Biochemical monitoring after haemopoietic stem cell transplant for Hurler syndrome (MPSIH): implications for functional outcome after transplant in metabolic disease

Bone Marrow Transplant. 2007 Feb;39(4):207-10. doi: 10.1038/sj.bmt.1705569. Epub 2007 Jan 15.

Abstract

Hurler Syndrome is corrected by allogeneic BMT by the action of donor enzyme on recipient tissue. In this paper, we describe monitoring of 39 patients transplanted in two centres to determine donor chimerism, enzyme level and residual substrate - expressed as dermatan sulphate to chondroitin sulphate ratio. We show that in fully engrafted recipients, the enzyme level, expressed as mumol/g total protein/h, post-transplant is 24.2 from an unrelated donor and 10.2 from a heterozygote family donor (P<0.0001). There is a tight relationship between mean post-transplant enzyme level and residual substrate - Spearman's rank correlation coefficient (Rho) was -0.76 and -0.80 at 12 and 24 months, respectively (P<0.0001). We propose that these differences affect patient outcome. As unrelated donor transplant outcomes improve and especially given the higher levels of donor cell engraftment following cord transplants, our data might influence donor selection where only heterozygote-matched family members are available.

Publication types

  • Multicenter Study

MeSH terms

  • Chimerism*
  • Chondroitin Sulfates / metabolism
  • Chondroitin Sulfates / urine
  • Cord Blood Stem Cell Transplantation
  • Dermatan Sulfate / metabolism
  • Dermatan Sulfate / urine
  • Glycosaminoglycans / urine
  • Hematopoietic Stem Cell Transplantation*
  • Heterozygote
  • Histocompatibility Testing
  • Humans
  • Iduronidase / metabolism*
  • Mucopolysaccharidosis I / therapy*
  • Transplantation, Homologous / physiology
  • Treatment Outcome

Substances

  • Glycosaminoglycans
  • glucosaminoglycans
  • Dermatan Sulfate
  • Chondroitin Sulfates
  • Iduronidase