Raynier Devillier教授：聚焦老年造血干细胞移植的疾病状态、预处理强度与供者选择三大关键

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Raynier Devillier教授：聚焦老年造血干细胞移植的疾病状态、预处理强度与供者选择三大关键

血液时讯发表时间：2025/12/16 19:02:18

随着人口老龄化进程，老年血液系统疾病患者接受造血干细胞移植的需求日益增长，然而其临床决策也面临着更为复杂的挑战。在平衡疗效与安全性的过程中，如何综合考量疾病状态、患者年龄与合并症、预处理方案强度以及供者选择等多重因素，成为移植领域备受关注的核心议题。2025年11月13-16日，2025国际细胞与免疫治疗大会（CTI 2025）在浙江杭州召开。会议期间，《肿瘤瞭望-血液时讯》特邀法国保利-卡尔梅特研究所Raynier Devillier教授基于国际视野，深入探讨了老年患者移植的个体化策略，旨在为优化老年移植患者的治疗路径提供重要参考。

您在实践中，是如何将 “疾病状态（CR vs 非CR）”与“年龄／合并症”结合用于决策？在老年患者中，您是否设定一个“最低疾病反应门槛”才考虑移植？

Raynier Devillier教授：众所周知，在考虑为患者施行移植治疗时，我们仍需审慎权衡其获益与风险，这一考量对于老年患者群体尤为重要。该类患者不仅发生治疗相关毒性的风险较高，同时疾病复发的风险也较为显著。因此，若患者为高龄且合并其他疾病，则可预期其非复发死亡率将相应升高。若在此基础上，患者所患疾病仍属难治性，则其可能并非移植治疗的理想候选者。

然而，为所有患者制定统一的明确诊疗路径存在困难。在我们的临床实践中，通常对年龄超过70岁且患有难治性疾病的患者不考虑进行移植治疗，原因是预期其生存率极低。不过，此领域仍存在改进空间，特别是随着新型药物的不断涌现，有望使患者在移植时的疾病状态得到更好的改善。

Q1、In your practice, how do you integrate disease status (CR vs non‑CR) with age/comorbidities in decision‑making? Do you establish a “minimum response threshold” (e.g., CR status) before offering transplant to older patients?

As is well known, when considering transplantation therapy for patients, we still need to carefully weigh its benefits and risks—a consideration that is particularly crucial for the elderly patient population. Not only are such patients at a higher risk of developing treatment-related toxicity, but they also face a significant risk of disease recurrence. Therefore, in elderly patients with comorbidities, non-relapse mortality (NRM) is expected to increase accordingly. On this basis, if the patient’s disease is refractory, they may not be ideal candidates for transplantation therapy.

However, it is challenging to develop a unified and clear diagnostic and therapeutic pathway for all patients. In our clinical practice, transplantation therapy is generally not considered for patients over 70 years of age with refractory diseases, due to the expectation of extremely low survival rates. Nevertheless, there is room for improvement in this field—especially with the increasing availability of novel agents, which are expected to better improve patients’ disease status prior to transplantation.

您在65‑75岁或>75岁患者的移植方案制定中，是如何权衡 “减少毒性” 与 “保留疗效” 的条件化强度（如RIC／非肌抑制）？哪类患者您会选择较温和方案？

Raynier Devillier教授：在老年患者群体中，预处理方案的强度，或者说剂量强度，如何在疗效与毒性之间取得最佳平衡。包括我们在内的多项研究均已表明，对于60岁以上的患者，试图通过增强预处理方案的强度来改善预后通常难以实现。因此，在当前临床实践中，我们更倾向于对60岁以上患者采用较低强度的预处理方案，旨在将早期治疗相关毒性控制在较低水平。

与此同时，我们可能通过移植后增加维持治疗等后续策略，来强化移植物抗白血病效应，从而获益，而非一味提升预处理强度。当然，采取此策略的前提是，患者在移植时必须达到良好的疾病缓解状态。此外，对于某些特定的患者亚群，我们仍可探讨使用更高强度预处理方案的可能性，但这通常要求患者身体状况极佳，且年龄可能需在70岁以下。

Q2、In your 65–75 yrs or >75 yrs cohort, how do you balance “toxicity reduction” versus “efficacy preservation” in selecting RIC or non‑myeloablative conditioning? In which patient sub‑groups do you favour milder regimens?

