摘要：近日，“2025年中欧血液与骨髓移植科学会议”在广州成功召开。本次会议由中国医疗保健国际交流促进会血液学分会和欧洲血液和骨髓移植协会基金会（荷兰）上海代表处共同主办，国家血液系统疾病临床医学研究中心-北京大学血液病研究所、中山大学肿瘤防治中心和中南大学湘雅二医

编者按：近日，“2025年中欧血液与骨髓移植科学会议”在广州成功召开。本次会议由中国医疗保健国际交流促进会血液学分会和欧洲血液和骨髓移植协会基金会（荷兰）上海代表处共同主办，国家血液系统疾病临床医学研究中心-北京大学血液病研究所、中山大学肿瘤防治中心和中南大学湘雅二医院共同承办。会上，德国柏林夏里特大学医学院Olaf Penack教授带来了题为《GVHD–standard management in Europe and upcoming strategies》的精彩内容，全面介绍了欧洲在移植物抗宿主病（GVHD）管理方面的最新进展与前沿方向。《肿瘤瞭望-血液瞭望》在会议现场特别邀请Olaf Penack教授，就相关内容进行了深入专访。

《肿瘤瞭望-血液时讯》：移植物抗宿主病（GVHD）是造血干细胞移植后最常见且严重的并发症之一，直接影响患者的生存率和生活质量。当前欧洲在GVHD的标准预防和治疗方面已形成较为系统的方案。请问这些标准管理措施具体包括哪些内容？它们在临床实践中取得了哪些显著成效？

Olaf Penack教授：当然，我很高兴就欧洲GVHD管理方面的关键要点进行交流。目前我们正在发布EBMT的最新建议，其中我认为最重要的仍然是GVHD的预防策略。在匹配相关供者、匹配无关供者和不匹配无关供者的移植中，我们建议使用抗胸腺细胞球蛋白（ATG）或移植后环磷酰胺进行预防。而在半相合供者的移植中，推荐采用移植后环磷酰胺，这也是目前全球广泛认可的标准方案。

在治疗方面，急性和慢性GVHD的一线治疗仍然是糖皮质激素。近年来，芦可替尼已成为激素难治性急性和慢性GVHD的标准治疗方案，应用也越来越广泛。对于急性GVHD的三线治疗，目前尚无明确获批的标准方案，相关的临床研究正在积极推进中，已有多家药企表现出浓厚兴趣。我期待这一领域在不久的将来能取得实质性进展。

在慢性GVHD方面，一些国家如美国、英国和日本，已批准了包括贝舒地尔（belumosudil）等在内的治疗药物；伊布替尼（ibrutinib）也已在美国获批。然而在欧洲，目前尚未有正式批准的治疗方案，主要使用的是其他国家已批准的药物。同时，我们也在积极开展相关的临床试验，努力推动新的治疗方案尽快落地。

Oncology Frontier-Hematology Frontier：Graft-versus-host disease (GVHD) remains one of the most common and serious complications following hematopoietic stem cell transplantation, significantly affecting patient survival and quality of life. Europe has developed relatively systematic strategies for the standard prevention and treatment of GVHD. Could you elaborate on the key components of these standard management approaches, and what notable outcomes have been achieved in clinical practice?

Professor Olaf Penack：Absolutely. I'm happy to comment on the key components of GVHD management in Europe. Europe. So we are publishing the recommendations of the EBMT, and I think most important is really prophylaxis of graft-versus-host disease. So we now recommend to use either antithymocyte globulin (ATG) or post-transplant cyclophosphamide in matched-related, matched-unrelated, and mismatched-unrelated setting. In the haplo setting we're recommending post-transplant cyclophosphamide, which is, I think, also standard of care worldwide.

When coming to the treatment, first-line treatment of acute and chronic GVHD remains to be steroids. And relatively new in the last years, ruxolitinib has become the standard therapy of steroid-refractory acute and as well as chronic GVHD. When we're now talking about third-line treatment in the setting of acute GVHD, there is no approved standard so far and currently trials are running. We have different manufacturers interested here and I hope that we can make progress in the near future.

In the setting of chronic GVHD, outside of Europe, we have already approved drugs such as belumosudil in some parts of the world, I believe in the US, in the UK, in Japan, for instance. And ibrutinib is also approved, at least in the US.In Europe, we don't have approved options. We are using options which are, as mentioned, approved in the other countries.But we're of course also focusing on clinical trials in this setting.

《肿瘤瞭望-血液时讯》：随着免疫学研究和精准检测技术的发展，早期诊断和风险分层成为提升GVHD治疗效果的重要环节。欧洲在GVHD的早期诊断及生物标志物应用方面有哪些最新进展？这些新技术对患者预后有何积极影响？

Olaf Penack教授：我必须说，在GVHD这个方面，欧洲目前还算不上一个成功的案例。虽然关于GVHD生物标志物的研究已发表了大量文献，其中部分指标也已经得到了验证，例如由美国MAGIC联盟提出的生物标志物，以及其他一些经过测试的指标。但坦率地说，这些生物标志物尚未被广泛应用于临床标准实践中。

以MAGIC的生物标志物为例，目前在欧洲仍很难获得。我们正积极推动这些标志物在欧洲的引进与使用，以便科研人员和临床医生能够更方便地开展相关工作。因此，我认为这一领域仍有较长的路要走。

众所周知，GVHD的早期识别和干预对于提高治疗效果至关重要，我们也正在这一方向不断努力。但如果要具体回答，这些研究进展目前对实际临床管理和患者预后带来了哪些改变？恐怕现实还是不够理想。必须承认，这些正在进行的临床试验成果还没有真正转化为临床常规实践。

Oncology Frontier-Hematology Frontier：With advances in immunology and precision diagnostics, early identification and risk stratification have become essential for improving GVHD outcomes. What are the latest developments in Europe regarding early diagnosis and the use of biomarkers for GVHD? How have these innovations positively impacted patient prognosis?

