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Trends in day 100 and 2-year survival after auto-SCT for AL amyloidosis: outcomes before and after 2006

Bone Marrow Transplantation volume 46, pages 970–975 (2011)Cite this article

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Abstract

The role of auto-SCT in the management of Ig light-chain (AL) amyloidosis remains undefined. In this study, we report 422 patients who received auto-SCT for AL amyloidosis to compare outcomes of patients treated before January 2006 with those treated from January 2006 to 1 December 2009. Day 100 all-cause mortality decreased over this time period from 12 to 7% (P=0.09). Survival at 2 years increased from 78 to 82%. The major determinants of early mortality (before day 100) were the presence of cardiac involvement by amyloid with increased levels of cardiac biomarkers, lower serum albumin, higher serum creatinine and a higher number of organs involved. On multivariate survival analysis, higher levels of serum troponin T and N-terminal pro-brain natriuretic peptide were the only predictors of early mortality after auto-SCT. Improved supportive care and refined patient selection have improved the safety margin of patients undergoing auto-SCT; short-term mortality showed a more than 40% decrease after 2005.

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References

  1. Dember LM . Modern treatment of amyloidosis: unresolved questions. J Am Soc Nephrol 2009; 20: 469–472.

    Article  Google Scholar 

  2. Mhaskar R, Kumar A, Behera M, Kharfan-Dabaja MA, Djulbegovic B . Role of high-dose chemotherapy and autologous hematopoietic cell transplantation in primary systemic amyloidosis: a systematic review. Biol Blood Marrow Transplant 2009; 15: 893–902.

    Article  CAS  Google Scholar 

  3. 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.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  5. 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.

    Article  CAS  Google Scholar 

  6. Gertz MA, Lacy MQ, Dispenzieri A, Hayman SR, Kumar S . Transplantation for amyloidosis. Curr Opin Oncol 2007; 19: 136–141.

    Article  CAS  Google Scholar 

  7. Comenzo RL . Managing systemic light-chain amyloidosis. J Natl Compr Canc Netw 2007; 5: 179–187.

    Article  CAS  Google Scholar 

  8. Saba N, Sutton D, Ross H, Siu S, Crump R, Keating A et al. High treatment-related mortality in cardiac amyloid patients undergoing autologous stem cell transplant. Bone Marrow Transplant 1999; 24: 853–855.

    Article  CAS  Google Scholar 

  9. Mollee PN, Wechalekar AD, Pereira DL, Franke N, Reece D, Chen C et al. Autologous stem cell transplantation in primary systemic amyloidosis: the impact of selection criteria on outcome. Bone Marrow Transplant 2004; 33: 271–277.

    Article  CAS  Google Scholar 

  10. Gertz MA, Lacy MQ, Dispenzieri A, Ansell SM, Elliott MA, Gastineau DA et al. Risk-adjusted manipulation of melphalan dose before stem cell transplantation in patients with amyloidosis is associated with a lower response rate. Bone Marrow Transplant 2004; 34: 1025–1031.

    Article  CAS  Google Scholar 

  11. Deshmukh M, Elderfield K, Rahemtulla A, Naresh KN . Immunophenotype of neoplastic plasma cells in AL amyloidosis. J Clin Pathol 2009; 62: 724–730.

    Article  CAS  Google Scholar 

  12. Yoshida T, Matsuda M, Katoh N, Tazawa K, Shimojima Y, Gono T et al. Long-term follow-up of plasma cells in bone marrow and serum free light chains in primary systemic AL amyloidosis. Intern Med 2008; 47: 1783–1790.

    Article  Google Scholar 

  13. Kyle RA . High-dose therapy in multiple myeloma and primary amyloidosis: an overview. Semin Oncol 1999; 26: 74–83.

    CAS  PubMed  Google Scholar 

  14. Dispenzieri A, Lacy MQ, Kyle RA, Therneau TM, Larson DR, Rajkumar SV et al. Eligibility for hematopoietic stem-cell transplantation for primary systemic amyloidosis is a favorable prognostic factor for survival. J Clin Oncol 2001; 19: 3350–3356.

    Article  CAS  Google Scholar 

  15. Dietrich S, Schonland S, Benner A, Bochtler T, Kristen AV, Beimler J et al. Treatment with intravenous melphalan and dexamethasone is not able to overcome the poor prognosis of patients with newly diagnosed systemic light chain amyloidosis and severe cardiac involvement. Blood 2010; 116: 522–528.

    Article  CAS  Google Scholar 

  16. Gertz MA, Leung N, Lacy MQ, Dispenzieri A, Zeldenrust SR, Hayman SR et al. Clinical outcome of immunoglobulin light chain amyloidosis affecting the kidney. Nephrol Dial Transplant 2009; 24: 3132–3137.

    Article  CAS  Google Scholar 

  17. Leung N, Dispenzieri A, Lacy MQ, Kumar SK, Hayman SR, Fervenza FC et al. Severity of baseline proteinuria predicts renal response in immunoglobulin light chain-associated amyloidosis after autologous stem cell transplantation. Clin J Am Soc Nephrol 2007; 2: 440–444.

    Article  Google Scholar 

  18. Lebovic D, Hoffman J, Levine BM, Hassoun H, Landau H, Goldsmith Y et al. Predictors of survival in patients with systemic light-chain amyloidosis and cardiac involvement initially ineligible for stem cell transplantation and treated with oral melphalan and dexamethasone. Br J Haematol 2008; 143: 369–373.

    Article  CAS  Google Scholar 

  19. 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.

    Article  Google Scholar 

  20. Comenzo RL, Vosburgh E, Falk RH, Sanchorawala V, Reisinger J, Dubrey S et al. Dose-intensive melphalan with blood stem-cell support for the treatment of AL (amyloid light-chain) amyloidosis: survival and responses in 25 patients. Blood 1998; 91: 3662–3670.

    CAS  PubMed  Google Scholar 

  21. Gertz MA, Lacy MQ, Dispenzieri A . Myeloablative chemotherapy with stem cell rescue for the treatment of primary systemic amyloidosis: a status report. Bone Marrow Transplant 2000; 25: 465–470.

    Article  CAS  Google Scholar 

  22. Comenzo RL, Gertz MA . Autologous stem cell transplantation for primary systemic amyloidosis. Blood 2002; 99: 4276–4282.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  24. Dimopoulos MA, Kastritis E, Rajkumar SV . Treatment of plasma cell dyscrasias with lenalidomide. Leukemia 2008; 22: 1343–1353.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  26. Palladini G, Russo P, Nuvolone M, Lavatelli F, Perfetti V, Obici L et al. Treatment with oral melphalan plus dexamethasone produces long-term remissions in AL amyloidosis. Blood 2007; 110: 787–788.

    Article  CAS  Google Scholar 

  27. Gertz MA, Merlini G, Treon SP . Amyloidosis and Waldenstrom's macroglobulinemia. Hematology Am Soc Hematol Educ Program 2004, 257–282.

    Article  Google Scholar 

  28. Dispenzieri A, Lacy MQ, Katzmann JA, Rajkumar SV, Abraham RS, Hayman SR et al. Absolute values of immunoglobulin free light chains are prognostic in patients with primary systemic amyloidosis undergoing peripheral blood stem cell transplantation. Blood 2006; 107: 3378–3383.

    Article  CAS  Google Scholar 

  29. Sanchorawala V, Seldin DC, Magnani B, Skinner M, Wright DG . Serum free light-chain responses after high-dose intravenous melphalan and autologous stem cell transplantation for AL (primary) amyloidosis. Bone Marrow Transplant 2005; 36: 597–600.

    Article  CAS  Google Scholar 

  30. Matsuda M, Yamada T, Gono T, Shimojima Y, Ishii W, Fushimi T et al. Serum levels of free light chain before and after chemotherapy in primary systemic AL amyloidosis. Intern Med 2005; 44: 428–433.

    Article  Google Scholar 

  31. Kyle RA, Greipp PR, Garton JP, Gertz MA . Primary systemic amyloidosis: comparison of melphalan/prednisone versus colchicine. Am J Med 1985; 79: 708–716.

    Article  CAS  Google Scholar 

  32. Skinner M, Anderson J, Simms R, Falk R, Wang M, Libbey C et al. Treatment of 100 patients with primary amyloidosis: a randomized trial of melphalan, prednisone, and colchicine versus colchicine only. Am J Med 1996; 100: 290–298.

