High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for severe systemic sclerosis: Long-term follow-up of the US multicenter pilot study

Richard A. Nash, Peter A. McSweeney, Leslie J. Crofford, Muneer Abidi, Chien Shing Chen, J. David Godwin, Theodore A. Gooley, Leona Holmberg, Gretchen Henstorf, C. Fred LeMaistre, Maureen D. Mayes, Kevin T. McDonagh, Bernadette McLaughlin, Jerry A. Molitor, J. Lee Nelson, Howard Shulman, Rainer Storb, Federico Viganego, Mark H. Wener, James R. SeiboldKeith M. Sullivan, Daniel E. Furst

Research output: Contribution to journalArticlepeer-review


More effective therapeutic strategies are required for patients with poor-prognosis systemic sclerosis (SSc). A phase 2 single-arm study of high-dose immunosuppressive therapy (HDIT) and autologous CD34-selected hematopoietic cell transplantation (HCT) was conducted in 34 patients with diffuse cutaneous SSc. HDIT included total body irradiation (800 cGy) with lung shielding, cyclophosphamide (120 mg/kg), and equine antithymocyte globulin (90 mg/kg). Neutrophil and platelet counts were recovered by 9 (range, 7 to 13) and 11 (range, 7 to 25) days after HCT, respectively. Seventeen of 27 (63%) evaluable patients who survived at least 1 year after HDIT had sustained responses at a median follow-up of 4 (range, 1 to 8) years. There was a major improvement in skin (modified Rodnan skin score, -22.08;P < .001) and overall function (modified Health Assessment Questionnaire Disability Index, -1.03;P < .001) at final evaluation. Importantly, for the first time, biopsies confirmeda statistically significant decrease of dermal fibrosis compared with baseline (P < .001). Lung, heart, and kidney function, in general, remained clinically stable. There were 12 deaths during the study (transplantation-related, 8; SSc-related, 4). The estimated progression-free survival was 64% at 5 years. Sustained responses including a decrease in dermal fibrosis were observed exceeding those previously reported with other therapies. HDIT and autologous HCT for SSc should be evaluated in a randomized clinical trial.

Original languageEnglish (US)
Pages (from-to)1388-1396
Number of pages9
Issue number4
StatePublished - Aug 15 2007
Externally publishedYes

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