Incidence and characteristics of cytokine release syndrome in patients with systemic sclerosis undergoing autologous haematopoietic stem cell transplantation

Background Systemic sclerosis (SSc) is a debilitating autoimmune connective tissue disease associated with high morbidity and mortality. Autologous hematopoietic stem cell transplantation (HSCT) improves survival in diffuse cutaneous SSc. Cytokine release syndrome (CRS), a potentially fatal inflammatory response, is a complication of HSCT associated with anti-thymocyte globulin use. This study aimed to systematically describe the incidence and characteristics of ATG-related CRS in SSc patients undergoing HSCT. Methods SSc patients undergoing autologous HSCT according to the (adjusted) ASTIS protocol (2011-2025) were analysed retrospectively. CRS was graded according to American Society for Transplantation and Cellular Therapy (ASTCT) criteria. Associations between CRS ≥2 and clinical characteristics were explored, and overall survival was assessed using Kaplan–Meier analysis. Results Of the 91 eligible for grading, 81 (89.0%) were classified as having CRS: 40 (44.0%) as grade 1 (fever only), 26 (28.6%) as grade 2, ten (11.0%) as grade 3, three (3.3%) as grade 4, and two (2.2%) as grade 5 (fatal). Among the 41 patients with grade ≥2 CRS, grading was based solely on respiratory criteria in 61.0%. No significant associations with grade ≥2 CRS remained after multiple-testing correction. Overall survival did not differ significantly, although the Kaplan-Meier curves separated early. Follow-up lung function and skin scores were similar between groups. Conclusion CRS is highly prevalent and clinically relevant in SSc patients undergoing autologous HSCT. The frequent respiratory manifestations may reflect SSc-related pre-existing cardiopulmonary involvement, vasculopathy, and fluid exposure during conditioning, suggesting a distinct CRS phenotype.