1. ¹Department of Immunology/BMT, Wilhelmina Children's Hospital, Utrecht Medical Center, Utrecht, The Netherlands
2. ²Willink Biochemical Genetics Unit and Department of Haematology/BMT, Royal Manchester Children's Hospital, Manchester, UK
3. ³Department of Haematology and Oncology, Our Lady's Hospital for Sick Children, Dublin, Ireland
4. ⁴Department of BMT, Great Ormond Street Hospital, London, UK
5. ⁵Department of Paediatric Immuno-Hematology and Bone Marrow Transplantation, Debrousse Hospital, Lyon, France
6. ⁶Department of Pediatric Immuno-Hematology, Necker-Enfants Malades Hospital, Paris, France
7. ⁷Department of Biotherapy, Hopital Necker-Enfants Malades, Paris, France
8. ⁸Department of Pediatric Hematology and Oncology, Children's Hospital Hannover Medical University, Hannover, Germany
9. ⁹Department of Pediatric Hematology and Oncology, University Hospital Motol, Prague, Czech Republic
10. ¹⁰Centro Trapianto Midollo Osseo, Clinica Pediatrica dell'Università di Milano-Bicocca, Ospedale San Gerardo, Monza, Italy
11. ¹¹Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands

Correspondence: Dr JJ Boelens, Department of Immunology/BMT, Wilhelmina Children's Hospital, University Medical Center Utrecht, Lundlaan 6, Utrecht 3584 EA, The Netherlands. E-mail: J.J.Boelens@umcutrecht.nl

¹²For the Working Party Inborn Errors of the European Blood and Marrow Transplantation (EBMT) group.

Received 1 February 2007; Revised 17 April 2007; Accepted 19 April 2007; Published online 28 May 2007.

Abstract

Hurler's syndrome (HS), the most severe form of mucopolysaccharidosis type-I, causes progressive deterioration of the central nervous system and death in childhood. Allogeneic stem cell transplantation (SCT) before the age of 2 years halts disease progression. Graft failure limits the success of SCT. We analyzed data on HS patients transplanted in Europe to identify the risk factors for graft failure. We compared outcomes in 146 HS patients transplanted with various conditioning regimens and grafts. Patients were transplanted between 1994 and 2004 and registered to the European Blood and Marrow Transplantation database. Risk factor analysis was performed using logistic regression. 'Survival' and 'alive and engrafted'-rate after first SCT was 85 and 56%, respectively. In multivariable analysis, T-cell depletion (odds ratio (OR) 0.18; 95% confidence interval (CI) 0.04–0.71; P=0.02) and reduced-intensity conditioning (OR 0.08; 95% CI 0.02–0.39; P=0.002) were the risk factors for graft failure. Busulfan targeting protected against graft failure (OR 5.76; 95% CI 1.20–27.54; P=0.028). No difference was noted between cell sources used (bone marrow, peripheral blood stem cells or cord blood (CB)); however, significantly more patients who received CB transplants had full-donor chimerism (OR 9.31; 95% CI 1.06–82.03; P=0.044). These outcomes may impact the safety/efficacy of SCT for 'inborn-errors of metabolism' at large. CB increased the likelihood of sustained engraftment associated with normal enzyme levels and could therefore be considered as a preferential cell source in SCT for 'inborn errors of metabolism'.