Anyone else have Clonal Cytopenia of Undetermined Significance (CCUS)?

Hello everyone,
At first, they thought I had MDS, but then another doctor said CCUS. My bone marrow showed only the DNMT3A mutation with an 11q deletion. I am receiving EPO injections when my hemoglobin is below ten, and it is checked monthly. I recently saw another hematologist who is an expert in these blood disorders and asked if I should have another bone marrow biopsy since my first and only was several years ago. She said that unless something dramatic or suddenly changes in my bloodwork or how I feel, she should keep doing what I am doing.
I am also studying epigenetics. I am trying to read Ben Lynch's Dirty Genes and Dawson Church's Genie in Your Genes.

Hi, first, I was going to try to respond just to Audrey, but try as I might, I can't make that happen.

I was diagnosed with low platelets in 2017, and going back through my medical records, I had them since at least 2014, and no one thought to mention them. Since 2017, my platelets have been in the 30 - 50 range, but lately, they have been closer to the mid-30s. I've had no treatment, and my doctor is hesitant to treat my low platelets now because, other than exhaustion and bruising easily, I didn't have any other symptoms until recently. She felt that most of the treatments could have side effects worse than my general health now.

None of my other blood work is abnormal. Yet.

However, over the past few months, I've had bone pain. My doctor says she isn't sure why this is; I don't have MDS or anything else yet. That answer annoys me because it seems worse at night and wakes me up. Because of my platelets, I can only take Tylenol, and that barely helps at all. So I'm left with very painful bones and now exhaustion like I've never had before in my life.

So we have been in watch-and-wait mode since 2017, and I guess I didn't really take any of this very seriously because no doctor was saying, "Oh wow." So I thought I was ok. At my most recent appointment in May 2024, my doctor pushed harder about what was happening to me. I think she realized I was in la-la land and wanted me to understand that this was a lot more serious than I thought. Since May, I have not had a single day that I have not thought about this - a lot. Between the worry, exhaustion, and bone pain, my quality of life is awful.

I don't have any of the information you and many others seem to possess: mutations, NGS, VAF (I don't even know what those mean). I don't know why I don't. And since I was in la-la land for a while (mostly because nothing was changing with my health or blood, and I felt OK), maybe they think I'm not bright enough to take it all in. For the record, I consider myself fairly intelligent and a critical thinker. 😉

The only thing I do know is that my TP53 gene has some mutation, and the TP53 gene is responsible for fighting aggressive cancers. I feel doomed.

I feel my hematologist is good, but how would I really know that? She is on staff at Dana Farber Cancer Institute in Boston, specializes in leukemia, and teaches at Harvard. She sounds good on paper, and I like her. But I do feel left in the dark in some ways.

The lack of support is challenging. When they first found my low platelets, they thought I had Immune Thrombocytopenia, and I joined a support group on Facebook with 10,000 people from all over the world. That was great and always so supportive. However, it turns out that isn't what I have. It's CCUS, and other than this group with a few people in it here at Mayo Clinic, I can't find another group for it at all. My PC is clueless.

Thanks for listening.

Hi @pixiesusan. Here’s how to make sure you can respond directly to a member’s comment. ☺️
In this case, you wanted to respond to @audreyl23 and her lovely response to you.
Right under her reply is a little oval ‘button’ that says Reply. If you click there, it will open up a little blue box where you can type your reply. It will have the notification right on top to Audrey, in your reply, that she has a message. ☺️

Another way, if you see a comment or a member where you’d like to reply and make sure they get a notification, type in their @name as it was written in their comment. Always put the @ sign in front of the name. The official user name for all of us should include that @ sign..like mine is @loribmt

I’m so happy you joined Connect. I know you’re having a difficult time finding other people who have CCUS and it really can help to not feel so alone when there are others who share the same diagnosis. We all need a lifeline sometimes!
In no way should you admonish yourself for not understanding your diagnosis. You mentioned even your PC is clueless. That’s because this out of the scope of your primary doctor and the reason that having a leukemia specialist is an important part of your health team to monitor your CCUS.
Dana Farber is a top cancer institute and from what you’ve mentioned of your doctor there, I don’t think you need to have any misgivings about her credentials or expertise. But if you don’t feel as though you are being seeing frequently enough then you need to discuss that with your doctor.
You have legitimate questions and would like some clarification on the potential for your disease to progress. You’d like to know what to expect for treatment options if things do change. You’d like to better understand what caused this disease and how this is impacting your life.

