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!

Out with the old 2009...

Greetings one and all and thank you for checking on me and I hope everyone has a very happy new year!

I suppose I am way past due on posting something here. We are currently in the throws of winter here in Columbus, MS the likes of which we have not seen for a good long while with single digit lows at night and highs during the day in the upper twenties and yes, we did have a bit of show this morning but you had to pay close attention or you might miss it.

I recall back in December of 2005 when we were at Mayo Clinic in Rochester, MN (south eastern corner of the state about one and a half hour drive south of Minneapolis). They were having a mild winter. They were complaining of the warmish temperatures and absence of show before Thanksgiving. They were experiencing low temperatures in the single negative digits with highs in the positive single digits. I recall speaking with folks back home in the south who would tell me about the 72 degree weather. I think it took me four months to get warm after I got back home and didn't really get warm until the summer. I think some of that was due to my stem cell transplant recovery.

Speaking of that, the number we have been following which we think is a good indication of disease progression (monoclonal protein level) has been on a slightly declining plateau for about the last eight months or so. I am taking this as an answer to prayer and an over all good thing. The number is hovering around .2 gm/dl. The latest was .17 gm/dl. I am told that even if it was to go to zero (which is normal), they would want me to stay on some dose of Revlimid until disease progression at which point we would try something else. If I can behave myself, I may be in this game for quite a few more years (I hope).

Next subject. I decided it was about time to get into Windows 7. I did a small amount of homework in advance and realized I would most likely have to purchase a new model computer with Windows 7 preinstalled which is what I did. Vinita and I went to our nearest Sam's Club in Tuscaloose, AL to shop back in December. I knew I wanted one of the new all-in-one computers but wasn't sure what brand. Sam's had the new HP TouchSmart which is extremely attractive affordable so we bought one.

I have spent about the last two months off and on getting out of our five year "old" DELL. We have them side by side on our desk which is cramped for space now but I am optimistic this will be temporary especially in view of the fact I just ordered a HP Pavilion dv6t Notebook PC. It should be here around the end of January give or take. I did way more homework on this one than the all-in-one. There aren't many all-in-one's right now so not that many choices. Laptop computers are another story. The choices are mind boggling so I decided to go with a pair of HP's. I ordered a TV modulator so I can set the laptop up in the bedroom and use it as a 15.6" wide screen TV. Best of all, HP offered me a 30% discount so I didn't have to go to Sam's Club to shop :)

I'm planning on reformatting the hard drive on the DELL and reloading the original Windows XP software so it is like new. It is a DELL Dimension 2400 with a 17" high brightness flat panel monitor and extra RAM. The Altec Lansing speakers hang under the monitor which makes for a nice compact space friendly footprint on the desk top. If you know anyone who might be interested, this one is negotiable, your pig for my computer - ha.