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Hurler Syndrome

Outcome of 27 patients with Hurler's syndrome transplanted from either related or unrelated haematopoietic stem cell sources

Summary:

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/m2 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 × 108 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.

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Acknowledgements

We thank the assistant physicians, nurses and medical staff of the Immuno-haematology & Paediatric Bone Marrow Transplant Unit, Debrousse Hospital, for their support and commitment (Prof Philippe, Dr K Kebaili, Dr R Mardini) and the physicians and technicians of Histocompatibility Laboratory in Lyon, for their efforts and efficient collaboration (Dr A Eljaafari, Dr D Rigal, Dr JP Tremisi, JP Bourgeot, Ph Debost, S Rey). All of them have contributed to help the patients. We also address special thanks to Prof C Peters and Dr N Whitaker for their constructive and useful suggestions in reviewing the manuscript.

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Souillet, G., Guffon, N., Maire, I. et al. Outcome of 27 patients with Hurler's syndrome transplanted from either related or unrelated haematopoietic stem cell sources. Bone Marrow Transplant 31, 1105–1117 (2003). https://doi.org/10.1038/sj.bmt.1704105

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Keywords

  • Hurler's syndrome
  • mucopolysaccharidosis
  • unrelated donor
  • related donor
  • haematopoietic stem cell transplantation
  • HLA
  • thymoglobuline

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