Friday, March 13, 2015

CD5 in Follicular Lymphoma

Interesting article in the journal Modern Pathology last week: "CD5-Positive Follicular Lymphoma: Clinicopathologic Correlations and Outcome in 88 Cases."

As the title suggests, researchers looked at patients who had CD5 on their lymphoma cells. CD5 is a protein that is commonly found on cells of some blood cancers, but Follicular Lymphoma isn't usually one of them. We're more likely to find CD10, CD19, CD20 (which is the protein that attracts Rituxan) and CD22. But CD5 is much less common.

So when CD5 does show up, what does that mean?

The purpose of the article is to look at 88 Follicular Lymphoma patients with CD5, describe some trends, and try to figure out what it means.

To be clear: they didn't look at a large sample of FL patients and try to figure out what percentage of them had CD5; they looked specifically for patients who had it, and found 88. That's who they are focusing on.

Here's how it all breaks down:

66 of the patients had FL discovered in their lymph nodes, and 22 had in other places.

81 patients had swollen nodes, 66 had more than one lymph node site affected, 46 had bone marrow involvement, and 7 had enlarged spleens.

Staging information was available for 84 patients: 52 were at stage IV, 18 were at stage III, 12 at stage II, and 2 at stage I.

61 were grade 1 or 2, and 27 were grade 3.

So far, so good; these really aren't that far off from the whole FL population.

So now it gets a little more interesting.

In 64% of the cases, there was some kind of translocation or BCL2-related issue. (BCL2 is related to cancer cells not knowing how to kill themselves off like normal cells.)

43% of the patients also had Diffuse Large B-Cell Lymphoma (DLBCL), either before, after, or at the same time as their FL. All received some kind of chemotherapy, and some had a Stem Cell Transplant.

As for Overall Survival, with a median follow-up of 55 months (one with a follow-up of only 2 weeks, and one with 207 months, or more than 17 years), 15 patients had died, 46 were living with the disease, and 20 were in remission.

When the 88 patients were compared to a matched group of FL patients with CD5, the researchers found that the CD5 patients were more likely to develop DLBCL (about 43% of them did, compared to about 17% of the general FL population). They also had a shorter median Progression Free Survival that the overall FL group (44 months before the disease got worse, versus 89 months -- though this doesn't account for different types of treatment), and the CD5 group was a more likely to have a higher International Prognostic Index (a very general measurement of how aggressive their cancer might be).

It's these last three things (more likely DLBCL, shorter PFL, and higher IPI) that make up their conclusion: if you want to put those things together, they are basically saying that having CD5 means you are more likely to be worse off than most other Follicular Lymphoma patients.

So here's my take on all of this, for what it's worth:

First, I hesitated to put in all of those numbers, because as I've said many times before, numbers don't mean anything to us individually. If anything, they are valuable to researchers because they might give them some clues as to what they might want to look into. In this case, for instance, they might find that it's worth looking into whether or not an anti-CD5 antibody might be valuable for some FL patients. That monoclonal antibody does exist -- remember, CD5 is common in some other blood cancers -- though my understanding is it never took off because those cancers also commonly have CD3, which is more sensitive to antibodies.

Second, I think this emphasizes how difficult it is to pin down a single source for attacking a cancer. I looked at those numbers -- 43% of CD5 FL patients had DLBCL, for example -- and thought, Yeah, but that's less than half. There is some connection, but having CD5 is no guarantee that you'll transform. Heck, one patient was still alive 17 years after diagnosis. So it's not just CD5 that's the problem -- it's CD5 plus....what? I don't know. But it has to be CD5 combined with some other stuff that make that form of FL tougher to handle, and these researchers weren't necessarily looking for that. As I said, it's a reminder of how difficult it is to pin down one source for cancer. We can't attack just one thing and assume everything will be OK. This is the direction that cancer research has been going -- looking for multiple operations, inside and around cancer cells, that work together to keep the cancer cells alive.

Finally, the part for some hope -- they found some information about Follicular Lymphoma patients with CD5! As tough as it's going to be to find all of the operations that work together to keep cancer cells alive, these researchers added their small piece to the big puzzle. And as more and more researchers add their pieces, that big puzzle is going to come into focus, and we're going to have our answer. It's going to take some time, of course, but considering how much we've learned about cancer in the last 10 years, compared to the 10 years before that, we are well on our way.

Stay hopeful, and ignore the numbers.

No comments: