Cord blood is the optimal graft source for the treatment of pediatric patients with lysosomal storage diseases: clinical outcomes and future directions
Cord blood is the optimal graft source for the treatment of pediatric patients with lysosomal storage diseases: clinical outcomes and future directions
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DOI：
10.1016/j.jcyt.2015.03.609
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发表时间：
2015-06-01
期刊：
影响因子：
4.5
通讯作者：
Kurtzberg, Joanne
中科院分区：
文献类型：
--
作者：
Aldenhoven, Mieke;Kurtzberg, Joanne
最初用作没有人类白细胞抗原匹配骨髓或外周血干细胞供体的患者的替代造血干细胞来源，无关脐带血（UCB）现在是使用造血干细胞移植（HSCT）治疗溶酶体贮积症（LSD）患者时的首选供体来源。如果不进行移植，这些患者会出现严重的进行性多系统恶化和过早死亡。 UCB 移植有利于改变这些疾病的自然史并延长生存期。它主要通过健康移植的供体细胞替代细胞酶来发挥作用，为全身提供连续的内源性酶供应，并在中枢神经系统中彻底移植供体来源的小胶质细胞。 LSD 中的 HSCT 大部分是在粘多糖增多症和白细胞营养不良患者中进行的，与非常高的植入率和存活率相关。重要的是，与其他供体来源相比，UCB 的受者更常实现完全供体嵌合和酶水平正常化，这与优异的长期临床预后相关。此外，UCB 单位很容易获得，减少了移植时间，从而提供了年轻时接受移植的机会，这是长期神经发育功能的另一个非常重要的预测因素。由于这些原因，UCB 移植物现在被认为是 LSD 患者进行 HSCT 的最佳移植物来源。
Initially used as an alternative hematopoietic stem cell source for patients without a human leukocyte antigen matched bone marrow or peripheral blood stem cell donor, unrelated cord blood (UCB) is now the preferred donor source when hematopoietic stem cell transplantation (HSCT) is used to treat patients with lysosomal storage disorders (LSD). Without transplantation, these patients have serious progressive multi-system deterioration and premature death. UCB transplantation favorably alters the natural history of these diseases and prolongs survival. It primarily works through cellular enzyme replacement by healthy engrafted donor cells providing a continuous endogenous supply of enzyme throughout the body and, thorough engraftment of donor-derived microgial cells, in the central nervous system. HSCT in LSD, the majority performed in patients with mucopolysaccharidoses and leukodystrophies, is associated with remarkably high rates of engraftment and survival. Importantly, recipients of UCB, as compared with other donor sources, more often achieve full-donor chimerism and normalization of enzyme levels, which has been associated with superior long-term clinical prognosis. Additionally, UCB units are readily available, reducing time to transplantation and thereby providing access to transplant at young ages, another highly important predictor for long-term neuro-developmental function. For these reasons, UCB grafts are nowadays considered to be the optimal graft source for HSCT in patients with LSD.