Safety and efficacy of enzyme replacement therapy in combination with hematopoietic stem cell transplantation in Hurler syndrome
Safety and efficacy of enzyme replacement therapy in combination with hematopoietic stem cell transplantation in Hurler syndrome
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DOI：
10.1097/01.gim.0000154299.22120.6a
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发表时间：
2005-02-01
影响因子：
8.8
通讯作者：
Peters, C
中科院分区：
文献类型：
--
作者：
Grewal, SS;Wynn, R;Peters, C
目的：Hurler综合征是一种使人衰弱的遗传性疾病，典型的寿命为5至8年。早期造血干细胞移植（HSCT）可减轻疾病症状并提高生存率。然而，与HSCT相关的发病率和死亡率可能限制其成功。我们描述了在Hurler综合征中联合使用酶替代疗法（ERT，laronidase）和HSCT的初步经验。方法：12例患者共进行了13次移植。ERT的标准剂量为0.58 mg/kg/周。移植预处理方案和供体移植物来源由机构方案确定。结果：开始ERT治疗时的中位年龄为12个月（范围：8 - 18个月）。HSCT前ERT的中位持续时间为12周（范围：4 - 28周）。除1例患者外，所有检测患者均显示ERT期间尿GAG排泄减少。ERT输注相关毒性仅限于轻度反应。laronidase抗体的产生与输注反应或尿GAG排泄反应无关。HSCT后给予ERT中位时间为7周（范围3 - 20周）。移植后，8例患者表现出完全的供体植入和4个移植失败。2例患者需要呼吸机支持，3例发生急性GVHD。12例患者中有11例存活，中位随访时间为3个月（范围：1至7个月）。结论：在Hurler综合征患儿中，ERT联合HSCT是可行的，耐受性良好。抗外源性酶抗体的产生似乎与输注反应或对ERT的反应无关。需要进行一项前瞻性研究来确定伴随ERT对移植结局的影响。
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.