Hi @sjjs. I have had stable and asymptomatic CCUS for many years with DNMT3a and TET2 mutations. Both had high VAFs (the frequency at which a variant/mutation is detected in a specimen). For many years my Platelet count was in the 90-120K range. (Normal is 150-450K). Five or so years ago, my platelets dropped into the 90-100K range. I have recently acquired a new mutation (CUX-1). Along with the new mutation, my platelets have decreased to the mid-70 to 80K range over four months in a row. Other than fatigue, I still have been asymptomatic. I have seen many hematologists over the years due to change in job/insurance; MD retiring and/or leaving the practice. I’ve been to both BI/Lahey and Dana Farber for my care. (Dana Farber exclusively now for close to 5 years). I have also seen a hematologist for second opinion at Sloan Kettering. Everyone has told me the same thing you describe above. Unless something suddenly or dramatically changes in bloodwork or symptoms, a wait and see approach is standard of care. This is because treatment has the potential to make an otherwise asymptomatic person become sick. Since you are receiving EPO injections monthly, it seems you are anemic/ have a low hemoglobin. Watch your numbers for hemoglobin and hematocrit. If they change dramatically, it is time to do something more. You can have a test called NGS or rapid heme panel. This test was developed at DF for clinical decision making for patients who have CCUS/MDS. “It is a high-tech genetic test that provides an unprecedented amount of critical information to aid in the choice of treatment in a matter of days.” This can be done with a simple blood test. If your doctor isn’t ready to repeat the bone marrow biopsy, you can request this test. First be sure you are covered by your insurance, as this test can be expensive. You mentioned you are interested in learning more on Epigenetics. You may want to read the Biology of Belief, by Bruce Lipton. It is an excellent resource. Best wishes to you.