With my leukemia diagnosis and subsequent bone marrow transplant, believe me, I had no clue! That was never on my radar! My husband and I asked a ton of questions and not one time, did any of my doctors balk at having to take time to explain the details of what was taking place. We had a little notebook with questions so we could go right down the list without wasting time. Armed with extensive knowledge I learned about my disease and the transplant, I went from being a bystander to an integral part of my own health team and now I help others.

So I absolutely understand you feel as though you’re sitting on the sidelines watching what’s ’happening to you’ when you want to be an integral part of your team! It’s ok to be that person! We have to be our own advocates for health.
For your peace of mind, I encourage you to check in with your doctor soon instead of waiting until next year’s appointment. What do you think? ☺️

@loribmt
Hi Lori. I responded to both you and Susan @pixiesusan early this am. Currently in a different time zone. I am unable to see my posted message. Is there anything other than directly replying to a message that I have to do to have access to the entire thread of messages?

Hi Audrey, I can see your lovely reply to both @pixiesusan and myself. Here’s the link for you. https://connect.mayoclinic.org/comment/1138649/

I’m not sure why you’re not able to see your message. You did everything perfectly.

One way to check if a message has posted is to click on the little avitar (silhouette of a person) in either the upper right corner of the page or the larger one to the left of your name. That takes you to your profile page.
You’ll see 3 options:
Comments
Reactions
Bookmarks.
If you click on comments you’ll see all over your comments in chronological order. I hope this helps!
Now I’m going to pop up into your lovely reply and respond there. ☺️

Hi @loribmt and @pixiesusan. First, thank you, Lori, for being willing to share your story and for serving as support to those who have blood cancer or their precursors. Having someone who has gotten so sick (then received successful transplantation) as a resource and patient advocate is invaluable. 🙂

@pixiesusan I am so sorry for what you are going through. I agree with @loribmt. Please do not admonish yourself for not understanding what is happening with your body. ITP is an autoimmune cause of low platelets. I assume this is why you may have fallen through the cracks early on…. When were you formally diagnosed with CCUS? When was your bone marrow biopsy done that confirmed CCUS? Have you had any others since then? I have done a lot of reading over my ten plus year course with CCUS. I also happen to be a nurse. So it is easier for me to read and understand what is happening. However, this can be both a blessing and a curse. I also tend to worry… it’s hard not to… when we know CCUS is a precursor to MDS or AML .
Having a standard of care that is to simply follow blood work closely without early treatment is somehow counterintuitive. I have been to several specialists over the span of my illness. (This is due to change in insurance, MD retiring, another changing to academia.) I have also had a second opinion. I have received care from both BI/Lahey Health and Dana Farber, where I am now. I’ve had a second opinion at Sloan Kettering in NY. These are all top institutions. They all have the same thoughts about treating only for symptomatic patients or those whose numbers are declining. This is because the treatment can make patients sicker sooner than if they had just taken a wait and see approach.

I am concerned about your bone pain and declining platelet counts. As a note of reference, normal platelet counts should be in the range of 150k-450K. Mild “thrombocytopenia” or (low platelets) is 101K-140K; Moderate thrombocytopenia is between 51K and 100K and severe thrombocytopenia is below 51K. (Cleveland Clinic 2022). Your platelet counts have been severely low for a long time, thus the easy bruising. It is imperative you see your hematologist sooner than later, especially since you are now also having additional symptoms. (Bone pain and severe exhaustion.)

You mentioned not having any other blood work abnormalities. In CCUS, there are many variations in the course of the disease. It seems no two patients are exactly the same. You can have changes in platelets, white blood counts and/or red blood cell counts. The standard of care for treatment is based on the IPSS or International Prognostic Scoring System. This uses three prognostic indicators to predict the course of a patient’s disease.

