Transplantation of allogeneic CD34-selected stem cells after fludarabine-based conditioning regimen for children with mucopolysaccharidosis 1H (M. Hurler). 
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.