Promising Outcomes Using Reduced-Intensity Conditioning Autologous Stem Cell Transplantation for Autoimmune Diseases

Autologous stem cell transplantation (ASCT) is a promising strategy for resetting the immune system and attaining long-term remission in patients with autoimmune diseases (AID). Although traditional myeloablative regimens are effective, they carry considerable risks, whereas reduced-intensity conditioning (RIC) offer a safer alternative with encouraging outcomes. This study reports ASCT outcomes at our institution for patients with AID using RIC. Data of adult patients, aged >/=18 years, with AID receiving ASCT between 5/2020- 8/2025 were analyzed. All patients received cyclophosphamide (Cy) 2 g/m 2 + G-CSF stem cell mobilization. Conditioning regimens were either Cy-ATG (Cy 50 mg/kg/day IV on D-5 to D-2 and ATG on D-5 to D-1 (total dose of 5.5 mg/kg), N=6 or Lite-BEAM-R (BCNU 300 mg/m 2 , etoposide 100 mg/m 2 and cytarabine 100 mg/m 2 q 12 h on D −5 to D−2, melphalan 100 mg/m 2 on D −1 and Rituximab 375 mg/m 2 on D+1 and D+8); N=17 Twenty-three patients were included in the analysis, including relapsing-remitting multiple sclerosis (RRMS; N=11), primary progressive MS (PPMS; N=7), secondary progressive MS (SPMS; N=2), stiff-person syndrome (SPS; N=2), and systemic sclerosis (N=1). The median age was 43 years (range 30-74). The median duration from diagnosis to ASCT was 4.7 years (range 1.2-16.5), with a median of 3 lines (range 0-6) of disease-modifying treatments (DMTs) administered. Indications for transplant included DMT failure (78%, N=18), intolerance (8.6%, N=2), and relapse after first ASCT/cellular therapy (13%, N=3). The median Expanded Disability Status Scale (EDSS) score was 5 (range 3-8), and pre-transplant MRI showed active demyelination lesions in 10 (50%) MS patients. Median hospitalization was 19 days (range 16-30). All patients achieved neutrophil and platelet engraftment by D+30 with median of 11 (range 10-20) and 12 (range 7-27) days, respectively. Twelve of 16 evaluated MS patients (75%) had decreased EDSS >/= 2 and none had active/new MRI lesion at 1 year. Median EDSS for all MS, RRMS, PPMS and SPMS at 1 year was 2 (range 0-7); 1 (range 0-2); 3.5 (range 0-7) and 2.5 (range 2-3) (Figure 1). The Octave® MS disease activity (MSDA) test at 1 year was available in 11 patients with 9, 2 and 0 patients were in low, moderate and high -risk group, respectively. Transplant complications within 100 days were, neutropenic fever (N=8), bacteremia (N=1), COVID pneumonia (N=1) and grade 1-2 mucositis (N=3). Overall survival and progression-free survival, cumulative incidence of relapse and transplant-related mortality at 3 years was 100%, 92%, 8% and 0% respectively. Post-transplant relapse occurred in 2 patients with SPS and PPMS who received Cy-ATG regimen (Figure 1.) RIC ASCT is a safe and effective treatment approach for autoimmune diseases, yielding promising and durable clinical outcomes, without the need for long-term immunosuppression.