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

Vanderbilt University, Нашвилл, Michigan, United States
Genetics in Medicine (Impact Factor: 7.33). 03/2005; 7(2):143-6. DOI: 10.1097/01.GIM.0000154299.22120.6A
Source: PubMed


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.
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.
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).
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.

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Available from: Maged I Gharib, Jul 25, 2014
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    • "The proportion of unrelated versus related donors for HSCT has remained relatively stable as unrelated bone marrow donors have been replaced by unrelated cord blood donors. Use of laronidase in the peri-transplant period has been reported to be safe and well tolerated without interfering with engraftment or increasing the risk of graft-versus-host disease [6, 12, 16, 17, 31, 34]. Laronidase treatment may be particularly beneficial in patients in poor clinical condition prior to HSCT, to help improve their eligibility for transplant and tolerance of the full-intensity transplant conditioning [12, 16, 17, 24, 31]. "
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    • "Since ERT has shown to result in a significant and relatively rapid improvement of respiratory and cardiovascular function [7-11], ERT may ameliorate the pre-transplant condition of a patient. It was shown that ERT prior to HSCT is well tolerated and may significantly improve the pre-transplant condition in selected patients [33-36]. In addition, there is evidence that ERT does not negatively influence engraftment [33-36]. "
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    • "Eight patients had complete donor engraftment and 11 of 12 survived at a median time of follow-up of 3 months (1 child died of pulmonary hemorrhage). Based on these case studies, it was concluded that the ERT and HCT combination therapy is safe and feasible, but prospective studies were needed to further evaluate the outcomes of co-modality therapy (Grewal et al 2005). The European study lead by Cox-Brinkman et al (2006) also observed that ERT with HCT has been well tolerated. "
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