2015年慢性淋巴细胞白血病细胞治疗的引擎：CAR-T细胞异体...

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A drive through cellular therapy for CLL in 2015: allogeneic cell transplantation and CARs

2015年慢性淋巴细胞白血病细胞治疗的引擎：CAR-T细胞异体移植

介绍：

异基因造血干细胞移植（SCT）被认为是潜在治疗一些慢性淋巴细胞白血病（CLL）的方法。然而， CLL的治疗过程是一个持续变化的管理过程，有很多新的或很快会有前途的治疗方案观点，这些治疗方案有显著的活性、较低的毒性以及方便的管理计划。传统的化疗组合如使用氟达拉滨和利妥昔单抗，环磷酰胺仍然是护理具有良好状态CLL病人的标准方案。然而，直到现在，具有不良风险特征和身体状态不好年老的病人接受免疫化疗，以及难治性复发性病人的治疗方案非常有限。

虽然最新的治疗CLL的方案，例如使用药物ibrutinib或者idelalisib，几乎很少产生完全的缓解。它们仅有的部分缓解疾病的能力就更迫切了治疗CLL需要引入新的治疗方法。正如十年之前，引入酪氨酸激酶抑制剂（TKI）伊马替尼治疗慢性粒细胞白血病（CML）。现在也不再确定，使用能够起效但是会引起较高后遗症和死亡率的治疗方案是否是CLL疾病治疗所需要的。移植治疗方案的作用在新的治疗时代已经得到很好的证明。此外，转基因的嵌合抗原受体（CAR）为持久活性的T细胞治疗提供了机会，利用细胞治疗CLL而不需要SCT。虽然经验仍然有限，但是这种治疗不再是不可能实现的，并且我们相信会发展出一种新的安全的，确实有活性的免疫治疗方法来治疗CCL。

Introduction

Allogeneic stem cell transplantation (SCT) is considered potentially curative for some patients with chronic lymphocytic leukemia(CLL). However, there is an ongoing transformation in CLL management with a plethora of new or soon-to-be-available promising experimental treatment options with remarkable activities, favorable toxicity profiles, and convenient administration schedules.

Conventional immunochemotherapy combinations such as fludarabine, cyclophosphamide, and rituximab remain the standard of care for CLL patients with a good performance requiring treatment. However, patients with poor-risk features and older patients have inferior outcomes following immunochemotherapy and treatment options in the relapse-refractory settings have been quite limited until recently.

Although the newest approved therapies for CLL such as ibrutinib or idelalisib rarely result in complete remissions (CRs), their abilities to partially overcome poor-risk prognostic features highlight why new therapies call into question the goals of treatment of CLL.As was the case more than a decade earlier with the introduction of the tyrosine kinase inhibitor (TKI) imatinib for chronic myelogenous leukemia (CML), it is now less clear that treatment with curative intention but with high treatment-related morbidity and mortality is required for long-term survival in CLL; the role for transplant in the new treatment era has recently been nicely reviewed. In addition, the suggestion of durable activity of genetically modified chimeric antigen receptor (CAR) T cells presents the opportunity to harness the power of cellular therapy for CLL without the need for SCT. Though experience remains limited and follow-up relatively short, it is no longer taboo or a great stretch of the imagination to think we will develop new safer immunotherapies for CLL that may indeed have curative activity.

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