Speculation about chemo-induced anemia (and possibly leukopenia as well)

[AlaskaAngel]

I know some prefer to see "just the facts" but I think some speculations are worth sharing. This post is, however, pure speculation on my part.

I have been thinking about Andrea Budin's post about her chemo-induced anemia:

http://www.her2support.org/vbulletin/showthread.php?t=27872

In considering Andrea Budin's circumstances (chemo-induced anemia), and reflecting only upon my own experience, I came to speculate that perhaps destruction of cancer cells by chemotherapy might not be solely (or even primarily) what produces sustained remission. I wonder whether there is any evidence of a higher rate of long remissions among those who have even mildly lower blood counts that are sustained.... My theory being, that there would then be perhaps less blood supply to support stray cancer cells in establishing the network for their further development.

If there is truth to that, maybe it would be especially helpful to not use as much of the drugs like Procrit.

Most of us do have chemo-related fatigue, some of which is related to blood counts. But perhaps some of the fatigue is not entirely a bad thing to have....

Any comments are welcome.

AlaskaAngel

[Becky]

There is probably a difference when looking at it via low red counts versus low white counts (and what is low in those white counts – ie: neutrophils, lymphocytes etc).


My thoughts on red counts fall into 2 schools. One is the fact that the makers of Procrit (in the product literature they had in 2004 which is when I had chemo) stated that in their own studies – they found a reduced survival statistic in cancer patients who used their product versus blood transfusion. Therefore, when all the data and posts here started talking about it, it was out there already – and by the manufacturer themselves in their own product insert. Because of reading that insert (that was laying around the cancer center), I always wanted to avoid having to use that product and worried about it because my natural red blood cell count (RBC) is low to begin with and continues to be. That, plus chemo plus my last menstrual cycle (where I bled like a pig for one month – I went out with a bang) scared me that I would need some RBC assistance. I ended up not to.

<O:p

But before I ended up not needing anything, I did a lot of research in case I did. I did find articles contrary to Procrit’s own literature. This data says that greatly upping RBC any way you can (and they touted Procrit) would enhance cancer survival because more red cells means more oxygenation of body tissues. Cancer survives best in a nonoxygen environment so – oxygen weakens cancer. Oxygenation weaking cancer is a probable fact (and probably also one of the many reasons why exercise reduces the recurrence rate of bc). That is all I want or can say about the red cell count aspect at this moment. I am sure some of you will comment and I can then think on this more. However, the horse is out of the barn in saying that red cell boosters are not necessarily good. But, I think if you really need them, you really need them. They just should not be used willy-nilly.

<O:p

White blood cell (WBC) boosters are a different story. Although preliminary data says that they too are not good (to include G-CSF (Neulasta and Neupogen) and GM-CSF (Leukine)), the benefit of dense dose chemo for bc (every 2 weeks for AC followed by taxol) versus the regular dosing (every three weeks) is great (especially for Her2+ and triple negative women). There is a 38% survival benefit for dense dose overall (including all pathologies of which most are plain old ER+/PR+ cancers). So, it makes good sense for the more concerning pathologies to use dense dose chemotherapy utilizing a WBC booster. The main point is what booster to use – Neulasta or Leukine. Many of you know that I refused Neulasta and used Leukine instead. My rationale is that Neulasta (or Neupogen which is the same drug by a different company) only boosts the neutrophils (that fight short term infection) while Leukine boosts all components of the white blood cell system including monocytes and especially dendrites (the scouts that find cancer and induce the body to manufacture killer Tcells against that). Since both products could have potential negative effects, at least utilize dense dose chemo with Leukine (where one might have the potential to self vaccinate). All the Her2 vaccine trials use Leukine in conjunction with the active to further promote vaccination due to the dendritic effect.

<O:p

So, hopefully some of you will respond and we can have a healthy discussion on this. Hope you are doing well Angel. I am and will email you sometime this weekend.

[AlaskaAngel]

Thanks Becky. Do you know how far out the numbers for improved survival with blood boosting apply to? I'm tempted to do a poll of all of us old-timers here just to see if the blood boosting oxygenation is a short-term effect that maybe works best concurrently with chemo, or if it is a long-term one.

