Aplastic w/ 10% bone marrow and decent CBC?

[kubu]

13 months ago (Dec 2017) my neutrophils and WBC came back low from my annual physical. Doctor recommended a hematologist visit, which I did at UCLA.

The hema at UCLA totally blew it off. Basically saying nothing to worry about and if I am concerned, just get another CBC in a few months to be 100% certain.

Given how confident the hema was that it was a normal variance, I did not get CBC until my next physical one year later (Dec 2018). Here were those numbers, as well as prior years.

Neutrophils absolute
Dec 2018 1.01 [L]
Dec 2017 1.07 [L]
Dec 2016 2.13
Sep 2016 4.36
Dec 2015 7.05

WBC
Dec 2018 3.4 [L]
Dec 2017 3.8 [L]
Dec 2016 4.8
Sep 2016 7.1
Dec 2015 10.1

RBC
Dec 2018 4.17 [L]
Dec 2017 4.37
Dec 2016 4.68
Sep 2016 4.69
Dec 2015 4.59

HGB
Dec 2018 12.9 [L]
Dec 2017 13.8
Dec 2016 15.3
Sep 2016 14.9
Dec 2015 14.9

HCT
Dec 2018 38.5 [L]
Dec 2017 40.4
Dec 2016 48.2
Sep 2016 45.0
Dec 2015 47.1

I am 34 y/o male and very athletic (1.5-2 hours intense exercise 6 days/week). Therefore, the fatigue was something I definitely noticed. My primary referred me to a different hematologist and he was very concerned and ordered biopsy. Got results this past week and both pathologists who reviewed the results concurred:

SEVERELY HYPOCELLULAR BONE MARROW (EST. 10%) WITH REDUCED TRILINEAGE HEMATOPOIESIS

The morphologic and immunophenotypic findings show marked decrease in normal hematopoietic elements. No apparent etiology is noted. There is no evidence of acute leukemia, significant dysplasia or a lymphoproliferative disorder. Overall the findings are compatible with severe aplastic anemia. Causes of aplasia such as medications, systemic/autoimmune disorders, toxic exposures, viral infections (including EBV and hepatitis), etc. should be considered in this patient. Clinical and genetic correlation is recommended (cytogenetics pending). Two other issues should be noted. First, there is an increase in plasma cells seen for patient of this age. These are not specific but increases are seen in chronic infections and autoimmune disorders. Second, the peripheral blood lacks Howell-Jolly bodies, nucleated red blood cells and significant anisopoikilocytosis of red blood cells. Given the history of splenectomy, these findings are unusual and suggest that the patient may have an accessory spleen.

With 10% marrow remaining, shouldn't my numbers be a lot worse? My platelets in Dec 2018 were 351 (150-450 being referenced normal range).

Ultimately my question is... how much longer should I expect until my life really goes down hill and these not good - albeit decent - CBC results really take a nosedive?

[Marlene]

Marrow cellularity does not alway correlate to Peripheral blood counts. You can have low cellularity and normal counts, as well as normal cellularity and low counts. The most important reason for the biopsy is to rule out things like MDS and leukemia. SAA is a diagnosis of elimination. They should also check for genetic bone marrow diseases like fanconi's anemia or blackfan diamond anemia. I assume they have already checked for auto-immune issue.

Sometimes, they hit a dry pocket when doing the biopsy and don't get a good sample.

Your BM report says your spleen was removed. Do you think there's a connection to that and the drop in your counts?

Find out what your vitamin D, B12, copper, folate and iron are. You want your D and B12 to be at a optimal level. Low normals are suspect. Are you on any medication or taking anything else. Any digestive issues? Also, get your hormones checked. Get and keep copies of all lab test. You'd be surprised at what can get missed.

As far as timing goes, no one can really say. My husband's tanked in 9 months. Looks like yours has stabilized and may stay that way but I would pursue answers. There are others on this site who also live with lower than normal counts.

[kubu]

Thanks for providing a prompt and well thought reply. To answer some of your questions:

Vitamin B12, iron, vitamin D are all very healthy. Concurrently with the bone marrow biospy order, the hema ordered several blood tests - including those - and everything was good other than low testosterone (though still within "normal" range). Furthermore, I have never tested positive for any sort of nutritional deficiency before. Copper was not tested, though deficiency is unlikely given my diet and daily multi.

