Cellular therapies in acute lymphoblastic leukemia.
Cellular therapies in acute lymphoblastic leukemia.
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DOI：
10.1016/j.hoc.2011.09.015
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发表时间：
2011-12
期刊：
影响因子：
--
通讯作者：
Brentjens R
中科院分区：
文献类型：
--
作者：
Park JH;Sauter C;Brentjens R
大多数患有急性淋巴细胞白血病（ALL）的成年患者会死于他们的疾病。虽然儿科患者的预后明显更好，但在所有情况下，复发性或难治性疾病患者的预后均较差。来自相关供体的异基因造血干细胞移植（HSCT）可以为某些患者提供显着的潜在治疗益处。由于大多数患者缺乏合适的相关供体，替代的allo-HSCT方法，包括无关的，脐带血（UCB），和单倍体相合的allo-HSCT，已经开发出来，并越来越多地在临床环境中进行研究。降低强度预处理进一步扩展了老年合并症患者接受allo-HSCT的机会。虽然在HSCT后复发性ALL患者中使用供体来源的T细胞过继治疗的结果一致令人沮丧，但目前正在进行临床研究，其中包括输注富集的肿瘤靶向供体T细胞和遗传靶向T细胞。最后，针对ALL基因修饰的自然杀伤（NK）细胞也正在临床试验中进行研究，进一步扩大了难治性或复发性ALL患者的治疗选择。这些新的过继细胞疗法是否最终能改善临床结果还有待观察。
A majority of adult patients with acute lymphoblastic leukemia (ALL) will die of their disease. While the prognosis for pediatric patients is markedly better, in all cases, the prognosis in patients with relapsed or refractory disease is uniformly poor. Allogeneic hematopoietic stem cell transplantation (HSCT) from a related donor can offer a significant potential therapeutic benefit for some patients. Since most patients lack a suitable related donor, alternative allo-HSCT approaches, including unrelated, umbilical cord blood (UCB), and haploidentical allo-HSCT, have been developed and are increasingly being studied in the clinical setting. Reduced-intensity conditioning further extends access to allo-HSCT for older more comorbid patients. While the use of donor-derived T cell adoptive therapy has a uniformly dismal outcome in patients with relapsed ALL following HSCT, modified adoptive T cell regimens, including the infusion of enriched tumor-targeted donor T cells and genetically targeted T cells, are currently under clinical investigation with promising results. Lastly, natural killer (NK) cells genetically modified to target ALL are also being studied in clinical trials, further expanding therapeutic options for patients with refractory or relapsed ALL. What remains to be seen is whether these novel adoptive cell therapies will ultimately lead to improved clinical outcomes.
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