[Greg H]

Hi Patti,

First, congratulations on Dean's fantastic response to Dacogen. I am truly happy for you guys.

Like Birgitta, I have the impression that, normally, you continue with the Dacogen or Vidaza until it quits working.

It is possible to see blasts in peripheral blood, though usually, in the context of MDS, we are talking about seeing them in the marrow.

Remember, I'm not a doctor, just a guy who has read a lot of stuff above his pay grade. And this is a bit long and involved, but bear with me.

But, I think the problem here is the word "Remission."

That's a word from the world of cytotoxic chemotherapy -- what is properly called "chemo." Now, some patients, nurses, and even doctors will call Vidaza and Dacogen "chemo." And, of course, it is a chemical that you are putting into your body to try to control a kind of cancer.

But the more proper use of the term "chemo" in the world of cancer treatments, refers to cytotoxic -- "cell-killing" -- chemicals. The idea is to find a chemical that will kill fast-growing cells -- like cancer cells -- and not the rest of the cells in the body. Of course, some other cells in the body grow fast, too -- like hair and mucus membranes. That's why folks who have cytotoxic "chemo" for their cancer lose their hair and get sores in their mouths; the "chemo" is attacking the hair and mucus membranes along with the fast-growing cancer cells. These are the same kinds of drugs that are used prior to a bone marrow transplant, to kill off the fast-growing cells in the bone marrow.

So, folks with breast cancer or colon cancer -- or even acute myeloid leukemia -- are given this kind of chemo. It kills the tumor or the leukemia cells, the symptoms go away, and the cancer is "in remission." Often, the cancer sooner or later comes back, because the Chemo didn't get all of the cancer cells, and they stage a new attack. A lot of the early trials with cytotoxic chemotherapy involved figuring out how much and how many poisons the docs could give people without killing them, in order to wipe out as much of the cancer as possible.

So, that's true "chemo." "Cell-killing," that's the key.

As I understand it, this is not how dacogen and vidaza work. They don't actually kill the defective stem cells that are messing up blood production. Instead, they change the environment in the marrow in a way that messes with chemicals in the stem cells -- methyl groups -- that are involved in switching on and off various genes. I'm honestly not sure whether they turn off the bad cells, or just get them to clean up their act. But I'm sure they don't, in fact, kill those bad cells.

Most cytotoxic chemo just goes after fast-growing cells. But all the cells in the bone marrow are fast-growing; they have to be, to churn out the trillions of blood cells you need to stay alive. There is research out there to find targets other than growth rate and develop cell-killing drugs that would target MDS and leukemia cells and kill them, but Vidaza and Dacogen aren't those drugs.

So, "remission" is really not a useful word when talking about Dacogen and Vidaza. Real "chemo" actually kills cancer cells (though it doesn't get all of them, which is why we have relapse). Vidaza and Dacogen change the chemical environment in which the bad cells live, altering their "behavior" without actually killing them. Take away the drug, the chemical environment goes back to normal, and the MDS comes back.

You can see why it's tempting to talk about "remission" and "relapse" in MDS treated with Vidaza and Dacogen -- we are all familiar with those words from the world of solid tumor cancers. But we're really dealing with drugs that operate in very different ways.

That was a very long way of saying that I'm really skeptical about stopping the Dacogen. On the other hand, your doc is planning to use Revlimid, and he's a doctor, so he's bound to have some reason for that. And maybe that reason over-rules the general rule of thumb to stay with the Dacogen 'til it stops working. But he should be willing to explain all that to you.

Echoing Slip Up2, does Dean have an abnormality on Chromosome 5? That's the usual indication for Revlimid.

Echoing Linda, I think it's now time to make that trip up to Moffitt and get that second opinion from a real expert.

Take care!

Greg