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%). W e 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.