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IBC 2025 | Advances made in the understanding of CHIP & CCUS and challenges that remain
Sanam Loghavi, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, comments on the rapidly evolving field of clonal hematopoiesis of indeterminate potential (CHIP) and clonal cytopenia of unknown significance (CCUS), highlighting that novel technologies have led to identifying patients at a higher frequency. However, the field still lags behind in managing these patients and entities, presenting some challenging clinical scenarios. This interview took place at the 3rd Intercepting Blood Cancers (IBC) Workshop held in Nice, France.
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Transcript
The field of CHIP and CCUS is a rapidly evolving field. And I would say in the last few years, we have learned a lot about the biology of CH and CCUS. And we’ve also developed a lot of new and novel technologies that are able to detect clonal cytopenia of uncertain significance or clonal hematopoiesis that are more readily available and that are being used more often such as you know in the context of patients with solid tumors, the use of liquid biopsies...
The field of CHIP and CCUS is a rapidly evolving field. And I would say in the last few years, we have learned a lot about the biology of CH and CCUS. And we’ve also developed a lot of new and novel technologies that are able to detect clonal cytopenia of uncertain significance or clonal hematopoiesis that are more readily available and that are being used more often such as you know in the context of patients with solid tumors, the use of liquid biopsies. So we’re identifying these patients at a much higher frequency than we were before and this really provides us with the opportunity but also a lot of challenges because we detect these abnormalities in patients yet, where the field has not really caught up in terms of how we manage these patients and how we manage these entities with our knowledge of the biology of disease. So a few of the clinical scenarios that we’re going to discuss in the workshop today are really distinguishing clonal hematopoiesis from mosaic germline genetic mutations such as the case of mosaic Li-Fraumeni syndrome from clonal hematopoiesis with TP53 in a patient that’s being worked up for a solid tumor and is incidentally found to have a high VAF TP53 mutation. The other is distinguishing genetically high-risk clonal cytopenia of uncertain significance, meaning CCUS that has either multiple mutations or mutations that are in the genes that are known to be of higher risk, or several mutations together, and then distinguishing that from what is thought to be a phenotypically low-risk disease, right, low-risk MDS. So if we catch the patients early enough, they’re not necessarily going to be very cytopenic, right, because cytopenia develops over time, but they may have genetically high-risk disease that we know is destined to become high-risk MDS. So that’s the, you know, that’s the other challenging scenario. And then the third, I would say, not as much challenging, but, you know, intellectually intriguing scenario is the identification of donor-derived clonal hematopoiesis in patients that are recipients of allogeneic hematopoietic stem cell transplants.
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