I wondered also whether maybe one reason the younger women tend to have more aggressive cancer might be because their bones are better at producing blood cells whereas the older women's systems probably produce fewer blood cells.

I enjoy sharing thoughts, and marvel that you keep the busy schedule that you do, Becky!

A.A.

[Becky]

There were no numbers. The article was written by a guy who was touting supplements etc. The link was sent to me by my husband's cousin who is a nuceutical salesman (and the article sounded very charlitan to me) but the premise of boosting the red count to increase physiological oxygenation sounded reasonable. However, Procrit's own label states otherwise and they make the drug. The article/link was sent to me over 2 years ago but I am trying to look for it.

[Bev]

AA and Becky, I have been anemic most of my adult life. I did take iron supplements in the past 10 years as directed. Sometimes I worry that Iron could have fed things. Maybe anemic is normal. Maybe it's disastrous to feed iron to ER+. Maybe offering Procrit to cancer patients is wrong too. We just have to take our best guess. I turned down nuelasta after my first try at it. It made my counts skyrocket, but they also came back when I didn't do it either.

I just don't know. BB

[Mary Jo]

Hello,

I never became anemic during chemo, so never needed Procrit. Not sure if that's good or bad. Thinks it's good.http://www.her2support.org/vbulletin/images/icons/icon7.gif

Mary Jo

[dlaxague]

I love speculation. I'm not sure I follow the reasoning on this one, though. When we talk of circulation to tumors, aren't we usually talking about the actual network of blood vessels, rather than the number of red or white cells within them? I think that is two completely different things going on. For example, that article recently posted about surgery perhaps stimulating mets talked about angiogenesis (making a network of blood vessels to support tumor growth).

It will be interesting to see when they look closer at what's going on with the Procrit information whether the outcomes relate to actual levels of red blood cells achieved after its administration, or to dose of the med(s), or to something else altogether. The suggestion that its safer when tthe target Hgb is below 12 does lend support to the theory that AA proposed.

Just anecdotally, my Hgb is pretty high, it didn't take too hard a hit during treatment (no procrit), and I'm NED at 6 years out. I got LOTS of neupogen, however. Neupogen and Nuelasta are sort of the same drug, btw - both made by Amgen. Neulasta is the long-acting one, given once each cycle. Neupogen is the older version given daily for varying periods. I wonder now if that isn't the better choice, as probably not everyone needs the mega dose of Nuelasta and could get by with just one or two Neupogen injections, which could perhaps be safer. Perhaps. Maybe. So much to know.

As long as we're speculating and letting our mind wander - there has been discussion of treating lymphedema with vascular endothelial growth factors which might stimulate growth of new lymphatic pathways to make up for the ones lost to axillary surgery. But the question there is could that also stimulate cancer growth (perhaps as removing a tumor does)? Perhaps. Maybe.

And lastly, more speculation and rambling: As long term data emerge on the use of blood cell stimulants of all types, I wonder about myelodysplasias in the long term. We know that chemo increases risk of leukemia, but could the blood cell stimulants (I'm too lazy to look up the technical terms, sigh) contribute to this also? Again an anecdote: I have a friend who was diagnosed and treated for a relatively friendly breast cancer last fall (lumpectomy and rads only). Routine lab work during this time revealed thrombocytosis (too many platelets). I'll omit the discussion of that disease but it resulted in a referral to Stanford's bone marrow transplant program and the physician that she saw there first assumed that her condition (which will eventually require BMT) was secondary to treatment for breast cancer. That was not the case for her, but I wonder, since he quickly made that assumption, how many times he does see bone marrow failure post breast cancer chemo, and if anyone's looking at the incidence of that related to the different kinds of chemo, and also to the use of blood cell stimulants. The scenario for my friend's condition is that initially (now), her bone marrow is running amok, producing too much, but that over time this will lead to failure and no production (hence the need for BMT). Hmm. That's sort of what Nuepogen and Procrit do - cause production to run amok, right? Again, just speculation.

Debbie Laxague

[AlaskaAngel]

It is good to hear from you, Debbie! I enjoy hearing your thoughts on this, in combination with the article about possible implications of surgery....

