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Autografting

Tandem cycles of high-dose melphalan and autologous stem cell transplantation increases the response rate in AL amyloidosis

Bone Marrow Transplantation volume 40, pages 557–562 (2007)Cite this article

An Erratum to this article was published on 05 September 2007

Abstract

Clinical outcomes of patients with AL amyloidosis treated with high-dose melphalan and stem cell transplantation (HDM/SCT) are tightly linked to the achievement of a hematologic complete response (HCR). We conducted a prospective trial to determine whether a second cycle of HDM/SCT could induce HCR in patients in whom the plasma cell dyscrasia persisted following initial treatment with HDM/SCT. Sixty-two patients were enrolled. Nine patients (15%) were removed from the protocol. Of the 53 patients continuing in this study, four died within 100 days of treatment (8%), and 27 (55%) achieved an HCR at 6 months after the first cycle of HDM/SCT. Of the 22 patients who did not achieve an HCR after initial treatment, 17 received a second HDM/SCT, 1 died within 100 days of treatment (6%), while 5 (31%) achieved an HCR. Thus, the HCR rate was 67% (32/48) for surviving patients on study, 60% (32/53) for all patients who received initial cycle of HDM/SCT, and 56% (35/62) by intention-to-treat. The median survival for all patients enrolled on the trial has not yet been reached. Thus, tandem cycles of HDM/SCT can increase the proportion of patients who achieve an HCR.

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References

  1. 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  PubMed  Google Scholar 

  2. Kyle RA, Gertz MA, Greipp PR, Witzig TE, Lust JA, Lacy MQ et al. A trial of three regimens for primary amyloidosis: colchicine alone, melphalan and prednisone, and melphalan, prednisone, and colchicine. N Engl J Med 1997; 336: 1202–1207.

    Article  CAS  PubMed  Google Scholar 

  3. 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  PubMed  Google Scholar 

  4. Barlogie B, Jagannath S, Vesole DH, Naucke S, Cheson B, Mattox S et al. Superiority of tandem autologous transplantation over standard therapy for previously untreated multiple myeloma. Blood 1997; 89: 789–793.

    CAS  PubMed  Google Scholar 

  5. Seldin DC, Anderson JJ, Sanchorawala V, Malek K, Wright DG, Quillen K et al. Improvement in quality of life of patients with AL amyloidosis treated with high-dose melphalan and autologous stem cell transplantation. Blood 2004; 104: 1888–1893.

    Article  CAS  PubMed  Google Scholar 

  6. Attal M, Harousseau JL, Facon T, Guilhot F, Doyen C, Fuzibet JG et al. Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med 2003; 349: 2495–2502.

    Article  CAS  PubMed  Google Scholar 

  7. 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  PubMed  Google Scholar 

  8. Oran B, Wright DG, Seldin DC, McAneny D, Skinner M, Sanchorawala V . Spontaneous rupture of the spleen in AL amyloidosis. Am J Hematol 2003; 74: 131–135.

    Article  CAS  PubMed  Google Scholar 

  9. 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  PubMed  Google Scholar 

  10. Goodman HJ, Gillmore JD, Lachmann HJ, Wechalekar AD, Bradwell AR, Hawkins PN . Outcome of autologous stem cell transplantation for AL amyloidosis in the UK. Br J Haematol 2006; 134: 417–425.

    Article  PubMed  Google Scholar 

  11. Chow LQ, Bahlis N, Russell J, Chaudhry A, Morris D, Brown C et al. Autologous transplantation for primary systemic AL amyloidosis is feasible outside a major amyloidosis referral centre: the Calgary BMT Program experience. Bone Marrow Transplant 2005; 36: 591–596.

    Article  CAS  PubMed  Google Scholar 

  12. Sanchorawala V, Wright DG, Seldin DC, Falk RH, Finn KT, Dember LM et al. High-dose intravenous melphalan and autologous stem cell transplantation as initial therapy or following two cycles of oral chemotherapy for the treatment of AL amyloidosis: results of a prospective randomized trial. Bone Marrow Transplant 2004; 33: 381–388.

    Article  CAS  PubMed  Google Scholar 

  13. 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  PubMed  Google Scholar 

  14. Sanchorawala V, Wright DG, Rosenzweig M, Finn KT, Fennessey S, Zeldis JB et al. Lenalidomide and dexamethasone in the treatment of AL amyloidosis: results of a phase 2 trial. Blood 2007; 109: 492–496.

    Article  CAS  PubMed  Google Scholar 

  15. 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  PubMed  Google Scholar 

  16. Barlogie B, Tricot GJ, van Rhee F, Angtuaco E, Walker R, Epstein J et al. Long-term outcome results of the first tandem autotransplant trial for multiple myeloma. Br J Haematol 2006; 135: 158–164.

    Article  PubMed  Google Scholar 

  17. 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  PubMed  Google Scholar 

  18. Seldin DC, Choufani EB, Dember LM, Wiesman JF, Berk JL, Falk RH et al. Tolerability and efficacy of thalidomide for the treatment of patients with light chain-associated (AL) amyloidosis. Clin Lymphoma 2003; 3: 241–246.

    Article  CAS  PubMed  Google Scholar 

  19. Dispenzieri A, Lacy MQ, Rajkumar SV, Geyer SM, Witzig TE, Fonseca R et al. Poor tolerance to high doses of thalidomide in patients with primary systemic amyloidosis. Amyloid 2003; 10: 257–261.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This clinical research was supported by Grants from the National Institutes of Health (P01 HL68705), the Gerry Foundation and the Amyloid Research Fund at Boston University. Preliminary and final reports of this trial were presented as oral presentations at the Annual Meeting of the American Society of Hematology in December 2003 and December 2006, respectively. We gratefully acknowledge our colleagues in the Amyloid Treatment and Research Program, Clinical Trials Office and Center for Cancer and Blood Disorders at Boston University Medical Center who assisted with the multidisciplinary evaluation and treatment of the patients and particularly the patients themselves who participated in this research study. We thank Dr Michael LaValley for assistance with study design.

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Authors and Affiliations

  1. Stem Cell Transplantation Program of the Section of Hematology-Oncology, Boston University School of Public Health, Boston, MA, USA

    V Sanchorawala, D G Wright, K Quillen, K T Finn, C Fisher & D C Seldin

  2. Department of Medicine, Amyloid Treatment and Research Program, Boston University School of Public Health, Boston, MA, USA

    V Sanchorawala, D G Wright, K T Finn, L M Dember, J L Berk, M Skinner & D C Seldin

  3. Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston University School of Public Health, Boston, MA, USA

    K Quillen

  4. Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA

    G Doros

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  1. V Sanchorawala
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  2. D G Wright
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  3. K Quillen
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  4. K T Finn
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  5. L M Dember
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  8. C Fisher
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  9. M Skinner
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  10. D C Seldin
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Correspondence to V Sanchorawala.

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Sanchorawala, V., Wright, D., Quillen, K. et al. Tandem cycles of high-dose melphalan and autologous stem cell transplantation increases the response rate in AL amyloidosis. Bone Marrow Transplant 40, 557–562 (2007). https://doi.org/10.1038/sj.bmt.1705746

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