Professor Olaf Penack：Yeah, I mean, I must say that is that part of GVHD is not really a success story so far, at least in Europe. Of course, there have been many publications on biomarkers, which can be used. Some of them are also validated, when you think of the biomarkers by the MAGIC consortium from the US. Also, other biomarkers have been tested. But to be very honest, they are not broadly used in clinical standard. For instance, the MAGIC biomarkers — it’s very difficult to get them in Europe. We're currently trying to bring them to Europe so that investigators and physicians can offer these biomarkers. So I think that is still a pretty long way to go.

Everybody appreciates, I think, that an early detection of graft-versus-host disease and early treatment is much, much better, and we're working on it. But to very precisely answer to the question — so which differences did it already make for current management and patients? I think that part is really disappointing. And I have to say currently there was the translation of the progress which is there in clinical trials to standard practice has not happened.

《肿瘤瞭望-血液时讯》：难治性和复发性GVHD一直是临床治疗中的难点。针对这部分患者，欧洲目前有哪些创新治疗手段或正在进行的临床试验？您认为哪些新疗法有望改变未来GVHD的治疗格局？

Olaf Penack教授：众所周知，对于难治性GVHD患者，其预后普遍较差，因此迫切需要开展更多前瞻性临床试验。这类患者通常已经接受过多种免疫抑制治疗，因此在后续方案选择上需开拓新的治疗机制。我认为，未来具有潜力的策略不仅限于T细胞靶向治疗。有两种新的治疗方法值得关注。

一个是Axatilimab，这是一种靶向集落刺激因子1受体（CSF1R）的单克隆抗体，CSF1R主要在髓系细胞，特别是巨噬细胞上表达。该药物作为慢性GVHD的创新治疗手段，不仅能够有效抑制炎症反应，还可直接干预纤维化过程，具有良好的应用前景。

另一个是微生物治疗。目前正在开展的相关临床研究，主要包括利用同种异体肠道菌群制剂用于难治性急性GVHD的治疗，以及在异基因造血干细胞移植过程中用于预防GVHD的探索。我认为，这一治疗理念为GVHD的精准干预提供了全新的研究视角，潜力较大，值得持续关注。

Oncology Frontier-Hematology Frontier：Refractory and relapsed GVHD continue to pose significant clinical challenges. What novel therapeutic approaches or ongoing clinical trials are currently being pursued in Europe for these difficult cases? In your opinion, which of these emerging therapies holds the greatest promise for reshaping the future treatment landscape of GVHD?

Professor Olaf Penack：Yes, so I think for patients with refractory GVHD, it is well known that these patients have a worse outcome and clinical trials are needed. So most of these patients have been treated with multiple immunosuppressive drugs. So I think the options which do not only target T-cell biology are most promising. I would like to mention two approaches here.

One, there is axatilimab, an antibody targeting the CSF1 receptor, which is mostly expressed on myeloid cells such as macrophages. It is a novel treatment in chronic GVHD. And it not only inhibits inflammation, but it also directly targets fibrosis. So I think that is very promising.

And I would also like to highlight the treatment with microbiota. There are currently trials ongoing with allogeneic microbiota products in refractory acute GVHD and as prophylaxis of graft-versus-host disease around allotransplant. And I think that is also a very new development and it holds promise.

《肿瘤瞭望-血液时讯》：未来GVHD管理正逐步向个体化和多学科综合治疗方向发展。您如何看待个体化治疗策略及多学科协作在欧洲推广的现状与挑战？这些策略将如何推动GVHD患者治疗效果的提升？

Olaf Penack教授：我认为，多学科团队在患者护理中起着关键作用。然而，这样的团队并不容易建立。血液科医生往往需要主动协调其他科室的参与，这在多数中心仍存在不小困难。尽管科室间有一定联系，但要形成长期、稳定的合作机制并不容易。在我所在的中心也面临类似情况，一些科室医生对干细胞移植较为感兴趣，而其他科室的医生则不然。因此，如何激发各科室的主动参与，是当前面临的重要挑战，也是多学科协作能否落地的核心问题。我认为，我们应高度重视多学科团队的建设，真正认识到其在提升患者管理质量中的重要作用。

Oncology Frontier-Hematology Frontier：The management of GVHD is increasingly moving toward personalized and multidisciplinary care models. How do you view the current progress and challenges in implementing individualized treatment strategies and cross-disciplinary collaboration in Europe? In what ways could these approaches enhance outcomes for GVHD patients in the future?

Professor Olaf Penack：I think the critical point is really multidisciplinary teams. I think they are absolutely important for patient care. And on the same side, they are not so easy to achieve. Because hematologists need to reach out to other disciplines and need to involve them. So in most centers, hematologists have contacts to some disciplines, but it's very difficult to really build and hold up a really multidisciplinary team which stays. So I can also confirm from my center — there are doctors from disciplines which seem to be more interested in stem cell transplantations and others are not. And it's not so easy, because how do we want to give them — how is it possible to give them incentives for doing that? So it is a challenge, but I think a critical point. And I think we should really focus on building up these teams and really appreciating that they're critical for our patients.

来源：肿瘤瞭望