Understanding Transformed FL

Two articles from The Journal of Clinical Oncology on Transformation in Follicular Lymphoma. The first, "Risk Factors and Outcomes for Patients With Follicular Lymphoma Who Had Histologic Transformation After Response to First-Line Immunochemotherapy in the PRIMA Trial,"describes the results from a large study of FL patients. The second, "Will a Better Understanding of the Problem With Transformed Follicular Lymphoma Lead to Better Outcomes?" is a commentary on the first article. They both have some interesting things to tell us.

The research article is the latest in a bunch of studies that are trying to understand Transformation a little bit better. There's still a whole lot we don't know about transformation, even basic stuff like why it happens. We know what happens, but we don't know enough about why it happens to be able to predict it. It's always kind of sad surprise when it happens. And a study seems to suggest something about Transformation, but then other studies contradict it, or can't confirm it strongly. It's frustrating, and partly why Transformation is such a scary thing.

The research article looked at over 1000 FL patients over 6 years. A few things that struck me as important:

They identified certain things as risk factors for Transformation. I'll say it again -- these are RISK FACTORS, not guarantees that Transformation is going to take place: altered performance status (I assume they mean a change in your ability to care for yourself, which is what "performace status" usually means), high LDH (Lactate Dehydrogenase, common in FL blood tests, it measues cell damage) “B” symptoms, a grade of 3a, and a high FLIPI score.

Again, those are RISK FACTORS -- it means you have to be a little more careful in keeping an eye out for symptoms. Patients with risk factors aren't guaranteed to transform, and patients without risk factors can also transform.

Like I said it's unpredictable, and that's what makes it scary.

The research article also suggests that an Autologous Stem Cell Transplant might be a good idea for transformed patients, and that a biopsy should be taken when the FL comes back after the first treatment, to be sure it hasn't transformed. (There are some other results, too -- worth looking at the link.)

The second article, the one that comments on the research article, is also interesting, but also a little frustrating in some of the things it says.

The article looks at the research article above, plus three other articles about Transformation, all published in the last 3 years. The author says that these four articles together tell us a lot about what we know about Transformation, and it's a lot that we didn't know before.

For example, in addition to confirming the risk factors from the research article above (high LDH, grade 3, and a high FLIPI), the studies also seem to agree on a transformation rate of 2% over the 10 years after diagnosis, or a 20% change of transforming (a lot lower than some estimates I have seen, though a little higher than others).

But the article also makes it clear that the four studies are hard to compare to one another, since they all look at slightly different groups of patients, and look for slightly different things. So while there are some common risk factors, I'm still a little hesitant to use stronger language than "risk factors." I think we're all on the look out for transformation (it is, as the article says, "the greatest fear of patients and their medical teams.") Interesting that they say it's a fear for the medical team, too -- I think that reflects the kind of frustration that our oncologists have in trying to predict where our disease will go, and then what they should do to treat it.

The article ends with a wish that we will someday soon have a better way to predict Transformation. It cites a few articles that have done some early identification of possible markers for Transformation, including IRF-4 (a gene that codes proteins), miR-31 (which helps suppress tumors, so having less of it is a bad thing), bcl-2 (which helps control cell death), pleuripotency (which describes cells that can develop into any cell in the body), and nuclear factor kappa B pathway genes (which helps cells divide normally). There is no strong proof that any of these things are responsible for Transformation, but there is some suggestion that they might play a part.

Maybe we'll find that there is a combination of these factors that work together to make Transformation happen? And then we'll be able to target those things with new treatments?

It would just be nice to know something, wouldn't it?

In the meantime, we seem to know a little bit more with every new study -- even if what we know is that we don't know as much as we wish we knew. The best thing we can do as patients is, I think, stay alert to changes in our selves, and try not to panic.

You know, the stuff we're used to doing anyway.