摘要：2025年8月22日至23日，由中国北京健康促进会与广州市红棉肿瘤和罕见病公益基金会联合主办、北京陆道培血液病研究院承办的第十三届陆道培血液病学术大会在京隆重召开。本次会议汇集全球顶尖血液学专家，聚焦造血干细胞移植、细胞治疗、血液肿瘤精准诊疗等核心议题，为千余

2025年8月22日至23日，由中国北京健康促进会与广州市红棉肿瘤和罕见病公益基金会联合主办、北京陆道培血液病研究院承办的第十三届陆道培血液病学术大会在京隆重召开。本次会议汇集全球顶尖血液学专家，聚焦造血干细胞移植、细胞治疗、血液肿瘤精准诊疗等核心议题，为千余名参会者呈现了一场高规格、深层次的学术盛宴。会议期间，EBMT当选主席、法国里尔大学附属医院Ibrahim Yakoub-Agha教授分享了“骨髓增生性肿瘤的异基因造血干细胞移植（Allo-HCT for Myeloproliferative Neoplasms）”的精彩报告。《肿瘤瞭望-血液时讯》特邀Ibrahim Yakoub-Agha教授围绕核心问题展开深入对话，以期为优化细胞治疗领域提供重要的实践指导与理论参考。

PART.1

在目前以JAK 抑制剂作为桥接治疗的实践中，您如何判断患者从药物控制期过渡到尽早进行异基因造血干细胞移植的最佳时机？在您中心，这一决策主要受哪些预后指标影响？

Ibrahim Yakoub-Agha教授：骨髓纤维化（MF）是一种慢性骨髓增殖性肿瘤，其治疗决策需基于个体化风险评估。对于部分患者而言，异基因造血干细胞移植可作为潜在治愈性手段，但需严格把握适应证。并非所有患者均适合移植，且诊断后无需立即启动移植程序，而应通过动态监测评估疾病进展风险。

动态国际预后评分系统（DIPSS）作为经典且仍具临床价值的评估工具，强调需在不同时间节点对患者进行重复评估，依据血红蛋白水平、白细胞计数、骨髓原始细胞比例、体质性症状及是否存在染色体核型异常等指标，将患者划分为高风险组与低风险组。

对于高风险患者，异基因造血干细胞移植可作为推荐治疗策略；而低风险患者则以定期监测为主，辅以JAK抑制剂等靶向药物控制症状。临床决策需综合考虑患者整体状况：首先评估是否存在影响移植耐受性的合并症（如严重心肺功能不全），通常以70岁作为移植年龄上限；其次需精准评估疾病本身特征，通过DIPSS等工具明确风险分层；最后需优化移植方案，包括供者选择（如HLA匹配程度、供者年龄及健康状况）及移植预处理方案的制定，以确保治疗安全性与有效性。

With JAK inhibitors commonly used as a bridging therapy, how do you determine the optimal timing to proceed to allo-HCT for a patient with MF? Which prognostic factors most influence that decision in your center?

Pro. Ibrahim Yakoub-Agha：Myelofibrosis (MF) is a chronic disease. For some patients, allogeneic hematopoietic stem cell transplantation is required as it represents a more effective therapeutic option. However, not all patients are candidates for allogeneic transplantation, and intervention is not necessarily indicated immediately after diagnosis. In practice, patients require ongoing dynamic monitoring. If high-risk features are identified during surveillance, transplantation should be pursued. Otherwise, continued observation is recommended. The Dynamic International Prognostic Scoring System (DIPSS) serves as an example—a longstanding yet clinically relevant risk stratification tool. As indicated by its name, DIPSS emphasizes the importance of serial evaluations over time. This system categorizes patients into higher-risk and lower-risk groups. Higher-risk patients are generally advised to undergo transplantation, whereas lower-risk patients are managed with ongoing monitoring and non-transplant therapies, such as JAK inhibitors. Key factors influencing the decision to proceed with transplantation include patient-specific factors, such as the presence of comorbidities that may contraindicate transplantation, with age being a notable consideration—where 70 years is often regarded as a reasonable cutoff. Disease-related factors must also be evaluated, including risk stratification based on prognostic scoring systems. Finally, transplant-specific considerations, such as the identification of a suitable donor, play a critical role in the treatment decision.