Numerous studies, including our own, have demonstrated that for patients over 60 years of age, attempting to improve outcomes by increasing the intensity of conditioning regimens is generally ineffective. Therefore, in current clinical practice, we are more inclined to adopt reduced-intensity conditioning (RIC) regimens for patients over 60, aiming to minimize early treatment-related toxicity.

Meanwhile, instead of blindly enhancing conditioning intensity, we may strengthen the graft-versus-leukemia (GVL) effect through subsequent strategies such as post-transplant maintenance therapy to derive clinical benefits. Of course, a prerequisite for this strategy is that patients must achieve a favorable disease remission status prior to transplantation. Additionally, for certain specific patient subgroups, the possibility of using more intensive conditioning regimens may still be explored—but this typically requires patients to have an excellent physical status, and their age may need to be under 70 years old.

随着年龄增长，传统的全剂量／高强度造血干细胞移植（HCT）风险显著增加。基于最近汇总结果指出，对于 ≥50 岁患者，选择 “年纪较轻供者”比配偶／亲缘供者更具生存优势。您在老年患者移植中对“供者优先顺序”的看法是怎样？在临床实践中，您是否将这种“供者年轻化”作为决策准则？

Raynier Devillier教授：如今，我们已能够为同一患者从多种类型的供者中做出选择，这是近年来的重要进展。这一变化主要得益于两项技术突破：一是单倍体相合移植技术的成熟，使患者子代可作为可行供者来源；二是基于移植后环磷酰胺的错配无关供者移植方案的发展。因此，当前的核心问题已转变为如何在多位潜在供者中进行选择，而相关选择标准的确立仍是一个开放性的重要课题。

传统上，供者选择主要依据人类白细胞抗原配型相合程度，这也是同胞全相合供者始终被视为“金标准”的原因。然而，现有大量证据表明，供者年龄同样是关键影响因素。多项临床观察一致显示，对于老年移植受者，若接受年龄较大的同胞全相合供者移植，与接受年轻供者相比，总生存率较低，且复发风险显著升高——其中年轻供者包括无关供者或单倍体相合供者。

因此，现阶段有必要重新审视传统供者选择策略，将“更年轻”和“更快可用”作为重要考量因素。这对于提高高危疾病患者的移植疗效具有关键意义。

Q3、As patients age, the risks of full‑intensity hematopoietic cell transplantation (HCT) rise markedly. Recent analysis suggests for patients ≥50 yrs that younger unrelated donors may confer better outcomes than related donors. How do you view donor‑priority strategies in older recipients? In your practice, do you treat “younger donor age” as a decision criterion?

Today, we are able to select from multiple types of donors for the same patient, which represents a significant advancement in recent years. This transformation is primarily attributed to two technological breakthroughs: first, the maturation of haploidentical transplantation technology, enabling patients’ offspring to serve as viable donor sources; second, the development of mismatched unrelated donor transplantation protocols based on post-transplant cyclophosphamide (PTCy). Consequently, the core issue has now shifted to how to choose among multiple potential donors, and the establishment of relevant selection criteria remains an important open question.

Traditionally, donor selection has been mainly based on the degree of human leukocyte antigen (HLA) matching—this is why HLA-matched sibling donors have long been regarded as the "gold standard." However, a large body of existing evidence indicates that donor age is also a key influencing factor. Multiple clinical observations consistently show that for elderly transplant recipients, receiving transplantation from older HLA-matched siblings is associated with lower overall survival and a significantly higher risk of recurrence compared to receiving transplantation from younger donors, including unrelated donors or haploidentical donors.

Therefore, it isnecessary to re-examine traditional donor selection strategies at this stage, incorporating "younger age" and "faster availability" as important considerations. This is crucial for improving transplantation outcomes in patients with high-risk diseases.