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P580 Allogeneic hematopoetic stem cell transplantation to treat refractory Inflammatory Bowel Disease in an X-CGD carrier with non-random X-inactivation

F. Hauck1, S. Koletzko*2, P. Bufler2, A. Klenk1, I. Schmid1, C. Klein1, M.H. Albert1

1Dr. von Hauner Children's Hospital, Ludwig Maximilians University , Pediatric Hematology/Oncology/Immunology/Stem Cell Transplantation,, Munich, Germany, 2Dr. von Hauner Children's Hospital, Ludwig Maximilians University , Pediatric Gastroenterology/Hepatology, Munich, Germany

Background

Five genetic traits are known to cause chronic granulomatous disease (CGD), but the most common one is X-linked CGD (X-CGD) due to hemizygous mutations in CYBB. CGD is characterized by invasive bacterial and fungal infections accompanied by granulomatous inflammation. Inflammatory bowel disease (IBD) can be an additional or isolated manifestation. Allogenic hematopoietic stem cell transplantation (alloHSCT) is the standard curative treatment. X-CGD carriers normally show random X-chromosome inactivation and retain 50% of NADPH-oxidase activity. Nevertheless, they can develop aphthous stomatitis and discoid lupus erythematosus. In rare cases, X-CGD carriers present with non-random X-chromosome inactivation and, depending on the remaining NADPH-oxidase activity, can develop invasive bacterial and fungal infections (activity <10%) or autoinflammatory manifestations (activity 10-15%).

Methods

We report on an X-CGD carrier with non-random X-chromosome inactivation and NADPH-oxidase activity of 30%. At the age of 12 years, she developed severe Crohn-like IBD that was refractory to treatment with exclusive enteral nutrition, immunosuppression (steroids, methotrexate, azathioprine and 3 different anti-TNF drugs. As her clinical course aggravated over time she received 03/2014 alloHSCT from a matched unrelated donor (10/10) after conditioning with submyeloablative targeted busulfan, fludarabine and alemtuzumab at the age of 20 years.

Results

The patient engrafted at day +15 without any major complications and no signs of graft versus host disease (GVHD). Four months post-tx being off any IBD-medication her colon had macroscopically healed with normalization of fecal calprotectin, but the known stenosis in the left colon remained. A recent clinical and endoscopic flare was successfully treated with short term antibiotics.

Conclusion

Screening for CGD is recommanded in young patients with refractory IBD. To our knowledge, this is the first case of an X-CGD carrier with non-random X-chromosome inactivation and IBD who has been successfully treated with alloHSCT.