PART.2

近期文献强调移植前对分子学（JAK2/CALR/MPL/高危突变）和骨髓病理学的系统评估以预测移植结局。请问您在移植前如何将这些分子信息用于分层、预处理强度选择以及移植后监测策略？

Ibrahim Yakoub-Agha教授：骨髓纤维化患者的治疗决策需基于多维度风险评估体系。动态国际预后评分系统（DIPSS）作为核心评估工具，可将患者明确划分为高风险组与低风险组：高风险患者具备明确的移植指征，无需争议；低风险患者则以观察等待为主，暂不考虑移植干预。对于介于两者之间的中危组患者，分子生物学标志物的检测具有重要临床价值。

例如，CALR基因Ⅰ型突变或ASXL1等驱动基因突变的存在，可显著提示疾病进展风险，从而为移植时机的选择提供关键依据。此类分子标志物的动态监测有助于精准识别潜在高风险亚群，指导临床医师在疾病进展前及时介入移植治疗，同时避免对低风险患者过度治疗。这一决策流程需严格遵循循证医学原则，结合患者个体化特征（如体能状态、合并症）及供者匹配情况，最终制定个体化治疗策略。

Recent studies emphasize pre-transplant molecular profiling (JAK2/CALR/MPL and high-risk mutations) and marrow assessment to predict outcomes. How do you integrate molecular data into risk-stratification, conditioning-intensity selection (myeloablative vs RIC), and post-transplant surveillance in your practice?

Pro. Ibrahim Yakoub-Agha：As previously mentioned, risk stratification systems categorize patients into higher-risk and lower-risk groups. For patients classified as very high-risk, the indication for transplantation is unequivocal and not subject to debate, while those with low-risk disease typically do not require transplantation. However, there remains an intermediate-risk group for which the decision is less straightforward. In such cases, molecular profiling can assist in determining the appropriate timing for transplantation. For example, the absence of a type 1 CALR mutation is associated with an adverse prognosis and may prompt consideration of transplantation. Other molecular alterations, such as ASXL1 mutations, among others, also contribute to risk assessment and clinical decision-making.

PART.3

随着分子监测、早期免疫干预与个体化再治疗策略的发展，您认为未来 3–5年内哪些研究方向或临床试验最有可能显著改善MPN患者在allo-HCT后的长期无病生存？

Ibrahim Yakoub-Agha教授：骨髓纤维化患者接受异基因造血干细胞移植后的管理具有复杂性，主要挑战包括移植失败、移植排斥反应及疾病复发风险。因此，移植后需建立动态监测体系，重点关注分子标志物的变化，例如疾病相关基因突变或微小残留病的检测，这些指标可为早期识别复发或移植排斥提供关键依据。

针对潜在风险，可采取免疫调节干预策略：通过调整免疫抑制治疗强度以平衡移植物抗宿主病（GVHD）预防与移植物抗白血病（GVL）效应；在必要时采用供体淋巴细胞输注（DLI）增强免疫效应，或联合其他免疫调节手段以维持移植物的长期功能。此类干预措施的核心目标在于降低移植相关并发症发生率，同时有效控制疾病复发，最终实现移植疗效的最大化。

With advances in molecular monitoring, early immune interventions and personalized post-transplant therapies, which research directions or clinical trials do you think are most likely to improve long-term disease-free survival for MPN patients after allo-HCT in the next 3–5 years?

Pro. Ibrahim Yakoub-Agha：Transplantation in patients with myelofibrosis is a complex procedure due to potential complications such as graft failure, graft rejection, or disease relapse following the procedure. Therefore, post-transplant monitoring of molecular markers is critically important. This monitoring may facilitate timely immunotherapeutic interventions—such as reducing immunosuppressive therapy, administering donor lymphocyte infusion (DLI), or employing other forms of immunomodulation—to preserve graft function and ensure transplant success. Accordingly, the primary focus in management should be on preventing and addressing graft rejection or post-transplant relapse.

来源：肿瘤瞭望