Anita D'Souza1, Angela Dispenzieri1, Baldeep Wirk1, Mei-Jie Zhang1, Jiaxing Huang1, Morie A Gertz1, Robert A Kyle1, Shaji Kumar1, Raymond L Comenzo1, Robert Peter Gale1, Hillard M Lazarus1, Bipin N Savani1, Robert F Cornell1, Brendan M Weiss1, Dan T Vogl1, César O Freytes1, Emma C Scott1, Heather J Landau1, Jan S Moreb1, Luciano J Costa1, Muthalagu Ramanathan1, Natalie S Callander1, Rammurti T Kamble1, Richard F Olsson1, Siddhartha Ganguly1, Taiga Nishihori1, Tamila L Kindwall-Keller1, William A Wood1, Tomer M Mark1, Parameswaran Hari1. 1. Anita D'Souza, Mei-Jie Zhang, Jiaxing Huang, and Parameswaran Hari, Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin; Mei-Jie Zhang, Institute for Health and Society, Medical College of Wisconsin, Milwaukee; Natalie S. Callander, University of Wisconsin Carbone Cancer Center, Madison, WI; Angela Dispenzieri, Morie A. Gertz, Robert A. Kyle, and Shaji Kumar, Mayo Clinic, Rochester, MN; Baldeep Wirk, Seattle Cancer Care Alliance, Seattle, WA; Raymond L. Comenzo, Tufts Medical Center, Boston; Muthalagu Ramanathan, University of Massachusetts Memorial Medical Center, Worcester, MA; Robert Peter Gale, Hematology Research Centre, Imperial College London, London, United Kingdom; Hillard M. Lazarus, Seidman Cancer Center, University Hospitals Case Medical Center, Cleveland, OH; Bipin N. Savani and Robert F. Cornell, Vanderbilt University Medical Center, Nashville, TN; Brendan M. Weiss and Dan T. Vogl, Abramson Cancer Center, University of Pennsylvania Medical Center, Philadelphia, PA; César O. Freytes, South Texas Veterans Health Care System and University of Texas Health Science Center San Antonio, San Antonio; Rammurti T. Kamble, Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX; Emma C. Scott, Center for Hematologic Malignancies, The Knight Cancer Institute, Oregon Health and Science University, Portland, OR; Heather J. Landau, Memorial Sloan Kettering Cancer Center; Tomer M. Mark, Weill Cornell Medical College, New York, NY; Jan S. Moreb, Shands HealthCare and University of Florida, Gainesville; Taiga Nishihori, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Luciano J. Costa, University of Alabama at Birmingham, Birmingham, AL; Richard F. Olsson, Karolinska Institutet, Stockholm; Centre for Clinical Research Sörmland, Uppsala University, Uppsala, Sweden; Siddhartha Ganguly, University of Kansas Medical Center, Kansas City, KS; Tamila L. Kindwall-Keller, University of Virginia Health Sys
Abstract
PURPOSE: Autologous hematopoietic cell transplantation, or autotransplantation, is effective in light-chain amyloidosis (AL), but it is associated with a high risk of early mortality (EM). In a multicenter randomized comparison against oral chemotherapy, autotransplantation was associated with 24% EM. We analyzed trends in outcomes after autologous hematopoietic cell transplantation for AL in North America. PATIENTS AND METHODS: Between 1995 and 2012, 1,536 patients with AL who underwent autotransplantation at 134 centers were identified in the Center for International Blood and Marrow Transplant Research database. EM and overall survival (OS) were analyzed in three time cohorts: 1995 to 2000 (n = 140), 2001 to 2006 (n = 596), and 2007 to 2012 (n = 800). Hematologic and renal responses and factors associated with EM, relapse and/or progression, progression-free survival and OS were analyzed in more recent subgroups from 2001 to 2006 (n = 197) and from 2007 to 2012 (n = 157). RESULTS: Mortality at 30 and 100 days progressively declined over successive time periods from 11% and 20%, respectively, in 1995 to 2000 to 5% and 11%, respectively, in 2001 to 2006, and to 3% and 5%, respectively, in 2007 to 2012. Correspondingly, 5-year OS improved from 55% in 1995 to 2000 to 61% in 2001 to 2006 and to 77% in 2007 to 2012. Hematologic response to transplantation improved in the latest cohort. Renal response rate was 32%. Centers performing more than four AL transplantations per year had superior survival outcomes. In the multivariable analysis, cardiac AL was associated with high EM and inferior progression-free survival and OS. Autotransplantation in 2007 to 2012 and use of higher dosages of melphalan were associated with a lowered relapse risk. A Karnofsky score less than 80 and creatinine levels 2 mg/m(2) or greater were associated with worsened OS. CONCLUSION: Post-transplantation survival in AL has improved, with a dramatic reduction in early post-transplantation mortality and excellent 5-year survival. The risk-benefit ratio for autotransplantation has changed, and randomized comparison with nontransplantation approaches is again warranted.
PURPOSE: Autologous hematopoietic cell transplantation, or autotransplantation, is effective in light-chain amyloidosis (AL), but it is associated with a high risk of early mortality (EM). In a multicenter randomized comparison against oral chemotherapy, autotransplantation was associated with 24% EM. We analyzed trends in outcomes after autologous hematopoietic cell transplantation for AL in North America. PATIENTS AND METHODS: Between 1995 and 2012, 1,536 patients with AL who underwent autotransplantation at 134 centers were identified in the Center for International Blood and Marrow Transplant Research database. EM and overall survival (OS) were analyzed in three time cohorts: 1995 to 2000 (n = 140), 2001 to 2006 (n = 596), and 2007 to 2012 (n = 800). Hematologic and renal responses and factors associated with EM, relapse and/or progression, progression-free survival and OS were analyzed in more recent subgroups from 2001 to 2006 (n = 197) and from 2007 to 2012 (n = 157). RESULTS: Mortality at 30 and 100 days progressively declined over successive time periods from 11% and 20%, respectively, in 1995 to 2000 to 5% and 11%, respectively, in 2001 to 2006, and to 3% and 5%, respectively, in 2007 to 2012. Correspondingly, 5-year OS improved from 55% in 1995 to 2000 to 61% in 2001 to 2006 and to 77% in 2007 to 2012. Hematologic response to transplantation improved in the latest cohort. Renal response rate was 32%. Centers performing more than four AL transplantations per year had superior survival outcomes. In the multivariable analysis, cardiac AL was associated with high EM and inferior progression-free survival and OS. Autotransplantation in 2007 to 2012 and use of higher dosages of melphalan were associated with a lowered relapse risk. A Karnofsky score less than 80 and creatinine levels 2 mg/m(2) or greater were associated with worsened OS. CONCLUSION: Post-transplantation survival in AL has improved, with a dramatic reduction in early post-transplantation mortality and excellent 5-year survival. The risk-benefit ratio for autotransplantation has changed, and randomized comparison with nontransplantation approaches is again warranted.
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