What does "PNH Clone" mean?

[Lbrown]

Hi guys,

I keep seeing the terms "PNH clone", "clone size", "clonal disorder" and "monoclonal antibodies". What do these mean? I am not even sure what a clone is.

Thanks and sorry if that is a question that's going to take a long reply, I tried Google but couldn't find the basic definitions I was looking for.

[Lisa V]

As I understand it, Lbrown, a "clone" refers to a cell with a particular set of traits (in the case of diseases, abnormal traits) which can replicate itself and potentially replace normal cells. Cancers are considered clonal disorders because the cancerous cells tend to multiply more rapidly than the healthy ones, but there are also non-cancerous clones. A PNH clone, then, would be a marrow cell which has the characteristics of PNH.

A normal BMB sampling only looks at 20 marrow cells. If only one cell out of the 20 they look at shows abnormal characteristics (whether it's PNH, AML, or a chromosomal mutation like trisomy 8 or 5q deletion), the size of the clone for that disorder is said to be 5%. If 7 out of the 20 have it, the clone is 35%, etc. Clearly with such a small sampling, the margin of error can be pretty high, so it's hard to get a true picture of what's going on without multiple biopsies. If your BMB results consistantly show that 25% of the cells have a particular mutation, then your clone is likely stable. If the percentage increases with every BMB, however, your disease is probably progressing. If it's decreasing, then that's cause for celebration!

Hope this helps,

[Lbrown]

Hi Lisa,

Thanks for the explanation. Does that mean bone marrow failure diseases do not have clones?

[Lisa V]

Originally Posted by Lbrown

Hi Lisa,

Thanks for the explanation. Does that mean bone marrow failure diseases do not have clones?

It depends on how broad your definition of bone marrow failure diseases is, Lbrown. "Aplastic anemia" and "myelodysplastic syndrome" are merely descriptions of symptoms rather than actual clones, so they are really catch-all categories for a set of disorders that meet certain criteria. Within that, however, you can have clonal disorders, like the chromosome mutations I mentioned earlier.

I'm pretty sure leukemia qualifies as a bone marrow failure disease, since AA and MDS are often considered "pre-leukemic" diseases. I have a friend with AML who was sheduled for a sibling marrow transplant, but because of some other complications they decided to try an autologous transplant instead. This is where they take your own marrow, remove the AML clone, and infuse it back into you. It still involves nuking your remaining marrow, which is risky in itself, but since you are getting your own cells back, you don't have the graft-vs-host problems that you would with an allogenic (donor) transplant, so it's somewhat easier on your system. He's doing great after 3 or 4 years. No sign of recurrence, although the impression I got is that relapses are more common if you get your own cells back. I could be wrong about that.

At any rate, you can't do that for AA because there is no clone to remove, although I've often wondered what would happen with my husband if they just tried to remove his trisomy 8 clone. Whether or not that would help him would depend on whether the mutation is what is causing his auto-immune attack, or whether it came on as a secondary result of it, and I think they don't really know that. The same may be true for other chromosomal anomalies in MDS. If they are not the whole picture it may not be worth trying to just remove the clone rather than doing a full-on transplant. I'm just thinking out loud here, I don't know if this is ever even considered as an option. I'm not sure if it would work for PNH either, but maybe someone will know.

[Susan]

Hi,

Do you have or think you might have PNH? I hope not. In the case of PNH the clone is an mutation which often occurs in the setting of Aplastic Anemia. Many with PNH got AA first but most people with AA do not have PNH. There are fewer people with both MDS and PNH.The size of the clone is measured by flow cytometry (done by simple blodd draw). A 25% clone for example means 25% of the white blood cells, also called granulocytes, are PNH affected cells.

When you saw monclonal antibody it may have been describing Soliris, one of the treatment options for PNH. Soliris blocks a part of the immune system which is involved in attacking the red blood cells. Sorry not a scientist but for more explaination on PNH take a look at this PNH overview article, about the best around, Diagnosis and Management of PNH:

http://bloodjournal.hematologylibrar...06/12/3699.pdf

suz

[Lbrown]

Hi Suz and Lisa,

No I don't think I have PNH, my hematologist says she doesn't think I have a hemolytic anemia. Thanks for the explanations about clones and the link to the article about PNH.

