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…

All you ever wanted to know about serum free light chains…and more…

A blog reader, thank you!, sent me the link to an online educational resource with continuously updated information on serum free light chain and Hevylite™ analysis set up and maintained by a Binding Site scientific team: http://www.wikilite.com/wiki/index.php/Main_Page Its focus is on serum free light chains in multiple myeloma…impressive, really impressive. Ah, and yes, I agree, it’s overwhelming, I myself am still going through it (and, at this rate, it will take me about 10 years to finish!)…but you can narrow down your search by clicking on “Contents” (on the left). For instance, Chapter 30 is devoted to questions and answers. Have a look…

Vitamin D levels and multiple myeloma

This is a continuation of yesterday’s post. Well, knock me down with a cat’s whisker! I am really pleased with what I found on PubMed: quite a few studies on multiple myeloma and vitamin D levels. Almost 100, in fact! I don’t have time to go through ALL of them (hah)…I have looked only at some of the studies listed on page 1, and I don’t have the full studies with one exception (see below), but the abstracts contain enough information—for now, at least.

For instance, this July 2009 Mayo Clinic study concludes that vitamin D deficiency may portend poorer outcomes in subjects with MM (see: http://tinyurl.com/yz67bxn). Of the 148 newly diagnosed multiple myeloma patients scrutinized at the Mayo Clinic over a period of four years, the ones with vitamin D deficiency had higher levels of C-reactive protein (CRP) and creatinine AND lower serum albumin compared to patients with normal vitamin D levels. Eh that’s not good at all! Furthermore, the D-deficiency increased in parallel with the International Staging System…that is, patients in Stage III were more vitamin-D deficient compared to those in Stage II.

A more recently-published study, http://tinyurl.com/yzxt288, simply mentions myeloma: A vitamin D deficiency has also been documented in patients with prostate cancer, ovarian cancer, as well as multiple myeloma. Larger randomized clinical trials should be undertaken in humans to establish the role of vitamin D supplementation in the prevention of these cancers. I couldn’t agree more.

Truth be told, I am very busy today, so I have time only to post about one more study, titled “Prevalence and significance of vitamin D deficiency in multiple myeloma patients,” published in the British Journal of Haematology in May 2008. The full text is available for free online: http://tinyurl.com/yf8fahx It’s only three pages long, so please go have a look. Good stuff!

This study was conducted on 100 myeloma patients seen at the University of Maryland between September 2006 and October 2006. Of these, 40% turned out to be vitamin D-deficient. FORTY PERCENT…makes you pause for thought, eh? And have a look at this percentage: only 25% had adequate vitamin D levels, defined as more than 75 nmol/l. Eh.

Important: There were no significant correlations between vitamin D status and MM activity (remission, relapsed or newly diagnosed), presence or absence of lytic bone disease and/or fractures or history of osteonecrosis of the jaw (ONJ). So vitamin D didn’t do any harm, which is an important bit of news for us. I was concerned about increased serum calcium and whatnot when I began supplementing with vitamin D last spring. No worries now…

The following excerpt confirms what my endocrinologist told me, that is, that my highish parathyroid hormone, or PTH, levels (for info on PTH, see http://tinyurl.com/ch8za) are connected to my low vitamin D levels: Patients in the vitamin D deficient and insufficient groups had higher serum PTH levels than those in the sufficient group. Interestingly, PTH levels were also higher in patients with renal insufficiency. And in patients with bone pain. Gee whiz. If you have high PTH levels, read this part carefully…

Then on page 2 we are given actual vitamin D supplementation numbers, which is very helpful. The vitamin D-deficient patients were given a huge amount of vitamin D (you will find the exact numbers in the study) until they reached the optimal level of 75 nmol/l, at which point they received maintenance therapy consisting of 1000 IU (international units) of vitamin D3 per day.

Wait. Pause for a moment…a question just popped into my head: on the recommendation of my endocrinologist, I am taking vitamin D3, cholecalciferol, but the folks in the study were given vitamin D2, ergocalciferol. Any comments on this? What form of vitamin D are you taking?

Let’s read on: Responses were favourable in most patients, with increases in 25(OH)D and decreases in PTH levels, even in patients with renal insufficiency. Many symptoms of vitamin D deficiency resolved after supplementation, including muscle weakness (n = 7), fatigue (n = 7) and chronic bone pain (n = 10). Well, this is very good to know. Unfortunately, many of these patients relapsed after one year, but this had nothing to do with their vitamin D levels.

A final excerpt: The present study found a high incidence of vitamin D deficiency in MM patients. Vitamin D deficiency was independent of age, sex and disease status; the lack of sun exposure because of limited activity may play a role. A recent update of the American Society of Clinical Oncology recommendations for bisphosphonates use in MM did not mention the role of Ca and vitamin D supplementation (Kyle et al, 2007); this emphasizes the need for education about the role of vitamin D in maintaining bone health (Guise, 2006). In conclusion, the recommended daily 400 IU of vitamin D is inadequate for healthy adults and a higher daily supplementation (1000 IU) should be standard maintenance, after correction of the deficit, guided by vitamin D serum level. The current study found no correlation between vitamin D status and MM activity.

Okay, in my opinion, the message is clear: get your vitamin D levels tested immediately and, if need be, discuss vitamin D supplementation with your MM specialist. Don’t put it off!

Vitamin D levels associated with survival in lymphoma patients

A new study has found that the amount of vitamin D in patients being treated for diffuse large B-cell lymphoma was strongly associated with cancer progression and overall survival. After rereading that sentence for the hundredth time, I realized how ambiguous it actually sounds…does it imply that high vitamin D levels are good or bad for lymphoma patients? Let me reassure you…it’s the former! 

Vitamin D deficiency has been linked to poor outcomes in other types of cancer (breast, colon, neck and head, e.g.), but this happens to be THE first lymphoma-vitamin D study. Let’s first have a look at the December 9th Science Daily article (from which the potentially alarming excerpt was taken): http://tinyurl.com/yatz6yy.

Here we learn that 50% of the group (374 patients) of large B-cell lymphoma patients evaluated in this study were found to be vitamin D deficient. 50%! Well, it turned out that the vitamin D-deficient patients were more likely to progress and…die…compared to patients with optimal vitamin D levels.

And read this: Recent studies have suggested that vitamin D deficiency may play a role in causing certain cancers as well as impacting the outcome once someone is diagnosed with cancer. I mean, even if you tend to scoff at the health benefits of vitamins and herbal supplements (as I used to do…and I still don’t take vitamins on a regular basis, with ONE big exception–vitamin D!), you cannot possibly ignore the significance of these findings.

Incidentally, this study was conducted by a Mayo Clinic/University of Iowa research team and financed by the National Cancer Institute and the Mayo Hematologic Malignancies Lymphoma Fund. The Mayo Clinic, need I say more? The team presented their results at the ASH annual meeting on December 5th, so I looked for and found the  paper on the ASH websitehttp://tinyurl.com/y9oad45

It’s easy to read and provides a lot of details, so please go have a look. The paper concludes that Vitamin D deficient patients have an inferior event-free and overall survival compared to patients with vitamin D levels within the normal range. Okay, that statement is crystal clear…not ambiguous at all. The researchers recommend that vitamin D testing for lymphoma patients be conducted in a clinical setting. Good idea.

Well, this question popped into my head, of course: what about myeloma patients? Is vitamin D testing the norm for us? Probably not. It certainly is not the norm here in Italy. In fact, the first person who insisted that I have my vitamin D levels checked was my friend Sherlock. If that is the case everywhere, then I think we should put pressure on our MM organizations to check out the possible link between myeloma progression and vitamin D levels…But I have to do some research first. There may already be a myeloma-vit D study out there (doubt it…).  

Okay, let’s see…back to the paper…based on the vitamin D reference range given here, I am (or was, in October) borderline vit D deficient. Ouch! (Okay, okay, no surprise there, I already knew that…) Since I have always hated being in the sun and never used to take vitamins…or anything else, for that matter!…I bet that my levels of vitamin D have always been low. Unfortunately, it never occurred to me that the vitamin D test might be important, so I never had one. Hmmm, come to think of it, I rarely had any blood tests done before 1999. Ah, how things have changed!!!

Well, better late than never. May this be a good lesson for all of us: 1. we should have our vitamin D levels tested, 2. go see a good endocrinologist, and 3. if need be, supplement with vitamin D. Yes, I have definitely become a vitamin D believer…! And let’s not forget that vitamin D may prevent H1N1. Oh, by the way, a TON of information can be found on the Vitamin D Council website: http://www.vitamindcouncil.org/ Okay, I have to get off the computer now and go fold the laundry…ciao a tutti! Oh, and thanks, LPC, for sending me the link to the SD article!

Curcumin, the Indian solid gold

If you are new to the fantastic world of curcumin, and even if you are an old hand at it!, go have a look at a website set up by the Cytokine Research Laboratory at the Department of Experimental Therapeutics, MD Anderson Cancer Center, University of Texas: http://www.curcuminresearch.org/ You will find tons of information there…all sorts of interesting items, ranging from curcumin clinical trials to bioavailability issues. Graphs, pretty photos, how to say “turmeric” many different languages…it’s all there!

Ah, this is important: the website provides the curcumin protocol that Prof. Aggarwal kindly gave to me in January 2006 and that I followed to the letter. Yes, it’s the protocol for “beginners.” Just go to the FAQs page and click on “How should I take curcumin?” Of course, you can find the exact same “beginners'” protocol here on my blog (just scroll down my list of Pages on the right until you reach “Margaret’s curcumin protocol”). By the way, if you intend to begin taking curcumin and/or are currently on chemotherapy, please make sure that you read my Warnings/side effects page, in addition to informing your doctor (goes without saying). Best to be cautious!

Let’s see. Back to the website…it also provides a list of curcumin suppliers in various countries (again, see the FAQs page). Europe is not well-represented, unfortunately, and Italy isn’t even listed. I should really submit my Italian sources to Prof. Aggarwal so this particular page can be updated.

I was made aware of this website’s existence only recently, after an exchange with Prof. Aggarwal. At the time I intended to post the link but, ahem!, forgot about it until now, when a blog reader, thank you!, reminded me. A great source of information…that I still have to finish perusing…but it’s time for dinner here, so I have to dash off. Ciao!

Florence and Volterra in two days

We have had a faaabulous weekend. It involved a huge amount of walking, which was tiring but well worth the effort. On Saturday, Stefano and I went into town to stretch our legs (this turned into a five-hour nonstop trek…ooofff, I thought my legs were going to fall off toward the end!), take some photos and check out the festive street decorations/lights as well as the cute Xmas market in piazza Santa Croce. [Note: on your first visit to Florence, make sure that the square and church of Santa Croce are on your not-to-be-missed list.]

Our trek began in Piazza Beccaria and continued through Piazza Sant’Ambrogio, Piazza Santa Croce, Piazza della Signoria, Piazza Duomo and finally through the market of San LorenIMG_3716zo where we hoped to grab a bite in one of our favourite eateries is (but by the time we arrived, there was at least an hour’s wait so we just ended up having a revolting slice of pizza elsewhere, yuck!). Then back to Piazza Beccaria where we had parked our car.

But it was when we reached Piazza Duomo, = Florence’s cathedral square, that my eyes almost popped out of my head. In late October, you see, Piazza Duomo became a traffic-free zone…but Stefano and I hadn’t yet been into town, so what we saw was new to us.

I used to hate to go into town, truth be told. Too much traffic, too much foul polluted air, too much noise from honking cars and so on. But now, without cars, scooters, taxis or buses…only people strolling about or riding their bikes right smack in the middle of the formerly traffic-congested streets…the square actually seems much larger. It was fantastic…hats off to the municipality of Florence for making such a brilliant decision. I took the above photo (baptistery in the foreground) standing in the middle of via de’Cerretani, which used to be a nightmarish street…from a pedestrian’s point of view, of course. Taking a photo from this angle would have been impossible just a couple of months ago…IMG_3786

Yesterday morning we woke up and decided to go to Volterra, a gorgeous ancient Tuscan city to the southwest of Florence, which was settled by the Etruscans in the 8th century BC and conquered by Rome about five centuries later, as I recall. I haven’t been to Volterra since I was a kid with an enormous interest in all things Etruscan, an interest that I still have.

This (above) is a photo I took of Volterra’s cathedral, built in the early 12th century. The façade is Romanesque, as you can see…the marble geometric frame around the main entrance was added in the 13th century.

IMG_3805This photo (left) gives you an intentionally distorted (by me) view of a couple of the buildings in Piazza dei Priori. The one on the right is the early 13th century Palazzo dei Priori studded with Della Robbia glazed terracotta coats of arms dating to the 15th and 16th centuries (I hope to make a blog banner out of them at some point, which should give you a better view of them). It looks familiar, doesn’t it? Well, in fact, I read that it was the inspiration for Florence’s own Palazzo Vecchio, built at the end of the 13th century. Curiosity: I read that some scenes from “New Moon” were filmed inside this ancient building. Not that I am a huge fan of the “Twilight” series…

When you are in Volterra, don’t forget to look down at the stone pavement. Yesterday the massive stones, IMG_3785some of which contain fossil shells, were slightly wet, thanks to a bit of light rain…ah, what amazing colours. At the time, I wasn’t thinking about posting a photo of the city’s pavement on the blog so this, unfortunately, is the best I can offer.

