Myeloablative Autologous Stem-Cell Transplantation for Severe Scleroderma
| Autor: | M. B. Kahaleh, Mark H. Wener, Daniel E. Furst, Chitra Hosing, Ashley Pinckney, Oana Craciunescu, Dinesh Khanna, Beverly Welch, Karen K. Ballen, Shin Mineishi, Richard M. Silver, Jan Storek, Lynette Keyes-Elstein, Stephen J. Forman, Shelly Heimfeld, Robert W. Simms, Julia S. Goldstein, Leslie J. Crofford, Maureen D. Mayes, Jonathan G. Goldin, George E. Georges, E. W. Clair, Kristine Phillips, Peter A. McSweeney, Sharon LeClercq, R. Brasington, Rodney J. Folz, Barry Eggleston, Linda M. Griffith, Sharon Castina, Keith M. Sullivan, Dennis Wallace, Christopher Bredeson, L. Griffing, James R. Seibold, Richard A. Nash, R.T. Domsic, Carolyn A. Keever-Taylor, Suzanne Kafaja, Mary Ellen Csuka, Thomas A. Medsger, Ellen Goldmuntz |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Transplantation Conditioning medicine.medical_treatment Kaplan-Meier Estimate Medical and Health Sciences Scleroderma 0302 clinical medicine Autologous stem-cell transplantation Stem Cell Research - Nonembryonic - Human education.field_of_study integumentary system Hematopoietic Stem Cell Transplantation Immunosuppression General Medicine Middle Aged Intention to Treat Analysis 6.1 Pharmaceuticals Female Autologous Immunosuppressive Agents medicine.drug Adult medicine.medical_specialty Cyclophosphamide Adolescent Population Clinical Trials and Supportive Activities Infections Transplantation Autologous Autoimmune Disease Article Disease-Free Survival 03 medical and health sciences Young Adult Clinical Research Internal medicine General & Internal Medicine medicine Humans education SCOT Study Investigators Aged 030203 arthritis & rheumatology Transplantation Intention-to-treat analysis Scleroderma Systemic business.industry Inflammatory and immune system Systemic Evaluation of treatments and therapeutic interventions medicine.disease Stem Cell Research 030104 developmental biology Good Health and Well Being business Follow-Up Studies |
| Zdroj: | The New England journal of medicine, vol 378, iss 1 |
| Popis: | BackgroundDespite 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.MethodsWe 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.ResultsIn 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.ConclusionsMyeloablative 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 .). |
| Databáze: | OpenAIRE |
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