You already know I don't give up easily and I know you don't take offense if I question the idea that the building of the vascular network and the actual volume of blood cells mean 2 different things are going on. Sometimes my thinking can be too simplistic, so if I don't fully understand what you mean I trust you will explain further. I'm thinking that building a network of vessels could still be stimulated by some body response, but isn't it the blood cells themselves that provide the "fuel" for the growth of the cancer cells? So the network itself would be there but there would still be inadequate supply of the right materials to adequately encourage cancer cell growth?

I don't want to rush the discussion too much. But a bigger question I have is, if there is a less toxic substance than the chemotherapy that messes with the GI system and the integumentary system, but that still brings on the condition of lower blood counts, and if it were also controllable by dose or frequency of dose so that it was reversible, and if it wasn't otherwise toxic (admittedly lots of ifs), would it work well enough to allow us to move away from chemotherapy? Or even at least move toward using less chemotherapy in conjunction with the lowered blood counts?

AlaskaAngel

[TSund]

Dr. Lee made reference in his book to "chemotherapy-like approaches to figting metastatic cancer, including inducing a high fever for a number of days and insulin potentiation therapy that hold much promise with less potential damge done to the body. They are much more widely used in Europe than the United States"

I haven't researched these at all, but this might tie in with your thoughts?

Terri

[Margerie]

The oxygenation discussion- I have been pondering the effects of high altitude and cancer. Haven't found decisive facts, but it is pretty well known that areas of high altitude have lower cancer rates. I know some people move to higher altitudes to help "cure" themselves after a cancer dx. Basically your body pumps up your RBC to compensate for less O2 in the air- would follow the more oxygentation- less cancer theory.

We have a place in the mountains and I can feel the sustained effects for a few days upon my return- my hard hike is easy for a few days, less fatigue during the day, etc.
Wondering if we should move there- LOL my DH would be thrilled!

Also the angiogensis process, immensely complicated. Interestingly enough, as a grad student, studied angiogenic factors' (TIMP specifically) ability to inhibit endothelial call migration. The thinking was we could inhibit new blood vessel formation for tumor growth and shut it down. Now they have found that patients with higher naturally occurring TIMP actually have a worse prognosis. Can't remember the details, but was shocking nonetheless.

[AlaskaAngel]

Marjorie,

I spent many years working at high altitudes seasonally. I'm wondering if maybe the greater exposure one gets at high altitudes gives greater protection due to whatever beneficial effects one gets from the sunshine/vitamin D in the thinner atmosphere, such that it would be protective in the thinner atmosphere whether or not more rbc's are produced.

Being at high altitudes consistently forces the body to produce more rbc's because the oxygen content of the air is lower at high altitudes. I don't know whether it actually ends up creating a situation of extensive oxygen saturation simply because of rbc production stimulation. The hemoglobin content is also important.

A.A.

[Margerie]

AA- love these speculation discussions. I have always had good hemoglobin counts (high side of normal) even during chemo. Wished it would have saved me from + nodes. But who knows- possibly they saved me from distant mets. Knock on wood.

Maybe we should enter the contest some investment companies are having- one million dollars for the best new cancer treatment idea:

http://www.msnbc.msn.com/id/18823390/

I will be up in ALaska, via cruise, at the end of the month. I'll holler and wave!

(I don't think my altitude will change that much unless I go up to the 10th floor of the ship for an extended period...)

[Andrea Barnett Budin]

Following all the above post (from Apr to today) I marvel at yr wealth of info. I do my best to keep up. I just wanted to add that re chemo-related anemia my oncs have told me iron is not the answ for what I have. My NY onc/hematol/supplement and nutrition expert has helped me in the last mnth re my low energy and less access to even the half strength (150) Aranesp.

It believes soy to be taken only naturally or in powder form. It is the main (of 15 or so) ingredient in Phyto Formula (w/soy lechitin powder, spirulina barley grass powder, tomato powder, what grass powder + multiple powdered anti cancer lycopenes and antiox -- 1 scoop in potassium rich OJ. This plus NADH 5 mg Co Enz 1 X 2 (AM/PM on an empty stomach) -- biological rocket fuel, the biological form of hydrogen which reacts with the oxygen present in our cells to produce energy. Took a mnth to kick in, but I am clearly better, even without the Aranesp.

