A  single-centre cohort of patients with systemic light chain AL-amyloidosis  treated with conventional chemotherapy or with high-dose chemotherapy and autologous  stem cell transplantation

Joelle Raschle; Yara Banz; Thomas Suter; Thomas Pabst

doi:10.4414/smw.2014.13922

Original article

Vol. 144 No. 0708 (2014)

A single-centre cohort of patients with systemic light chain AL-amyloidosis treated with conventional chemotherapy or with high-dose chemotherapy and autologous stem cell transplantation

Joelle Raschle
Yara Banz
Thomas Suter
Thomas Pabst

DOI: https://doi.org/10.4414/smw.2014.13922
Cite this as:: Swiss Med Wkly. 2014;144:w13922
Published: 09.02.2014

Summary

BACKGROUND: High-dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT) has been reported to confer better prognosis in systemic light chain AL-amyloidosis as compared with conventional chemotherapy. However, only limited data are available so far on treatment and outcome of AL-amyloidosis patients in Switzerland.

METHODS: Within a single-centre cohort of patients with biopsy confirmed AL-amyloidosis diagnosed between January 1995 and December 2012, we aimed to investigate treatment effects in patients treated with conventional chemotherapy versus HDCT with ASCT.

RESULTS: We identified 50 patients with AL-amyloidosis treated with conventional chemotherapy and 13 patients who received HDCT with ASCT. Clinical characteristics differed between the groups for the age of the patients (59 years for patients with ASCT/HDCT vs 69 years; p= 0.0006) and the troponin-T value (0.015 μg/l vs 0.08 μg/l; p = 0.0279). Patients with ASCT showed a trend towards better overall survival, with median survival not yet reached compared with 53 months in patients on conventional chemotherapy (p = 0.0651).

CONCLUSION: Our results suggest that light chain AL-amyloidosis patients considered fit to undergo HDCT and ASCT may have a better outcome than patients treated exclusively with conventional chemotherapy regimens; however, the better performance status of patients receiving HDCT may have added to this treatment effect.

