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P365 Autologous haematopoietic stem cell transplantation in refractory Crohn’s disease: experience of a Brazilian tertiary centre

J. Oba*1,2, F. Steinwurz2, A. Scanavini Neto3, O. Ambrogini4, C. Silva5, S. Nakashima5, M. Santos5, N. Hamerschlak6

1São Paulo University Medical School, Pediatric, São Paulo, Brazil, 2Hospital Israelita Albert Einstein, GI, São Paulo, Brazil, 3Hospital Israelita Albert Einstein, Surgery, São Paulo, Brazil, 4UNIFESP-EPM, GI, SP, Brazil, 5Hospital Israelita Albert Einstein, Research, São Paulo, Brazil, 6Hospital Israelita Albert Einstein, Oncology-hematology, São Paulo, Brazil

Background

A significant percentage of Crohn’s disease (CD) patients suffer an aggressive disease course, refractory to available approved medical therapies. Increasing evidence supports Autologous Haematopoietic Stem Cell Transplantation (AHSCT) could be a therapeutic option.1

Methods

Six patients between 19 years and 43 years, with refractory CD were submitted to AHSCT. Median course of illness was 14 years (5–23 years) and all were negative for X-linked inhibitor apoptosis protein (XIAP). Four patients had penetrating disease and two had non-stricturing, non-penetrating phenotype. All patients failed to a median of 6 lines mono or combined therapies. Five patients had 2 to 3 previous intestinal surgeries and four had ileostomy and extraintestinal manifestations. Two patients had tuberculosis previously. All patients completed the mobilisation, apheresis, conditioning and transplantation phases, during a time of hospitalisation of 35 days (21–58 days). We postulate the use of CD34(+) selection with Miltenyi Biotec system to improve the results based on the memory cells decrease.2 Stem cells were mobilised from the peripheral blood using cyclophosphamide (2 g/m2) and G-CSF (10 μg/kg/day), enriched ex vivo by CD34(+) selection, and reinfused after immune suppressive conditioning with cyclophosphamide (200 mg/kg) and (rabbit antithymocyte globulin [ATG] (5 mg/kg))

Results

During mobilisation and after transplantation all six patients had life-threatening complications and severe infectious as KPC and Staphylococcus aureus blood infection, reactivation of cytomegalovirus disease and septic shock by E. coli. All had febrile neutropenia, mucositis, anaemia. We did not have any deaths. After 1y follow-up all six patients achieved the primary and secondary outcomes: clinical and endoscopic remission (images 1 and 2)

Sigmoid colon CD patient 1 year 4 months post-AHSCT.

Pre-AHSCT.

and steroid and immunosuppressive free remission (CDAI <150). Currently, all six patients are alive without any malignancy complications and the longest period is 3 years 3 months. All patients relate viral and bacterial infections. Only one patient restarted adalimumab, 1 years 11 months post-AHSCT

Conclusion

We consider AHSCT may be a promising therapeutic option for treatment refractory CD patients. The high complexity, toxicity, risk of death and infections, more accurate protocols need to be discussed between GI and onco-haematology professionals and centre around the world.

References

1. Snowden JA, Panés J, Alexander T, et al. Autologous Haematopoietic Stem Cell Transplantation (AHSCT) in severe Crohns's disease. J Crohns Colitis 2018;12:476–488.

2. Burt RK, Taylor A, Oyama Y, et al. High-dose immune suppression and autologous hematopoietic stem cell transplantation in refractory Crohn disease. Blood, 2003;101:2064–2066.