INCIDENTAL DIAGNOSIS OF CLONAL HEMATOPOIESIS AMONG HEALTHY, UNRELATED, HEMATOPOIETIC STEM CELL DONORS: A FEASIBILITY STUDY OF PSYCHOSOCIAL, ETHICAL, AND CLINICAL ISSUES - ABSTRACT THE OVERALL GOAL OF THIS LINE OF RESEARCH IS TO EXAMINE THE PSYCHOSOCIAL, ETHICAL, AND CLINICAL IMPLICATIONS OF INCIDENTAL MEDICAL FINDINGS OF CLONAL HEMATOPOIESIS (CH) IN HEALTHY VOLUNTEER HEMATOPOIETIC STEM CELL (HSC) DONORS. THE PROPOSED PROJECT FOCUSES ON FEASIBILITY. CH REFERS TO THE PRESENCE OF MUTATIONS ACQUIRED DURING A PERSON'S LIFETIME IN THE HEMATOPOIETIC STEM CELLS. CH IN HEALTHY INDIVIDUALS IS NOT CONSIDERED A DISEASE STATE, ALTHOUGH IT IS ASSOCIATED WITH INCREASED RISK FOR CARDIOVASCULAR DISEASES, INCREASED RISK FOR HEMATOLOGIC MALIGNANCIES, AND LOWER SURVIVAL RATES. CURRENTLY, MOST PEOPLE BECOME AWARE OF CH AS AN INCIDENTAL FINDING DURING WORKUP FOR ANOTHER DISEASE. MANY CLINICAL QUESTIONS ABOUT CH REMAIN, INCLUDING WHETHER (1) DIFFERENT CH MUTATIONS ARE ASSOCIATED WITH DIFFERENT LONG-TERM HEALTH OUTCOMES, (2) THERE IS MUTATION FREQUENCY THRESHOLD ASSOCIATED WITH INCREASED RISKS, AND (3) THERE ARE ANY MODIFIABLE/LIFESTYLE FACTORS THAT ALTER THE RISKS ASSOCIATED WITH CH. THIS PROPOSAL PRESENTS A UNIQUE OPPORTUNITY TO ASSESS THE PSYCHOSOCIAL, CLINICAL, AND ETHICAL IMPLICATIONS OF IDENTIFYING INCIDENTAL CH FINDINGS AMONG HEALTHY HEMATOPOIETIC STEM CELL (HSC) DONORS AT THE NATIONAL MARROW DONOR PROGRAM (NMDP), WHICH MANAGES THE LARGEST WORLDWIDE REGISTRY OF INDIVIDUALS WHO HAVE VOLUNTEERED TO DONATE TO UNRELATED PATIENTS IN NEED OF HSC TRANSPLANTS. AFTER STEM CELL TRANSPLANT, CH THAT ORIGINATED FROM THE DONOR MAY BE IDENTIFIED IN RECIPIENTS. THE NMDP RECENTLY FORMALIZED A PROCESS FOR NOTIFYING DONORS WITH POTENTIAL CH. THIS INVESTIGATION WILL EVALUATE THE FEASIBILITY OF TRACKING THE PSYCHOSOCIAL IMPACT AND CLINICAL MARKERS AMONG THIS OTHERWISE HEALTHY GROUP OF DONORS. SPECIFICALLY, WE WILL (1) QUALITATIVELY EXAMINE THE PSYCHOSOCIAL IMPACT OF RECEIVING INFORMATION ABOUT INCIDENTAL MEDICAL FINDINGS IN A GROUP OF RECENT HSC DONORS BY CONDUCTING A SERIES OF FOCUS GROUPS (N=30-40; AIM 1), (2) DEMONSTRATE THE FEASIBILITY OF CONDUCTING LONGITUDINAL STRUCTURED HEALTH-RELATED QUALITY-OF-LIFE (HRQOL) TELEPHONE INTERVIEWS WITH HSC DONORS DIAGNOSED WITH CH (N=30; AIM 2), AND (3) DEMONSTRATE THE FEASIBILITY OF PROSPECTIVELY TRACKING CLINICAL MARKERS (IN BLOOD, STOOL, AND CALCIUM SCORES) IN HSC DONORS DIAGNOSED WITH CH (N=30; AIM 3). THIS INVESTIGATION IS SIGNIFICANT BECAUSE IT WILL LAY THE GROUNDWORK FOR A LARGER INVESTIGATION OF INCIDENTAL FINDINGS OF CH AND WILL HAVE IMPLICATIONS FOR HOW SUCH FINDINGS ARE COMMUNICATED TO INDIVIDUALS RECEIVING THIS INFORMATION THROUGH STANDARD HEALTH SCREENINGS. THE INVESTIGATION IS INNOVATIVE BECAUSE IT (1) WILL BE THE FIRST TO INVESTIGATE CH IN A HEALTHY DONOR POPULATION, (2) PRESENTS A UNIQUE, LOW-RESOURCE, LOW-BURDEN OPPORTUNITY TO IDENTIFY INDIVIDUALS WITH CH, (3) FOCUSES ON POTENTIAL PSYCHOSOCIAL ISSUES IN THE DELIVERY OF INCIDENTAL FINDINGS TO HEALTHY DONORS, AND (4) DEMONSTRATES OUR ABILITY TO COLLECT LONGITUDINAL CLINICAL MARKER INFORMATION FROM A YOUNG, HEALTHY COHORT. FINDINGS FROM THIS STUDY WILL LEAD DIRECTLY TO A LARGER INVESTIGATION OF INCIDENTAL FINDINGS IN THIS HEALTHY DONOR GROUP, WHICH WILL HAVE IMPLICATIONS NOT ONLY FOR HSC DONORS, BUT FOR A BROAD RANGE OF HEALTHY AND ILL INDIVIDUALS IN WHOM INCIDENTAL MEDICAL FINDINGS ARE DISCOVERED.