Stable hematopoietic cell engraftment after low-intensity nonmyeloablative conditioning in patients with immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome.
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.
Burroughs
Lauri M
LM
Fred Hutchinson Cancer Research Center, Seattle, Wash 98109-1024, USA. burroug@fhcrc.org
Torgerson
Troy R
TR
Storb
Rainer
R
Carpenter
Paul A
PA
Rawlings
David J
DJ
Sanders
Jean
J
Scharenberg
Andrew M
AM
Skoda-Smith
Suzanne
S
Englund
Janet
J
Ochs
Hans D
HD
Woolfrey
Ann E
AE
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
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists; D016572:Cyclosporine; D014740:Vidarabine; D009173:Mycophenolic Acid; C024352:fludarabine