在骨髓纤维化的治疗领域，异基因造血干细胞移植（allo-HSCT）作为根治性手段，其相关策略的优化显得尤为关键。近期，在第十二届陆道培血液病学术论坛上，《血液时讯》有幸特邀德国汉堡艾本德大学医学中心Nicolaus Kroger教授，详细解读了骨髓纤维化治疗中移植策略的最新优化方向与实践经验。此次分享不仅拓宽了我们的认知边界，更为提升患者长期生存率提供了宝贵的国际视野与科学指导。

《血液时讯》目前，在骨髓纤维化的治疗中，异基因造血干细胞移植（allo-HSCT）被认为是可能治愈的治疗方法。请问您认为如何优化移植策略能提高长期生存率？

Nicolaus Kroger教授：针对骨髓纤维化这一疾病，其临床表现具有高度异质性。部分患者即便未接受造血干细胞移植，也能享有较长的生存期。然而，若患者存在多个风险因素且预期生存期较短，则推荐进行allo-HSCT。
 

目前，allo-HSCT是此类患者的唯一根治性治疗手段。该治疗过程复杂多样，不仅涉及化疗与干细胞输注，还包括移植后的干预措施及患者预处理，以确保患者能够妥善准备接受干细胞移植。预处理措施之一便是减小脾脏体积，另一项则是采用减低强度预处理方案，该方案对患者而言毒性较低，适用于老年或高龄患者。
 

尤为重要的是，过去一年中我们深刻认识到移植后干预的重要性。在移植过程中，患者会获得新的造血系统。随后，在移植后的头几年，尤其是前6个月内，新的免疫系统开始发挥作用，试图清除骨髓纤维化细胞，但同时也可能引发移植物抗宿主病。因此，医生在移植后需进行严密的监测，以充分利用移植物抗骨髓纤维化效应，从而治愈患者并避免复发及非复发死亡的发生。

Hematology Frontier：In the treatment of myelofibrosis, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered the potentially curative therapy. What do you think about optimizing transplant strategies to improve long-term survival rates?

Dr.Nicolaus Kroger：So for myelofibrosis, the disease can be very heterogeneous. So we have patients who can live very long without stem cell transplantation. But if patient has several risk factors and the survival is short, then we would recommend allogeneic hematopoietic stem cell transplantation.

So allogeneic stem cell transplantation is currently the only curative treatment approach for these patients. And the treatment is is many times. It's not only the chemotherapy and the stem cells. It's also the post transplant intervention and the pretreatment of the patient to prepare the patient properly for the stem cell transplantation. To reduce, for instance, spleen size, which is one of the options. And the other options is to use more reduced intensity conditioning, which is not so toxic for the patient and can be done also for older patients or elderly patients. And very important what we learned in the last year is the so called post transplant intervention because in the transplant the patients are receiving a new haematopoietic system.

And then in the first years or let's say the 6 months after transplantation, then the new immune system is working and is trying to kill the myelofibrosis cells, but is also causing graft versus host disease.

Therefore it's up to the physician to monitor after transplantation very carefully. To harness this graft versus myelofibrosis effect and in order to cure this patient and to avoid relapse, so called non-relapse mortality.

《血液时讯》针对骨髓纤维化患者，您认为如何通过改善预处理方案来降低移植后的复发风险？

Nicolaus Kroger教授：在骨髓纤维化治疗中，预处理方案的强度对治疗结果并无显著影响。这意味着，若想降低复发风险，并非通过增强预处理强度来实现。因此，我们推荐对所有患者采用减低强度预处理方案，并在此基础上采取移植后措施以降低复发风险。若患者已成功接受移植，应密切通过分子标志物进行监测，以检查是否存在残留病灶。若确实存在残留病灶，且可通过这些标志物进行监测，则可考虑采取例如减少免疫抑制治疗以增强T细胞活性，从而杀灭残留骨髓纤维化细胞的方法。因此，在预防复发方面，移植后的管理较预处理方案的强度更为重要。

Hematology Frontier：For patients with myelofibrosis, how do you think we can improve conditioning regimens to reduce the risk of relapse after transplantation?

Dr.Nicolaus Kroger：In myelofibrosis, the intensity of the conditioning regimen has no major impact in outcome. That means if you want to reduce the risk of relapse, it's not the intensity of the conditioning. So we would recommend to go in all these patients with reduced intensity and then regarding reduce the risk of relapse. You should do something post transplantation. If patient has in grafted, you can monitor this patient very closely with molecular markers. And you can check, is there still residual disease? If there still is residual disease, which you can monitor with these markers, then you can, for instance, reduce immunosuppression to increase the t cells, to kill the residual myelofibrosis cells. So for relapse prevention, post transplant is more important than intensity of the conditioning regimen.

《血液时讯》您认为，有哪些新的发现或方法可以用于评估骨髓纤维化患者移植后的预后？

Nicolaus Kroger教授：近年来，我们深刻认识到，移植治疗并不仅仅局限于预处理方案和干细胞输注这两个步骤本身。它还包括了为减小脾脏体积所做的准备，以及移植后的一系列管理。我们应更为重视的是，在移植后对患者进行密切监测，以判断是否存在残留病灶。患者可能拥有正常的实验室检查结果，骨髓状况也看似正常。但通过分子标志物监测微小残留病灶至关重要，因为这意味着可以通过增加供体T细胞数量、减少免疫抑制治疗来进行治疗，或者在后续阶段通过供体淋巴细胞输注来达成，以在复发前彻底清除残留的纤维化细胞。

Hematology Frontier：what new findings or methods have been identified for assessing the prognosis of myelofibrosis patients after transplantation?

Dr.Nicolaus Kroger：So what we learned in the last years is that the transplant is not only conditioning regimen and then the stem cells infusion. It's only the preparation to reduce the spleen size, but also to some post transplant. The most important what we learned as to monitor this patient after transplantation, whether there is still residual disease. They can have a normal blood count, they look good, the bone marrow is good. But if you look molecular markers where you can take minimal residual disease, this is important because this can be treated then by increasing the donor t cells, either by reducing immunosuppression, or later by giving donor lymphocyte infusion, to kill also the myelofibrosis cells before they can relapse.

会议回放

请扫描下方二维码以观看会议回放，其中Nicolaus Kroger教授的讲座及讨论环节位于123:50至165:00。