Submyeloablative Cord Blood Transplant Corrects Clinical Defects Seen in IPEX Syndrome.

IPEX syndrome (immune dysfunction, polyendocrinopathy, enteropathy, X-linked) is a disorder of regulatory T cell function caused by mutations in the FOXP3 gene. This disorder is generally associated with a fatal outcome early in life from complications related to bleeding, infection, or enteritis. Allogeneic stem cell transplant (SCT) can be curative for this disorder, but pre-transplant disease-related complications may preclude a full myeloablative conditioning regimen. We report a seven year old boy with IPEX whose pre-transplant course was complicated by recurrent laryngeal papillomas and severe airway obstruction, frequent pulmonary infections, and recurrent gastrointestinal hemorrhage. Due to these problems he underwent a submyeloablative conditioning regimen consisting of fludarabine 30 mg/m2/day for 6 days, Busulfan 0.8 mg/kg/dose every 6 hours for 2 days, then anti-thymocyte globulin 2.5 mg/kg/dose for 4 days. Mycophenylate and cyclosporine were used for graft versus host disease (GVHD) prophylaxis. This patient received an HLA 5/6 matched (A,B,DR) unrelated donor cord blood transplant with 1.1 ×10⁸ total nucleated cells/kg and 3 × 10⁵ CD34+ cells/kg. His diarrhea and airway issues resolved following the conditioning regimen. The patient achieved myeloid engraftment on day 14, and was platelet and red cell transfusion independent by day 29 and 56, respectively. He had 81% and 98% donor chimerism at 2 and 9 months post-transplant, respectively. While tapering cylcosporine he developed graft versus host disease of the lower GI tract, which was sucessfully treated with a course of corticosteroids. He also experienced reactivation of EBV and was treated with 4 weekly doses (375 mg/m2) of anti-CD20 monoclonal antibody. This patient has had full resolution of his clinical symptoms and is currently 17 months post-transplant, with no signs of GVHD. For those children who do not respond or have only partial improvement following immunosuppressive therapy, allogeneic SCT using a submyeloablative approach can be well tolerated and result in sustained donor chimerism.