OP05 Efficacy and safety of autologous hematopoietic stem cell transplantation in refractory Crohn’s disease: outcomes from the international stem cell transplant consortium
Authors: Guisado D , Colombel J F , Sands B , Gupta A , Makwana K , Masamunt M , Rovira M , Etra A , Salas A , Lindsay J O , Ricart E , Cohen L ,   international stem cell transplant consortium
Published: January 2025

Background

Autologous hematopoietic stem cell transplant (HSCT) emerged as a treatment for refractory CD after several clinical studies including a randomized clinical trial (ASTIC).1,2 In CD patients at risk for bowel failure these studies demonstrated an endoscopic response in over 80% of patients with two transplant related deaths. A recent randomized trial using an alternative fludarabine-based conditioning regimen had unexpected safety outcomes with 2 deaths and renal failure secondary to thrombotic microangiopathy.3 Here we report recent long-term clinical and safety outcomes of HSCT for refractory CD using a cyclophosphamide-ATG conditioning regimen from 3 international centers.

Methods

Data from 100 patients was reviewed from 3 international centers (Barts Health, UK; Hospital Clinic Barcelona, Spain and Mount Sinai, US) for subjects with medically refractory CD that underwent HSCT. We compiled clinical (CDAI) and endoscopic (SES-CD) evaluations at baseline and the last documented follow-up after HSCT for 68 patients that underwent HSCT since the ASTIC trial. We further compiled additional outcomes including new initiation of advanced therapy, IBD-related surgery, need for parental nutrition, hospitalizations and death.

Results

As of the last follow-up (median 2 years) post-HSCT, 75% of patients had endoscopic improvement (SES CD↓50%) and 53% endoscopic remission (SESCD&lt;4 ulcer sub-score&lt;1) (N = 56)(Figure 1). 65% of patients were in clinical remission. 46% did not require advanced therapy following HSCT and of patients that started an advanced therapy 84% required a single therapy over 120 patient-years of follow-up (Figure 2). After HSCT there were 7 CD-related surgeries of which 2 were ileostomy reversals. No patients progressed to bowel failure and there were no long-term (&gt;100 days post-HSCT) complications related to transplant including hospitalization, renal failure, death or malignancy.

Conclusion

In this multicenter international study, the majority of patients demonstrated sustained endoscopic and clinical improvement without progression to bowel failure or with long-term transplant related adverse events over 120 patient-years of follow up. These results support HSCT as a therapy for highly refractory CD patients and the need to refer these patients to international centers of expertise to prevent CD-related morbidity and mortality.

References

1.Lindsay JO, Allez M, Clark M, et al. Autologous stem-cell transplantation in treatment-refractory Crohn's disease: an analysis of pooled data from the ASTIC trial. Lancet Gastroenterol Hepatol. Jun 2017;2(6):399-406. doi:10.1016/S2468-1253(17)30056-0

2.Lopez-Garcia A, Rovira M, Jauregui-Amezaga A, et al. Autologous Hematopoietic Stem Cell Transplantation for Refractory Crohn's Disease: Efficacy in a Single-Centre Cohort. Journal of Crohn's & colitis. Apr 13 2017;doi:10.1093/ecco-jcc/jjx054

3.Lindsay JO, Hind D, Swaby L, et al. Safety and efficacy of autologous haematopoietic stem-cell transplantation with low-dose cyclophosphamide mobilisation and reduced intensity conditioning versus standard of care in refractory Crohn's disease (ASTIClite): an open-label, multicentre, randomised controlled trial. Lancet Gastroenterol Hepatol. Apr 2024;9(4):333-345. doi:10.1016/S2468-1253(23)00460-0