References

Merlini G, Seldin DC, Gertz MA. Amyloidosis: pathogenesis and new therapeutic options. J Clin Oncol. 2011;29(14):1924–33.
Merlini G, Bellotti V. Molecular mechanisms of amyloidosis. N Engl J Med. 2003;349(6):583–96.
Falk RH, Comenzo RL, Skinner M. The systemic amyloidoses. N Engl J Med. 1997;337(13):898–909.
Comenzo RL. Amyloidosis. Curr Treat Options Oncol. 2006;7(3):225–36.
Leung N, Nasr SH, Sethi S. How I treat amyloidosis: the importance of accurate diagnosis and amyloid typing. Blood. 2012;120(16):3206–13.
Sack FU, Kristen A, Goldschmidt H, Schnabel PA, Dengler T, Koch A, et al. Treatment options for severe cardiac amyloidosis: heart transplantation combined with chemotherapy and stem cell transplantation for patients with AL-amyloidosis and heart and liver transplantation for patients with ATTR-amyloidosis. Eur J Cardiothorac Surg. 2008;33(2):257–62.
Merlini G, Wechalekar AD, Palladini G. Systemic light chain amyloidosis: an update for treating physicians. Blood. 2013;121(26):5124–30.
Kumar S, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, Colby C, et al. Revised prognostic staging system for light chain amyloidosis incorporating cardiac biomarkers and serum free light chain measurements. J Clin Oncol. 2012;30(9):989–95.
Dispenzieri A, Kyle RA, Lacy MQ, Therneau TM, Larson DR, Plevak MF, et al. Superior survival in primary systemic amyloidosis patients undergoing peripheral blood stem cell transplantation: a case-control study. Blood. 2004;103(10):3960–3.
Bahlis NJ, Lazarus HM. Multiple myeloma-associated AL amyloidosis: is a distinctive therapeutic approach warranted? Bone Marrow Transplant. 2006;38(1):7–15.
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(2):85–93.
Kyle RA, Therneau TM, Rajkumar SV, Offord JR, Larson DR, Plevak MF, et al. A long-term study of prognosis in monoclonal gammopathy of undetermined significance. N Engl J Med. 2002;346(8):564–9.
Schonland SO, Lokhorst H, Buzyn A, Leblond V, Hegenbart U, Bandini G, et al. Allogeneic and syngeneic hematopoietic cell transplantation in patients with amyloid light-chain amyloidosis: a report from the European Group for Blood and Marrow Transplantation. Blood. 2006;107(6):2578–84.
Passweg JR, Halter J, Bucher C, Gerull S, Heim D, Rovo A, et al. Hematopoietic stem cell transplantation: a review and recommendations for follow-up care for the general practitioner. Swiss Med Wkly. 2012;142:w13696.
Passweg JR, Baldomero H, Bargetzi M, Bucher C, Chalandon Y, Duchosal MA, et al. Haematopoietic stem cell transplantation: activity in Switzerland compared with surrounding European countries. Swiss Med Wkly. 2013;143:w13757.
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(10):3561–3.
Dispenzieri A, Seenithamby K, Lacy MQ, Kumar SK, Buadi FK, Hayman SR, et al. Patients with immunoglobulin light chain amyloidosis undergoing autologous stem cell transplantation have superior outcomes compared with patients with multiple myeloma: a retrospective review from a tertiary referral center. Bone Marrow Transplant. Apr 22 2013.
Gertz MA, Lacy MQ, Dispenzieri A, Hayman SR, Kumar SK, Leung N, et al. Effect of hematologic response on outcome of patients undergoing transplantation for primary amyloidosis: importance of achieving a complete response. Haematologica. 2007;92(10):1415–8.
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(12):2181–7.
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(6):1888–93.
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(7):549–55.
Gertz MA, Lacy MQ, Dispenzieri A, Hayman SR, Kumar S. Transplantation for amyloidosis. Curr Opin Oncol. 2007;19(2):136–41.
Kumar S, Dispenzieri A, Gertz MA. High-dose melphalan versus melphalan plus dexamethasone for AL amyloidosis. N Engl J Med. 2008;358(1):91; author reply 92–93.
Sanchorawala V, Wright DG, Seldin DC, Dember LM, Finn K, Falk RH, et al. An overview of the use of high-dose melphalan with autologous stem cell transplantation for the treatment of AL amyloidosis. Bone Marrow Transplant. 2001;28(7):637–642.
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(16):4346–52.
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(4):557–61.
Frossard V, Ketterer N, Rosselet A, Meier P, Cairoli A, Duchosal MA, et al. Early intensification and autologous stem cell transplantation in patients with systemic AL amyloidosis: a single-centre experience. Ann Hematol. 2009;88(7):681–5.
Gertz MA, Greipp PR, Kyle RA. Classification of amyloidosis by the detection of clonal excess of plasma cells in the bone marrow. J Lab Clin Med. 1991;118(1):33–39.
Perfetti V, Garini P, Vignarelli MC, Marinone MG, Zorzoli I, Merlini G. Diagnostic approach to and follow-up of difficult cases of AL amyloidosis. Haematologica. 1995;80(5):409–15.
Bradwell AR, Carr-Smith HD, Mead GP, Tang LX, Showell PJ, Drayson MT, et al. Highly sensitive, automated immunoassay for immunoglobulin free light chains in serum and urine. Clin Chem. 2001;47(4):673–80.
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(4):319–28.
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(11):1083–93.

How to Cite

1.

Raschle J, Banz Y, Suter T, Pabst T. A single-centre cohort of patients with systemic light chain AL-amyloidosis treated with conventional chemotherapy or with high-dose chemotherapy and autologous stem cell transplantation. Swiss Med Wkly [Internet]. 2014 Feb. 9 [cited 2024 Nov. 23];144(0708):w13922. Available from: https://smw.ch/index.php/smw/article/view/1830

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

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[1] Merlini G, Seldin DC, Gertz MA. Amyloidosis: pathogenesis and new therapeutic options. J Clin Oncol. 2011;29(14):1924–33.

[2] Merlini G, Bellotti V. Molecular mechanisms of amyloidosis. N Engl J Med. 2003;349(6):583–96.

[3] Falk RH, Comenzo RL, Skinner M. The systemic amyloidoses. N Engl J Med. 1997;337(13):898–909.

[4] Comenzo RL. Amyloidosis. Curr Treat Options Oncol. 2006;7(3):225–36.

[5] Leung N, Nasr SH, Sethi S. How I treat amyloidosis: the importance of accurate diagnosis and amyloid typing. Blood. 2012;120(16):3206–13.

[6] Sack FU, Kristen A, Goldschmidt H, Schnabel PA, Dengler T, Koch A, et al. Treatment options for severe cardiac amyloidosis: heart transplantation combined with chemotherapy and stem cell transplantation for patients with AL-amyloidosis and heart and liver transplantation for patients with ATTR-amyloidosis. Eur J Cardiothorac Surg. 2008;33(2):257–62.

