Myeloablative Autologous Stem-Cell Transplantation for Severe Scleroderma.
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 .).
Sullivan, KM; Goldmuntz, EA; Keyes-Elstein, L; McSweeney, PA; Pinckney, A; Welch, B; Mayes, MD; Nash, RA; Crofford, LJ; Eggleston, B; Castina, S; Griffith, LM; Goldstein, JS; Wallace, D; Craciunescu, O; Khanna, D; Folz, RJ; Goldin, J; St Clair, EW; Seibold, JR; Phillips, K; Mineishi, S; Simms, RW; Ballen, K; Wener, MH; Georges, GE; Heimfeld, S; Hosing, C; Forman, S; Kafaja, S; Silver, RM; Griffing, L; Storek, J; LeClercq, S; Brasington, R; Csuka, ME; Bredeson, C; Keever-Taylor, C; Domsic, RT; Kahaleh, MB; Medsger, T; Furst, DE; SCOT Study Investigators,
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