Editor's note: Clonal hematopoiesis usually refers to myeloid cell proliferation caused by genetic mutations in hematopoietic stem cells, and is also the basis of the pathogenesis of various blood diseases; monitoring clonal hematopoiesis can enable early detection of hematological malignancies. At the 4th CASH held recently, Professor Jinghui Zhang from St. Jude Children's Research Hospital shared the report "Treatment-Related Clonal Hematopoiesis in Adult Survivors of Childhood Cancer". After the meeting, " Oncology Frontier-Hematology Frontier" specially invited Professor Jinghui Zhang to give an in-depth sharing on the treatment-related causes, monitoring value and long-term impact of clonal hematopoiesis.
Professor Jinghui Zhang
Department of Computational Biology, St. Jude Children’s Research Hospital
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.
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.
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.
