Jan. 28, 2023
Clonal hematopoiesis is the acquisition of somatic pathogenic variants in hematopoietic stem and progenitor cells. These variants can expand over time, and it is difficult to know the potential impact a variant may have on a patient's health in the future. Clonal hematopoiesis of indeterminant potential (CHIP) can lead to increased risk of blood cancers, including myeloid neoplasms, and is associated with an increased all-cause mortality rate, largely from cardiovascular disease.
Mrinal S. Patnaik, M.B.B.S., a hematologist at Mayo Clinic Comprehensive Cancer Center in Rochester, Minnesota, leads the Cancer Center's efforts to detect variants in the CHIP clinic. The clinic is designed to screen patients for CHIP and consult on plans of care to ensure all necessary risk factors are monitored.
"In the CHIP clinic, we identify who is more at risk," says Dr. Patnaik. "This ensures patients are educated and empowered when they make decisions throughout their care plan."
Many of the therapeutics involved in treating solid tumors are associated with increased risk of developing blood cancers because of damage to the hematopoietic cells. Dr. Patnaik estimates that 40% to 50% of patients with cancer should be screened for CHIP.
Individualized screening for each patient's risk
The CHIP clinic is a collaborative effort between the Cancer Center and Mayo Clinic's Center for Individualized Medicine. Many patients are referred for screening by the oncology teams managing their cancer therapeutics, but CHIP is a concern across a variety of specialty areas.
"It really encompasses all aspects of medicine," says Dr. Patnaik.
The CHIP clinic can be helpful for patients who have or need:
- Clonal hematopoiesis mutations identified on next-generation sequencing, whole-genome sequencing or whole-exome sequencing.
- Clonal hematopoiesis suspected from cell-free DNA assays.
- Clonal hematopoiesis suspected due to mosaic results from germline testing for cancer and hereditary syndromes.
- Clonal hematopoiesis screening for clonal cytopenia of undetermined significance.
- Clonal hematopoiesis screening prior to autologous hematopoietic cell transplantation for non-Hodgkin lymphoma or multiple myeloma, and radioimmunotherapy for non-Hodgkin lymphoma.
- Clonal hematopoiesis screening prior to peptide receptor radionuclide therapy for neuroendocrine tumors.
- Clonal hematopoiesis screening prior to chemotherapy or poly (ADP-ribose) polymerase inhibitor therapy for breast or ovarian cancer.
Advancements in early cancer detection and interception
While there is no treatment yet available to reverse CHIP, education and monitoring of risk factors provide opportunities to detect blood cancers early. Dr. Patnaik explains that knowledge of CHIP allows patients to make lifestyle changes as well as informed decisions. It also provides a good indication of the continued surveillance each patient may need as part of the care plan.
The concept of early detection of pre-malignant states has been around for several years and was first defined as monoclonal gammopathy of undetermined significance by Robert A. Kyle, M.D., a supplemental emeritus consultant in hematology research at Mayo Clinic with an interest in plasma cell malignancies. Advancements in sequencing techniques have brought efforts like the CHIP clinic to life, and they continue to inform the future of cancer detection, interception and treatment.
"The vision is that what we're doing in the blood space can eventually be done for every tumor," says Dr. Patnaik. "A lot of that will be based on high-resolution genotyping and single-cell profiling."
Growth of the program will include expansion of the current genome — which is standardized to white people — to better serve all racial and ethnic profiles. Dr. Patnaik also hopes to extend this work further into the community, increasing access for those who may need CHIP screening.
The CHIP clinic and other genomics advances are transforming the landscape of cancer care. This individualized approach allows care teams to provide the right treatment to the right patient at the right time. The model of this clinic will inform early cancer detection efforts throughout the Cancer Center until all patients with cancer can receive genetic testing in the treatment model.
For more information
Refer a patient to Mayo Clinic.