You mentioned not knowing what VAF and NGS is. VAF is Variant Allelle Frequency. This refers to mutations and its definition is the “frequency with which a variant is detected in the specimen.” My understanding of this is that the higher the VAF, the higher the risk the particular mutation is of contributing to progression of the disease. NGS (next generation sequencing) is a blood test that is often used to “determine the mutation status of recurrently mutated genes that play an important role in the diagnosis, prognosis and clinical management of blood cancers. It is also used in CCUS for timely and accurate diagnosis.” Dana Farber developed a rapid heme panel. I am unsure of how or even if this is different from NGS. But the RHP is defined as “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.”

From what you have shared, I would encourage you to reach out to your hematologist at Dana Farber. I would ask her to repeat your bone marrow biopsy and also to order a rapid heme panel. This test may require a call to your insurance company to ensure coverage, as it can be expensive.

If you should have any further questions, please reach out to me at any time. I hope that I have helped in some small way. I will keep you in thought and prayer. It is my hope you will receive timely and effective treatment in the very near future.

Audrey, thank you so much for this incredibly helpful reply for @pixiesusan! Sharing your experience with CCUS and all of this information you’ve provided…well, it’s priceless! What a lifeline for someone like Susan who is just recently diagnosed and looking for answers. Your compassion as a nurse is showing through loud and clear. 🥰

This is what I just love about Connect! It’s such a caring and supportive forum where we help take care of each other. Your post today has left me feeling so uplifted and grateful for you, for your taking the time to write such a helpful and informational reply.
Audrey, are you still active in nursing or retired?

Hi @loribmt

Thank you for your kind words. I am glad to share anything I can. I'm very grateful to have found this support network. Although my progression (fortunately) has been slow, it has been always on my mind. Recent changes have me keeping my guard up. It's really great knowing there's a network of support for all of us experiencing this disease. I hope anyone feeling frightened or alone can be comfortable reaching out to me. We're in this together. One thing I've learned is to always try to appreciate my life, my family, my friends. I try to take one day at a time. And I always ask questions... even if they seem irrelevant. Knowledge is power.

And yes, I am still working.I have been in practice as a nurse for nearly 40 years... the last 21 as a nurse anesthetist/anesthesiologist..

Going back a few bits in this thread, I guess when I said I didn't know how to reply, I meant "privately," but if I do that, it doesn't help others learn. I should have picked a different "handle" for this forum because I haven't told most people about my diagnosis, except my immediate family (2) and a friend.

I had a BMB back in 2017 by a local hemo. He sent me to Dana Farber saying something bad was wrong (he mentioned HES and MDS). At Dana, they got that BMB, ran more tests on it, and said I looked Okay other than my platelets. That maybe I had ITP. I went with that. Then, I think it was in 2022, at my annual appointment at Dana, I was told that something had changed with my bloodwork; looking back over my doctor's notes from that visit, it says they did an RHP, and that was normal except for a single mutation on my TP53.

I guess I was formally diagnosed with CCUS in 2022. But I didn't really understand that until my visit in May 2024.

Another RHP was not run at my visit in May. The visit notes said I didn't want it, but I don't remember being asked or saying that. Until your post, I didn't even know what RHP was.

At that appointment, we discussed my platelets, and Dana has no desire to treat them unless they get down to about 20 or I have some sort of bleeding issue, which I have never had.

My doctor at Dana said if I want a second opinion, she can set that up for me, or I can do it on my own; she is fine with either option. It sounded like she was sure that doing nothing is the way to go right now. My initial feeling (and again, I don't know anything about this) is not to get a second opinion yet but to wait until maybe they recommend some sort of treatment and decide then.

Are BMBs always done in office? I had mine in a local community hospital but in the hemo exam room. I was on my first visit to the local home due to another doctor catching (finally) my low platelets, and he said, "let's do one now." It hurt. Can I get sedated for it?