Thursday, June 13, 2013

Detecting Disease in Follicular Lymphoma

The most recent issue of Therapeutic Advances in Hematology has a dense but fascinating article called "Clinical Implications and Prognostic Role of Minimal Residual Disease Detection in Follicular Lymphoma," written by a team of researchers from Turin, Italy. The article has some important implications for detecting residual disease -- those little bits of cancer that hang around after what seems like a successful treatment, and which can be very hard to find.

As most of us know, Follicular Lymphoma has a bad habit of coming back after treatment, even successful treatment. Sometimes it comes back more aggressively (and I mean that it returns as FL, not as a transformed disease), and the earlier the returned lymphoma can be caught and treated, the more successful the treatment generally is. Right now, it's hard to predict how Follicular Lymphoma will behave. About the best we have is a FLIPI score (which I'm not going to explain.  See's typically excellent description of what FLIP is. Or just ignore it, if, like me, you're the type that hates numbers).

The authors of the article discuss PCR-based MRD detection: PCR stands for Polymerase Chain Reaction, and MRD for Minimal Residual Disease. So this is a method for detecting whether or not any cancer remains after treatment. It's the "PCR" part that is so exciting.

Even after what is deemed to be a Complete Response, some cancer cells might remain, including cells that can hang around for a few years and then explode into a full relapse. (OK, "explode" is a little dramatic, but sometimes things do happen quickly -- always a concern). A PET scan might not be able to detect the tiny amounts that remain, and that are enough to potentially cause such a relapse.

The PCR-based method, however, is sensitive enough to find them. Basically, it works by detecting cells that have a particular molecular mutation. In this case, that mutation is a switch of two chromosomes (14 and 18) that is typical of Follicular Lymphoma. The mutation causes some other things to happen (I'm going to skip the details), and this results in "antiapoptosis" -- the cell is prevented from dying a normal death. Right now, about 55-70% of Follicular Lymphoma patients have the molecular structure described above (the skipped details) that would allow detection by PCR-based methods. The authors of the article argue that it wouldn't be too tough to develop a test that allow most, if not all, of the remaining FL patients to have residual disease detected, too.

PCR-based methods, then, are superior to what we have now because they can detect disease at such a small level. PET scans work well in detecting disease in lymph nodes, but not in bone marrow. By looking at individual cells, PCR-based methods can detect tiny amounts of disease no matter where they're hiding.

These method have been used for some time in other blood cancers, such as Acute Lymphocytic Leukemia. Their use in Follicular Lymphoma has a bright future, particularly, say the authors, as a tool in clinical trials, allowing researchers to understand in a more detailed way just how well a treatment is working.

So, this isn't about a breakthrough treatment, but it supports potential breakthrough treatments. It may be a quiet way of helping us all out some day.

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