Elenga Narcisse, Loko Gylna, Etienne-Julan Maryse, Al-Okka Randa, Adel Ahmad M, Yassin Mohamed A
Centre Hospitalier de Cayenne, Cayenne, France.
Centre de reference de la drepanocytose, CHU de la Guadeloupe, Pointe-à Pitre, Guadeloupe, France.
Front Med (Lausanne). 2022 Aug 1;9:931925. doi: 10.3389/fmed.2022.931925. eCollection 2022.
L-glutamine has been shown to play an important role in the regulation of oxidative stress which is one of the key contributors to the pathophysiology of sickle cell disease (SCD). In a Phase 3 clinical trial, L-glutamine demonstrated a significant reduction in SCD-related complications including vaso-occlusive crises (VOCs), hospitalizations, and acute chest syndrome (ACS) compared to placebo in patients with SCD.
The primary objective was to confirm the efficacy of L-glutamine (Endari) therapy in pediatric and adult patients with SCD at follow-up time points of 24, 48 and 72 weeks.
In the observational study, nineteen patients with SCD were treated orally with L-glutamine twice daily for 72 weeks. Clinical and laboratory parameters were measured at baseline and follow-up time points. Patients with severe VOC and ACS were hospitalized. Blood transfusion was given in case of ACS and uncontrolled pain associated with VOC despite administration of the highest dose of intravenous (IV) narcotic.
Compared to baseline, patients had significantly fewer pain crises (median change from 3.0 to 0.0; < 0.00001), hospitalizations (median change from 3.0 to 0.0; < 0.00001), days of hospitalization (median change from 15.0 to 0.0; < 0.00001), and blood transfusions (median change from 3.0 to 0.0; < 0.00001) at 24, 48, and 72 weeks following L-glutamine therapy. Moreover, there was a drastic decrease in the number of ACS events during this time. A significant increase was observed in mean hemoglobin levels and hematocrit proportions from baseline to 72 weeks ( < 0.001). Conversely, compared to baseline, mean reticulocyte counts and lactate dehydrogenase (LDH) levels were considerably lower at follow-up time points ( = 0.003 and < 0.001, respectively). No patient reported treatment-related adverse events.
Although the sample size was small, our data clearly demonstrated that L-glutamine therapy was safe and significantly improved clinical outcomes and hemolysis parameters in patients with SCD.
L-谷氨酰胺已被证明在氧化应激调节中发挥重要作用，氧化应激是镰状细胞病（SCD）病理生理学的关键促成因素之一。在一项3期临床试验中，与安慰剂相比，L-谷氨酰胺在SCD患者中显著降低了与SCD相关的并发症，包括血管闭塞性危机（VOCs）、住院次数和急性胸综合征（ACS）。
主要目的是在24、48和72周的随访时间点确认L-谷氨酰胺（Endari）疗法对小儿和成人SCD患者的疗效。
在这项观察性研究中，19例SCD患者每天口服L-谷氨酰胺两次，持续72周。在基线和随访时间点测量临床和实验室参数。患有严重VOC和ACS的患者住院治疗。尽管给予了最高剂量的静脉（IV）麻醉剂，但如果发生ACS和与VOC相关的无法控制的疼痛，则进行输血。
与基线相比，在L-谷氨酰胺治疗后的24、48和72周，患者的疼痛危机显著减少（中位数从3.0降至0.0；<0.00001）、住院次数（中位数从3.0降至0.0；<0.00001）、住院天数（中位数从15.0降至0.0；<0.00001）和输血次数（中位数从3.0降至0.0；<0.00001）。此外，在此期间ACS事件的数量急剧下降。从基线到72周，平均血红蛋白水平和血细胞比容比例显著增加（<0.001）。相反，与基线相比，随访时间点的平均网织红细胞计数和乳酸脱氢酶（LDH）水平显著降低（分别为=0.003和<0.001）。没有患者报告与治疗相关的不良事件。
尽管样本量较小，但我们的数据清楚地表明，L-谷氨酰胺疗法是安全的，并且显著改善了SCD患者的临床结局和溶血参数。
