title: Fludarabine-based protocol for haploidentical peripheral blood stem cell transplantation in Hurler syndrome.
abstract: To assess the feasibility of performing a haploidentical peripheral blood stem cell transplantation (PBSCT) in a child with Hurler syndrome after a novel conditioning regimen consisting of fludarabine monophosphate, anti-T-lymphocyte globulin, low-dose busulfan, and single-dose total body irradiation of 750 cGy. A 16-month old boy with Hurler syndrome underwent haploidentical PBSCT from his 3/6 HLA-matched sister. Pretransplant conditioning consisted of fludarabine (30 mg/m2 per day) from day -10 to day -5, busulfan (4 mg/kg per day) on days -7 and -6, rabbit anti-T-lymphocyte globulin (10 mg/kg per day) from day -4 to day -1, and total body irradiation of 750 cGy on day -1. In vitro T-cell depletion was carried out with rat antihuman CDw52 monoclonal antibody (Campath-1G). The fludarabine-based protocol was well-tolerated, with mild toxicity and no major transplant-related complications or graft-versus-host disease. Engraftment was complete and stable. Chimerism was 100% donor origin, as determined by restriction fragment length polymorphism. Cytogenetic and polymerase chain reaction-various number of tandem repeats (PCR-VNTR) analyses of peripheral blood and bone marrow showed 100% reconstitution with female donor cells. The patient underwent the transplant 30 months ago and is in good clinical condition, with normal counts, no signs of graft-versus-host disease, and no infectious episodes; neurologic signs have stabilized. Haploidentical PBSCT, T-cell-depleted by means of Campath-1G, may serve as a therapeutic alternative for patients with Hurler syndrome when a fully matched sibling is not available.
authors.affiliation: Department of Bone Marrow Transplantation, Hadassah University Hospital, Jerusalem, Israel.
authors.forename: J
authors.initials: J
authors.lastname: Kapelushnik
authors.forename: H
authors.initials: H
authors.lastname: Mandel
authors.forename: G
authors.initials: G
authors.lastname: Varadi
authors.forename: A
authors.initials: A
authors.lastname: Nagler
mesh_terms: D000293:Adolescent; D000818:Animals; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008059:Mucopolysaccharidosis I / Q000628:therapy*; D011817:Rabbits; D051381:Rats; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D007166:Immunosuppressive Agents; D014740:Vidarabine; C024352:fludarabine