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

Abstract

Based on the seminal SCOT trial, 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). In patients with SSc, normal organs are more radiosensitive and prone to compromised function, and therefore lungs and kidneys require dose reduction. With traditional techniques, TBI requires heavy and thick physical blocks, which can be cumbersome and have poor reproducibility. We hypothesized that intensity modulated radiation therapy (IMRT) TBI compared to standard anteroposterior (AP)/posteroanterior (PA) TBI would facilitate improvements in dosimetry and reproducibility (due to not requiring physical blocks) without compromising outcomes. Herein, we report a single-institution retrospective analysis of patients with SSc treated with an IMRT TBI. 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 administered twice-daily to a total dose of 800 cGy in 200 cGy fractions. A minimum of 80% of the PTV was to receive prescription dose. Mean lung and kidney dose were to be less than 200 cGy. Patients were then replanned using an AP/PA technique for dosimetric comparison. The primary endpoint was planning target volume (PTV), lung, and kidney dosimetry. Secondary endpoints included event-free survival (EFS), overall survival (OS), disease-modifying antirheumatic drug-free survival (DMARD-FS), treatment related mortality (TRM), and toxicity. A total of 14 patients were eligible for our analysis. On dosimetric analysis, the mean dose to the 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 (204.9 cGy versus 281.2 cGy, p<0.001) was significantly lower. 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). No patients experienced clinically significant pneumonitis or nephritis that were deemed to be a likely consequence of TBI. Five patients subsequently initiated DMARDs, but three did so due to worsening skin symptoms without other major organ dysfunction. Use of IMRT TBI as part of the conditioning regimen for HSCT for SSc yields improved dosimetry relative to a standard AP/PA technique, with efficacy and toxicity outcomes comparable with published data. This technique should be considered for patients undergoing HSCT for SSc and warrants inclusion in prospective trials for SSc that involve TBI.