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

Abstract

This EBMT Autoimmune Disease Working Party study aimed to evaluate the influence of CD34+ positive graft selection (CD34+) on the outcome of systemic sclerosis (SSc) patients after autologous hematopoietic stem cell transplantation (AHSCT). Clinical and laboratory data from 138 SSc patients at diagnosis, before and after AHSCT were retrospectively analyzed. CD34+ selection was performed in 47.1% (n = 65) patients. By multivariate analysis adjusting for all factors differing between the two groups (without or with CD34+), there was no statistically significant difference in terms of overall survival (hazard ratio (HR): 0.98, 95% confidence interval (CI) 0.40-2.39, P = 0.96), PFS (HR: 1.55, 95% CI 0.83-2.88, P = 0.17) and incidence of relapse or progression (HR: 1.70, 95% CI 0.85-3.38, P = 0.13). We demonstrate that CD34+ does not add benefit to the outcome of SSc patient treated with AHSCT. These findings should be further confirmed by prospective randomized trials.

Autologous hematopoietic stem cell transplantation has better outcomes than conventional therapies in patients with rapidly progressive systemic sclerosis

“…We adopted the strategy of CD34+ selection for AHSCT at the beginning of our survey, following some literature data which, at that time, indicated a potential beneficial effect of this procedure in autoimmune diseases, probably due to the preliminary elimination of auto-reactive cells. 20 In the present study, we observed an early drastic reduction of skin thickening in the AHSCT-treated group. Such a result is most important, since persistently high mRss values have been shown to be a predictor of poor disease outcome and high mortality rate.…”

“…20 This finding should certainly be considered for future research protocols. We adopted the strategy of CD34+ selection for AHSCT at the beginning of our survey, following some literature data which, at that time, indicated a potential beneficial effect of this procedure in autoimmune diseases, probably due to the preliminary elimination of auto-reactive cells.…”

Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis

“…However, the only randomized study in which CD34-selected and unselected HSC grafts have been compared -conducted in patients with rheumatoid arthritis -showed no difference in outcomes 88 . Similarly, a retrospective analysis of AHSCT for systemic sclerosis failed to demonstrate any benefit of CD34 selection on patient outcomes 89 . Evidence in MS is limited to a small study of patients with progressive MS, but this work also demonstrated no obvious advantage of CD34 selection 90 .…”

Immune rebound associates with a favorable clinical response to autologous HSCT in systemic sclerosis patients

“…19,33 Indeed, the noticeable presence of overlapping clones in nonresponder patients, early after transplant, suggests that further immunosuppression after engraftment, or perhaps CD34 1 graft selection, may be beneficial for this subgroup. 62,63 Expansion of the Treg compartment following transplantation starts with lymphopenia-induced proliferation, followed by thymic generation of natural Tregs. 64 This mechanism appears to be nondisease-specific and has been reported in other autoimmune diseases.…”