Abstract
High-dose melphalan with autologous stem cell transplantation (HDM/ASCT) is a promising treatment option for eligible patients with systemic immunoglobulin light chain (AL) amyloidosis. We present the results of ASCT following risk-adapted melphalan conditioning on the basis of criteria proposed by our group, including B-type natriuretic peptide (BNP). Ten patients with primary systemic AL amyloidosis treated at our institute were evaluated. A full dose of melphalan (200 mg/m2) was administered to patients who met all the following: performance status, 0 or 1; number of organs involved, 2 or less; serum creatinine, 1.5 mg/dL or less; EF 50 % or more and BNP 200 pg/mL or less; otherwise 140 mg/m2. The hematologic complete response was achieved in four and organ response was seen in two patients. The median event-free survival (EFS) of all patients was 21.5 months, and median overall survival (OS) was 47.0 months. EFS and OS were significantly longer for patients who received 200 mg/m2 of melphalan than for those who received lower dose (EFS: not reached vs. 13.9 months, P = 0.0217; OS: not reached vs. 13.8 months, P = 0.0186). No treatment-related mortality within 100 days from ASCT was observed. Evaluation of cardiac diastolic function may contribute to safer HDM/ASCT and improve outcome of AL amyloidosis.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Merlini G, Bellotti V. Molecular mechanisms of amyloidosis. N Engl J Med. 2003;349:583–96.
Kyle R, Gertz M, Greipp P. A trial of three regimens for primary amyloidosis: colchicine alone, melphalan and prednisone, and melphalan, prednisone, and colchicine. N Engl J Med. 1997;336:1202–7.
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;103:3960–3.
Moreau P, Leblond V, Bourquelot P, Facon T, Huynh A, Caillot D, 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;101:766–9.
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;140:85–94.
Gertz M, Lacy MQ, Dispenzieri A, Ansell SM, Elliott M, 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;34:1025–31.
Perfetti V, Siena S, Palladini G, Bregni M, Di Nicola M, Obici L, et al. Long-term results of a risk-adapted approach to melphalan conditioning in autologous peripheral blood stem cell transplantation for primary (AL) amyloidosis. Haematologica. 2006;91:1635–43.
Gertz M, 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;79:319–28.
Kanda Y. Investigation of the freely available easy-to-use software “EZR” for medical statistics. Bone Marrow Transplant. 2013;48:452–8.
Saito M, Hayashi T, Nojima M, Ikeda H, Tarasawa I, Yasui H, et al. Long-term survival after autologous peripheral blood stem cell transplantation in a patient with primary AL amyloidosis complicating congestive heart failure. Rinsho Ketsueki. 2007;48:1478–83.
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;48:557–61.
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;30:989–95.
Palladini G, Foli A, Milani P, Russo P, Albertini R, Lavatelli F, et al. Best use of cardiac biomarkers in patients with AL amyloidosis and renal failure. Am J Hematol. 2012;87:465–71.
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;33:381–8.
Scott EC, Heitner SB, Dibb W, Meyers G, Smith SD, Abar F, et al. Induction bortezomib in AL amyloidosis followed by high dose melphalan and autologous stem cell transplantation: a single institution retrospective study. Clin Lymphoma Myeloma Leuk. 2014 (in press). (Published Online: February 17, 2014).
Huang X, Wang Q, Chen W, Zeng C, Chen Z, Gong D, et al. Induction therapy with bortezomib and dexamethasone followed by autologous stem cell transplantation versus autologous stem cell transplantation alone in the treatment of renal AL amyloidosis: a randomized controlled trial. BMC Med. 2014;12:2.
Cibeira MMT, 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;118:4346–52.
Conflict of interest
The authors declare that they have no conflict of interests.
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Hayashi, T., Ikeda, H., Igarashi, T. et al. Autologous stem cell transplantation for AL amyloidosis: adjustment of melphalan dose by factors including BNP. Int J Hematol 100, 554–558 (2014). https://doi.org/10.1007/s12185-014-1680-1
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12185-014-1680-1