Myeloablative Autologous Stem-Cell Transplantation for Severe Scleroderma
Keith M Sullivan, Ellen A Goldmuntz, Lynette Keyes-Elstein, Peter A McSweeney, Ashley Pinckney, Beverly Welch, Maureen D Mayes, Richard A Nash, Leslie J Crofford, Barry Eggleston, Sharon Castina, Linda M Griffith, Julia S Goldstein, Dennis Wallace, Oana Craciunescu, Dinesh Khanna, Rodney J Folz, Jonathan Goldin, E William St Clair, James R Seibold, Kristine Phillips, Shin Mineishi, Robert W Simms, Karen Ballen, Mark H Wener, George E Georges, Shelly Heimfeld, Chitra Hosing, Stephen Forman, Suzanne Kafaja, Richard M Silver, Leroy Griffing, Jan Storek, Sharon LeClercq, Richard Brasington, Mary E Csuka, Christopher Bredeson, Carolyn Keever-Taylor, Robyn T Domsic, M Bashar Kahaleh, Thomas Medsger, Daniel E Furst, SCOT Study Investigators, David Amrani, Peter Bianchine, Alan Braun, Erica H Brittain, Alan Brown, Sharon Castina, Christine Czarniecki, Margaret Eren, Barri Fessler, Avram Goldberg, Parameswaran Hari, Laura Hummers, Sergio Jimenez, Joseph Korn, Kristine Lohr, Megan MacNeil, Janet Markland, Kevin McKown, James McNamara, Jerry Molitor, Catherine Paarz-Largay, Marcelo Pasquini, Roberto Rodriquez, Scott Rowley, Joseph Shanahan, Lee Shapiro, Jean Shearin, Robert Spiera, Virginia Steen, Anthony Turkiewicz, John Varga, Jasmine Zain, Keith M Sullivan, Ellen A Goldmuntz, Lynette Keyes-Elstein, Peter A McSweeney, Ashley Pinckney, Beverly Welch, Maureen D Mayes, Richard A Nash, Leslie J Crofford, Barry Eggleston, Sharon Castina, Linda M Griffith, Julia S Goldstein, Dennis Wallace, Oana Craciunescu, Dinesh Khanna, Rodney J Folz, Jonathan Goldin, E William St Clair, James R Seibold, Kristine Phillips, Shin Mineishi, Robert W Simms, Karen Ballen, Mark H Wener, George E Georges, Shelly Heimfeld, Chitra Hosing, Stephen Forman, Suzanne Kafaja, Richard M Silver, Leroy Griffing, Jan Storek, Sharon LeClercq, Richard Brasington, Mary E Csuka, Christopher Bredeson, Carolyn Keever-Taylor, Robyn T Domsic, M Bashar Kahaleh, Thomas Medsger, Daniel E Furst, SCOT Study Investigators, David Amrani, Peter Bianchine, Alan Braun, Erica H Brittain, Alan Brown, Sharon Castina, Christine Czarniecki, Margaret Eren, Barri Fessler, Avram Goldberg, Parameswaran Hari, Laura Hummers, Sergio Jimenez, Joseph Korn, Kristine Lohr, Megan MacNeil, Janet Markland, Kevin McKown, James McNamara, Jerry Molitor, Catherine Paarz-Largay, Marcelo Pasquini, Roberto Rodriquez, Scott Rowley, Joseph Shanahan, Lee Shapiro, Jean Shearin, Robert Spiera, Virginia Steen, Anthony Turkiewicz, John Varga, Jasmine Zain
Abstract
Background: Despite current therapies, diffuse cutaneous systemic sclerosis (scleroderma) often has a devastating outcome. We compared myeloablative CD34+ selected autologous hematopoietic stem-cell transplantation with immunosuppression by means of 12 monthly infusions of cyclophosphamide in patients with scleroderma.
Methods: We randomly assigned adults (18 to 69 years of age) with severe scleroderma to undergo myeloablative autologous stem-cell transplantation (36 participants) or to receive cyclophosphamide (39 participants). The primary end point was a global rank composite score comparing participants with each other on the basis of a hierarchy of disease features assessed at 54 months: death, event-free survival (survival without respiratory, renal, or cardiac failure), forced vital capacity, the score on the Disability Index of the Health Assessment Questionnaire, and the modified Rodnan skin score.
Results: In the intention-to-treat population, global rank composite scores at 54 months showed the superiority of transplantation (67% of 1404 pairwise comparisons favored transplantation and 33% favored cyclophosphamide, P=0.01). In the per-protocol population (participants who received a transplant or completed ≥9 doses of cyclophosphamide), the rate of event-free survival at 54 months was 79% in the transplantation group and 50% in the cyclophosphamide group (P=0.02). At 72 months, Kaplan-Meier estimates of event-free survival (74% vs. 47%) and overall survival (86% vs. 51%) also favored transplantation (P=0.03 and 0.02, respectively). A total of 9% of the participants in the transplantation group had initiated disease-modifying antirheumatic drugs (DMARDs) by 54 months, as compared with 44% of those in the cyclophosphamide group (P=0.001). Treatment-related mortality in the transplantation group was 3% at 54 months and 6% at 72 months, as compared with 0% in the cyclophosphamide group.
Conclusions: Myeloablative autologous hematopoietic stem-cell transplantation achieved long-term benefits in patients with scleroderma, including improved event-free and overall survival, at a cost of increased expected toxicity. Rates of treatment-related death and post-transplantation use of DMARDs were lower than those in previous reports of nonmyeloablative transplantation. (Funded by the National Institute of Allergy and Infectious Diseases and the National Institutes of Health; ClinicalTrials.gov number, NCT00114530 .).
Figures
Source: PubMed