title: Stable hematopoietic cell engraftment after low-intensity nonmyeloablative conditioning in patients with immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome.
abstract: BACKGROUND
  Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is characterized by severe systemic autoimmunity caused by mutations in the forkhead box protein 3 (FOXP3) gene. Hematopoietic cell transplantation is currently the only viable option for long-term survival, but patients are frequently very ill and may not tolerate traditional myeloablative conditioning regimens.
  
  
  OBJECTIVE
  Here we present the outcome of hematopoietic cell transplantation using a low-intensity, nonmyeloablative conditioning regimen in 2 patients with IPEX syndrome and significant pretransplant risk factors.
  
  
  METHODS
  Two high-risk patients with IPEX syndrome received HLA-matched related bone marrow or unrelated peripheral blood stem cell grafts following conditioning with 90 mg/m(2) fludarabine and 4 Gy total body irradiation. Postgrafting immunosuppression consisted of mycophenolate mofetil and cyclosporine. Immune reconstitution and immune function was evaluated by measurement of donor chimerism, regulatory T-cell numbers, absolute lymphocyte subsets, and T-cell proliferation assays.
  
  
  RESULTS
  Both patients experienced minimal conditioning toxicity and successfully engrafted after hematopoietic cell transplantation. With a follow-up of 4 and 1 years, respectively, patients 1 and 2 have full immune function and normal FOXP3 protein expression.
  
  
  CONCLUSIONS
  A low-intensity, nonmyeloablative conditioning regimen can establish stable engraftment and correct the life-threatening immune deficiency and enteropathy of IPEX syndrome despite the presence of comorbidities that preclude conventional hematopoietic cell transplantation.
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Wash 98109-1024, USA. burroug@fhcrc.org
authors.forename: Lauri M
authors.initials: LM
authors.lastname: Burroughs
authors.forename: Troy R
authors.initials: TR
authors.lastname: Torgerson
authors.forename: Rainer
authors.initials: R
authors.lastname: Storb
authors.forename: Paul A
authors.initials: PA
authors.lastname: Carpenter
authors.forename: David J
authors.initials: DJ
authors.lastname: Rawlings
authors.forename: Jean
authors.initials: J
authors.lastname: Sanders
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Scharenberg
authors.forename: Suzanne
authors.initials: S
authors.lastname: Skoda-Smith
authors.forename: Janet
authors.initials: J
authors.lastname: Englund
authors.forename: Hans D
authors.initials: HD
authors.lastname: Ochs
authors.forename: Ann E
authors.initials: AE
authors.lastname: Woolfrey
mesh_terms: D000293:Adolescent; D002469:Cell Separation; D002648:Child; D016572:Cyclosporine / Q000627:therapeutic use; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics; D040181:Genetic Diseases, X-Linked / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D006086:Graft vs Host Disease / Q000209:etiology / Q000473:pathology / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007223:Infant; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D019653:Myeloablative Agonists / Q000627:therapeutic use; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013577:Syndrome; D019172:Transplantation Conditioning / Q000379:methods*; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use; D014916:Whole-Body Irradiation
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists; D016572:Cyclosporine; D014740:Vidarabine; D009173:Mycophenolic Acid; C024352:fludarabine