P967 Allogeneic bone marrow-derived mesenchymal stromal cell therapy for complex perianal and rectovaginal fistulas in Crohn´s disease: a retrospective single-centre study

Abstract

Abstract Background Perianal fistulising Crohn´s disease (CD) is associated with a high burden of disease and treatment of fistulas remains challenging. Promising data on short-term efficacy of bone marrow-derived mesenchymal stromal cell (bmMSC) treatment emerged in the recent past, but there is limited data regarding long-term efficacy and safety. Methods Between February 2013 and January 2016, patients with non-active CD (Harvey-Bradshaw Index < 5) and draining complex, treatment-refractory perianal or rectovaginal fistulas underwent local bmMSC therapy as compassionate use. After curettage of the fistula tract, patients received three local bmMSC injections biweekly with 20 million cells each. In case of incomplete clinical and radiological healing 3 to 12 months after the first treatment, up to six additional injections with 40 million cells each were administrated, resulting in a maximal cumulative dose of 300 million bmMSC (table 1). We retrospectively analysed patient records for disease course and documentation of adverse events. Clinical remission was defined by closure of external fistula openings without discharge at digital pressure. The modified Van Assche index was assessed before bmMSC treatment as well as in short- and long-term MRI follow-up. Results Six female patients (median age 35 years, range 19 – 46 years) with two or three complex fistulas each were included. In total, 13 fistulas (9 transsphincteric, 2 extrasphincteric and 2 rectovaginal) underwent local bmMSC application (table 1). Median radiological and clinical follow up was 80 months (range, 44 – 98 months) after first local bmMSC injection. 8 of 13 fistulas (62%) exhibited complete closure at last observation. For rectovaginal fistulas, long-term remission was 50 % (1 of 2). Excluding rectovaginal fistulas, 4 of 6 patients (67%) showed long-term closure of all other fistulas. Pelvic MRI showed a decrease in modified Van Assche index from baseline (median score 7.8, range 6.2-9.7) to long-term follow up (median score 2.1, range 1.5-11.7). No immediate adverse events related to bmMSC injections were observed. One patient (p1) was diagnosed with a local adenocarcinoma of the rectum (pT1, pN0, R0) 106 months after first bmMSC injection. MRI control 11 months prior showed complete fistula remission. The tumor exhibited a female karyotype, while bmMSC had been derived from a male volunteer. Conclusion More than 60% of all treatment-refractory CD perianal fistulas showed long-term remission up to 8 years after local allogenic bmMSC therapy.