Stem Cell Transplant Preferred over Cyclophosphamide for Severe Scleroderma

Myeloablative autologous hematopoietic stem cell transplantation is a superior treatment in the long term as compared to cyclophosphamide for severe scleroderma, according to research presented on Nov. 15 at the American College of Rheumatology annual meeting in Washington, D.C. Keith Sullivan, M.D., Duke University School of Medicine, Durham, N.C., presented data on his trial that evaluated the long-term benefit of myeloablative autologous hematopoietic stem cell transplantation compared to 12 monthly pulses of the immunosuppressive drug cyclophosphamide. The findings:  ·        The study demonstrates long-term superiority of myeloablative autologous hematopoietic stem cells over intravenous cyclophosphamide. ·        It also shows a significant reduction in the use of DMARDS among stem cell recipients. ·        Transplant-related mortality was lower and overall survival was better than projected both during the peri-transplant period and long term. ·        "The SCOT trial supports myeloablative HSCT as a significant advance in the care of diffuse cutaneous systemic sclerosis,” researchers wrote in their presentation abstract. Dr. Sullivan and colleagues studied 75 patients, ages 18 to 69, with diffuse cutaneous systemic sclerosis, who had or were at high risk for lung or renal involvement. Patients received 750 mg/m2/mo cyclophosphamide or myeloablation (800 cGy total body irradiation with lung and kidney shielding, 120 mg/kg cyclophosphamide and 90 mg/kg antithymocyte globulin) followed by CD34+selected autologous hematopoietic stem cell transplantation. The global rank composite score, which ordered patients on a hierarchy of outcomes, including death, event-free survival, forced vital capacity, scleroderma health assessment questionnaire and modified Rodnan skin score, favored hematopoietic stem cell transplantation in the randomized sample at 54 and 48 months. The global rank composite score was stronger in subjects who were transplanted or received 9 or more cyclophosphamide doses. The researchers’ secondary analyses of treated subjects were similar. Event-free survival at 54 months was 50 percent in the cyclophosphamide arm, versus 79 percent in the hematopoietic stem cell transplantation group. Overall survival at 54 months was 77 percent in the cyclophosphamide group versus 91 percent among subjects receiving hematopoietic stem cell transplantation. Treatment-related deaths were higher in the stem cell group, which had a mortality rate of 3 percent, versus zero in the cyclophosphamide arm. Nine percent of those in the hematopoietic stem cell transplantation group started disease-modifying antirheumatic drugs by 54 months, versus 44 percent in the cyclophosphamide arm Kaplan-Meier estimates for event-free survival (in which events are death or renal, cardiac or respiratory failure) and overall survival were significantly different between groups. Serious adverse events were similar in the two groups. Treatment-related cytopenias were more common among those receiving hematopoietic stem cell transplantation, as was herpes zoster. Therapeutic options for diffuse cutaneous systemic sclerosis are limited, and this trial supports myeloablative hematopoietic stem cell transplantation as an important advance in the treatment of diffuse cutaneous systemic sclerosis, according to the authors. 

References:

American College of Rheumatology annual meeting 2016. “Myeloablative Autologous Transplantation of CD34+ -Selected Hematopoietic Stem Cells (HSCT) Vs Monthly Intravenous Cyclophosphamide (CYC) for Severe Scleroderma with Internal Organ Involvement: Outcomes of a Randomized North American Clinical Trial,” Sullivan K, Keyes-Elstein L, et al. Abstract Number 6L. Nov. 15, 2016.