I've been diagnosed with pure red cell aplasia, so I've been reading up a lot about aplastic anemia as it seems similar. I'm trying to educate myself on the terms and different bone marrow diseases and treatments.

I am convinced my disease is caused by some sort of undetected infection. 18 yrs ago I was hospitalized with FUO and agranulocytosis. I responded to cyclosporine then, but this time cyclosporine was only partially successful - it stabilized my HGB at 100 but I felt terrible on it. I decided to try the Marshall Protocol before I committed to more drastic treatment with ATG or cytoxan (treatment of L-form bacterial infection as the cause of autoimmune diseases). If the MP doesn't work then I'll have to look into those treatments.

I've found some articles about effects of infections on bone marrow at Pubmed, so I know I'm not totally out in left field, but it sure is a long, slow process. In the meantime, I'm trying to research and get as much info as I can, especially when I come across new terms.

Thanks,
Deb

[Greg H]

Hey LBrown!

LisaV and other have given you good info. I just thought I'd add that, basically, when we are talking about bone marrow failures diseases, a "clone" is a blood-producing (hematapoietic) stem cell.

These stem cells are where the whole process of making blood starts. When they divide in order to multiply, they can either start a process that while make a cell that will develop into a blood cell that will circulate in your veins and arteries OR they can make an exact duplicate of themselves -- a clone -- which can then later clone itself, and so on. (It's more complicated than this, I'm sure, but that the basic version that I can understand.)

So, if you have a messed up stem cell (say, one missing the long arm of Chromosome 5) it can eventually clone more and more stem cells that are also missing the long arm of Chromosome 5. The ability of these defective cells to clone themselves is what makes MDS a "clonal" disorder.

Hope that's useful.

Take care.

Greg

[Lbrown]

Thanks Greg.

I apparently don't have any clones, and no genetic abnormalities. They're pretty much convinced I have something that is immune-mediated. The dr explained that somewhere along the line, my immune system learned to attack my red cells & precursors. I'm still sticking to a viral / bacterial cause, but who knows for sure. At least I still have some CD34 cells.

I quit taking tacrolimus on the weekend, I posted in my LDN thread. I am supposed to start taking cyclosporine again - neoral this time in the hopes of not having so many side effects.

I decided to take Feb "off" and see if the LDN kicks in, as I've been taking it since Nov with tacrolimus. I took 18mg of tacrolimus a day - apparently a whopping big dose - and it had no effect. The dr is not hopeful cyclosporine will work now either, and I'm really not looking forward to cyclosporine after the side effects the last 2 times I took it.

So my plan is to start the cyclosporine in March if nothing has changed by then. My current doctor is a little more open to me making suggestions and I see him again April 20. He was the one who brought up autologous stem cell transplant.

Deb

[lindy]

Am wondering if thrombocytopenia + hematuria has any relationship with PNH?

[Neil Cuadra]

Originally Posted by lindy

Am wondering if thrombocytopenia + hematuria has any relationship with PNH?

Yes, both can be symptoms of PNH. But having one or more symptoms of PNH does not necessarily mean it's PNH. A flow cytometry test can help determine that.

Technically, hematuria refers to red cells in the urine, which can result from an infection, kidney problems, or other cause unrelated to bone marrow. However, the word hematuria is sometimes used to mean hemoglobin in the urine (which in PNH results form the break-up of red cells). Hemoglobin in the urine is more correctly called hemoglobinuria.

Whole (unbroken) red cells in the urine can still indicate PNH but from what I've read that's weaker evidence for PNH than having hemoglobin from broken cells in the urine.

The most noticeable symptom produced by the mutated gene in PNH is the effect on red blood cells, but platelets can be affected too, producing thrombocytopenia.

[lindy]

Neil, thanks for your post.

I heard someone has low platelets but other counts are normal & is diagnosed with PNH. So its possible.