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Amyloidosis

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 Transplantation volume 33, pages 381–388 (2004)Cite this article

Summary:

A prospective randomized trial was conducted to study the timing of high-dose intravenous melphalan and autologous stem cell transplantation (HDM/SCT) in AL amyloidosis. In all, 100 newly diagnosed patients were randomized to receive HDM/SCT, either as initial therapy (Arm-1) or following two cycles of oral melphalan and prednisone (Arm-2). The objectives of the trial were to compare survival and hematologic and clinical responses. With a median follow-up of 45 months (range 24–70), the overall survival was not significantly different between the two treatment arms (P=0.39). The hematologic response and organ system improvements after treatment did not differ between the two groups. Fewer patients received HDM/SCT in Arm-2 because of disease progression during the oral chemotherapy phase of the study, rendering them ineligible for subsequent high-dose therapy. This affected patients with cardiac involvement particularly, and led to a trend for an early survival disadvantage in Arm-2. Hence, newly diagnosed patients with AL amyloidosis eligible for HDM/SCT did not benefit from initial treatment with oral melphalan and prednisone, and there was a survival disadvantage for patients with cardiac involvement if HDM/SCT was delayed by initial oral chemotherapy.

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References

  1. Kyle RA, Linos A, Beard CM et al. Incidence and natural history of primary systemic amyloidosis in Olmsted County, Minnesota, 1950 through 1989 (see comments). Blood 1992; 79: 1817–1822.

    CAS  PubMed  Google Scholar 

  2. Simms RW, Prout MN, Cohen AS . The epidemiology of AL and AA amyloidosis. Baillieres Clin Rheumatol 1994; 8: 627–634.

    Article  CAS  PubMed  Google Scholar 

  3. Kyle RA, Bayrd ED . Amyloidosis: review of 236 cases. Medicine 1975; 54: 271–299.

    Article  CAS  PubMed  Google Scholar 

  4. Kyle RA, Greipp PR . Amyloidosis (AL). Clinical and laboratory features in 229 cases. Mayo Clin Proc 1983; 58: 665–683.

    CAS  PubMed  Google Scholar 

  5. Kyle RA, Gertz MA . Primary systemic amyloidosis: clinical and laboratory features in 474 cases. Semin Hematol 1995; 32: 45–59.

    CAS  PubMed  Google Scholar 

  6. Falk RH, Comenzo RL, Skinner M . The systemic amyloidoses (see comments). N Engl J Med 1997; 337: 898–909.

    Article  CAS  PubMed  Google Scholar 

  7. Dubrey SW, Cha K, Anderson J et al. The clinical features of immunoglobulin light-chain (AL) amyloidosis with heart involvement. Q J Med 1998; 91: 141–157.

    Article  CAS  Google Scholar 

  8. Kyle RA, Greipp PR, Garton JP, Gertz MA . Primary systemic amyloidosis. Comparison of melphalan/prednisone vs colchicines. Am J Med 1985; 79: 708–716.

    Article  CAS  PubMed  Google Scholar 

  9. Kyle RA, Gertz MA, Greipp PR et al. A trial of three regimens for primary amyloidosis: colchicine alone, melphalan and prednisone, and melphalan, prednisone, and colchicine (see comments). N Engl J Med 1997; 336: 1202–1207.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  11. Merlini G . Treatment of primary amyloidosis. Semin Hematol 1995; 32: 60–79.

    CAS  PubMed  Google Scholar 

  12. Gianni L, Bellotti V, Gianni AM, Merlini G . New drug therapy of amyloidoses: resorption of AL-type deposits with 4′-iodo-4′-deoxydoxorubicin. Blood 1995; 86: 855–861.

    CAS  PubMed  Google Scholar 

  13. Gertz MA, Lacy MQ, Lust JA et al. Phase II trial of high-dose dexamethasone for previously treated immunoglobulin light-chain amyloidosis. Am J Hematol 1999; 61: 115–119.

    Article  CAS  PubMed  Google Scholar 

  14. Gertz MA, Lacy MQ, Lust JA et al. Prospective randomized trial of melphalan and prednisone vs vincristine, carmustine, melphalan, cyclophosphamide, and prednisone in the treatment of primary systemic amyloidosis. J Clin Oncol 1999; 17: 262–267.

    Article  CAS  PubMed  Google Scholar 

  15. Lokhorst HM, Sonneveld P, Wijermans P et al. Intermediate-dose melphalan (IDM) combined with G-CSF (filgrastim) is an effective and safe induction therapy for autologous stem cell transplantation in multiple myeloma. Br J Haematol 1995; 92: 44–48.

    Article  Google Scholar 

  16. Attal M, Harousseau J-L, Stoppa A-M et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. N Engl J Med 1996; 335: 91–97.

    Article  CAS  PubMed  Google Scholar 

  17. Barlogie B, Jagannath S, Vesole D, Tricot G . Autologous and allogeneic transplants for multiple myeloma. Semin Hematol 1995; 32: 31–44.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  19. Sanchorawala V, Wright D, Seldin D et al. Use of high dose melphalan with autologous stem cell transplantation for the treatment of AL amyloidosis. Bone Marrow Transplant 2001; 28: 637–642.

