Abstract
Cardiac involvement in light-chain amyloidosis (AL) predicts poor prognosis and is associated with higher TRM and morbidity during high-dose therapy and auto-SCT (HDT–ASCT). We studied the outcomes of 30 patients with cardiac amyloidosis undergoing HDT–ASCT at our center between January 1998 and March 2012. The median age of the patients was 53 years (range, 36–74) with a median follow-up of 35 months (range, 0.4–97 months). Twenty-seven patients (90%) had more than one organ involved besides the heart with 37% with cardiac stage ⩾3. Melphalan-based conditioning regimen (140–200 mg/m2) was used for HDT–ASCT. One-year TRM is 10%. Three-year OS and EFS from HDT–ASCT was 83% and 56.8%, respectively. Cumulative incidence of relapse at 3 years was 38.5%. Negative factors affecting survival included age >60 years, lack of novel induction therapy and BM plasmacytosis >10%. We conclude that HDT–ASCT is well tolerated in patients with high-risk cardiac amyloidosis and can lead to improved overall outcomes.
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References
Merlini G, Seldin DC, Gertz MA . Amyloidosis: pathogenesis and new therapeutic options. J Clin Oncol 2011; 29: 1924–1933.
Kyle RA, Gertz MA . Primary systemic amyloidosis: clinical and laboratory features in 474 cases. Semin Hematol 1995; 32: 45–59.
Dispenzieri A, Kyle RA, Gertz MA, Therneau TM, Miller WL, Chandrasekaran K et al. Survival in patients with primary systemic amyloidosis and raised serum cardiac troponins. Lancet 2003; 361: 1787–1789.
Dispenzieri A, Gertz MA, Kyle RA, Lacy MQ, Burritt MF, Therneau TM et al. Serum cardiac troponins and N-terminal pro-brain natriuretic peptide: a staging system for primary systemic amyloidosis. J Clin Oncol 2004; 22: 3751–3757.
Dispenzieri A, Gertz MA, Kyle RA, Lacy MQ, Burritt MF, Therneau TM et al. Prognostication of survival using cardiac troponins and N-terminal pro-brain natriuretic peptide in patients with primary systemic amyloidosis undergoing peripheral blood stem cell transplantation. Blood 2004; 104: 1881–1887.
Palladini G, Campana C, Klersy C, Balduini A, Vadacca G, Perfetti V et al. Serum N-terminal pro-brain natriuretic peptide is a sensitive marker of myocardial dysfunction in AL amyloidosis. Circulation 2003; 107: 2440–2445.
Kumar S, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, Colby C et al. Revised prognostic staging system for light chain amyloidosis incorporating cardiac biomarkers and serum free light chain measurements. J Clin Oncol 2012; 30: 989–995.
Dhodapkar MV, Hussein MA, Rasmussen E, Solomon A, Larson RA, Crowley JJ et al. 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 2004; 104: 3520–3526.
Palladini G, Perfetti V, Obici L, Caccialanza R, Semino A, Adami F et al. Association of melphalan and high-dose dexamethasone is effective and well tolerated in patients with AL (primary) amyloidosis who are ineligible for stem cell transplantation. Blood 2004; 103: 2936–2938.
Sanchorawala V, Wright DG, Seldin DC, Falk RH, Berk JL, Dember LM et al. Low-dose continuous oral melphalan for the treatment of primary systemic (AL) amyloidosis. British journal of haematology 2002; 117: 886–889.
Perz JB, Schonland SO, Hundemer M, Kristen AV, Dengler TJ, Zeier M et al. 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 2004; 127: 543–551.
Skinner M, Sanchorawala V, Seldin DC, Dember LM, Falk RH, Berk JL et al. High-dose melphalan and autologous stem-cell transplantation in patients with AL amyloidosis: an 8-year study. Ann Intern Med 2004; 140: 85–93.
Sanchorawala V, Wright DG, Seldin DC, Dember LM, Finn K, Falk RH et al. An overview of the use of high-dose melphalan with autologous stem cell transplantation for the treatment of AL amyloidosis. Bone Marrow Transplant 2001; 28: 637–642.
Madan S, Kumar SK, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK et al. High-dose melphalan and peripheral blood stem cell transplantation for light-chain amyloidosis with cardiac involvement. Blood 2012; 119: 1117–1122.
Comenzo RL, Gertz MA . Autologous stem cell transplantation for primary systemic amyloidosis. Blood 2002; 99: 4276–4282.
Jaccard A, Moreau P, Leblond V, Leleu X, Benboubker L, Hermine O et al. High-dose melphalan versus melphalan plus dexamethasone for AL amyloidosis. N Engl J Med 2007; 357: 1083–1093.
Gertz MA, Comenzo R, Falk RH, Fermand JP, Hazenberg BP, Hawkins PN et al. Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL): a consensus opinion from the 10th International Symposium on Amyloid and Amyloidosis, Tours, France, 18-22 April 2004. Am J Hematol 2005; 79: 319–328.
Kaplan El, Meier P . Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457–481.
Cox D . Regression models and life tables (with discussion). J R Stat Soc B 1972; 34: 187–220.
Wechalekar AD, Schonland SO, Kastritis E, Gillmore JD, Dimopoulos MA, Lane T et al. A European collaborative study of treatment outcomes in 346 patients with cardiac stage III AL amyloidosis. Blood 2013; 121: 3420–3427.
Gertz MA, Lacy MQ, Gastineau DA, Inwards DJ, Chen MG, Tefferi A et al. Blood stem cell transplantation as therapy for primary systemic amyloidosis (AL). Bone Marrow Transplant 2000; 26: 963–969.
Girnius S, Seldin DC, Meier-Ewert HK, Sloan JM, Quillen K, Ruberg FL et al. Safety and efficacy of high-dose melphalan and auto-SCT in patients with AL amyloidosis and cardiac involvement. Bone Marrow Transplant 2014; 49: 434–439.
Gertz MA, Lacy MQ, Dispenzieri A, Hayman SR, Kumar SK, Leung N et al. Effect of hematologic response on outcome of patients undergoing transplantation for primary amyloidosis: importance of achieving a complete response. Haematologica 2007; 92: 1415–1418.
Mikhael JR, Schuster SR, Jimenez-Zepeda VH, Bello N, Spong J, Reeder CB et al. Cyclophosphamide-bortezomib-dexamethasone (CyBorD) produces rapid and complete hematologic response in patients with AL amyloidosis. Blood 2012; 119: 4391–4394.
Kourelis TV, Kumar SK, Gertz MA, Lacy MQ, Buadi FK, Hayman SR et al. Coexistent multiple myeloma or increased bone marrow plasma cells define equally high-risk populations in patients with immunoglobulin light chain amyloidosis. J Clin Oncol 2013; 31: 4319–4324.
Landau H, Hassoun H, Rosenzweig MA, Maurer M, Liu J, Flombaum C et al. Bortezomib and dexamethasone consolidation following risk-adapted melphalan and stem cell transplantation for patients with newly diagnosed light-chain amyloidosis. Leukemia 2013; 27: 823–828.
Cohen AD, Zhou P, Chou J, Teruya-Feldstein J, Reich L, Hassoun H et al. Risk-adapted autologous stem cell transplantation with adjuvant dexamethasone +/- thalidomide for systemic light-chain amyloidosis: results of a phase II trial. Br J Haematol 2007; 139: 224–233.
Gertz MA, Lacy MQ, Dispenzieri A, Kumar SK, Dingli D, Leung N et al. Refinement in patient selection to reduce treatment-related mortality from autologous stem cell transplantation in amyloidosis. Bone Marrow Transplant 2013; 48: 557–561.
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Kongtim, P., Qazilbash, M., Shah, J. et al. High-dose therapy with auto-SCT is feasible in high-risk cardiac amyloidosis. Bone Marrow Transplant 50, 668–672 (2015). https://doi.org/10.1038/bmt.2015.21
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DOI: https://doi.org/10.1038/bmt.2015.21
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