Over the last 15 years, we have performed a total of 30 haematopoietic stem cell transplants on 27 children suffering from
Hurler's syndrome. These children were of median age 11 months at the time of diagnosis and 25 months at the time of
transplantation. The phenotype was severe in 21 cases (78%). The donor was familial in 13 cases: nine genotypically identical, one phenotypically identical father and three HLA-mismatched donors. Unrelated donors were selected in 17 cases: four phenotypically identical and 13 with 1-4 HLA mismatches. The conditioning regimen generally consisted of
busulphan 600 mg/m(2) plus
cyclophosphamide (
Endoxan) 260 mg/kg and
cyclosporin with
methotrexate for GvHD prophylaxis. Rabbit
anti-thymocyte globulin (Thymoglobuline) was given for all unrelated or familial mismatched
transplantations. The median nucleated cell dose infused was 6.00 x 10(8) TNC/kg. No bone marrow (apart from one) was T cell depleted. For first transplants, engraftment was observed in 23/27 patients (pts) (85%). Primary graft failure was observed in 4/27 patients (16%), two were retransplanted from an unrelated donor, one with success. Four patients have died. The primary cause of death was
infection in three cases (TRM : 11%) and
disease progression in one case, after primary graft failure. Of the 23 living patients, two have
disease progression after graft failure and 21 (78%) have functional grafts with a favourable long-term outcome after a median follow-up of 4.7 years, having either full or mixed chimaerism. Among surviving patients with functional grafts, 13 (62%) were transplanted from unrelated donors of whom 10 (77 %) had HLA disparities. There was a remarkably low incidence of GvHD. In our experience, haematopoietic
stem cell transplantation using an HLA-matched familial donor or an HLA-matched or -mismatched unrelated donor without T cell depletion or irradiation can achieve a favourable outcome in
Hurler's syndrome, with improved cognitive function, but with a limited effect on the corneas and skeleton.