《肿瘤瞭望-血液时讯》：首先请您谈谈何为克隆性造血，在癌症幸存者中监测克隆性造血的意义？

Jinghui Zhang教授：监测克隆性造血研究的关键发现在于确定了化疗和放疗是癌症患者克隆造血的促进因素。这一发现对于儿科患者尤为重要，因为我们的首要目标不仅仅是拯救生命，还要确保这些儿童在成年后不会受到童年治疗的严重影响。我们发现，化疗是加速克隆造血的原因之一，这可以进一步指导后续研究，进而可以减少癌症治疗过程中的短期和长期毒性。此外，我们的研究还强调了对癌症患者进行分子水平监测的至关重要性，这使我们能够追踪克隆性造血的生长并评估其长期影响，包括可能导致的心血管问题或继发性癌症等其他疾病。

Oncology Frontier-Hematology Frontier: Firstly, could you please talk about what is clonal hematopoiesis and the significance of monitoring clonal hematopoiesis among cancer survivors?

Professor Jinghui Zhang: The pivotal aspect of our study is that we've identified chemotherapy and radiation therapy as accelerants of clonal hematopoiesis in cancer survivors. This revelation is particularly significant in pediatric cancer cases. Our primary objective is not only saving lives but also ensuring that these children, as they grow into adulthood, do not suffer drastic impacts from their childhood treatments. Our finding that chemotherapy is a cause of accelerated clonal hematopoiesis directs us towards further research. This in turn may reduce short- and long-term toxicities during cancer treatment. Our study also underscored the critical importance of molecular-level surveillance for cancer survivors. This approach allows us to track the growth of clonal hematopoiesis and assess its long-term effects, potentially leading to other diseases like cardiovascular issues or secondary cancers.

《肿瘤瞭望-血液时讯》：本次会议上，您报告了《儿童癌症成年幸存者的治疗相关克隆性造血》。请您谈谈哪些治疗会导致克隆性造血，以及该如何优化这些治疗？

Jinghui Zhang教授：我们在研究中分析了儿科癌症群体，超过3000人，中位生存时间超过20年。令人惊讶的是，即使在癌症治愈20年后，我们仍然可以通过分析观察到化疗的影响，这进一步凸显了优化儿科患者癌症治疗的重要性。具体而言，我们发现STAT3基因与霍奇金淋巴瘤患者的治疗相关克隆性造血存在联系，并且与甲基苄肼治疗相关。这一发现具有重要意义，表明我们需要重新评估甲基苄肼在霍奇金淋巴瘤中的治疗作用，可能会减少或完全停止该药物的使用。

Oncology Frontier-Hematology Frontier: During this conference, you presented a report on “Therapy-related Clonal Hematopoiesis in Adult Survivors of Pediatric Cancer”. Could you please talk about which treatments can lead to clonal hematopoiesis and how to optimize these treatment?

Professor Jinghui Zhang: Certainly. Our study examined a large cohort of pediatric cancer survivors, numbering over 3,000, with a median survival time exceeding 20 years. It's striking that even after 20 years post-cancer cure, the effects of chemotherapy can still be observed through our analyses. This highlights the importance of optimizing pediatric cancer therapies. Specifically, we discovered STAT3 as a novel therapy-related change in survivors of Hodgkin's lymphoma, associated with the drug procarbazine. This discovery is significant—it suggests that we need to reevaluate the use of procarbazine in treating Hodgkin's lymphoma, potentially reducing or stopping its use altogether.

《肿瘤瞭望-血液时讯》：对于已经出现克隆性造血的癌症幸存者，有哪些挽救措施可以避免其进一步恶化？

Jinghui Zhang教授：遗憾的是目前还没有立即可用的挽救措施，但上述提到的监测环节至关重要。这需要定期（最好每三到五年一次）采集血样并监测克隆性造血。这种策略有助于早期检测发现任何快速生长或扩大的克隆，这也可能意味着继发性肿瘤正在发展。此外，我们也需要更深入地研究影响某些幸存者加速克隆性造血的遗传因素。确实部分幸存者（而非全部）会表现出这种现象，而且我们已经发现错配修复缺陷与化疗和放疗相关。如果我们能够进行足够大的队列分析，那么分析遗传变异及其与克隆性造血的关联可能就会非常有益于患者。这些研究结果可为前期治疗提供信息，从而根据患者的遗传背景制定个体化的治疗方案。我们的最终目标是精准医疗，这不仅可以挽救生命，还可以减少因过度治疗而带来的长期副作用。

Oncology Frontier-Hematology Frontier：What rescue measures can be taken to prevent further deterioration of cancer survivors with clonal hematopoiesis?

Professor Jinghui Zhang: There aren't immediate rescue measures available, but as I mentioned earlier, surveillance is essential. This entails the regular collection of blood samples, ideally every three to five years, to monitor clonal hematopoiesis. This strategy helps in early detection of any rapidly growing or expanding clones, which could be indicative of a developing secondary tumor. Furthermore, we need to delve deeper into the genetic factors influencing accelerated clonal hematopoiesis in certain survivors. While not all survivors exhibit this phenomenon, a subset does, and we've already linked mismatch repair deficiencies to this, combined with chemotherapy and radiation. If we can assemble a sufficiently large cohort, examining genetic variations and their association with the emergence of clonal hematopoiesis could be immensely beneficial. This knowledge could inform upfront therapy, allowing treatment customization based on individual genetic backgrounds. The ultimate goal is precision medicine—not only saving lives but also ensuring reduced long-term side effects from therapy exposure. We need to avoid overtreatment and consider the potential long-term damage caused by therapy when treating cancer patients.

专家简介

Jinghui Zhang教授

圣犹达儿童研究医院