P575 Safety and efficacy of autologous haematopoietic stem cell transplantation for refractory Crohn’s disease after cyclophosphamide-free mobilisation: Preliminary Results
Giordano, A.(1);Rovira, M.(2);Barastegui, R.(1);Marín, P.(2);Martínez, N.(2);Fernández-Aviles, F.(2);Suárez-Lledó, M.(2);Doménech, A.(2);Ordás, I.(1);Fernández-Clotet, A.(1);Caballol, B.(1);Gallego, M.(1);Vara, A.(1);Masamunt, M.C.(1);Giner, A.(1);Corraliza, A.M.(3);Panés, J.(1);Salas, A.(3);Ricart, E.(1);
(1)IDIBAPS. Hospital Clínic, Inflammatory Bowel Disease Unit. Gastroenterology Department., Barcelona, Spain;(2)ICMHO. IDIBAPS. Institut Josep Carreras. Hospital Clínic, BMT Unit- Hematology Department., Barcelona, Spain;(3)Institut d'Investigacions Biomèdiques August Pi i Sunyer IDIBAPS, Inflammatory Bowel Disease Unit, Barcelona, Spain;
Background
Autologous haematopoietic stem cell transplantation [AHSCT] is a therapeutic option for patients with refractory Crohn's disease [CD]. Although the safety of the procedure has been improved over the last decade, AHSCT is still burdened by high adverse event rate due to chemotherapy toxicity and immunosuppression. The aim of this study was to evaluate the safety and efficacy of AHSCT by using a cyclophosphamide (Cy)-free mobilisation regimen followed by a standard conditioning approach.
Methods
A prospective observational study was conducted at Hospital Clínic of Barcelona in refractory CD patients undergoing AHSCT. Outpatient regimen with G-CSF 12-16 μg/kg/daily for 5 days was used for mobilisation. Patients who failed to achieve >2x106 CD34+ cells received Plerixafor 240 μg/d (1-2 doses). For conditioning, Cy and ATG were administered according to standard protocols. After transplant, patients were followed-up at regular intervals. Colonoscopy and/or magnetic resonance imaging were performed at baseline and at weeks 26, 52, 104 after AHSCT. Crohn's Disease Activity Index (CDAI) and SES-CD were used for clinical and endoscopic disease assessment.
Results
From June 2017 to October 2021, 14 refractory CD patients were enrolled (9F, median age 40 yr, median CDAI 204, median SES-CD 13); all of them achieved successful mobilisation (median collected CD34+ cells 7.7x106±2.8) and were transplanted. Patients were followed-up during a median of 71.5 months [0-104]. No SAEs or CD worsening were observed during mobilisation. The proportion of patients in clinical remission (CDAI<150) was 70% at 6 months, 43% at 1 yr and 60% at 2 yr. Median SES-CD was 3 at 6 months and 9 at 1 yr. The proportion of patients who restarted CD therapy for clinical relapse and/or endoscopic/radiological activity was 0% at 6 months, 30% at 1 yr and 40% at 2 yrs. AEs and SAEs during and after conditioning were comparable to previous series, being neutropenic fever the most frequently observed (54%). Colectomy due to refractory severe relapse was needed in one patient at 70 weeks from transplant.
Conclusion
Cy-free mobilisation is feasible and safe in refractory CD patients undergoing AHSCT but early relapse is observed in a significant proportion of patients. While representing an improvement on safety, studies exploring early reintroduction of drugs to decrease relapse rate after transplant are warranted.