Medications; montelukast (Singulair) for asthma, retinol cream for skin, loratadine (Claritin) almost daily for allergies, diphenhydramine (Benadryl) for sleep.

Hema thought Fanconi and other genetically derived causes were not to blame, given my older age, as those tend to show themselves much earlier. Plus, I had normal CBCs up until relatively recently (early 30's).

Spleen was removed in 2003 following auto accident. Since it was 16 years ago, hema said not a factor. Though I agree with you it seems like it may affect progression of disease and possibly cause variances in how it goes down.

When your husband was diagnosed, do you remember appx what his CBC numbers were? Also, what his marrow percentage was at that time? If he was 9 months until tanking, I'm just trying to gauge if his timeline may or may not be similar.

Thanks!

[Marlene]

John was 50 when he acquired SAA. I think his cellularity was at 25% but not 100% sure. Back then I didn't think to get copies of labs but I think it was at 25%. He had to have two BMB because the first was insufficient. John had some fluctuations in his counts over most of his adult life prior to SAA. His platelets usually stayed in the low-normal range and a couple of times, his HGB would drop to around 12 -13. But his doctors alway said it was his normal.

SAA 4/2002
--------------
WBC: 2.6
ANC: 1.1
HGB: 5.6
HCT: 15.8
PLT: 20

CBC 7/2001
-------------
WBC: 5.4
ANC: 3.9
HGB 15.0
HCT: 41.9
PLT: 142

Even though he was 50yrs old, Hopkins still tested for genetic/heredity causes. As strange as it sounds, it can still be a factor.

I'm sending you a private message with some other info for your consideration.

[Hopeful]

Hi Kubu,

Because your marrow is hypocellular, the doctors are probably trying to figure out whether the "marrow factory" is broken or whether something is attacking your marrow/cells (autoimmune).

Since your counts are holding, and the cells that are being produced are healthy, it seems like something could be destroying them. (I'm not an expert though. This is just my opinion.)

I thought the comment about an accessory spleen was interesting. I did a little google research, and it does say that people without spleens have Howell Jolly bodies in their peripheral blood. Since you don't, perhaps you do have an accessory spleen and perhaps it is inflamed and behaving badly (destroying blood cells), although it is odd that your platelets are still good. It may be interesting to get an ultrasound to learn more.

Also, there are some anecdotal reports linking Singulair to Aplastic Anemia (again from google research). So you may want to discuss this with your doctor. Also you may consider getting tested for Vitamin A toxicity, which can happen from retinol A.

I agree with Marlene that you should rule out the hereditary causes despite being "older than typical". Are you still waiting for the cytogenetic reports? Those could be very telling.

[David M]

Kubu,

As Marlene mentioned, some of us have lived for quite some time with hypocellular marrow and below normal blood counts. In my case, I first detected that I had low blood counts and corresponding hypocellular marrow back in the year 2000 -- about 19 years ago! Of course I was shocked at first, and I expected a counts crash to happen an any moment... but thankfully, it didn't in my case. We've been keeping an eye on it since then with quarterly CBCs (and a few bone marrow biopsies thru the years).

The good news is, I have not had to take any meds, have not had any transfusions, and have not needed to be hospitalized or treated in any way because of this. The bad news is, my counts have slowly trended downward over the years and really have not improved. (For a more complete description, see my "history" in the "Tell Your Story" forum on this web site, entitled "Slow-moving AA / Pancytopenia, or What?"). So, I have been in "watch and wait" mode for several years... which is not really that bad of a thing.

Others I have met on this site have had stable counts for several years until something caused a "crash" and treatment was required. Others, like me, have never experienced a crash. Several others with AA crash almost immediately and require treatment. We are all different... and I've always considered my case to be sort of an oddity on this site -- but there are a few with similar symptoms.

I wish you the best, and if I can ever help you in any way, please contact me!

David M

[kubu]

Agree on checking genetics regardless. I did take a glance at my raw genetic data for DNMT3A and ASXL1 last night. Those were mentioned in med journal requiring login for you to view so I can't post direct link, but if you access via Google search you should be able to see it or at least partial preview of article. Search those along with aplastic anemia. I will inquire during my appt with specialist next week.

Marlene, responded to your PM. As far as those numbers you posted here for your husband John... those are quite alarming how fast he progressed in 9 months. Going from 15 to 5.6 on HGB is shocking. Though from what I hear, SAA and VSAA really do cascade fast, once it gets going. It's the moderate cases that can coast along for a while without a nosedive, usually.

Hopeful, I should find out soon enough on the accessory spleen, as I have the ultrasound for that tomorrow. Admittedly I only did a superficial search, but wasn't able to find info on montelukast and aplastic. Could you post or PM me with it please.

David, that's encouraging to hear about your pancytopenia. Per your comment I did search your posts and skimmed a couple, seeing this:

I have had 3 bone marrow biopsy & aspirations through the years... The first one about 10 years ago showed me as hypocellular with ~25% cellularity ("normal" should have been ~64%).

I think that was posted 2009. So you started with 25% cellularity. When was your last reading and what was it?

[David M]

My last Bone Marrow Biopsy was June 2009. Since then, things have been reasonably stable -- although my counts have still been low. So, the last word I have re: cellularity is 15-20%, and that was 10 years ago.

[kubu]

David, I am surprised you have chosen to go 10 years without an update on your marrow biopsy!

Turns out I have 2 small accessory spleens. Results of ultrasound say:

"There are two adjacent, round 2.8-2.9 cm isoechoic structures in the left upper quadrant which likely reflect regenerated splenules in this setting."

Liver, kidneys, gallbladder, biliary, pancreas, and aorta of heart all reported as normal.

Went to City of Hope last week and basically the response was hold off on treatment until CBCs drop further. Both doctor and I seemed to agree that starting with Promacta alone would be best. Given that my platelets are still high, he said it would be dangerous to go on now.

I've been on low dose testosterone (50 mg daily) for almost 2 weeks. While it may be a coincidence, during my labs at City of Hope last week, my WBC were way up; 6.5. They haven't been that high since 2016. Among them, neutrophils were also markedly increased at 3.5. I also have to go back to 2016 to see them at that number.

Unfortunately the RBC, HGB, HCT, and MCV all continue to trend lower versus January.

[Barbara K]

Hi, Kubu,

Welcome and sorry you are here. I don't check the forums often and just happened to see your post today.

Previously, btw, I posted as Barbara K, but I couldn't manage to log on or do a password reset, so I just set up a new account.

I wanted to tell you that my spouse had a somewhat similar story. He went to give blood in fall 2011 (a very fit and health-aware age 48) and was turned away due to low hematocrit (around 32 maybe?). Trip to the doctor turned up pancytopenia. Hemoglobin around 10; platelets about 120-130?; white cells about 2; ANC maybe around .9 or 1. So mild, relatively speaking. BMB gave about 20-25% cellularity. His iron stores were very low, but they said that wouldn't explain the platelet and white cell counts. They gave diagnosis of suspected mild aplastic anemia. Iron supplementation made him less anemic but didn't bring his red cells up to normal and had no impact on white cell counts or platelets. They also on some tests said he had hypogammaglobulenemia, but then he was also listed as having monoclonal gammopathy of IGM. I mean, for a while it was dizzying, and I was in a panic.

Here we are several years later, and the situation is pretty much the same. His hematocrit is usually in the upper 30s and hemoglobin around 3.8. Platelets usually around 120-130; white blood cells around 2 and ANC around 1, esp. if they test in afternoon; if he goes in the morning his white cells and ANC are usually a bit lower. ANC has never gone below .6 I don't think. His numbers never ever go up noticeably, though. I'd be shocked at this point if he had a test that showed a white count of even 3 or 4. What does change is that his level of IGM is steadily going up, so that could perhaps be an early sign of impending Waldenstrom's Macroglobulenimia. (I'm sure i'm spelling that wrong.) Maybe he doesn't have mild AA at all but instead his body is producing limited blood to keep the monoclonal IGM antibody in check? If it is smoldering WM, he has quite a few years to go before he would reach levels requiring treatment. I mean, a lot of years unless it suddenly ramps up fast. Meanwhile, he has to take about 70 mg of iron a day just to keep his ferritin from tanking, so something is weird about his iron storage. But he did not test positive for celiac disease, so that doesn't seem to be a cause.

