Re-evaluating inclusion criteria for autologous hematopoietic stem cell transplantation in advanced systemic sclerosis: Three successful cases and review of the literature

Abstract

Systemic sclerosis is a chronic autoimmune disease with a poor prognosis, particularly when a patient has rapidly progressive skin or pulmonary involvement. Autologous hematopoietic stem cell transplant is an emerging treatment for this condition, that has been demonstrated to be more effective than immunosuppressants. Careful selection of patients has reduced the transplant-related mortality and maximized the likelihood of benefit. In this report, we present three cases of successful autologous hematopoietic stem cell transplant in patients who would not have met inclusion criteria for entrance into the completed hematopoietic stem cell transplant. After >18 months of follow-up, three patients had clinically significant benefit in terms of skin tightening and pulmonary function tests. Future studies of hematopoietic stem cell transplant in systemic sclerosis may aim to carefully liberalize inclusion criteria to include patients who may not have otherwise been treated while still maintaining an acceptable safety profile.

Autoantibodies as Biomarker and Therapeutic Target in Systemic Sclerosis

“…The first aHSCT was performed in 1997 in SSc [ 179 ]. Since then, around 500 aHSCTs have been reported [ 180 ] and more than 1000 SSc patients have been transplanted worldwide [ 181 ]. Furthermore, three randomized controlled trials have shown superiority of aHSCT versus intravenous cyclophosphamide therapy (ASSIST trial [ 182 ], ASTIS trial [ 183 ], SCOT trial [ 184 ]).…”

“…Recently, the German Society for Rheumatology (DGRh) suggested criteria for patient selection [ 188 ]. Moreover, optimal timing of aHSCT in SSc is still under discussion [ 180 ]. Therefore, timing of aHSCT is currently investigated in the UPSIDE study (NCT04464434).…”

Hematopoietic Cell Transplantation for Systemic Sclerosis—A Review

“…Despite the conventional selection criteria, recent reports of successful HCT transplants in SSc patients who would have been excluded from randomized studies primarily due to poor cardiopulmonary status [ 28 , 109 ] highlight the heterogeneity of patient response and the need to refine inclusion criteria. In particular, when the combination of fludarabine, low-dose cyclophosphamide, ATG, and rituximab is used instead of high-dose cyclophosphamide-based conditioning [ 28 ], more liberal criteria can likely be applied ( Table 2 ).…”

The Treatment of Lung Involvement in Systemic Sclerosis

“…It is based on the use of high-intensity immunosuppression (conditioning regimen) aimed at a strong reduction/eradication of the "auto-reactive" immune system, followed by a re-population with antigen-naïve T cells previously isolated from the same individual [76]. It has been proposed for patients with dcSSc (with or without SSc-ILD) that is severe and refractory to standard therapy, who will probably benefit from the procedure but are more unlikely to develop post-transplant complications [44,77]. Indeed, improved survival compared to CYC has been reported by three trials, i.e., Autologous Stem Cell Systemic Sclerosis Immune Suppression Trial (ASSIST), Autologous Stem Cell Transplantation International Scleroderma trial for (ASTIS), and Scleroderma: Cyclophosphamide Or Transplantation trial (SCOT).…”