Used to get Aranesp if under 12. Now must wait for half dose under 11. As long as I feel like I have rocket fuel working for me, I don't care. Will see where 11.9 count 3 wks ago now is.

Also take 150 Co-Enz 10 X 2 a day for energy.

Does anyone know re the chromium link to ca what chromium 6 is vs the chromium picolinate4 that's supposed to boost energy and help regulate bld sgr?

The more I learn, the more questions I have. I LOVE -- ARE WE THERE YET? I'm adopting it. Whimsy is so full of positivity! Sending all you brilliant radiant Souls loving, healing energy along with my questions... ANDI

[Hopeful]

Here is a link to an opinion piece in the latest New England Journal of Medicine on weighing the dangers of these drugs:

http://content.nejm.org/cgi/content/full/356/24/2445?query=TOC

Of particular interest for this thread:

" The mechanism underlying the enhanced growth of tumors withhigher doses of ESAs remains uncertain. There is good evidencethat hypoxic tumors resist chemotherapy and radiotherapy. Thebiology of tumor hypoxia, with enhanced cell signaling throughthe Akt–mammalian target of rapamycin (mTOR) axis andsubsequent up-regulation of hypoxia-inducible factor 1http://content.nejm.org/math/alpha.gif, is whatinspired the clinical trials in which ESA treatment was combinedwith radiotherapy, cytotoxic chemotherapy, or both in an attemptto overcome hypoxia-induced resistance. But another possibilityis that certain tumor cells have erythropoietin receptors thatstimulate cell growth when they are bound by erythropoietinor an erythropoietin-like ligand. Squamous-cell lung cancer,squamous-cell tumors of the head and neck, and breast adenocarcinomasseem to express erythropoietin receptors, but such receptors'role, if any, in tumor growth is unclear. Henke et al. showedthat erythropoietin receptors were expressed by two thirds oftumors in their study and that expression of such receptorsin erythropoietin-treated patients was associated with shortersurvival.⁵ (http://content.nejm.org/cgi/content/full/356/24/2445?query=TOC#R5) Conversely, in vitro studies have shown that stimulatingerythropoietin receptors in cell lines from head and neck cancerand breast cancer causes the death of cells, though the questionablequality of the reagents used to detect erythropoietin receptorsmust be considered in interpreting these data."

Hopeful

[dlaxague]

I don't know why it happens but again, I wrote a long reply and when I hit submit, I was re-directed to sign in before posting (but I had already signed in), and the post disappeared. Sigh. Usually I give up at that point but this topic is really intriguing so I'll try again.

I am confused by the discussions. My understanding is that there is fairly good evidence that something about ESA's decreases survival in at least some cancer patients. The reason for that could be related to the increase in Hg, to the possible growth-stimulating effect if there are epoetin receptors on the cancer cells, or to something not-yet-understood.

The best evidence for the above seems to come from studies that took the observation that cancer cells that were operating in a hypoxic manner were resistant to chemo and rads, and they looked at the possibility that increasing Hg. might counteract that resistance. But weren't those cancer cells choosing hypoxia? Weren't they choosing not to use the already-available oxygen? Then why would increasing Hg (which is not necessarily the same as increasing oxygen) change the way they functioned? The reason that they thought that might make a difference is my first area of confusion.

Then there's my anemia/hypoxia confusion. Anemia is not the same thing as hypoxia. Anemia is less-than-normal numbers of red blood cells. Hypoxia is decreased oxygen levels in tissue. Red blood cells carry oxygen to the tissues, so sometimes these two things correlate, sometimes not. I do not think that people who are mildly anemic (Hg 10 to 12) have decreased oxygen delivery to their tissues - the body adapts pretty well, especially when the changes are gradual. Otoh, the people who DO have significantly decreased levels of oxygen in blood and tissue are those with chronic lung disease, and they typically do not raise their Hg much, to try to compensate (hmm - 'wonder why not?). Nor, to my knowledge, do they have a difference in their incidence of cancer.

So if the link in decreased survival were r/t purely to Hg levels, surely by now this would have been noticed, r/t Hg levels or to oxygenation, independent of ESA administration.

