L-leucine improves anemia and growth in patients with transfusion-dependent Diamond-Blackfan anemia: Results from a multicenter pilot phase I/II study from the Diamond-Blackfan Anemia Registry.
L-leucine improves anemia and growth in patients with transfusion-dependent Diamond-Blackfan anemia: Results from a multicenter pilot phase I/II study from the Diamond-Blackfan Anemia Registry.
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DOI：
10.1002/pbc.28748
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发表时间：
2020-12
影响因子：
3.2
通讯作者：
Lipton JM
中科院分区：
文献类型：
--
作者：
Vlachos A;Atsidaftos E;Lababidi ML;Muir E;Rogers ZR;Alhushki W;Bernstein J;Glader B;Gruner B;Hartung H;Knoll C;Loew T;Nalepa G;Narla A;Panigrahi AR;Sieff CA;Walkovich K;Farrar JE;Lipton JM
Diamond Blackfan贫血（DBA）是一种遗传性骨髓衰竭综合征，以贫血、身材矮小、先天性异常和癌症易感性为特征。大多数病例是由于编码核糖体蛋白（RP）的基因突变导致RP单倍不足。DBA贫血的有效治疗方法包括长期输注红细胞、长期糖皮质激素治疗或造血干细胞移植。在一个小的患者系列和动物模型中，对L-亮氨酸有血液学反应，并改善贫血。本临床试验的研究目的是确定L-亮氨酸在输血依赖型DBA患者中的可行性、安全性和有效性。年龄≥2岁的患者口服L-亮氨酸700 mg/m2，每日3次，持续9个月，以确定血液学应答和生长的任何改善。（NCT01362595）。这项多中心、I/II期研究入组了55例受试者; 43例可评价。有21名男性;入组时的中位年龄为10.4岁（范围：2.5-46.1岁）。没有显著的不良事件归因于L-亮氨酸。2例受试者有完全红系反应，5例有部分反应。在治疗结束时，25例受试者中的9例和25例受试者中的11例分别发生了正的体重和身高百分位数变化。L-亮氨酸是安全的，导致16%的DBA受试者出现红系反应，并分别导致36%和44%的可评价受试者体重和线性生长速度增加。进一步的研究对于了解L-亮氨酸在DBA患者管理中的作用至关重要。
Diamond Blackfan anemia (DBA) is an inherited bone marrow failure syndrome characterized by anemia, short stature, congenital anomalies and cancer predisposition. Most cases are due to mutations in genes encoding ribosomal proteins (RP) leading to RP haploinsufficiency. Effective treatments for the anemia of DBA include chronic red cell transfusions, long-term corticosteroid therapy or hematopoietic stem cell transplantation. In a small patient series and in animal models there have been hematologic responses to L-leucine with amelioration of anemia. The study objectives of this clinical trial were to determine feasibility, safety and efficacy of L-leucine in transfusion-dependent patients with DBA. Patients ≥2 years of age received L-leucine 700 mg/m2 orally three times daily for 9 months to determine a hematologic response and any improvement in growth. (NCT01362595). This multicenter, phase I/II study enrolled 55 subjects; 43 were evaluable. There were 21 males; median age at enrollment was 10.4 years (range, 2.5–46.1 years). No significant adverse events were attributable to L-leucine. Two subjects had a complete erythroid response and five had a partial response. Nine of 25, and 11 of 25, subjects experienced a positive weight and height percentile change, respectively, at the end of therapy. L-leucine is safe, resulted in an erythroid response in 16% of subjects with DBA, and led to an increase in weight and linear growth velocity in 36% and 44% of evaluable subjects, respectively. Further studies will be critical to understand the role of L-leucine in the management of patients with DBA.
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影响因子：
20.3
作者：
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通讯作者：
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影响因子：
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DOI：
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发表时间：
2014-06
影响因子：
6.2
作者：
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通讯作者：
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影响因子：
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