Safety and efficacy of enzyme replacement therapy in combination with hematopoietic stem cell transplantation in Hurler syndrome
| Autor: | James E. Wraith, Annet van Royen-Kerkhof, Charles Peters, Martha Dudek, Guy Young, Paul Woodard, Claudia Haase, Satkiran S. Grewal, Robert Wynn, Barbara K. Burton, Jose E. Abdenur, Nico M Wulffraat, Maged I. Gharib, David Sillence, Shalini Shenoy, Chester B. Whitley, Robert J. Hayashi, George E. Tiller |
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| Rok vydání: | 2005 |
| Předmět: |
Graft Rejection
Male congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty Mucopolysaccharidosis I Mucopolysaccharidosis medicine.medical_treatment Graft vs Host Disease Hematopoietic stem cell transplantation Gastroenterology Iduronidase Internal medicine medicine Humans Hurler syndrome Genetics (clinical) Transplant Conditioning business.industry Hematopoietic Stem Cell Transplantation Infant nutritional and metabolic diseases Enzyme replacement therapy medicine.disease Combined Modality Therapy Respiration Artificial Recombinant Proteins Transplantation Regimen Treatment Outcome surgical procedures operative Concomitant Acute Disease Immunology Female business |
| Zdroj: | Genetics in Medicine. 7:143-146 |
| ISSN: | 1098-3600 |
| DOI: | 10.1097/01.gim.0000154299.22120.6a |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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