More About Neutrophils and Dexamethasone

This post will be a bit technical and will likely appeal more to the Myeloma patients among us with an analytical streak like me. However, I picked this up from an article describing the cancer microenvironment in the most recent Cure magazine so I suppose it has an application for anyone curious about the role neutrophils play in angeogenesis.

Illustration of the cancer microenvironment:
http://www.curetoday.com/index.cfm/fuseaction/article.show/id/2/article_id/1305

If you can link to this web site, you need to do it. This illustration is truly worth a thousand words, or more. This provided the bit of information about the role played by neutrophiols I needed to explain why it is necessary to take dexamethasone with Revlimid.

One thing they constantly remind you of if you are taking Revlimid is that it will reduce your white blood cell count. After you take the drug for a year or two, you begin to wonder how many other things they AREN'T telling you about. One thing I wasn't told is that something about Revlimid makes neutrophils stick to blood vessel walls. This is a normal response to localized infection but highly undesirable when it is happening all over your body because if your white blood cell count has been reduced by Revlimid, your neutrophil count is already low, it doesn't need to be lowered even more by neutrophils sticking to blood vessel walls.

This is where dexamethasone helps out. Something about dexamethasone causes neurtophils not to stick to blood vessel walls and allows them to circulate in the blood. The difference between not taking any dexamethasone and taking 10 to 20 mg or so is a neutrophil count well below 1000 or well above 1000. Normal is 3000 or above. Below 1000 is getting into dangerous territory where you become susceptible to any bacteria or virus you are exposed to and some good bacteria you carry around that is held in check by neutrophils but can grow out of control and cause infection without neutrophils.

According to the cancer microenvironment illustration, "Neutrophils and lymphocytes are immune system cells that can tip the balance toward a cancer-promoting or cancer-inhibiting microenvironment. An abundance of neutrophils is associated with increased growth of cancer blood vessels and poor prognosis. High levels of lymphocytes have been linked to a better prognosis."

My local oncologist reminded me during our last visit we still do not know how Revlimid does what it does, sort of like saying it is what it is. Nevertheless, we do know some things about the behavior of the drug. For example, it is known to inhibit angiogenesis (new blood vessel formation) and inflammation. The angiogenesis inhibition is likely the "something" about Revlimid that tends to inhibit neutrophils.

We are told dexamethasone causes cell death of myeloma cells (apoptosis). Therefore, the goal is to find a dosing level which will sustain the therapeutic effects of revlimid and dexamethasone. I don't think serious myeloma cell kills are realized with low dexamethasone dose levels below 40 or 80 mg and maybe below the high dose level of 160 mg spread out over four days.

Something about Revlimid provides serious myeloma cell kills in most patients. Therefore, the combination of low dose (equal or less than 40 mg once a week) dexamethasone and Revlimid is a powerful combination. There was a time years ago when dexamethasone was one of the only drugs used to treat Myeloma. With Revlimid, it is possible to reduce dexamethasone dosage to an almost tolerable level if there is such a thing. If elimination of dexamethasone does not cause neutrophil count to go below 1000 and Revlimid alone holds the disease at bay, then this would be the best because the side effects of dexamethasone are no fun and in all likelihood reduce life expectancy due to deterioration of the adrenal and other associated glands which produce the hormones that make us feel like living.

By the way, Mississippi is going through the big thaw. The capitol building is flooded. Pipes have burst all over town here in Columbus reducing water pressure and keeping public works workers busy. You can get an appointment with a plumber but it is like some doctors - month after next - ha. The South is not geared to single digit weather. This always happens. Therefore, global warming doesn't worry me as much as what follows, global freezing!