[7] Merlini G, Wechalekar AD, Palladini G. Systemic light chain amyloidosis: an update for treating physicians. Blood. 2013;121(26):5124–30.

[8] Kumar S, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, Colby C, et al. Revised prognostic staging system for light chain amyloidosis incorporating cardiac biomarkers and serum free light chain measurements. J Clin Oncol. 2012;30(9):989–95.

[9] Dispenzieri A, Kyle RA, Lacy MQ, Therneau TM, Larson DR, Plevak MF, et al. Superior survival in primary systemic amyloidosis patients undergoing peripheral blood stem cell transplantation: a case-control study. Blood. 2004;103(10):3960–3.

[10] Bahlis NJ, Lazarus HM. Multiple myeloma-associated AL amyloidosis: is a distinctive therapeutic approach warranted? Bone Marrow Transplant. 2006;38(1):7–15.

[11] 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(2):85–93.

[12] Kyle RA, Therneau TM, Rajkumar SV, Offord JR, Larson DR, Plevak MF, et al. A long-term study of prognosis in monoclonal gammopathy of undetermined significance. N Engl J Med. 2002;346(8):564–9.

[13] Schonland SO, Lokhorst H, Buzyn A, Leblond V, Hegenbart U, Bandini G, et al. Allogeneic and syngeneic hematopoietic cell transplantation in patients with amyloid light-chain amyloidosis: a report from the European Group for Blood and Marrow Transplantation. Blood. 2006;107(6):2578–84.

[14] Passweg JR, Halter J, Bucher C, Gerull S, Heim D, Rovo A, et al. Hematopoietic stem cell transplantation: a review and recommendations for follow-up care for the general practitioner. Swiss Med Wkly. 2012;142:w13696.

[15] Passweg JR, Baldomero H, Bargetzi M, Bucher C, Chalandon Y, Duchosal MA, et al. Haematopoietic stem cell transplantation: activity in Switzerland compared with surrounding European countries. Swiss Med Wkly. 2013;143:w13757.

[16] 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(10):3561–3.

[17] Dispenzieri A, Seenithamby K, Lacy MQ, Kumar SK, Buadi FK, Hayman SR, et al. Patients with immunoglobulin light chain amyloidosis undergoing autologous stem cell transplantation have superior outcomes compared with patients with multiple myeloma: a retrospective review from a tertiary referral center. Bone Marrow Transplant. Apr 22 2013.

[18] Gertz MA, Lacy MQ, Dispenzieri A, Hayman SR, Kumar SK, Leung N, et al. Effect of hematologic response on outcome of patients undergoing transplantation for primary amyloidosis: importance of achieving a complete response. Haematologica. 2007;92(10):1415–8.

[19] 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(12):2181–7.

[20] 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(6):1888–93.

[21] 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(7):549–55.

[22] Gertz MA, Lacy MQ, Dispenzieri A, Hayman SR, Kumar S. Transplantation for amyloidosis. Curr Opin Oncol. 2007;19(2):136–41.

[23] Kumar S, Dispenzieri A, Gertz MA. High-dose melphalan versus melphalan plus dexamethasone for AL amyloidosis. N Engl J Med. 2008;358(1):91; author reply 92–93.

[24] Sanchorawala V, Wright DG, Seldin DC, Dember LM, Finn K, Falk RH, et al. An overview of the use of high-dose melphalan with autologous stem cell transplantation for the treatment of AL amyloidosis. Bone Marrow Transplant. 2001;28(7):637–642.

[25] 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(16):4346–52.

[26] 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(4):557–61.

[27] Frossard V, Ketterer N, Rosselet A, Meier P, Cairoli A, Duchosal MA, et al. Early intensification and autologous stem cell transplantation in patients with systemic AL amyloidosis: a single-centre experience. Ann Hematol. 2009;88(7):681–5.

[28] Gertz MA, Greipp PR, Kyle RA. Classification of amyloidosis by the detection of clonal excess of plasma cells in the bone marrow. J Lab Clin Med. 1991;118(1):33–39.

[29] Perfetti V, Garini P, Vignarelli MC, Marinone MG, Zorzoli I, Merlini G. Diagnostic approach to and follow-up of difficult cases of AL amyloidosis. Haematologica. 1995;80(5):409–15.

[30] Bradwell AR, Carr-Smith HD, Mead GP, Tang LX, Showell PJ, Drayson MT, et al. Highly sensitive, automated immunoassay for immunoglobulin free light chains in serum and urine. Clin Chem. 2001;47(4):673–80.

[31] 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(4):319–28.

[32] 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(11):1083–93.