title: Transplantation of allogeneic CD34-selected stem cells after fludarabine-based conditioning regimen for children with mucopolysaccharidosis 1H (M. Hurler).
abstract: Hurler syndrome (MPS1H) is a progressive inborn error of mucopolysaccharide metabolism leading to premature death. Allogeneic hematopoietic cell transplantation (HCT) can achieve stabilization and improve long-term survival. However, large studies have shown that preparative regimen-related toxicity (RRT) and graft failure rates have been relatively high. We transplanted five Hurler children with a fludarabine-based conditioning regimen, consisting of fludarabine/busulphan/ATG for matched family donor (MFD), with the addition of melphalan for mismatched family donor and matched unrelated donor (MUD) transplantations. Median age at HCT was 27 months (range 10-36). The source of stem cells was bone marrow in one MFD and CD34-selected PBSC in four patients. Median CD34+ cell dose was 25 x 10(6)/kg (range 11.5-54). No RRT > grade II was observed. All patients are surviving at a median of 32 months (range 14-41) and show sustained donor engraftment with 3/5 having full donor chimerism, and 2/5 mixed chimerism (> 85%). We conclude that this regimen is feasible and has low toxicity in Hurler children. In combination with high doses of CD34+ selected cells (> 10 x 10(6)/kg) and donor lymphocyte infusions, stable engraftment could be achieved in unrelated and mismatched related transplantations.
authors.affiliation: Pediatric Hematology and Oncology, Children's Hospital, Hannover Medical University, Hannover, Germany. Grigull.Lorenz@mh-hannover.de
authors.forename: L
authors.initials: L
authors.lastname: Grigull
authors.forename: A
authors.initials: A
authors.lastname: Beilken
authors.forename: M
authors.initials: M
authors.lastname: Schrappe
authors.forename: A
authors.initials: A
authors.lastname: Das
authors.forename: T
authors.initials: T
authors.lastname: Luecke
authors.forename: A
authors.initials: A
authors.lastname: Sander
authors.forename: M
authors.initials: M
authors.lastname: Stanulla
authors.forename: K
authors.initials: K
authors.lastname: Rehe
authors.forename: M
authors.initials: M
authors.lastname: Sauer
authors.forename: H
authors.initials: H
authors.lastname: Schmid
authors.forename: K
authors.initials: K
authors.lastname: Welte
authors.forename: Z
authors.initials: Z
authors.lastname: Lukacs
authors.forename: A
authors.initials: A
authors.lastname: Gal
authors.forename: K W
authors.initials: KW
authors.lastname: Sykora
mesh_terms: D018952:Antigens, CD34; D000961:Antilymphocyte Serum / Q000008:administration & dosage; D002066:Busulfan / Q000008:administration & dosage; D002675:Child, Preschool; D006085:Graft Survival; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006648:Histocompatibility; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D017710:Lymphocyte Transfusion; D008059:Mucopolysaccharidosis I / Q000628:therapy*; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage* / Q000031:analogs & derivatives*
chemical_list: D018952:Antigens, CD34; D000961:Antilymphocyte Serum; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine