To use or not to use aspirin in myeloma (conventional) treatments?

A blog reader (thanks!!!) sent me a couple of links that started me off on a unexpectedly startling and, in the end, rather confusing search mission. Who’d have thought that aspirin, = acetylsalicylic acid, might possibly be a bad thing for myeloma patients to take? (Please note my use of the conditional tense.) I concluded that it would probably be a good idea to write a post on this topic for two main reasons: 1. aspirin is currently being tested in more than a couple of myeloma clinical trials (check www.clinicaltrials.gov) and 2. there are more than 50 aspirin-myeloma studies in PubMed…

What does aspirin have to do with myeloma? The answer may be obvious to some, but it wasn’t to me…not immediately, anyway. It is because of aspirin’s blood-thinning properties. It’s because aspirin interferes with our blood’s clotting action, which is good, of course, if we are taking a drug that could cause potentially fatal blood clots, such as thalidomide. And, in fact, if you look at the clinical trials, aspirin is being given to patients on thalidomide or its derivatives. Okay, now we can keep going…

The first link led me to this letter, written by Dr. Kast and published in “Blood” in 2006: http://goo.gl/e1ZVn Here we learn that aspirin and other COX inhibitors have a long documented history of increasing the circulating levels of tumour necrosis factor-alpha…What what whaaaaaat? I didn’t know that. What I did and do know is that TNF-alpha is a major GROWTH FACTOR for myeloma cells…not quite as bad as IL-6, but most definitely one of the really really bad guys… 

Dr. Kast suggests that TNF levels simply be monitored in myeloma patients who take aspirin as part of their therapy. Should their TNF levels increase, he writes, then steps to reverse that elevation or alternative thrombosis prevention measures should be taken. That sounds reasonable…but let’s keep reading…

The second link took me to a 1996 study, published in “Immunology”: http://goo.gl/mrgsV This study examined the effects of aspirin and ibuprofen not just on TNF-alpha but also on other myeloma growth and survival factors such as IL-6 and IL-1 beta. By now I think all myeloma patients must be familiar with IL-6. As for IL-1 beta, well, among other things, it is implicated in the progression from SMM to MM, so those of us with asymptomatic myeloma (SMM) should pay particular attention: https://margaret.healthblogs.org/life-with-myeloma/what-is-multiple-myeloma/myeloma-supplements-and-il-1-beta/).

The “Immunology” study is available for free online and is quite easy to read (just click on “complete article” and wait until it downloads). The gist: a few weeks after a group of healthy volunteers had stopped taking their daily aspirin and ibuprofen doses, their IL-1 beta and TNF levels had increased compared to the pre-experiment period.

Another bad thing that happened is that IL-2, = another pro-inflammatory cytokine, also increased quite a lot. Two observations, though: 1. some sort of different stimuli were used in this study, and I am not entirely sure what that means (I would need more time, more time than I have right now, to check out all this stuff…); 2. the study was published 15 years ago, so it is a bit dated…Still, since I found the data a bit alarming, I decided to do a bit more digging…

I found two other 2006 studies on this topic. I couldn’t find any more recent (than 2006) studies, I mean on the possibly dangerous consequences of using aspirin in conventional myeloma treatments, which I found very odd, but I might have missed a study or two. Anyway, let’s begin with the first, which is, again, available for free online and starts off from Dr. Kast’s above-mentioned letter: http://goo.gl/FgkV8

Let’s look at a couple of key sentences: aspirin, according to these authors, may, in fact, have positive effects on survival in patients with MM. […] Malignant plasma cells often overexpress cyclooxygenase 2 (COX-2) and this overexpression has been found to be a predictor of poor outcomes in MM patients. A few paragraphs later, we read that aspirin inhibits both COX-1 and COX-2 and this may serve as a rationale for possible antineoplastic properties in MM.

The authors then refer to a study they carried out in 2005 (this full study is also available for free (yaaay!): http://goo.gl/ryG3S) on myeloma patients following the DVd-T regimen and divided into three groups. The group that took aspirin apparently had a better response than the group that did not. And so the authors conclude: While these preclinical and clinical observations suggest that low-dose aspirin may have antineoplastic properties in patients with MM, they are not definitive and render the alternate hypothesis (that aspirin has a deleterious effect on the survival of patients with MM) much less likely.

Dr. Kast, author of the above-mentioned “Blood” letter, wrote a response, titled “Aspirin, TNF-alpha, NFkB, and survival in multiple myeloma: the importance of measuring TNF-alpha”: http://goo.gl/RXfoU The abstract tells us that there are conflicting reports on aspirin. On the one hand it has been shown to slightly increase survival duration in multiple myeloma, which obviously is a good thing…on the other, caution is raised about use of aspirin and COX inhibitors generally in inflammatory states and specifically in myeloma. Should they increase tumor necrosis factor-alpha they could exacerbate disease. Exacerbate disease, eh? Well, we certainly do not want that!

