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 ؋ 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)

Long-Term Functional Outcomes of Children with Hurler Syndrome Treated with Unrelated Umbilical Cord Blood Transplantation

“…The safety and efficacy of UCBT from unrelated donors was similar to that reported by previous studies (Staba et al 2004;Martin et al 2006;Prasad et al 2008). However, this is the only comprehensive prospective longitudinal study on a large cohort of patients with Hurler syndrome who were evaluated before and after transplanta- Fig.…”

“…Somatic disease was evaluated at various departments at Duke University, University of North Carolina, or University of Minnesota. The transplant data of all the patients were previously reported (Prasad et al 2008;Orchard et al 2010). This study was reviewed by the institutional review board of the University of North Carolina at Chapel Hill.…”

“…Prophylaxis against graft-versus-host disease (GvHD) was given using cyclosporine for 9 months and methylprednisolone for 2-3 months. Supportive care was provided as previously described (Staba et al 2004;Thomas et al 2006;Prasad et al 2008). Most patients underwent tonsillectomy, adenoidectomy, and pressure-equalizing tube placement before transplant.…”

“…There is evidence of improved neurocognitive outcomes after umbilical cord blood transplantation (UCBT) in children with Hurler syndrome, adrenoleukodystrophy, and Krabbe disease, particularly when performed early in the disease course (Staba et al 2004;Escolar et al 2005;Beam et al 2007;Prasad et al 2008). Various studies of UCBT in Hurler syndrome patients report high rates of sustained engraftment with full donor chimerism and normal IDUA activity (Staba et al 2004;Martin et al 2006;Prasad et al 2008). Furthermore, umbilical cord blood is readily available, reducing the time between diagnosis and transplantation, which is important for optimal prognosis (Staba et al 2004;Escolar et al 2005).…”

Early Umbilical Cord Blood-Derived Stem Cell Transplantation Does Not Prevent Neurological Deterioration in Mucopolysaccharidosis Type III

“…The lower enzyme activity in the heterozygous donor cells may have impacted on the efficacy of enzymatic cross-correction, as has been demonstrated for MPS I (Wynn et al 2009). Indeed, a more recent study suggested a moderate positive effect of UCBT on CNS disease in MPS III patients, with a more prominent effect in patients that were transplanted at a younger age (Prasad et al 2008).…”