    Article  CAS  Google Scholar 

  33. Reece DE, Sanchorawala V, Hegenbart U, Merlini G, Palladini G, Fermand JP et al. Weekly and twice-weekly bortezomib in patients with systemic AL amyloidosis: results of a phase 1 dose-escalation study. Blood 2009; 114: 1489–1497.

    Article  CAS  Google Scholar 

  34. 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.

    Article  CAS  Google Scholar 

  35. Vesole DH, Perez WS, Akasheh M, Boudreau C, Reece DE, Bredeson CN . 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 2006; 81: 880–888.

    Article  Google Scholar 

  36. 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.

    Article  CAS  Google Scholar 

  37. Gertz M, Lacy M, Dispenzieri A, Hayman S, Kumar S, Buadi F et al. Troponin T level as an exclusion criterion for stem cell transplantation in light-chain amyloidosis. Leuk Lymphoma 2008; 49: 36–41.

    Article  CAS  Google Scholar 

  38. 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.

    Article  CAS  Google Scholar 

  39. Moreau P, Leblond V, Bourquelot P, Facon T, Huynh A, Caillot D et al. Prognostic factors for survival and response after high-dose therapy and autologous stem cell transplantation in systemic AL amyloidosis: a report on 21 patients. Br J Haematol 1998; 101: 766–769.

    Article  CAS  Google Scholar 

  40. Comenzo RL, Sanchorawala V, Fisher C, Akpek G, Farhat M, Cerda S et al. Intermediate-dose intravenous melphalan and blood stem cells mobilized with sequential GM+G-CSF or G-CSF alone to treat AL (amyloid light chain) amyloidosis. Br J Haematol 1999; 104: 553–559.

    Article  CAS  Google Scholar 

  41. Bahlis NJ, Lazarus HM . Multiple myeloma-associated AL amyloidosis: is a distinctive therapeutic approach warranted? Bone Marrow Transplant 2006; 38: 7–15.

    Article  CAS  Google Scholar 

  42. 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.

    Article  CAS  Google Scholar 

  43. Vela-Ojeda J, Garcia-Ruiz Esparza MA, Padilla-Gonzalez Y, Sanchez-Cortes E, Garcia-Chavez J, Montiel-Cervantes L et al. Multiple myeloma-associated amyloidosis is an independent high-risk prognostic factor. Ann Hematol 2009; 88: 59–66.

    Article  CAS  Google Scholar 

  44. Leung N, Leung TR, Cha SS, Dispenzieri A, Lacy MQ, Gertz MA . Excessive fluid accumulation during stem cell mobilization: a novel prognostic factor of first-year survival after stem cell transplantation in AL amyloidosis patients. Blood 2005; 106: 3353–3357.

    Article  CAS  Google Scholar 

  45. Leung N, Slezak JM, Bergstralh EJ, Dispenzieri A, Lacy MQ, Wolf RC et al. Acute renal insufficiency after high-dose melphalan in patients with primary systemic amyloidosis during stem cell transplantation. Am J Kidney Dis 2005; 45: 102–111.

    Article  CAS  Google Scholar 

  46. 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.

    Article  CAS  Google Scholar 

  47. Gertz MA, Ansell SM, Dingli D, Dispenzieri A, Buadi FK, Elliott MA et al. Autologous stem cell transplant in 716 patients with multiple myeloma: low treatment-related mortality, feasibility of outpatient transplant, and effect of a multidisciplinary quality initiative. Mayo Clin Proc 2008; 83: 1131–1138.

    Article  Google Scholar 

  48. Dispenzieri A, Lacy MQ, Zeldenrust SR, Hayman SR, Kumar SK, Geyer SM et al. The activity of lenalidomide with or without dexamethasone in patients with primary systemic amyloidosis. Blood 2007; 109: 465–470.

    Article  CAS  Google Scholar 

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Authors and Affiliations

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

    M A Gertz, M Q Lacy, A Dispenzieri, S K Kumar, F K Buadi, D Dingli, W J Hogan & S R Hayman

  2. Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA

    N Leung

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  1. M A Gertz
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Correspondence to M A Gertz.

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Gertz, M., Lacy, M., Dispenzieri, A. et al. Trends in day 100 and 2-year survival after auto-SCT for AL amyloidosis: outcomes before and after 2006. Bone Marrow Transplant 46, 970–975 (2011). https://doi.org/10.1038/bmt.2010.234

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