Harry P. Erba, MD, PhD: I want to point out 1 other thing in the small print. Because is the case for many pathologists on that committee, they say “If you don’t do it, you miss some important prognostic information on the presence of fibrosis.” Of course, I don’t know what to do with that prognostic information, so that doesn’t sway me 1 way or the other. How about you?
Srdan Verstovsek, MD, PhD: That’s a good point because the patients always worry about the long-term outcome of the disease. By default, they say it’s benign, but there is a proportion of the patients, about 20% to 25% of patients who, over their life span, may progress to myelofibrosis, and a certain small percentage who will develop leukemia.
Myelofibrosis in particular is the worry because, when you transform officially, the life expectancy can shorten. The bone marrow biopsy can provide some useful information to semi-intelligently prognosticate for the future. This is all relative, but if you have a cytogenetic abnormality, an abnormality of chromosomes, which is very rare but not impossible, that would perhaps prejudice most people to have a high risk of change.
The presence of fibrosis at the time of diagnosis of PV [polycythemia vera] is present in up to 20% of the cases; on a scale from 0 to 3, grade 2 is already seen in up to 20% of the patients. I repeat it because it’s important. These patients with PV are at a higher risk of a change to full-blown myelofibrosis during their life span.
This is the kind of information that we would like to have at the beginning for full understanding not only about diagnosis but also possible prognosis for transformation. Not for the thrombotic risk, which I already mentioned as a primary goal of therapy, but for the future. That needs to be highlighted: the presence of the fibrosis does not mean myelofibrosis by default. Fibrosis can to some degree be seen in PV.
Harry P. Erba, MD, PhD: Thanks, Srdan. Ruben, do you want to add to that?
Ruben A. Mesa, MD, FACP: I just wanted to add an important point that I share with patients, which is that I agree that baseline bone marrow biopsy is helpful. The challenge is if we see a bit of fibrosis and they have that higher risk, we still don’t know what that means in absolute terms. If I compare 2 patients—1 without that fibrosis and 1 with—yes, the patient who has the fibrosis has a higher likelihood of progression through myelofibrosis, but that might be in 10 years compared with the other patient who will never progress during their life span.
As we think about these prognostic factors, it is worse as a population, but it’s always difficult to translate for a patient what that means. Additionally, all of that is in current science. We may well develop therapies, or some of our current therapies might alter that natural history further. So prognostic always has to be taken in appropriate consideration; sometimes patients can become very distressed by some of these prognostic findings as well.
Harry P. Erba, MD, PhD: Jamile, would you like to add?
Jamile S. Shammo, MD, FASCP, FACP: As everybody said, the bone marrow biopsy may or may not be important. The 1 piece I wanted to add in PV is for patients who may not meet the criteria. Let’s say you have a JAK2 V617F positivity, and you’re entertaining an MPN [myeloproliferative neoplasm]. Perhaps the hemoglobin isn’t 16.5 or 18.5 g/dL, where you don’t have to do a marrow, but perhaps it’s 13 g/dL. If you did the bone marrow and then you get an iron stain, which I highly recommend on anybody who has a marrow with the suspicion of an MPN, that has 0 iron in it. If you have absent iron stores, then your patient clearly is iron deficient and may have PV, even though the hemoglobin doesn’t necessarily meet the criteria.
In that sense, when the heme parameters do not fit the WHO [World Health Organization classification and diagnostic criteria for myeloproliferative neoplasms] 2016 as opposed to 2017, as it says in the NCCN [National Comprehensive Cancer Network] Guidelines, it has to be performed so that you can characterize the MPN a bit better and pay attention to the iron piece. I often see it done, yet nobody comments on it, and we could improve a lot on the prognostic accuracy of the characteristics of the MPN we’re looking for.
Harry P. Erba, MD, PhD: I agree with that. The iron stain can be helpful in those borderline cases, and I often look for iron deficiency.
Transcript Edited for Clarity