CHAPTER: Clonal Haematopoiesis Assessment: Prevention, Treatment and Research

Overview

People identified to have CH or thought to have possible CH due to unexplained low blood cell counts, including low red blood cells, white blood cells, or platelets will be asked to take part in the study. Individuals who are confirmed to have CH and provide informed consent to participate in the study will have monitoring of their CH, assessment of the risk of heart diseases, blood cancers and personalised support. The researchers will also measure people's understanding of CH and how they feel after learning about CH. Researchers will then record the relevant information from people with CH in a central database over time to track long-term health outcomes. The information collected from the study will help create a blueprint for doctors to provide care for people with CH in the future, and guide further research into CH in Australia. Participants will be asked to donate blood samples for the study for research purposes including CH monitoring and testing and also provide health information for the central database.

Clonal Haematopoiesis (CH) refers to the clonal outgrowth of a population of hematopoietic stem cells in the absence of haematologic neoplasms. The clonal cells share an acquired 'driver' mutation., and the presence of dysplasia and/or cytopenia. CH is common in older populations, with a frequency of 10-30% in people above 70 years of age. Most individuals with CH are asymptomatic; however, the condition increases the risk of multiple life-limiting complications, including myeloid neoplasms (MN), cardiovascular disease (CVD), cerebrovascular disease (CeVD) by 11.1, 1.4, and 2-fold, respectively. While CH is not yet treatable, identifying the condition may assist individuals in making informed decisions, including an individualised management plan for early detection of CH-associated complications. CH screening is not currently performed in routine clinical practice. The optimal approach to surveillance for myeloid neoplasms in individuals with CH remains undefined. Some individuals undergo active surveillance with regular blood count monitoring to detect early progression to MN. Early detection of MN may also broaden the therapeutic window for individuals. Additionally, this allows individuals to connect with suitable clinical trials. CVD is the most common CH-associated complication; hence CV (cardiovascular) risk modification is important both from an individual and public health standpoint. CH screening may also refine the evaluation of individuals with unexplained cytopenia, as they may have underlying CH that has not been identified. Given the uncertainties surrounding the identification and management, dedicated research clinics have been developed in the United States to evaluate the impact of screening of CH. These clinics provide a supportive environment to discuss the condition and engage multidisciplinary management. In addition to haematologists, individuals are supported by other specialities and allied health professionals. However, dedicated CH clinics are not yet available in Australia. There is an urgent need for more research into CH as there are crucial knowledge gaps. This includes the role of CH screening and interventions to modify the biology and risks of CH-associated complications. Given the widespread use of next-generation sequencing (NGS) panels in Australia, it is likely that CH will be increasingly identified in routine clinical practice, creating a pool of individuals who may benefit from counselling and follow-up in a dedicated service. This cohort study will establish a screening clinic and a prospectively characterised registry of individuals with CH to serve as the basis for clinical and translational studies in CH. With consent, individuals with possible CH will undergo screening by molecular testing in the first dedicated multidisciplinary CH clinic in Australia whereby the health outcomes of participants with CH can be evaluated.