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Autografting

Modified high-dose melphalan and autologous SCT for AL amyloidosis or high-risk myeloma: analysis of SWOG trial S0115

Bone Marrow Transplantation volume 48, pages 1537–1542 (2013)Cite this article

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Abstract

We designed a trial using two sequential cycles of modified high-dose melphalan at 100 mg/m2 and autologous SCT (mHDM/SCT) in AL amyloidosis (light-chain amyloidosis, AL), AL with myeloma (ALM) and host-based high-risk myeloma (hM) patients through SWOG-0115. The primary objective was to evaluate OS. From 2004 to 2010, 93 eligible patients were enrolled at 17 centers in the United States (59 with AL, 9 with ALM and 25 with hM). The median OS for patients with AL and ALM was 68 months and 47 months, respectively, and has not been reached for patients with hM. The median PFS for patients with AL and ALM was 38 months and 16 months, respectively, and has not been reached for patients with hM. The treatment-related mortality (TRM) was 12% (11/93) and was observed only in patients with AL after SCT. Grade 3 and higher non-hematologic adverse events were experienced by 81%, 67% and 57% of patients with AL, ALM and hM, respectively, during the first and second HDM/SCT. This experience demonstrates that with careful selection of patients and use of mHDM for SCT in patients with AL, ALM and hM, even in the setting of a multicenter study, OS can be improved with acceptable TRM and morbidity.

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References

  1. Merlini G, Bellotti V . Molecular mechanisms of amyloidosis. N Engl J Med 2003; 349: 583–596.

    Article  CAS  PubMed  Google Scholar 

  2. Kyle RA, Linos A, Beard CM, Linke RP, Gertz MA, O’Fallon WM et al. Incidence and natural history of primary systemic amyloidosis in Olmsted County, Minnesota, 1950 through 1989. Blood 1992; 79: 1817–1822.

    CAS  PubMed  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. 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  PubMed  PubMed Central  Google Scholar 

  5. Sanchorawala V . Role of high-dose melphalan and autologous peripheral blood stem cell transplantation in AL amyloidosis. Am J Blood Res 2012; 2: 9–17.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. 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  PubMed  Google Scholar 

  7. 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.

    Article  CAS  PubMed  Google Scholar 

  8. Tsai SB, Seldin DC, Quillen K, Berk JL, Ruberg FL, Meier-Ewert H et al. High-dose melphalan and stem cell transplantation for patients with AL amyloidosis: trends in treatment-related mortality over the past 17 years at a single referral center. Blood 2012; 120: 4445–4446.

    Article  CAS  PubMed  Google Scholar 

  9. 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  PubMed  PubMed Central  Google Scholar 

  10. Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Francais du Myelome. N Engl J Med 1996; 335: 91–97.

    Article  CAS  PubMed  Google Scholar 

  11. Child JA, Morgan GJ, Davies FE, Owen RG, Bell SE, Hawkins K et al. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med 2003; 348: 1875–1883.

    Article  CAS  PubMed  Google Scholar 

  12. Badros A, Barlogie B, Siegel E, Morris C, Desikan R, Zangari M et al. Autologous stem cell transplantation in elderly multiple myeloma patients over the age of 70 years. Br J Haematol 2001; 114: 600–607.

    Article  CAS  PubMed  Google Scholar 

  13. Siegel DS, Desikan KR, Mehta J, Singhal S, Fassas A, Munshi N et al. Age is not a prognostic variable with autotransplants for multiple myeloma. Blood 1999; 93: 51–54.

    CAS  PubMed  Google Scholar 

  14. Seldin DC, Anderson JJ, Skinner M, Malek K, Wright DG, Quillen K et al. Successful treatment of AL amyloidosis with high-dose melphalan and autologous stem cell transplantation in patients over age 65. Blood 2006; 108: 3945–3947.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. 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 

  16. Blade J, Samson D, Reece D, Apperley J, Bjorkstrand B, Gahrton G et al. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant. Br J Haematol 1998; 102: 1115–1123.

    Article  CAS  PubMed  Google Scholar 

  17. Berenson JR, Crowley JJ, Grogan TM, Zangmeister J, Briggs AD, Mills GM et al. Maintenance therapy with alternate-day prednisone improves survival in multiple myeloma patients. Blood 2002; 99: 3163–3168.

    Article  CAS  PubMed  Google Scholar 

  18. 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.

    Article  CAS  PubMed  Google Scholar 

  19. 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  PubMed  Google Scholar 

  20. Facon T, Mary JY, Hulin C, Benboubker L, Attal M, Pegourie B et al. Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99-06): a randomised trial. Lancet 2007; 370: 1209–1218.

    Article  CAS  PubMed  Google Scholar 

  21. Palumbo A, Triolo S, Argentino C, Bringhen S, Dominietto A, Rus C et al. Dose-intensive melphalan with stem cell support (MEL100) is superior to standard treatment in elderly myeloma patients. Blood 1999; 94: 1248–1253.

    CAS  PubMed  Google Scholar 

  22. Palumbo A, Bringhen S, Bertola A, Cavallo F, Falco P, Massaia M et al. Multiple myeloma: comparison of two dose-intensive melphalan regimens (100 vs 200 mg/m(2)). Leukemia 2004; 18: 133–138.

    Article  CAS  PubMed  Google Scholar 

  23. McCarthy PL, Owzar K, Hofmeister CC, Hurd DD, Hassoun H, Richardson PG et al. Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med 2012; 366: 1770–1781.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Attal M, Lauwers-Cances V, Marit G, Caillot D, Moreau P, Facon T et al. Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. N Engl J Med 2012; 366: 1782–1791.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This investigation was supported in part by the following PHS Cooperative Agreement grant numbers awarded by the National Cancer Institute, DHHS: CA32102, CA38926, CA37981, CA76448, CA35431, CA20319, CA76132, CA04919, CA46441, CA14028, CA58861, CA58416, CA12644, CA22433, CA46368, CA45377, CA35090 and CA46113.

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Authors and Affiliations

  1. Boston Medical Center, Boston, MA, USA

    V Sanchorawala, D C Seldin, K T Finn & S A Fennessey

  2. SWOG Statistical Center, Seattle, WA, USA

    A Hoering & R Sexton

  3. Wichita CCOP, Wichita, KS, USA

    B Mattar

  4. Tulane University Health Science Center, New Orleans, LA, USA

    H F Safah

  5. Puget Sound Oncology Consortium, Seattle, WA, USA

    L A Holmberg

  6. Cleveland Clinic, Cleveland, OH, USA

    R M Dean

  7. MD Anderson Cancer Center/University of Texas, Houston, TX, USA

    R Z Orlowski

  8. University of Arkansas, Little Rock, AR, USA

    B Barlogie

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  1. V Sanchorawala
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  2. A Hoering
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  4. K T Finn
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Corresponding author

Correspondence to V Sanchorawala.

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Competing interests

VS received research funding from Celgene, Onyx and Millennium; DCS received research funding from Celgene; and RZO received research funding from Celgene, Onyx, Johnson and Johnson and Millennium. Other authors declare no conflict of interest.

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Author contributions

VS: concept and design, data analysis and interpretation, manuscript writing; AH: concept and design, collection and assembly of data, data analysis and interpretation, final approval of manuscript; DCS: data analysis and interpretation, final approval of manuscript; KTF: collection and assembly of data, data analysis and interpretation, final approval of manuscript; SAF: collection and assembly of data, data analysis and interpretation, final approval of manuscript; RS: concept and design, collection and assembly of data, data analysis and interpretation, concept and design, data analysis and interpretation; BM: final approval of manuscript; HFS: final approval of manuscript; LAH: final approval of manuscript; RMD: final approval of manuscript; ROZ: final approval of manuscript; and BB: concept and design, data analysis and interpretation, final approval of manuscript.

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Sanchorawala, V., Hoering, A., Seldin, D. et al. Modified high-dose melphalan and autologous SCT for AL amyloidosis or high-risk myeloma: analysis of SWOG trial S0115. Bone Marrow Transplant 48, 1537–1542 (2013). https://doi.org/10.1038/bmt.2013.98

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