title: Allogeneic hematopoietic cell transplantation (HCT) in Hurler's syndrome using a reduced intensity preparative regimen.
abstract: Allogeneic hematopoietic cell transplantation (HCT) in patients with Hurler's syndrome can improve survival and ameliorate many aspects of Hurler's syndrome including neurologic decline and cardiac compromise. Unfortunately, the toxicity of traditional preparative regimens to organs affected by the syndrome may have deleterious effects. Additionally, despite the intensity of these regimens, achieving stable donor chimerism can be difficult. We report transplant outcomes following a reduced intensity, highly immunosuppressive preparative regimen consisting of alemtuzumab, fludarabine and melphalan prior to HCT in seven patients with Hurler's syndrome treated at two centers. Six patients received grafts from unrelated donors and one received a sibling donor graft. The preparative regimen was well tolerated. All patients had initial donor engraftment at 100 days; one patient had delayed loss of donor chimerism. There was no severe acute GVHD (no GI GVHD of grade II or more, no grade IV skin GVHD). Six of the seven children are surviving at a median of 1014 (726-2222) days post transplant. This reduced intensity preparative regimen has the potential to support engraftment and improve survival and outcome in patients with Hurler's syndrome undergoing HCT.
authors.affiliation: Division of Hematology/Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA. Matthew.Hansen@cchmc.org
authors.forename: M D
authors.initials: MD
authors.lastname: Hansen
authors.forename: A H
authors.initials: AH
authors.lastname: Filipovich
authors.forename: S M
authors.initials: SM
authors.lastname: Davies
authors.forename: P
authors.initials: P
authors.lastname: Mehta
authors.forename: J
authors.initials: J
authors.lastname: Bleesing
authors.forename: S
authors.initials: S
authors.lastname: Jodele
authors.forename: R
authors.initials: R
authors.lastname: Hayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Barnes
authors.forename: S
authors.initials: S
authors.lastname: Shenoy
mesh_terms: D000293:Adolescent; D000328:Adult; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000627:therapeutic use; D002648:Child; D005260:Female; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008558:Melphalan / Q000627:therapeutic use; D008059:Mucopolysaccharidosis I / Q000628:therapy*; D010865:Pilot Projects; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D007166:Immunosuppressive Agents; D000074323:Alemtuzumab; D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan