Safety and efficacy of enzyme replacement therapy in combination with hematopoietic stem cell transplantation in Hurler syndrome

Satkiran S. Grewal*, Robert Wynn, Jose E. Abdenur, Barbara K. Burton, Maged Gharib, Claudia Haase, Robert J. Hayashi, Shalini Shenoy, David Sillence, George E. Tiller, Martha E. Dudek, Annet Van Royen-Kerkhof, James E. Wraith, Paul Woodard, Guy A. Young, Nico Wulffraat, Chester B. Whitley, Charles Peters

*Corresponding author for this work

Research output: Contribution to journalArticle

71 Scopus citations

Abstract

Purpose: Hurler syndrome is a debilitating genetic disease with a typical life span of 5 to 8 years. Early hematopoietic stem cell transplantation (HSCT) mitigates disease symptoms and improves survival. However, morbidity and mortality associated with HSCT can limit its success. We describe the initial experience with combined use of enzyme replacement therapy (ERT, laronidase) and HSCT in Hurler syndrome. Methods: Thirteen transplants were performed in 12 patients. ERT was given at a standard dose of 0.58 mg/kg per week. Transplant conditioning regimen and donor graft source were determined by institutional protocol. Results: The median age at initiation of ERT was 12 months (range, 8 to 18 months). The median duration of pre-HSCT ERT was 12 weeks (range, 4 to 28). All but 1 patient tested showed decrease in urinary GAG excretion during ERT. ERT infusion-related toxicity was limited to mild reactions. Development of antibodies to laronidase did not correlate with infusion reactions or responses in urinary GAG excretion. ERT was given for a median of 7 weeks (range, 3 to 20) after HSCT. After transplantation, eight patients demonstrated complete donor engraftment and four suffered graft failure. Two patients required ventilator support and three developed acute GVHD. Eleven of the 12 patients are surviving with a median follow-up of 3 months (range, 1 to 7 months). Conclusions: In children with Hurler syndrome, ERT with HSCT is feasible and well tolerated. Development of antibodies against exogenous enzyme does not appear to correlate with infusion reactions or response to ERT. A prospective study is needed to determine the effect of concomitant ERT on transplant outcomes.

Original languageEnglish (US)
Pages (from-to)143-146
Number of pages4
JournalGenetics in Medicine
Volume7
Issue number2
DOIs
StatePublished - Feb 2005

Keywords

  • Enzyme replacement therapy
  • Hematopoietic stem cell transplantation
  • Hurler syndrome
  • Laronidase
  • Mucopolysaccharidosis

ASJC Scopus subject areas

  • Genetics(clinical)

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