At this point, I should announce that, even though I have read the full study, my NEW BLOG POLICY is NOT to quote directly from any copyrighted material. That doesn’t mean that I will stop reading full studies, of course, and reporting on any important bits…I just won’t use direct quotes, that’s all. So I can tell you that Dr. Kast concludes that the use of aspirin in myeloma conventional treatments is okay, provided that TNF levels are monitored, particularly should TNF levels increase together with myeloma progression…

I would also like to mention that, according to Dr. Kast’s review of the scientific literature on this topic, the data is conflicting. Aspirin, and similar COX inhibitors, he writes, can either delay or accelerate myeloma progression…Confused?

Okay, let’s see if we can figure this out.

  • First point: TNF-alpha is overexpressed in myeloma, which basically means that it is being produced in larger quantities than needed, and that is a bad thing, since TNF-alpha helps myeloma cells survive, as we have seen.
  • Second point: aspirin increases the levels of TNF-alpha. Dr. Kast reminds us that TNF levels go up as myeloma progresses…hence, lowering TNF may delay progression. That makes sense, right?

Well, it’s not that simple. Since 1996, different studies have shown that aspirin decreases, increases or does nothing to TNF levels. No kidding. Frustrating, eh?

So where does all this leave us? Well, just to be on the safe side, I will never take any aspirin again (UPDATE 2017: I have changed my mind on this matter, based on other readings, and I will take, and indeed have taken!, aspirin when needed). More importantly, if I were doing chemotherapy AND taking aspirin to counter any possible clotting problems, I would have my docs monitor my TNF levels frequently and carefully. Or I might ask for a different something-or-other to prevent the clotting…

You never know…

Hope…

My Mom told me about a program she had seen last week on the compelling brain cancer story of David Servan Schreiber, a French physician and neuroscientist. Among other things, she described, in detail, a very interesting (…really horrible, too!!!) electric shock experiment carried out on rats injected with malignant tumors (=a story recounted by Dr. Servan Schreiber). While she was talking, so many bells went off in my head that I decided to do a bit more research on this doctor…

Well, my search confirmed a few things that I already strongly believe in…and taught me quite a few things I didn’t know…

Before giving you the links, though, I want to describe a relevant episode from my own personal experience…and I have no doubt that many of you, if not all!, have a similar story to tell…no doubt at all…

Let’s see. Where to begin? Well, more or less in the fall of 2005, when I realized that my MGUS was progressing, I became quite concerned. Stefano and I went to see my Italian haematologist who, looking over my most recent (at the time) tests, advised me to begin chemotherapy immediately—three cycles of Velcade, then an autologous stem cell transplant in the summer of 2006. Mostly giving in to a gut feeling, I refused (by the way, this happened months before I found out about curcumin, and I would like to note that at that time I was in a conventional state of mind…I wasn’t even looking at anything remotely “alternative”). I immediately contacted three internationally-renowned myeloma specialists, two in the U.S. (both at the Mayo Clinic) and one here in Italy.

All three confirmed that, yes, I was definitely progressing towards active myeloma. But the important thing, as far as this post is concerned, is that I asked each expert what I could do at least to SLOW DOWN this progression. There had to be SOMETHING…

But they all answered: “No. Nothing. There is nothing you can do.”

Nothing??? I still remember my feelings of shock and frustration…

The only one who gave me a very slightly different take was one of the U.S. specialists, who suggested that I should simply continue with my daily life, have fun, do some exercise and follow a healthy diet. Nothing more. As for what that healthy diet entailed, or what kind of exercises I should do, well, I simply have no idea. I was in such a state of shock at the time that I didn’t press him any further…

Anyway, after those consultations, I began thinking that it was really horrible for doctors to say something like that to a patient…that it was simply unacceptable and, in fact, cruel of them to have taken away my HOPE…and that this had undoubtedly happened to who knows how many patients before me…and would happen to countless others after me…

Naturally, I don’t mean to imply that these specialists should have given me false hopes. I don’t want to be told, “everything is going to be fine,” if everything is NOT going to be fine. That would be extremely silly…But taking HOPE away from a patient is another matter…

The point of this entire section is that what I have discovered in the past five years (plus) has made me realize that, okay, while I may progress to active myeloma some day, those specialists were simply wrong (this is JUST MY OPINION, of course!)…

I have come to believe, very strongly, that we can indeed do something, indeed perhaps many things, to improve our situation, even if “only” on a psychological level. Had I known back in 1999 what I know now, if I had taken curcumin back then, I believe that my MM markers would be much lower today; I might even have remained in the MGUS category. Of course there is no way of proving that…that is, unless I can fix the technical problems I am having with my time machine… 😉

Okay, let’s put aside what happened in 2005…and my not-so-interesting ramblings…and instead go on to the central part of my post, which is Dr. David (his surname, Servan Schreiber, is soooo long that I will simply call him Dr. David from now on).

