为推动我国细胞治疗与免疫治疗领域的创新发展，深入交流关键科学问题，共享最新临床研究进展，以全球视野促进该领域的协同合作与临床转化，由浙江大学、国际临床血液学学会（IACH）、浙江省免疫学会及浙江省抗癌协会联合主办，浙江大学医学院附属第一医院与良渚实验室联合承办的2025国际细胞治疗与免疫治疗大会（CTI 2025），于2025年11月13-16日在浙江杭州召开。会议期间，《肿瘤瞭望-血液时讯》特邀EBMT候任主席、法国里尔大学附属医院lbrahim Yakoub-Agha教授，就MDS诊疗中基因组学整合应用、异基因造血干细胞移植时机决策及未来治疗路径探索等核心议题展开深度对话，旨在为临床实践提供前沿视角与国际参考。

Q1

随着分子学和基因组学在 MDS 分层中的应用不断推进，您如何在临床决策中将基因突变谱）与经典评分系统结合来决定治疗策略（包括何时推荐 allo-SCT）？在可及分子靶向药物或临床试验的情形下，您会如何调整治疗顺序？

lbrahim Yakoub-Agha教授：目前，二代测序技术（NGS）及其所揭示的基因突变信息对于深入理解骨髓增生异常综合征（MDS）的疾病本质及优化临床管理具有重要意义。该技术有望在全球范围内进一步推广，正如我在会议中所指出，尽管修订版国际预后评分系统（IPSS-R）仍是目前有效的风险评估工具，但整合了基因突变信息的分子国际预后评分系统（IPSS-M）可能更具临床价值。该系统可将患者进一步划分为六个亚类，在维持低危、中危和高危总体框架的同时，尤其有助于疾病早期阶段的精准分层，从而为部分患者提供重新分类的依据，并对治疗策略的制定（如是否进行移植）起到指导作用。

在异基因造血干细胞移植后，基因突变信息仍可用于患者的随访监测。当前MDS领域尚缺乏标准化的可测量残留病评估方法，而移植后二代测序检测可为这一方面提供有益补充。在部分病例中，例如存在IDH2突变的患者，可应用相应抑制剂进行靶向治疗；尽管针对TP53突变等目前仍缺乏有效手段，但未来有望实现更为个体化的治疗策略。总体而言，二代测序技术现阶段的主要价值体现在提升患者风险分层精度、优化治疗决策以及移植后疾病监测等方面。

With genomic profiling increasingly informing risk stratification in MDS, how do you integrate mutation data with traditional scores such as IPSS-R when deciding treatment—particularly timing of allogeneic SCT? In settings where targeted agents or trials are available, how do you alter treatment sequencing?

Actually, NGS and gene mutations are very important nowadays in understanding MDS and managing patients. Hopefully, these techniques will be disseminated worldwide because, as I mentioned during the conference, IPSS-R is still a valid scoring system, but IPSS-M, which integrates gene mutations, may be a better system. We can now break down the patient population into six categories, while still retaining the lower-risk, higher-risk, and intermediate-risk stratifications. This is important at the initial stage because we can reclassify some patients and decide whether to perform transplantation or not as a treatment option, for instance. 

Even after transplantation, we can follow up with those patients through these mutations. Currently, there is no true measurable residual disease (MRD) for MDS, but post-transplant NGS can assist with this. In a few cases, we can use some targeted molecules, as we now have inhibitors for IDH2, for example. For TP53 mutations, we do not have sufficient effective treatments, but perhaps we can achieve personalized treatment for MDS in the future. Currently, NGS helps us better classify patients, better determine the treatment plan, and may also support follow-up after transplantation.

Q2

关于移植时机与移植适应证，近年EBMT /大型队列研究和综述对“是否在低/中风险但具有恶性分子学标志或进行性血细胞减少的患者提前移植”存在不同观点。结合您在 allo-HCT 领域的临床实践，能否分享您在患者选择、移植前桥接策略的具体判定逻辑？

lbrahim Yakoub-Agha教授：对于年龄小于70岁且不伴有合并症的高危骨髓增生异常综合征患者，通常建议采用前期移植策略。然而，对于中危患者以及部分低危或较低危患者，是否实施移植仍存在一定争议。

若患者携带上述基因突变，正如前所述，临床实践中有时会转而选择前期移植，而非等待原始细胞比例升高等疾病进展迹象。这是由于此类突变往往提示疾病可能快速进展，因此有必要将移植纳入治疗考虑。

Recent EBMT and some studies present differing views on transplant timing—particularly whether to offer early allo-HCT for lower/intermediate-risk patients who harbour adverse molecular markers or progressive cytopenias. Based on your transplant practice, could you describe your decision logic for patient selection, pre-transplant bridging?

So for patients aged less than 70 years old with no comorbidities and higher-risk MDS, we would recommend upfront transplantation. We are still hesitant regarding patients with intermediate-risk MDS, as well as some patients with low-risk or lower-risk MDS. As you mentioned, for those patients harboring these gene mutations, we sometimes switch to upfront transplantation instead of waiting for an increase in the number of blasts, etc., because we can foresee rapid disease progression, so we need to consider transplantation for these patients.

Q3

展望未来，鉴于 MDS 治疗领域快速涌现的靶向药物，免疫治疗和细胞疗法，以及移植并发症防治的新进展，您认为未来对 MDS 临床管理会出现哪些最有可能改变临床路径的实践？对于临床人员与研究者而言，在哪些研究空白应当优先填补？

lbrahim Yakoub-Agha教授：这是一个至关重要的议题。目前我们尚未取得显著突破，因此无法给出明确答案。但需指出，对于低危MDS患者，当前管理策略已较过去显著优化——我们能够切实提供治疗以减少输血依赖，并有效实施铁过载管理方案。

针对高危患者群体，除移植治疗外，我强烈建议临床同仁在条件允许时优先纳入临床试验。鉴于诸多新型药物正处于研发阶段，通过系统性探索这些创新疗法，有望最终改善MDS患者的预后结局。

这种基于循证医学的决策框架，既体现了对现有治疗手段的科学评估，又为未来个体化治疗路径的拓展奠定了实践基础，符合现代血液病学精准化、规范化的发展方向。

Looking forward，with emerging targeted agents, immunotherapies/cellular approaches, and advances in transplant-related complication management, which advances do you expect will most likely change MDS clinical pathways in the future? For clinicians and researchers, which evidence gaps should be prioritised?

This is a very important question. I don't have a clear answer for this because we haven't made that much progress right now. However, I can tell you that for patients with lower-risk MDS, we can now manage those patients better than in the past, and we can really provide them with treatment to reduce transfusion dependency, for instance, or effectively manage iron overload in those patients. For patients with higher-risk MDS, beyond transplantation, I really encourage our colleagues to include those patients in clinical trials whenever possible, because we really need to explore all these emerging new drugs to see if we can truly change the prognosis of this disease.

专家简介

lbrahim Yakoub-Agha 教授

法国里尔大学附属医院

自2008 年起担任法国里尔大学医院造血干细胞移植及细胞治疗科（Hematopoietic Stem Cell Transplantation Unit）负责人。

在EBMT中担任多个重要职务：曾任“慢性恶性肿瘤工作组”(Chronic Malignancies Working Party, CMWP) 主席（2018-2022）

当前担任EBMT“实践协调与指南”（Practice Harmonisation & Guidelines）委员会主席。

曾任法国骨髓移植与细胞治疗学会(SFGM-TC)会长（2012-2016）。

在学术出版方面，他是期刊 Current Research in Translational Medicine 的主编。