Joseph Rosenthal教授：在肿瘤学领域，包括儿科肿瘤学，正在经历快速和戏剧性的变化。这种转变的核心是向更有针对性的靶向治疗过渡，旨在靶向精准杀灭癌细胞，同时对周围健康组织造成的伤害最小。在造血干细胞移植领域，这种变化的形式是从大剂量的清髓疗法转到移植物中包含的整个细胞库到输入选定的修饰细胞的更具体的过程，例如CAR-T细胞，或工程化的，由预定组合物中的选定细胞制成的移植物，例如使用TCRαβ和CD45RA缺失细胞，以实现足够的移植物抗白血病作用，同时进一步降低GVHD的风险。许多这类研究首先在儿科学方面开创了先河。 CD19 CAR-T细胞治疗首先在患有前B急淋的儿童中进行研究。类似地，在儿科中首次报道了移植工程，以证明在限制GVHD的严重性和程度的同时，保留甚至增强改良移植物的抗白血病作用的潜力。

The field of oncology in general， including pediatric oncology， is undergoing rapid and dramatic changes. The core of this transformation is the transition towards more targeted therapies， aimed at hitting cancer cells while causing minimal harm to surrounding healthy tissues. In the field of hematopoietic stem cell transplantation this change has the form of moving from mega-dose myeloablative therapy followed by transfusion the whole repertoire of cells contained in a graft to more specific processes  of either transfusion of selected modified cells， such as CAR-T cells， or engineering a graft made of selected cells in a pre-determined composition， such as the use of TCRαβ and CD45RA deleted cells， in order to achieve adequate graft-versus leukemia effect while minimizing the risks of GVHD. Many of these modalities have been first pioneered in pediatrics. CD19 CAR-T-cells therapy where first investigated in children with pre-B acute leukemia. Similarly， graft engineering was first reported in pediatrics to demonstrate the potential of preserving， and even augmenting the anti-leukemic effect of a modified graft while limiting the severity and extent of GVHD.

Joseph Rosenthal教授：CAR-T细胞疗法已被证明是有效的，并且初步结果显示CAR-T细胞疗法异基因造血干细胞移植相比具有相似的无白血病存活率，显示CAR-T治疗具有良好的毒性特征， CAR-T疗法的短期不良反应则可以取代移植带来的长期严重并发症。这些结果表明该治疗方式可能在治疗复发性或难治性白血病时取代异基因造血干细胞移植。该领域正在迅速发展，需要回答的问题是：（1）如何降低CAR-T细胞治疗后“逃逸”白血病的发生率。除CD19 CAR T细胞外，该产品是否应含有其他CAR-T细胞如CD22？ （2）如何维持CAR-T细胞的长寿命以提供持续的疗效？（3）减轻与当前CAR-T细胞疗法相关的严重急性毒性的最佳方法是什么？

此外，还存在很多挑战包括：（1）我们如何将CAR-T细胞疗法的使用扩展到B细胞恶性肿瘤（ALL和B细胞淋巴瘤）之外？ （2）AML的最佳目标是什么？ （3）治疗实体瘤需要多个靶点吗？如果是这样，未来可能在各种癌症类型中发挥最佳作用。

所有这些问题都指向我们有一个新型且有效的工具，但需要学习很多东西，我们才能在更广泛的条件下成功使用它。

The use of CAR-T-cell therapies has been shown to be effective， and preliminary results show similar leukemia free survival between allogeneic HCT and CAR-T-cell therapy， with a favorable toxicity profile， exchanging long-term severe complications of HCT with the short term effects of CAR-T therapy. These results suggest the possibility of this modality replacing allogeneic HCT in the treatment of relapsed or refractory leukemia. The field is rapidly evolving， questions that are left to be answered are: (1) how to decrease the rate of “escape” leukemia after CAR-T cell therapy. Should the product contain other CAR-T cells such as CD22 in addition to CD19 CAR T cells? (2) How to maintain long longevity of CAR-T cells to provide continuous efficacy (3) What are the best ways  to mitigate the severe acute toxicities associated with current CAR-T cell therapies. In addition， other challenges are: (1) How can we expand the use of CAR-T cell therapies beyond B cell malignancies (ALL and B-cell lymphomas)? (2) What would be the best target for AML? (3) Will we need multiple targets in treating solid tumors? And if so， which will work the best in various cancer types.

All these questions point out that we have a new effective tool， but a lot needs to be learned how can we use it successfully in a larger spectrum of conditions.