title: Unrelated donor umbilical cord blood transplantation for inherited metabolic disorders in 159 pediatric patients from a single center: influence of cellular composition of the graft on transplantation outcomes.
abstract: Outcomes of 159 young patients with inherited metabolic disorders (IMDs) undergoing transplantation with partially HLA-mismatched unrelated donor umbilical cord blood were studied to investigate the impact of graft and patient characteristics on engraftment, overall survival (OS), and graft-versus-host disease (GVHD). Patients received myeloablative chemotherapy (busulfan, cyclophosphamide, ATG) and cyclosporine-based GVHD prophylaxis. Infused cell doses were high (7.57 x 10(7)/kg) because of the patients' young age (median, 1.5 years) and small size (median, 12 kg). Median follow-up was 4.2 years (range, 1-11 years). The cumulative incidences of neutrophil and platelet engraftment were 87.1% (95% confidence interval [CI], 81.8%-92.4%) and 71.0% (95% CI, 63.7%-78.3%). A total of 97% achieved high (> 90%) donor chimerism. Serum enzyme normalized in 97% of patients with diseases for which testings exist. Grade III/IV acute GVHD occurred in 10.3% (95% CI, 5.4%-15.2%) of patients. Extensive chronic GVHD occurred in 10.8% (95% CI, 5.7%-15.9%) of patients by 1 year. OS at 1 and 5 years was 71.8% (95% CI, 64.7%-78.9%) and 58.2% (95% CI, 49.7%-66.6%) in all patients and 84.5% (95% CI, 77.0%-92.0%) and 75.7% (95% CI, 66.1%-85.3%) in patients with high (80-100) performance score. In multivariate analysis, favorable factors for OS were high pretransplantation performance status, matched donor/recipient ethnicity, and higher infused colony forming units.
authors.affiliation: Pediatric Blood and Marrow Transplant Program, Duke University Medical Center, Durham, NC, USA. vinod.prasad@duke.edu .
authors.forename: Vinod K
authors.initials: VK
authors.lastname: Prasad
authors.forename: Adam
authors.initials: A
authors.lastname: Mendizabal
authors.forename: Suhag H
authors.initials: SH
authors.lastname: Parikh
authors.forename: Paul
authors.initials: P
authors.lastname: Szabolcs
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Driscoll
authors.forename: Kristin
authors.initials: K
authors.lastname: Page
authors.forename: Sonali
authors.initials: S
authors.lastname: Lakshminarayanan
authors.forename: June
authors.initials: J
authors.lastname: Allison
authors.forename: Susan
authors.initials: S
authors.lastname: Wood
authors.forename: Deborah
authors.initials: D
authors.lastname: Semmel
authors.forename: Maria L
authors.initials: ML
authors.lastname: Escolar
authors.forename: Paul L
authors.initials: PL
authors.lastname: Martin
authors.forename: Shelly
authors.initials: S
authors.lastname: Carter
authors.forename: Joanne
authors.initials: J
authors.lastname: Kurtzberg
mesh_terms: D000293:Adolescent; D000328:Adult; D001792:Blood Platelets / Q000166:cytology; D002423:Cause of Death; D002648:Child; D002675:Child, Preschool; D036101:Cord Blood Stem Cell Transplantation; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000628:therapy; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D008661:Metabolism, Inborn Errors / Q000401:mortality / Q000628:therapy*; D015999:Multivariate Analysis; D009504:Neutrophils / Q000166:cytology; D015996:Survival Rate; D014019:Tissue Donors; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology