High-Dose Immunosuppressive Therapy (HDIT) for Severe Systemic Sclerosis (SSc): Long-Term Survivors Show Continued Improvement of Function and Skin with Stability in the Lungs.

Objective To evaluate long-term outcomes after HDIT and transplantation of autologous CD34+ hematopoietic progenitor cells in severe SSc. Methods: Eligibility required early ( 15) together with involvement of lungs, heart or kidneys (estimated median 5 year survival Results: Of 33 pts (median mRSS = 30) follow-up includes 25 patients at one year, 19 pts at two years, 13 pts at three years and 5 pts at four years. Progression was defined as further loss of organ function or use of immunosuppressive therapy after HDIT. Ten pts died of which 5 were due to disease progression and 5 to transplant complications. Estimated 3-year overall and progression-free survivals are 79% (95% CI 65–93%) and 52% (95% CI 33–72%), respectively. Three late deaths from progression occurred at 1343, 1511 and 1801 days after HDIT. Four pts are alive with progressive disease. At 1 and 3 years after HDIT there were significant improvements in skin score and function (Table) with lung function indices overall remaining stable. Small increases in serum creatinine and decreases in the left ventricular ejection fraction were found. Five pts developed renal insufficiency and 2 required dialysis. Conclusions: HDIT appears to be a promising therapy for high-risk SSc pts but limitations include transplant toxicities and disease progression in some pts. To more clearly define the role of HDIT in severe SSc, a NIH-supported randomized multicenter study has been initiated in North America to compare HDIT against 12 doses of monthly intravenous cyclophosphamide at 750 mg/m 2 . Changes at 1 and 3 years after HDIT*