This physician definitely shares my above-stated opinion that there are things we can do to improve our situation and also that it is terrible to take HOPE away from cancer patients. And he is a medical doctor, not just someone with a non-scientific Ph.D… (er, that would be yours truly…). So let’s pay careful attention to what he says…

Let’s start with the lecture that he gave at the MD Anderson Cancer Center in July 2009 (the full transcript can be found here: http://goo.gl/cvCST; incidentally, you will find the shocking rat story about 2/3 of the way down the page…). Even though I haven’t read the whole shebang, I really liked what he had to say about “false hopelessness”:

As a physician, I am very concerned about the idea of giving people false hopes, because I know this betrayed the only thing that is truly fundamental which is the authenticity of my relationship to a patient. And I don’t wanna have false hopes for myself. I need authenticity in the relationship to myself as well. However, when we do not tell our patients or we did not tell ourselves about all of the scientific information that shows that there are powerful ways in which we can regain control of our faith in our fight against cancer, then what we are doing is inducing false hopelessness. And all of what I am trying to do today, for this book really has talked about all of my actions, is to fight against false hopelessness.

There are powerful ways to fight against cancer…oh yes, indeed…I believe that, too…strongly.

And now we get to the most important link of this post. It will take you to a lecture that Dr. David gave last year at UCSF: http://goo.gl/Bz5pT It lasts an hour, which may seem like a long time, but let me tell you, this guy is the complete opposite of boring…his talk is very interesting and even funny here and there…So make yourselves a cup of tea or coffee and settle down in a comfy chair…

Now, if you don’t want or have time to watch the whole thing, then I suggest that you at least watch the last 30 minutes. After 34 minutes, for example, he explains why oncologists scoff at the very idea of diet intervention…why they think it won’t help one bit (he strongly disagrees, by the way…). Interesting…

And, after 48 minutes, he describes the shocking rat story, which, as I mentioned, you can also find in the MD Anderson transcript. This experiment is, I repeat, the reason why I got interested in writing this post in the first place. I mean, why did the third group of rats fare better than the first two, even though theoretically they should have been much worse off? The answer is that they had HOPE. They had some sort of control. And this goes to prove that if you take away hope (e.g., by telling your cancer patient, “oh no, there is nothing you can do…” OR “sorry, but there is nothing more we can do for you”)…well…you get the idea…

Here is the link to the 68% reduction in breast cancer mortality study that Dr. David mentions in the second half of the video…the study that didn’t make it into the New York Times, even though, as Dr. David points out, there is not one single conventional treatment that can compare with that result: http://goo.gl/Gjvqu Eh.

At one point, as I recall, he says that stress doesn’t cause cancer, and I don’t believe that, either, otherwise practically the entire world population would have cancer. But let’s not forget the 2008 study that linked the stress hormone norepinephrine to myeloma cell proliferation, see: https://margaret.healthblogs.org/life-with-myeloma/what-is-multiple-myeloma/multiple-myeloma-and-stress/ So this is an area that needs a bit more exploring, in my opinion.

Let me add a brief anecdote to what I just stated about stress and myeloma. I have a friend whose myeloma had been asymptomatic for a couple of decades…Then, five or six years ago, during a period of incredibly high stress at work–pressing deadlines and so on–her myeloma markers suddenly went sky high. She panicked and decided to quit working so hard. And she began going to the gym. Within a few months, her markers had returned to pre-stress levels. So there is something to be said about getting rid of stress, enjoying life and laughing as much as possible…

But, most importantly, don’t let anyone take away your hope…

Ever.

P.S. Here is a February 2010 “Huffington Post” article listing Dr. David’s suggestions for an anticancer lifestyle: http://goo.gl/6Cqww

The gadolinium used in MRIs makes myeloma cells proliferate

A friend of mine, who has just had his second autologous stem cell transplant here in Italy, wrote me a note this morning about a paper presented at the recent ASH meeting on gadolinium, which is used as a contrast agent in MRIs. The paper (March 2017: I replaced the original link, which no longer works, with this one, which will take you to the abstract: http://www.bloodjournal.org/content/114/22/1809?sso-checked=true) shows that the most common Gd-containing agent, Omniscan, has a proliferative effect on myeloma cells in vitro: Omniscan induced both time and dose dependent MM cell growth in vitro (8-20 fold increase relative to control). Importantly, the presence of BMSC enhanced the effect of Omniscan on growth of both MM cell lines and primary MM cells.

180px-Gadolinium-2[1]And this stuff is being injected into myeloma patients??? By the way, BMSCs (see above quote) stands for bone marrow stromal cells, which are part of the bone marrow microenvironment (discussed in previous posts) and play a crucial role in myeloma cell survival.