It seems possible that ESA's, while stimulating red cell production, might also stimulate angiogenesis. That could be one factor in this phenomenon.

And then there's the altitude discussion. There is less oxygen in the air at higher altitude and so over time (not days - I think it's more like months), people living at altitude produce a few more red blood cells, to compensate. This compensation, however, means that they that have exactly the same oxygen levels in their blood and available to their tissues - so why would that make a difference to cancer? Someone posted that it's well know that there's less cancer at altitude. I didn't know that. Can you post references, please?

I have more to ramble about but this is too long already. I'll save further comments for responses to other's thoughts on this.

Debbie Laxague

[Margerie]

Debbie,

I ran across lots of anecdotal evidence in my search. Can't get access to the good articles. Talked to a couple of families in the mountain area where we bought our vacation home. Their stories were the same: member of family dx with cancer (one was a child), diagnosis grim, moved to mountains and all went into remission. I figure it could be more than the altitude: less pollution, tendency for less fast food/better diet, more opportunity for exercise, more vit D, etc.

It may be all in my head- but I definitely feel a difference in my cardio abilitites for a few days on my return from the mountains (after just a 4 day trip).

A smattering of altitude/cancer discussions: (Will look more when I get back- out the door today)

http://www.asco.org/portal/site/ASCO/menuitem.34d60f5624ba07fd506fe310ee37a01d/?vgnextoid=76f8201eb61a7010VgnVCM100000ed730ad1RCR D&vmview=abst_detail_view&confID=34&index=y&abstractID=30083

http://carcin.oxfordjournals.org/cgi/content/abstract/3/5/461

http://members.westnet.com.au/pkolb/peat3.htm

[TSund]

This is fascinating. Has there been a simple study of whether there is less cancer at high altitudes?


Terri

[dlaxague]

Hi Margerie and all,

Thanks for the links. This is my favorite kind of discussion where we are all thinking, thinking, and sharing ideas.

I looked around a bit with google, also. I didn't find much, and most of what I found was looking at increased cosmic or ionizing radiation at high altitude and an increase in cancer incidence. One study of mice showed an increase in cancer at altitude over time (1969). There does not seem to be much interest in this subject (judging by the lack of research). There was a lot of interest in studying airline personnel, again r/t mostly to radiation exposure at altitude but also to interrupted circadian rhythms and other lifestyle factors.

Your first two links were interesting but hardly conclusive. The last one was pretty out-there - this MD evidently has his own theories and a very pricey clinic where people learn his special technique for relieving asthma, but his theories are not supported by mainstream medicine (which is not to say he might not be onto something but if he is, he needs to show some evidence.).

So I'd say that while it is intriguing and could be true (or not), it would not be accurate at this point to say that it is "pretty well known" that there is less cancer at altitude. And I'm not sure it will ever be known, given the many confounders that would exist when comparing populations.

Debbie Laxague

[Margerie]

Debbie-

Thanks for calling me out! Yes- I would say that it is not right for me to say "it is pretty well-known..." I was thinking about the incidence breast cancer of women living at altitude (mountains of Japan, other rural areas, indigenous populations) are low, versus the women with a very high incidence (Marin, CA) which is at or below sea level. Of course, more than just altitude playing with these numbers.

Anyway, like I said before- love to speculate.

[dlaxague]

What a good sport you are, Margerie. When my post appeared and I read it on the board, I was worried that it seemed harsh and critical. Email can be like that, I've found - the same thing said in the right voice face-to-face would be fine but the words without inflection on the screen can take on a different slant. So thank you for setting my mind at rest that we're just having a friendly discussion and speculation here. I love speculation, too - it's good to exercise our minds.

Debbie

[AlaskaAngel]

This site manages to be a wonderful and polite place for diverse opinions and speculations to be shared and challenged. I've been going over and over to some of the comments, and am thankful for the feedback. I appreciate polite directness without sarcasm or domination.

AlaskaAngel

[Bev]

Good thread. If we're polite, dissent is good. It means we are really thinking about issues rather than rushing to agree. Even the science minds don't agree so we are onto something. I do think all this internet dialogue will eventually speed up cancer R & D. Just hoping it's soon. Bev