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

Abstract

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 confirmed a statistically significant decrease of dermal fibrosis compared with baseline (P < .001). Lung, heart, and kidney func-

Does ex vi vo CD34+ positive selection influence outcome after autologous hematopoietic stem cell transplantation in systemic sclerosis patients?

“…Improved skin score and quality of life and at least stabilization of lung function were consistently reported in early phase II trials. [4][5][6][7][8] Recently, the phase II ASSIST 9 and the larger phase III ASTIS 10 prospective randomized trials showed better survival rates and improved skin, lung and functional status in patients treated with AHSCT as compared with monthly IV cyclophosphamide. Still, the transplant-related mortality reaching 10% and disease-progression rates of around 20-30% after AHSCT indicate that further improvements are still warranted.…”

“…Still, the transplant-related mortality reaching 10% and disease-progression rates of around 20-30% after AHSCT indicate that further improvements are still warranted. [6][7][8][9][10][11][12] Among current strategies to increase safety and efficacy of AHSCT, the benefit of ex vivo CD34+ positive selection of the graft remains debated. This study was therefore designed to evaluate the influence of ex vivo CD34+ selection on the outcome of SSc patients treated with AHSCT.…”

Hematopoietic Stem Cell Transplantation for Systemic Sclerosis: If You Are Confused, Remember: “It Is a Matter of the Heart”

“…An approach that began in patients about 14 years ago, hematopoietic stem cell transplantation (HSCT), has been demonstrated to improve both skin and lung function as well as quality of life in patients with SSc 6,7,8 . Transplantation has been performed safely in some studies 8 , but results have been complicated by high treatment-related mortality in others 9 . Mortality of HSCT for SSc can be markedly reduced, however, if the reasons for mortality are properly recognized.…”

Review: Hematopoietic Stem Cell Transplantation for Scleroderma: Effective Immunomodulatory Therapy for Patients With Pulmonary Involvement

“…Dark solid lines denote the mean and dashed lines represent the generalized estimating equation (GEE). Gray lines represent individual patient values (38). …”