Changes

[Rarity]

Hello, Hope everyone is doing well as can be expected.

Recent changes on my husbands situation. So, I have a couple of questions that are not clear. I was hoping someone could help.

Can there be a change from hypercellular to hypocellular?
What is the significance of a change in the LDH increasing to high levels (were normal level until now, it doubled) and can this level fluctuate too?

Nucleated rbc's, which I know there shouldn't be any but not clear on the relevance of those suddenly showing up. Are those considered blasts in the blood? Extensive loose fibrosis, loose collagen fiber.

Appreciate all of your knowledge. Still getting educated.

Rarity

[Hopeful]

Hi Rarity,

Has your husband been tested for PNH?
An elevated LDH is one of the signs (although it can show up for other reasons as well).

AA, MDS, and PNH can overlap. So if your husband's marrow is showing hypocellularity now, it could be another sign of cell destruction.

I found this article that mentions PNH, trisomy 8, and trisomy 21 showing up in PNH/MDS/AA transformation. Unfortunately, it is more observational in nature:

http://www.bloodjournal.org/content/...o-checked=true

Does his hematologist have expertise in PNH?

[DanL]

Rarity,

Yes, there can be a change from hyper-cellular to hypo-cellular, but I don't think that it is that common. Increasing LDH is a sign of additional stress in the marrow. I think that most bone marrow disorders have that as a common marker. An increase can be caused by a number of factors, including infection, but usually indicates an increase in cell destruction.

As for NRBC in the peripheral blood, they are considered blasts by my doctor, and they should not be present. RBCs have a nucleus prior to being released into the blood stream. An NRBC, is therefore one that has been released into the blood prior to maturation as a result of increased demand from the marrow. And per our friends at wikipedia:

Possible pathologic causes include anemia, myelofibrosis, thalassemia, miliary tuberculosis, cancers involving bone marrow (myelomas, leukemias, lymphomas), and in chronic hypoxemia.[4]

In addition to these, there are several other potential non-pathologic causes as well.

[maggiemag]

Well Dan, I didn't know that nucleated RBCs were considered blasts. I've had them mentioned on a diff, and also metamyelocytes which I think shouldn't be there. I guess that the amount or % is what matters? The other ones like teardrop cells, burr cells, schistocytes etc. I have too but I don't think are too significant. Hope I'm right! Interestingly, it says "present" for those types of cells, but it says "PRESENT" for giant platelets. Does that mean they are worse if present?
Sorry, Rarity, don't mean to hijack your thread!
Mags

[Naive]

I too have NRBCs, metamyelocytes and giant platelets. I asked my hemo about it and he basically said to not worry my silly little head. Not really impressed.

[Rarity]

Thanks for all of your replies.

Dan, The pathological reason makes sense. The NRBC in the blood does not and couldn't find a clear reason. Your other replies makes sense too. The LDH is most likely the cell destruction in this case.
Is it worse to change to hypo cellular?

I don't mind the hijacking Maggiemag We learn from others and try to understand the best we can.

Naive, Maybe more concerning because they aren't supposed to be there? Just trying to understand the significance of why.

Hopeful, Didn't see anything for PNH on reports. The dr. he sees is supposed to be top notch so, hope that he covers all basis. I will mention it.

[Hopeful]

Hi Rarity,

PNH is a separately ordered test. It is usually part of the differential diagnosis when a patient presents with unexplained bone marrow failure and anemia, especially in the presence of elevated LDH. If your husband hasn't had it done, I would not delay in requesting it.

Even having a small percentage of PNH cells is significant when determining a treatment plan. Having a large PNH clone may require a different treatment plan all together then typical MDS, even though the two may occur simultaneously. So, it is important to rule this out.

As I have a small PNH clone, my hematologist will periodically monitor my LDH to determine whether the clone is expanding in size. My LDH has never been elevated but I do have a sub-clinical PNH clone. I am sure if my LDH became elevated and I was severely anemic, my doctor would retest my PNH.

I also have NRBCs, schistocytes, teardrops, etc, but in small numbers. I agree with maggiemag that it is the percentage that matters.

Likewise, I think that it is the relative cellularity that matters. Mild hypocellularity would be less concerning than 10% cellularity, for example. Keep in mind that the marrow can be patchy and not consistently hyper- or hypo- cellular.

[Naive]

Hi rarity. I agree they shouldn’t be there (btw, my LDH and ALP are high too) and I get a bit annoyed at the hemo who assumes I don’t need to know things. I’ve been dealing with this for a while and it’s frustrating to be treated like a toddler.

He just said “no point doing a BMB, it’ll just show MDS”. Well, I might be a bit silly but I’m not stupid and I assume that if the blood cells start changing then the bone marrow is probably changing too. My transfusion requirement has increased too, just had second blood transfusion a week after the last one. Isn’t that what watch and wait is about? Monitoring and assessing and waiting for change so treatment can be implemented when necessary. Hemo said next appt in 3 months.

Sorry....ranting.

I hope you get some answers..I’ll sure be interested.

[DanL]

MaggieMag,

It is not uncommon to see immature white blood cells in the blood when you have infections or other illnesses that cause the marrow to work overtime. Viral infections can frequently allow immature white blood cells (not necessarily blasts) to go into the blood stream, although these immature granulocytes (IGs like metamyelocytes, myelocytes, and promyelocytes) don't really belong and could indicate marrow failure as well.

Rarity - as for the LDH, there are several different types (i believe 5), and one of them is actually used to determine if a patient has had a heart attack recently, or has liver issues. I am linking an article that goes into some detail.

https://www.healthline.com/health/la...drogenase-test

[Rarity]

Hi Naive, I know your frustration well. And I'm not the patient. Just trying to advocate and sometimes I feel like I'm not doing a good job. I like to know the particulars and fix it. This unfortunately I can't. I know he is scared and doesn't really want to know all the details. I do the researching to try and make sense of things that come up and make sure they are doing the best they can for him.

I think some dr.s although may be excellent at what they do, they lack communication. Maybe perhaps it's this particular disease because it's so very complicated, with so many variables, that they don't want to cause alarm with some of the changes that can happen.

He's been on a regular transfusion trend. The last visit showed some changes, which of course grew more concerned. It is also hard when you have to wait for the next appointment to discuss what comes next or just wait some more. I know that's better than the alternative.

You are not silly at all! Just keep asking questions and don't feel stupid for asking. Wishing you the best!

Hi Dan,

Thanks for the link. I did read through it. So, it's probably related to cell destruction that makes most sense here. I appreciate your help!