Meeting Abstract]. Blood. 2016; 128(22):645. 2016 DEC 2. PubMed PMID: WOS:000394446805134; English.
  • 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 Aug 03;130(5):597–605. PubMed PMID: 28550039. DOI:10.1182/blood-2017-03-771220
  • Kaufman GP, Schrier SL, Lafayette RA. et al. Daratumumab yields rapid and deep hematologic responses in patients with heavily pretreated AL amyloidosis. Blood. Jun 2017. PubMed PMID: 28615223; eng. Doi: 10.1182/blood-2017-01-763599
  • Zhou P, Ma X, Iyer L, et al. One siRNA pool targeting the lambda constant region stops lambda light-chain production and causes terminal endoplasmic reticulum stress. Blood. 2014 May 29;123(22):3440–3451. PubMed PMID: 24723680. DOI:10.1182/blood-2013-10-535187
  • Pepys M, Herbert J, Hutchinson W, et al. Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis. Nature. 2002 May;417(6886):254–259. PubMed PMID: 12015594; eng.
  • Richards DB, Cookson LM, Berges AC, et al. Therapeutic clearance of amyloid by antibodies to serum amyloid P component. N Engl J Med. 2015 Sep 17;373(12):1106–1114. PubMed PMID: 26176329. DOI:10.1056/NEJMoa1504942
  • Hrncic R, Wall J, Wolfenbarger D, et al. Antibody-mediated resolution of light chain-associated amyloid deposits. Am J Pathol. 2000 Oct;157(4):1239–1246. PubMed PMID: 11021828; eng.
  • 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 Mar;24(sup1):58–59. PubMed PMID: 28434347; eng. DOI:10.1080/13506129.2017.1292900
  • 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 Apr 1;34(10):1097–1103. PubMed PMID: 26858336. DOI:10.1200/JCO.2015.63.6530
  • Merlini G, Anesi E, Garini P, et al. Treatment of AL amyloidosis with 4ʹ-lodo-4ʹ-deoxydoxorubicin: an update. Blood. 1999 Feb;93(3):1112–1113. PubMed PMID: 10025983; eng.
  • Gertz M, Lacy M, Dispenzieri A, et al. A multicenter phase II trial of 4ʹ-iodo-4ʹdeoxydoxorubicin (IDOX) in primary amyloidosis (AL). Amyloid. 2002 Mar;9(1):24–30. PubMed PMID: 12000194; eng.
  • Merlini G, Ascari E, Amboldi N, et al. Interaction of the anthracycline 4ʹ-iodo-4ʹ-deoxydoxorubicin with amyloid fibrils: inhibition of amyloidogenesis. Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2959–2963. PubMed PMID: 7708755; PubMed Central PMCID: PMC42338. eng.
  • Cardoso I, Saraiva MJ. Doxycycline disrupts transthyretin amyloid: evidence from studies in a FAP transgenic mice model. Faseb J. 2006 Feb;20(2):234–239. DOI:10.1096/fj.05-4509com. PubMed PMID: 16449795.
  • Diomede L, Rognoni P, Lavatelli F, et al. A Caenorhabditis elegans-based assay recognizes immunoglobulin light chains causing heart amyloidosis. Blood. 2014 Jun 05;123(23):3543–3552. PubMed PMID: 24665135; PubMed Central PMCID: PMCPMC4047494. DOI:10.1182/blood-2013-10-525634
  • Wechalekar AD, Whelan C. Encouraging impact of doxycycline on early mortality in cardiac light chain (AL) amyloidosis. Blood Cancer J. 2017 Mar 24;7(3):e546. doi:10.1038/bcj.2017.26. PubMed PMID: 28338670.

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