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

Systemic sclerosis (SSc) is an autoimmune disease that can cause dysfunction of several organ systems and is associated with significant mortality. 1 Denton CP Khanna D. Systemic sclerosis. Lancet. 2017; 390: 1685-1699 Abstract Full Text Full Text PDF PubMed Scopus (1056) Google Scholar Autologous hematopoietic stem cell transplantation (HSCT) has been explored in patients with aggressive disease. 2 Tyndall A Black C Finke J et al. Treatment of systemic sclerosis with autologous haemopoietic stem cell transplantation. Lancet. 1997; 349: 254 Abstract Full Text Full Text PDF PubMed Scopus (117) Google Scholar , 3 Binks M. Phase I/II trial of autologous stem cell transplantation in systemic sclerosis: procedure related mortality and impact on skin disease. Ann Rheum Dis. 2001; 60: 577-584 Crossref PubMed Scopus (250) Google Scholar , 4 Nash RA Mcsweeney PA Crofford LJ et al. High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for severe systemic sclerosis: Long-term follow-up of the US multicenter pilot study. Blood. 2007; 110: 1388-1396 Crossref PubMed Scopus (218) Google Scholar , 5 Sullivan KM Muraro P Tyndall A. Hematopoietic cell transplantation for autoimmune disease: Updates from Europe and the United States. Biology of Blood and Marrow Transplantation. 2010; 16: S48-S56 Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar One randomized study (SCOT) studied cyclophosphamide (CY) 120 mg/kg along with myeloablative total body irradiation (TBI) and antithymocyte globulin (ATG), which yielded no early treatment-related mortality (TRM), improved event-free survival (EFS), and overall survival (OS) compared with cyclophosphamide alone. 6 Sullivan KM Shah A Sarantopoulos S Furst DE. Review: Hematopoietic stem cell transplantation for scleroderma: Effective immunomodulatory therapy for patients with pulmonary involvement. Arthritis Rheumatol. 2016; 68: 2361-2371 Crossref Scopus (21) Google Scholar ,7 Sullivan KM Goldmuntz EA Keyes-Elstein L et al. Myeloablative autologous stem-cell transplantation for severe scleroderma. N Engl J Med. 2018; 378: 35-47 Crossref PubMed Scopus (330) Google Scholar The TBI was performed with lungs and kidneys blocked via lead shields to decrease doses to 25% of prescription dose. 8 Craciunescu OI Steffey BA Kelsey CR et al. Renal shielding and dosimetry for patients with severe systemic sclerosis receiving immunoablation with total body irradiation in the scleroderma: Cyclophosphamide or transplantation trial. Int J Radiat Oncol Biol Phys. 2011; 79: 1248-1255 Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar These objectives are necessary in SSc patients who typically already have compromised organ function and are more sensitive to radiation. 9 Burt RK Kallunian K Patel D et al. The rationale behind autologous autoimmune hematopoietic stem cell transplant conditioning regimens: Concerns over the use of total-body irradiation in systemic sclerosis. Bone Marrow Transplant. 2004; 34: 745-751 Crossref PubMed Scopus (21) Google Scholar ,10 Varga J. Exaggerated radiation-induced fibrosis in patients with systemic sclerosis. JAMA. 1991; 265: 3292 Crossref PubMed Scopus (104) Google Scholar Lead shields can be cumbersome to use and thereby impede reproducibility. These limitations highlight a need for conformal dose delivery and organ sparing techniques offered through the use of intensity modulated radiation therapy (IMRT). 11 Zhuang AH Liu A Schultheiss TE Wong JYC. Dosimetric study and verification of total body irradiation using helical tomotherapy and its comparison to extended ssd technique. Medical Dosimetry. 2010; 35: 243-249 Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar Since 2017 our institution has been performing IMRT-based TBI conditioning for patients undergoing HSCT for SSc. Herein, we report treatment details, dosimetry, and clinical outcomes of these patients.