Autologous Stem Cell Transplantation With Intensity Modulated Total Body Irradiation Conditioning for Systemic Sclerosis

Abstract

Autologous stem cell transplantation (HSCT) using myeloablative total body irradiation (TBI) and anti-thymocyte globulin (ATG) as a conditioning regimen has become a standard treatment option for certain patients with systemic sclerosis (SSc). Normal organs are more radiosensitive and prone to compromised function in SSc, and therefore lungs and kidneys require dose reduction. We evaluated the role of intensity modulated radiation therapy (IMRT) TBI compared to standard anteroposterior (AP)/posteroanterior (PA) TBI technique. Patients with SSc who underwent HSCT with TBI between 2017 and 2022 were eligible. All patients underwent conditioning with equine ATG, cyclophosphamide 120 mg/kg, and IMRT TBI to a total dose of 800 cGy in 200 cGy fractions. Patients were replanned using an AP/PA technique for dosimetric comparison. Patients were evaluated for outcomes including event-free survival (EFS), overall survival (OS), disease-modifying antirheumatic drug-free survival (DMARD-FS), and treatment related mortality (TRM). 14 patients were eligible for our analysis. Median follow-up was 34.6 months (1.0-51.7 months). There was one case of TRM secondary to respiratory failure. The 24-month OS, EFS, and DMARD-FS estimates were 92.9%, 74.3%, and 70.0%, respectively. Three patients experienced adverse events, which included respiratory failure (n=1), renal failure (n=1), and death (n=1). Five patients subsequently initiated DMARDs, but three did so due to worsening skin symptoms without other major organ dysfunction. On dosimetric analysis, the mean dose to the planning target volume (PTV) was significantly higher on the IMRT compared to the AP/PA plans (809.4 cGy versus 728.5 cGy, p<0.001). The mean dose to the lungs (239.5 cGy versus 443.9 cGy, p<0.001) and kidneys (204.9cGy versus 281.2 cGy, p<0.001) was significantly lower. Use of IMRT TBI as part of the conditioning regimen for HSCT for SSc yields improved dosimetry with efficacy and toxicity outcomes comparable with published data.