Autologous stem cell transplantation in the treatment of systemic sclerosis: report from the EBMT/EULAR Registry

Abstract

Objective: To analyse the durability of the responses after haematopoietic stem cell transplantation (HSCT) for severe systemic sclerosis (SSc) and determine whether the high transplant related mortality (TRM) improved with experience. This EBMT/EULAR report describes the longer outcome of patients originally described in addition to newly recruited cases. Methods: Only patients with SSc, treated by HSCT in European phase I-II studies from 1996 up to 2002, with more than 6 months of follow up were included. Transplant regimens were according to the international consensus statements. Repeated evaluations analysed complete, partial, or non-response and the probability of disease progression and survival after HSCT (Kaplan-Meier). Results: Given as median (range). Among 57 patients aged 40 (9.1-68.7) years the skin scores improved at 6 (n = 37 patients), 12 (n = 30), 24 (n = 19), and 36 (n = 10) months after HSCT (p,0.005). After 22.9 (4.5-81.1) months, partial (n = 32) or complete response (n = 14) was seen in 92% and non-response in 8% (n = 4) of 50 observed cases. 35% of the patients with initial partial (n = 13/32) or complete response (n = 3/14) relapsed within 10 (2.2-48.7) months after HSCT. The TRM was 8.7% (n = 5/57). Deaths related to progression accounted for 14% (n = 8/57) of the 23% (n = 13/57) total mortality rate. At 5 years, progression probability was 48% (95% CI 28 to 68) and the projected survival was 72% (95% CI 59 to 75). Conclusion: This EBMT/EULAR report showed that response in two thirds of the patients after HSCT was durable with an acceptable TRM. Based on these results prospective, randomised trials are proceeding.

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.…”

Complications of autologous hematopoietic stem cell transplantation for patients with autoimmune diseases

“…This finding might be explained by the multisystemic nature of these diseases. In recent years, TRM was lower than reported in the early years (e.g., TRM of HSCT for SSc, the second most common indication for HSCT in ADs, was as high as 16% (6) before 2001, and in a later analysis TRM for patients with the same disease was 8.5%) (7). The reduction of TRM has been attributed to better patient selection and to adaption of conditioning regimens.…”

Autologous hematopoietic stem cell transplantation for autoimmune diseases

“…Marked improvement of high skin scores and lung function has been observed. 46 Concepts of irreversible tissue damage during the fibrotic process need to be revised. In immune thrombocytopenia, bleeding remains a major concern and was associated with the death of two patients.…”