P579 Complete disease resolution after allogenic hematopoietic stem cell transplantation in children with very early onset inflammatory disease and no identified monogenic mutation
Zambrano Perez A.*1, Elawad M.2, Kiparissi F.1, Shah N.1, Chadokufa S.1, Sider S.1, Huggett B.1
1Great Ormond Street Hospital for Children, Department of Gastroenterology, London, United Kingdom 2Sidra Medical and Research Center, Inflammatory Bowel Disorders Section, Doha, Qatar
Hematopoietic Stem Cell Transplantation (HSCT) may be curative in very early onset inflammatory bowel disease (IBD) when a monogenic defect is found. However, experience in paediatric patients without demonstrated underlying genetic defect is scarce. We present 4 children with severe IBD and unproven underlying monogenic disease who underwent reduced intensity conditioning HSCT.
Patient 1: A 3-year-old boy, born to consanguineous parents, presented with growth failure and chronic diarrhoea, investigations confirmed Crohn's disease (CD). He developed structuring gut disease, underwent colectomy and multiple ileal resections. He failed medical treatment including Infliximab and Basiliximab and became total parenteral nutrition (PN) dependent. He received HSCT from a matched family donor in 2008 at the age of 4. Patient 2: A 2-year-old girl presented with bloody diarrhoea. Histology confirmed unclassified IBD and she failed immunosuppressors and infliximab. At the age of 8 she developed a myelodisplastic syndrome and underwent a matched related donor HSCT for her hematologic condition in 2011. Patient 3: A 4-year-old boy born to non-consanguineous parents was found to have CD. He was refractory to standard medication, at age 6 he underwent colectomy and did not benefit from infliximab or adalimumab. He developed severe pyoderma gangrenosum. In 2013, at the age of 8 he received HSCT from a fully matched unrelated donor. Patient 4: A girl born to non-consanguineous parents had bloody diarrhoea and malnutrition at the age of 3. She had a panenteric granulomatous gut disease which did not respond to inmmunosuppressors and failed infliximab, adalimumab and sirolimus. She underwent a mismatched unrelated donor HSCT in 2014 when she was 9 years old.
Post BMT. Patient 1: One year post HSCT, he was asymptomatic, started to thrive and was weaned off PN. He has been in clinical and histological remission to date. Patient 2: After 7 months, bone marrow was in remission and colitis had completely resolved. She remains disease-free until date. Patient 3: After 3 months, pyoderma gangrenosum healed. He achieved sustained remission after one year and until date. Patient 4: One year post HSCT, she had developed a chronic skin graft versus host disease but her gut disease went into remission which sustained until now.
This is the first report of paediatric HSCT for refractory early onset IBD without identifiable monogenic disorder. Our patients went into sustained remission after HSCT having failed all medical treatment before that. Our cases illustrate that HSCT may still be curative to some selected patients with early onset IBD who are refractory to medical treatment. Larger studies are needed to support this.