Well, needless to say, I am hopping mad about this gadolinium news because my friend so far has had two MRIs with injections of this myeloma-friendly substance. I mean, this is simply OUT-RAGE-OUS! Has nobody ever tested these contrast agents to see if they could possibly be harmful to us??? I will check PubMed in a second. First, let me see what gadolinium is. Ah, okay, see here (I took this photo from Wikipedia, btw): http://en.wikipedia.org/wiki/Gadolinium

There is an overwhelming amount of info on gadolinium online. I learned that its use as a contrast agent for MRIs was approved in 1988 by the FDA, but it was only about 20 years later that the FDA issued a warning on five of the gadolinium-based contrast agents, which can be fatal for patients with moderate or severe kidney disease. Fatal? Oh, this is simply shocking…

And here (http://tinyurl.com/ybmtml8) we have the case of a relapsed IgA lambda patient…if you do a search for “gadolinium” in this study, you will find that the patient underwent a gadolinium-enhanced MRI on her brain shortly after admission (see Figure 1a and b). This study was published in September 2009…the authors confess to being puzzled as to why bortezomib treatment didn’t work. Could the use of gadolinium have played a part in her relapse? Who knows…

To be fair, I found a 2009 study stating that the use of gadolinium in myeloma MRIs is safe, see: http://tinyurl.com/ye9abar (the full study can be downloaded for free, just click on the “Full text article” link). The authors declare that doses of up to 5 times normally used may not induce significant adverse effects. (Note that they use the conditional tense: “may.”) Ah, but further on, I came upon a highly suspicious sentence (my emphasis): Furthermore, given that 95–98% of gadodiamide is cleared away by 24 h after injection (according to manufacturer data), there is probably only a very small amount remaining thereafter.

So, let’s see, in this study, “according to manufacturer data,” this toxic stuff is eliminated from the body within 24 hours? Uh, wouldn’t that be a bit like saying that an asbestos company guarantees that, based on their data, inhaling asbestos fibers isn’t harmful? Oh yeah, that is really reassuring! (=Please note the sarcasm in my tone…) Sloppy work, very sloppy work, guys.

If I had to put my money on one of these gadolinium studies, I would choose the above-mentioned Harvard Dana-Farber (etc.) one. No question. In the ASH-presented study, in fact, autopsies on eight myeloma patients with repeated exposure to Omniscan revealed massive quantities of gadolinium accumulation in tissues of these MM patients regardless of their renal function. Massive quantities…well, so much for the manufacturer data…phooey, I say!

In conclusion, if my doctor ever suggested that I have an gadolinium contrast MRI, you can imagine what my answer would be…

What I read earlier today is unbelievable…I don’t know whether to be appalled or teed off…I think I will go add a few ornaments to our Xmas tree to get my mind off this topic and cool down…bloody hell…

Pomegranates and Leaping Kittens

Peekaboo, leaping kittenLife has been relatively easy until now. This morning, as I was preparing breakfast for my four hungry cats, I looked up with unfocused eyes (before coffee!) and noticed something amiss: a pair of inquisitive blue eyes staring back at me and a flash of white. A second, more focused look confirmed that my five-month-old kitten has finally learned how to jump up onto the ledge overlooking the kitchen counter. Until this morning, only the other cats have been able to make that jump. She looked as surprised as I was, so this must have been her very FIRST jump! A major jump toward adultcathood, I would add. I darted upstairs as excited as a squirrel with a nut to tell Stefano about it. I walked into our bedroom as he was getting ready to go to work and said, as gravely as I could: Life as we have known it is over. Things will never be the same again. I didn’t fool him. He replied, grinning She jumped onto the ledge, right? I married a very smart guy (how the heck did he guess?)

Of course, this means that we may have kitten-prints all over my Xmas cookies! Drat. 😉

Second important event. The company where I teach English is conveniently located near a farm cooperative that has wonderfully fresh organic vegetables. I frequently shop there before returning home. Well, yesterday I saw some pomegranates for sale. I had never eaten a pomegranate, imagine that!, so I bought one, which we ate after dinner last night. We really liked it, and I can see that the seeds would taste fabulous in a salad. Pomegranates, by the way, are full of ellagic acid. Good stuff!

Okay, I am working on a couple of research posts so I will get back to them now, but I just thought I would share two rather significant moments of my life with you: my kitten’s first big leap and eating my first pomegranate

Oh, wait, one more thing. A few more interesting comments have been added to my November 1st post, so please have a look at them if you are interested in the issue of curcumin bioavailability. The lecithin idea is compelling, but I still have to have a closer look at it. One thing: I will not eat uncooked egg yolks. I also went to and read the transdermal link that Art provided. Hmmm, also interesting. I think JHope already brought up the patch possibility. Well, thanks, everyone!