Mixed haematopoietic chimerism for sickle cell disease prevents intravascular haemolysis.
Mixed haematopoietic chimerism for sickle cell disease prevents intravascular haemolysis.
复制标题
镰状细胞病的混合造血嵌合可防止血管内溶血。
DOI：
10.1111/j.1365-2141.2007.06803.x
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发表时间：
2007
影响因子：
6.5
通讯作者：
Krishnamurti,Lakshamanan
中科院分区：
文献类型：
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作者：
Wu,CatherineJ;Gladwin,Mark;Tisdale,John;Hsieh,Matthew;Law,Terence;Biernacki,Melinda;Rogers,Shelby;Wang,Xunde;Walters,Mark;Zahrieh,David;Antin,JosephH;Ritz,Jerome;Krishnamurti,Lakshamanan
最近的研究表明，持续性血管内溶血是镰状细胞病（SCD）的一个定义性特征，与严重的长期后果相关，包括肺动脉高压，其2年死亡率高达50%（Castro et al，2003）。因此，开发纠正血管内溶血及其并发症的疗法越来越被认为对SCD患者的长期预后很重要。造血干细胞移植（HSCT）是SCD的一种潜在治愈性疗法，最近支持性治疗的改善和强度降低的预处理方案的开发已大大减轻了移植手术即刻毒性的严重程度（Locatelli，2006）。当使用较低强度的预处理方案时，宿主造血不完全消除，并且经常导致混合造血嵌合体。持续性受体红细胞生成对血管内溶血的影响尚不清楚，但预计会使血管内溶血永久化。最近已经确定了几种血清生物标志物与SCD患者的内皮损伤、肺动脉高压和预期早期死亡率密切相关。这些包括可溶性血管细胞粘附分子1（sVCAM-1）水平增加、一氧化氮（NO）消耗增加、血浆游离血红蛋白（Hb）增加和精氨酸/鸟氨酸比值倒置（Solovey et al，1997; Reiter et al，2002; Morris et al，2005）。使用这些参数，我们研究了部分供体植入纠正9例SCD患者血管内溶血的潜力，从而有可能避免长期SCD相关并发症的发生。
Recent studies suggest that persistent intravascular haemolysis, a defining feature of sickle cell disease (SCD), is associated with severe long-term consequences, including pulmonary hypertension, which carries a 2-year mortality rate of up to 50%(Castro et al, 2003). Thus, the development of therapies that correct intravascular haemolysis and its complications are increasingly recognized as important for the long-term prognosis of the SCD patient. Haematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for SCD, and recent improvements in supportive care and the development of reduced-intensity conditioning regimens have substantially lessened the severity of the immediate toxicities of the transplant procedure (Locatelli, 2006). When lower intensity conditioning regimens are utilized, host haematopoiesis is incompletely eliminated, and mixed haematopoietic chimerism frequently results. The effects of persistent recipient erythro-poiesis on intravascular haemolysis are unknown, but would be anticipated to perpetuate intravascular haemolysis. Several serum biomarkers have been recently identified to strongly correlate with endothelial damage, pulmonary hypertension and prospective early mortality in SCD patients. These include increased soluble vascular cellular adhesion molecule 1 (sVCAM-1) levels, increased nitric oxide (NO) consumption, increased plasma free haemoglobin (Hb), and inverted arginine/ornithine ratio (Solovey et al, 1997; Reiter et al, 2002; Morris et al, 2005). Using these parameters, we examined the potential of partial donor engraftment to correct intravascular haemolysis in nine SCD patients, and hence to potentially avert the development of long-term SCD-associated complications.