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Autografting

Refinement in patient selection to reduce treatment-related mortality from autologous stem cell transplantation in amyloidosis

Bone Marrow Transplantation volume 48, pages 557–561 (2013)Cite this article

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Abstract

This study sought to develop selection guidelines to determine the eligibility for SCT of patients with light-chain amyloidosis. Patients with biopsy-confirmed lightchain amyloidosis who underwent SCT between 8 March 1996 and 31 December 2011 were reviewed in two cohorts by date of transplantation: between 8 March 1996 and 30 June 2009 (n=410) and between 1 July 2009 and 31 December 2011 (n=89). Also evaluated were patients who died before post-transplant day 100 to determine the features predictive of early death. After 1 July 2009, fewer transplant recipients had Mayo stage III cardiac involvement. Mortality before post-transplant day 100 was 10.5% (43/410) in the earlier group and 1.1% (1/89) in the later group. In the earlier group, one-quarter of transplant recipients with N-terminal pro-brain natriuretic peptide (NT-proBNP) >5000 pg/mL died by 10.3 months. When serum troponin T was >0.06 ng/mL, 25% died at 3.7 months. The Mayo staging system is predictive for OS but not useful for selecting transplant recipients. Patients with serum troponin T >0.06 ng/mL or NT-proBNP >5000 pg/mL (not on dialysis) should not be considered candidates for SCT because of early mortality.

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References

  1. Cohen AD, Comenzo RL . Systemic light-chain amyloidosis: advances in diagnosis, prognosis, and therapy. Hematology Am Soc Hematol Educ Program 2010; 2010: 287–294.

    Article  Google Scholar 

  2. Kumar SK, Gertz MA, Lacy MQ, Dingli D, Hayman SR, Buadi FK et al. Recent improvements in survival in primary systemic amyloidosis and the importance of an early mortality risk score. Mayo Clin Proc 2011; 86: 12–18.

    Article  Google Scholar 

  3. Comenzo RL, Vosburgh E, Simms RW, Bergethon P, Sarnacki D, Finn K et al. Dose-intensive melphalan with blood stem cell support for the treatment of AL amyloidosis: one-year follow-up in five patients. Blood 1996; 88: 2801–2806.

    CAS  PubMed  Google Scholar 

  4. 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 

  5. Jaccard A, Moreau P, Leblond V, Leleu X, Benboubker L, Hermine O 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: 1083–1093.

    Article  CAS  Google Scholar 

  6. Seldin DC, Andrea N, Berenbaum I, Berk JL, Connors L, Dember LM et al. High-dose melphalan and autologous stem cell transplantation for AL amyloidosis: recent trends in treatment-related mortality and 1-year survival at a single institution. Amyloid 2011; 18 (Suppl 1): 122–124.

    Google Scholar 

  7. 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 

  8. Palladini G, Russo P, Foli A, Milani P, Lavatelli F, Obici L et al. Salvage therapy with lenalidomide and dexamethasone in patients with advanced AL amyloidosis refractory to melphalan, bortezomib, and thalidomide. Ann Hematol 2012; 91: 89–92.

    Article  CAS  Google Scholar 

  9. Moreau P, Jaccard A, Benboubker L, Royer B, Leleu X, Bridoux F 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: 4777–4782.

    Article  CAS  Google Scholar 

  10. Reece DE, Hegenbart U, Sanchorawala V, Merlini G, Palladini G, Bladé J 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: 865–873.

    Article  CAS  Google Scholar 

  11. Picken MM . Amyloidosis: where are we now and where are we heading? Arch Pathol Lab Med 2010; 134: 545–551.

    PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  13. Chee CE, Lacy MQ, Dogan A, Zeldenrust SR, Gertz MA . Pitfalls in the diagnosis of primary amyloidosis. Clin Lymphoma Myeloma Leuk 2010; 10: 177–180.

    Article  CAS  Google Scholar 

  14. Jiménez EA, Blanco JCR, Orensanz MLM . The diagnosis of familial amyloid polyneuropathy. Neurologia 1996; 11: 310–312.

    Google Scholar 

  15. Burgstaler EA, Winters JL . Comparison of hematopoietic progenitor cell collections using the COBE Spectra version 7 and Amicus version 3.1 for patients with AL amyloidosis. J Clin Apher 2011; 26: 186–194.

    Article  Google Scholar 

  16. Gertz MA, Lacy MQ, Dispenzieri A, Hayman SR, Kumar SK, Dingli D et al. Autologous stem cell transplant for immunoglobulin light chain amyloidosis: a status report. Leuk Lymphoma 2010; 51: 2181–2187.

    Article  Google Scholar 

  17. 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 

  18. 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 

  19. Palladini G, Merlini G . Uniform risk-stratification and response criteria are paving the way to evidence-based treatment of AL amyloidosis. Oncology 2011 25 7: 637–638.

    Google Scholar 

  20. Manzano-Fernández S, Januzzi JL, Boronat-García M, Pastor P, Albaladejo-Otón MD, Garrido IP et al. Impact of kidney dysfunction on plasma and urinary N-terminal pro-B-type natriuretic peptide in patients with acute heart failure. Congest Heart Fail 2010; 16: 214–220.

    Article  Google Scholar 

  21. Thirusha L, Rannigan L, Foard D, Wechalekar A, Gibbs S, Pinney J et al. ALchemy: a large prospective ‘real word’ study of chemotherapy in AL amyloidosis [abstract]. Blood 2011; 118: 992.

    Article  Google Scholar 

  22. Nishihori T, Alsina M . Advances in the autologous and allogeneic transplantation strategies for multiple myeloma. Cancer Control 2011; 18: 258–267.

    Article  Google Scholar 

  23. Cibeira MT, Sanchorawala V, Seldin DC, Quillen K, Berk JL, Dember LM 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: 4346–4352.

    Article  CAS  Google Scholar 

  24. Dietrich S, Schönland SO, 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 

  25. 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 

  26. Landau H, Hassoun H, Bello C, Hoover E, Riedel ER, Nimer SD et al. Consolidation with bortezomib and dexamethasone following risk-adapted melphalan and stem cell transplant in systemic AL amyloidosis. Amyloid 2011; 18 (Suppl 1): 130–131.

    Google Scholar 

  27. 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.

    Article  CAS  Google Scholar 

  28. 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 

  29. 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.

    Article  CAS  Google Scholar 

  30. 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 

  31. 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 

  32. Gertz MA, Lacy MQ, Dispenzieri A, Gastineau DA, Chen MG, Ansell SM et al. Stem cell transplantation for the management of primary systemic amyloidosis. Am J Med 2002; 113: 549–555.

    Article  CAS  Google Scholar 

  33. 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 

  34. 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 

  35. 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, D Dingli, N Leung, W J Hogan, F K Buadi & S R Hayman

  2. Division of Clinical Biochemistry and Immunology, Mayo Clinic, Rochester, MN, USA

    A Dispenzieri

  3. Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA

    A Dispenzieri & D Dingli

  4. 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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All authors were involved in study conception, data analysis and acquisition.

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Gertz, M., Lacy, M., Dispenzieri, A. et al. Refinement in patient selection to reduce treatment-related mortality from autologous stem cell transplantation in amyloidosis. Bone Marrow Transplant 48, 557–561 (2013). https://doi.org/10.1038/bmt.2012.170

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