Correlation between VAF and BMB findings?

[LIGEBA]

I'm wondering if anyone has come across a report showing a direct correlation between VAF and amount of scarring determined via BMB. For instance if VAF is 20% and reticulin fibrosis is MF 0-1+/3, would it be expected that if VAF was say 50% that reticulin fibrosis might jump to MF 2/3 or even 3/3? Hope I have made sense.

[Bluetop]

Sorry can't point you to any relevant article, but it's an interesting question. I'd be interested in any responses you get.

[LIGEBA in reply to Bluetop]

Honestly I have no idea if the BMB (bone marrow biopsy) reading (reticulin fibrosis is MF 0-1+/3) is where the VAF (allele burden) number is derived from or the other way around, or completely independent of each other. Of course we can also get a VAF through bloodwork as well. Just so curious if there is any correlation. Hopefully someone here has some insight.

[EPguy]

This one report right on the subject, for PV. It's old (2013) and retrospective so there may be other data. But at least here the correlation is strong. The thin lines in the boxes are medians. They also found generally higher disease indicators for the highest VAFs, consistent with typical recent findings.

ncbi.nlm.nih.gov/pmc/articl...

This report is old enough that there is no discussion of reducing VAF as a possibility. Also old enough that some therapies I've never heard of were in the study group ( imatinib or dasatinib, thalidomide, P-32)

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There is a report in prior threads (I think from the Silver MPN group) that found a not-strong correlation with reducing VAF to improved fibrosis (VAF can often go down while MF fibrosis grade does not) But no doubt there are diverse findings in this area.

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Some other recent reports are tending to reticulin fibrosis being more benign while collagen fibrosis is more pathological. BMBs usually state which type, if any, is found,.

Sorry I don't have the threads on these two topics handy.

Fibro/ VAF

[LIGEBA in reply to EPguy]

EPguy thanks for the report. It certainly was an interesting read. I was familiar with reticulin fibrosis but had not come across collagen fibrosis. As I read through reports it's clear this disease is still in need of a lot more research. There are a lot of thoughts and findings by the experts, but I still don't see any definitive convergence that leads me to believe, "this is the correct path" to conquer this disease.

[EPguy in reply to LIGEBA]

From the reports below, PV pts would not be expected to have collagen while more advanced MF can show it. A low level of reticulin fibrosis is normal in healthy people, I posted in detail long time ago..

From and older report:

2007 " Increased reticulin staining (reticulin fibrosis) is associated with many benign and malignant conditions while increased trichrome staining (collagen fibrosis) is particularly prominent in late stages of severe myeloproliferative diseases"

pubmed.ncbi.nlm.nih.gov/179...

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and a newer one:

2018 "as higher WHO BM fibrosis grade in most cases is associated with higher amount of collagen and advanced osteosclerosis"

jhoonline.biomedcentral.com...

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You're right on the lack of a "correct" path. That applies to most serious diseases from what I can tell, including my other serious one. One example otherwise is Hep C, it used to be treated with IFN but now is curable with a pill "DAA tablets". So this one has a "correct" path for ~90% of pts.

Maybe we'll get a similar magic pill that also beats the limitations of IFN, Incyte is working on an early candidate for Jak2 as in recent posts.

[Roxanne22]

Hi I am late to the party as have been travelling away but from my own experience there is no current correlation between BMB finding and my very high (surprisingly so!) VAF reading - my recent biopsy showed no sign of reticulation/MF, and yet my VAF was 77%!

I will let you know if I discover any more insight as I am now due to take meds for the first time since my diagnosis 7 years ago now, as in the light of the VAF discovery, I wish to ensure that disease progress is minimalised/halted.

I currently have v few symptoms from my PV and so the high VAF was quite a surprise, even my haemotologist had to call the lab to double check that the results were mine as it did not seem to correlate. I start Besremi nxt week and now that I have my head around it am curious to see if it will enable me to feel even healthier. My platelets have been dropping steadily and are now lower than they have been for 6 years at around 700 (without meds) yet the WBC remains between 14/15m, which has also contributed to my decision to commence ITF.

Wishing you good health/ Sarah

[LIGEBA in reply to Roxanne22]

Sarah thanks for your input. Curious if there is a reason your platelets are dropping? How high had they been? Were you just doing phlebotomies? Aspirin?