I guess my message is don't assume you are headed straight for a crash. And I would think that is very good news that your white counts went back up. It shows your marrow is capable of producing them. I wouldn't over-worry the BMB results, as others recommend. I think those can vary a lot depending on where they stick the needle.

Hang in there. There are no guarantees in life, but it might not turn out to be so dire. It was good they caught my husband's problem b/c he does feel better taking the iron (he had a lot of fatigue when his hematocrit was in the low-30s), but otherwise had he not gone to give blood I think even to this day we would have no idea that his blood work is not normal. He gets sick a bit more than me, but it's nothing major, nothing that would have registered as unusual.

Oh--and I almost forgot: he has developed a problem with tension headaches that he hasn't been able to resolve. That has come about since his diagnosis. We assume it is unrelated but I thought I'd mention it. They hit about once a month and last always three days.

take care, barbara

[kubu]

Thanks for that story Barbara. That's fascinating to hear about the monoclonal IGM antibody theory. Do you know if he had tests showing low iron prior to that, when he was presumably healthy or thought to be healthy?

I got the results from my 2nd bone marrow biopsy at NIH and the differences are:

Jan: 10% cellularity
March: 5% cellularity

Jan: normal iron levels present in marrow (blood tests reported moderate to high iron, too)
March: zero iron in marrow (and low blood levels)

Jan: normal severe aplastic anemia pathology - e.g. few marrow cells and lots of fat cells
March: gelatinous marrow transformation, where the fat cells have converted to gelatinous marrow, sounds like no normal fat cells left in marrow

I have heard that gelatinous marrow transformation can manifest itself early in aplastic anemia, but there isn't a lot of data on it, and no individual case studies I can find. Based on 100+ tests, malnutrition of both macro and micronutrients can be ruled out, likewise for cancer. In short, nothing "wrong" can be found, other than the major hypocellularity.

I have been doing worse since January, so if iron malabsorption is happening it wouldn't surprise me, but it is a new development/side effect that wasn't happening in Jan when the first marrow was done. One theory I have is if the testosterone therapy, which was begun about 6 weeks prior to 2nd marrow biopsy, may have depleted iron stores as it ramped up hemoglobin production. However my red continues to go down and down with each test.

[Barbara K]

Hi, Kubu,

I apologize for the slow reply. (I was away at a family funeral.)

Let's see: My spouse had never previously had any low iron test results that I know of. And his hematocrit must have been OK whenever he had last given blood--which was usually maybe once a year, something like that. But we don't think his hematocrit dropped down to the low 30s all at once because his anemia symptoms didn't come on abruptly. It was only in retrospect that I realized, oh, yeah, he was really slow coming up the hills when we were out walking, etc.

Your theory about the potential impact of your testosterone therapy is intriguing. Maybe somebody else on the forums feels able to weigh in with thoughts, as I don't have a science background and don't want to pretend I know more than I do.

My spouse also showed no nutritional deficiencies or problems with anything other than iron.

If memory serves, I came up with the theory about how his body might be suppressing the IGM monoclonal antibody after doing various forms of internet sleuthing in medical research papers. But it was just an amateur hypothesis. I do recall reading one study where the researchers were speculating that the body does engage in certain self-protective mechanisms when abnormal cells arise, and that one might be reducing circulating iron. I'll see if I can find that paper again and post a link. I think at the time I was running searches using the terms "monoclonal gammopathy" and "iron deficiency" at the same time.

I'm sorry you have been doing worse since January and that your red cell counts have been going down. Please keep us updated. It is incredibly stressful knowing something isn't right but feeling in utter limbo as far as what actually is going on or what to expect. I'm going to be sending positive thoughts your way and hoping that your situation stabilizes or, better yet, that you rebound quickly. Hang in there.