1. ¹Pediatric Hematology and Oncology, Children's Hospital, Hannover Medical University, Hannover, Germany
2. ²Pediatric Metabolic Disease Section, Children's Hospital, Hannover Medical University, Hannover, Germany
3. ³Metabolic Laboratory, Department of Pediatrics, University Hospital Hamburg-Eppendorf, Hamburg, Germany
4. ⁴Institute of Human Genetics, University Hospital Hamburg-Eppendorf, Hamburg, Germany

Correspondence: Dr L Grigull, Pediatric Hematology and Oncology, Children's Hospital, Hannover Medical University, Carl-Neuberg-Str. 1, OE 6780, Hannover, Germany. E-mail: Grigull.Lorenz@mh-hannover.de

Received 29 April 2004; Accepted 25 October 2004; Published online 6 December 2004.

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 25 10⁶/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 (>10 10⁶/kg) and donor lymphocyte infusions, stable engraftment could be achieved in unrelated and mismatched related transplantations.