    Article  CAS  PubMed  Google Scholar 

  20. Comenzo RL, Vosburgh E, Simms RW 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 

  21. Comenzo RL, Vosburgh E, Falk RH 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 

  22. Comenzo RL, Sanchorawala V, Fisher C 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 

  23. Gillmore JD, Apperley JF, Craddock C et al. High-dose melphalan and stem cell rescue for AL amyloidosis. In: Kyle RA, Gertz MA (eds.). Amyloid and Amyloidosis 1998. Parthenon Publishing Group: New York, 1999, pp 102–104.

    Google Scholar 

  24. Majolino I, Marceno R, Pecoraro G et al. High-dose therapy and autologous transplantation in amyloidosis-AL. Haematologica 1993; 78: 68–71.

    CAS  PubMed  Google Scholar 

  25. 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  PubMed  Google Scholar 

  26. Gertz MA, Lacy MA, Gastineau DA et al. Blood stem cell transplantation as therapy for primary systemic amyloidosis (AL). Bone Marrow Transplant 2000; 26: 963–969.

    Article  CAS  PubMed  Google Scholar 

  27. Moreau P, Leblond V, Bourquelot P 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  PubMed  Google Scholar 

  28. Moreau P, Milpied N, de Faucal P et al. High-dose melphalan and autologous bone marrow transplantation for systemic AL amyloidosis with cardiac involvement (letter). Blood 1996; 87: 3063–3064.

    CAS  PubMed  Google Scholar 

  29. Desikan KR, Dhodapkar MV, Hough A et al. Incidence and impact of light chain associated (AL) amyloidosis on the prognosis of patients with multiple myeloma treated with autologous transplantation. Leuk Lymphoma 1997; 27: 315–319.

    Article  CAS  PubMed  Google Scholar 

  30. van Gameren II, Hazenberg BP, Jager PL et al. AL amyloidosis treated with induction chemotherapy with VAD followed by high dose melphalan and autologous stem cell transplantation. Amyloid 2002; 9: 165–174.

    Article  CAS  PubMed  Google Scholar 

  31. Dember LM, Sanchorawala V, Seldin DC et al. Effect of dose-intensive intravenous melphalan and autologous blood stem-cell transplant on AL amyloidosis-associated renal disease. Ann Int Med 2001; 134: 746–753.

    Article  CAS  PubMed  Google Scholar 

  32. Choufani EB, Sanchorawala V, Ernst T et al. Acquired factor X deficiency in patients with AL amyloidosis: incidence, bleeding manifestations, and response to high-dose chemotherapy. Blood 2001; 97: 1885–1887.

    Article  CAS  PubMed  Google Scholar 

  33. Carr-Smith HD, Showell P, Bradwell AR . Antigen excess assessment of free light chain assays on the Dade–Behring BN™II nephelometer. Clin Chem 2002; 48: A-71.

    Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  35. Seldin DC, Choufani EB, Dember LM et al. Tolerability and efficacy of thalidomide for treatment of patients with AL amyloidosis. Clin Lymphoma 2003; 3: 241–246.

    Article  CAS  PubMed  Google Scholar 

  36. Rajkumar SV, Hayman S, Gerta MA et al. Combination therapy with thalidomide plus dexamethasone for newly diagnosed myeloma. J Clin Oncol 2002; 20: 4319–4323.

    Article  CAS  PubMed  Google Scholar 

  37. Weber D, Rankin K, Gavino M et al. Thalidomide alone or with dexamethasone for previously untreated multiple myeloma. J Clin Oncol 2003; 21: 16–19.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by grants from the Food and Drug Administration (FD-R-001346), the National Institute of Health (HL 68705), the Gerry Foundation, and the Amyloid Research Fund at Boston University. Dr Seldin is a scholar of the Leukemia and Lymphoma Society of America. Results of this study were presented at the 43rd Annual Meeting of the American Society of Hematology. We gratefully acknowledge the numerous current and former colleagues in the Amyloid Treatment and Research Program, Clinical Trials Office and the Center for Cancer and Blood Disorders at Boston University Medical Center, who assisted with the multidisciplinary evaluation and treatment of the patients with AL amyloidosis. We thank Dr Michael LaValley for assistance with study design and randomization of participants.

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Author notes

  1. R L Comenzo

    Present address: The Hematology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Authors and Affiliations

  1. Department of Medicine, Hematology and Stem Cell Transplant Programs, Boston University Medical Center, Boston, MA, USA

    V Sanchorawala, D G Wright, D C Seldin, K T Finn, K Quillen & R L Comenzo

  2. Department of Medicine, Amyloid Treatment and Research Program, Boston University Medical Center, Boston, MA, USA

    V Sanchorawala, D G Wright, D C Seldin, R H Falk, K T Finn, L M Dember, J L Berk, J J Anderson, R L Comenzo & M Skinner

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  1. V Sanchorawala
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Correspondence to V Sanchorawala.

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Sanchorawala, V., Wright, D., Seldin, D. 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 33, 381–388 (2004). https://doi.org/10.1038/sj.bmt.1704346

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