CCUS is a condition in which a person has a low blood count — a low level of certain kinds of blood cells — without an apparent cause, and a portion of the blood cells carry an acquired genetic mutation. The condition, which is usually diagnosed after a routine blood test followed by specialized molecular testing, can place individuals at increased risk for certain blood-related cancers, such as myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
Most people with CCUS or another related blood condition called CHIP (clonal hematopoiesis of indeterminant potential) have a less than 1% chance of developing blood-related cancer within 10 years. However, a small percentage of people are at a higher risk.
Dana-Farber’s Lachelle D. Weeks, MD, PhD, director of the CHIP clinic within the Center for Early Detection and Interception of Blood Cancers, and colleagues have created a tool to estimate the risk of MDS or AML for patients with CCUS or CHIP. The tool, called the Clonal Hematopoiesis Risk Score, can help oncologists counsel patients, and guide them in terms of how best to follow up.
People identified as having high-risk CCUS are monitored closely with periodic blood tests to catch the onset of MDS or AML (if it occurs) as early as possible, when treatment can be most effective.
When is CCUS diagnosed?
When an individual is found to have a low blood count, doctors conduct a thorough exam to determine whether it’s caused by a vitamin deficiency, use of certain medications, heavy alcohol consumption, blood cancer, or other known triggers. When such causes are identified, the problem can often be remedied with medical treatment or lifestyle changes.
When no such explanation can be found, DNA testing of the blood for certain mutations can be considered. If some of the blood cells test positive for certain mutations, CCUS is diagnosed.
Patients undergoing treatment for cancer or who have a concern about a potential inherited predisposition to cancer may also be evaluated for CCUS or CHIP.
What are the symptoms of low blood counts?
Severely low blood counts can produce significant health problems, regardless of whether the blood cells harbor genetic mutations. People with sharply low red blood cell counts may experience fatigue or shortness of breath. Those with very low white blood cell counts may have an increased risk of infection, and those with low platelet counts may be at increased risk of bruising and bleeding.
Adam Sperling, MD, PhD, and Lachelle D. Weeks, MD, PhD, of the Center for Early Detection and Interception of Blood Cancers at Dana-Farber.
What is the focus of CCUS research now?
Risk stratification for people with CCUS and CHIP is a major step towards developing early detection and prevention programs for leukemia precursors. The next step is to identify safe and effective strategies for early intervention to prevent MDS and AML in people with CHIP/CCUS. Numerous clinical trials are in development to identify such interventions.
In addition, Weeks and others have shown that having CCUS or CHIP can increase the risk of non-cancerous diseases, like ischemic cardiovascular disease, a form of heart disease. Researchers in the Center for Early Detection and Interception of Blood Cancers are working to understand the mechanism underlying this risk and identify interventions that reduce non-cancer-related illness.
About the Medical Reviewer
Dr. Weeks is an Instructor in Medicine at Harvard Medical School and a physician-scientist in the adult leukemia program at Dana-Farber Cancer institute. Dr. Weeks received her MD and PhD from Case Western Reserve University School of Medicine. She completed residency in Internal Medicine at Brigham and Women's Hospital and fellowship in Hematology/Oncology at Dana-Farber/Mass General Brigham Cancer Care Program. Dr. Week's clinic focuses on the care of patients with precursors of the myeloid malignancies including clonal hematopoiesis of indeterminate potential (CHIP) and clonal cytopenia of undetermined significance (CCUS). Her research focuses on understanding features of CHIP and CCUS that impact the progression to overt myeloid diseases such as myelodysplastic syndrome (MDS) and acute leukemia.