Okay, my time is up. I am on a brief break (so please forgive any typos or repetitions) from a day spent on overdue housecleaning activities. Ah, joy! (not…!) Ciao!

P.S. by the way, I forgot to mention that my current blog banner is a photo I took of a wall fresco fragment in Herculaneum more than two years ago.  

Interview with Prof. Bharat Aggarwal: thinking outside the box

It is raining in Florence today, it’s damp, chilly and miserable out there, but for me it couldn’t be a lovelier, sunnier day. Ah yes, thanks to a December 2009 interview with Prof. Bharat Aggarwal that I read this morning, I am as happy as a purring cat. A blog reader sent me the link, thank you sooo much. The interview contains a huge amount of valuable information…in just two pages. The main thing, in my opinion, is that it answers many of our questions and doubts about the bioavailability of curcumin. But there is much more, too, so please have a look: http://tinyurl.com/yzbeptx

The issue of bioavailability is of particular relevance to those of us who take curcumin. Yes, Prof. Aggarwal is right, curcumin is cheap compared to conventional drugs. But it can still be a drain on our household finances (I am lucky to have very generous, loving parents!). Think of it this way: you wouldn’t buy a pair of jeans that was three sizes too big/too small for you, right? No, you buy a pair that fits. The same principle applies to curcumin or anything else, for that matter. You want to invest in something that fits/works/etc. That is why I always tell people who want to start taking curcumin to try it for a couple of months and see if their cancer markers go down. Ah, but I digress, as usual.

My point is, and I have written about this in previous posts, if curcumin does not show up in huge amounts in the bloodstream, it is probably working at some other level. Otherwise, how could I have remained stable for almost four years? How could it work for so many of my blog readers/myeloma list friends? That would make no sense. Well, we don’t have to wonder anymore. Prof. Aggarwal explains very clearly what happens when we swallow our daily dose of curcumin. I think that this interview provides us all with plenty of food for thought.

He points out that curcumin is circulated quickly and is taken up by tissues very quickly. Within 10 to 20 minutes it is already in the brain. Consequently, it is pointless for researchers to attempt to find traces of curcumin in the bloodstream. Aha.

I was particularly interested in his answer to the last question…I didn’t know that 30% of all cancers are indolent. Wow, that is quite a high percentage! And I loved the way he compared asymptomatic cancer to a tiger: With cancer, in some cases the tiger is sitting there somewhere and needs to be left alone. If you start throwing stones at the tiger, he will strike back. Indeed, I have thought the exact same thing since my 2005 diagnosis, but I had no scientific proof, just a gut feeling…

I will conclude with what Prof. Aggarwal says about prevention. In my opinion, he is absolutely right: If we continue to prevent and treat cancer the way we are currently doing and have been doing for the past 50 years, the next 50 years will not be any different. We have to learn to think outside the box. We have put too much emphasis on survival of the pharmaceutical companies and not enough focus on the survival of the patients.

This last sentence really struck a chord with me.

Precisely.

Thank you, Prof. Aggarwal.

Maintenance therapy for multiple myeloma: leeches, steel, quinine and urethane…

A blog reader (thank you!) reminded me of a historical overview of myeloma and myeloma treatment that I had read some time ago: http://tinyurl.com/2r7gw3 My post title refers in fact to the 19th century practice of treating myeloma with leeches (etc.). Eeek! Both my blog reader and I are glad that said practice is no longer, er, entertained.

Click on that link if you have ever wondered who (Henry) Bence Jones was, or if you want to know the name of the sadist who invented bone marrow biopsies. I was curious to know when the term “multiple myeloma” was actually introduced, but I had to look it up elsewhere. I found that a Russian doctor, J. von Rusitzky, apparently used it for the first time in 1873.

Oh heckaroni!, I just found out that I had already posted and commented on this link (March 12 2008: https://margaret.healthblogs.org/2008/03/12/the-history-of-multiple-myeloma/) Well, I am going to publish this post anyway, mainly because I am much amused, hehe. The joke’s on me! Plus, this is a good lesson: I should have done a “search” of my own blog first! (Yes, there is a “search” box on the right-hand side, just scroll down almost to the end.)

P.S. By the way, do you know how I discovered that I had already posted on this topic? Nope, I didn’t have a memory flashback. What I did was google these four words: “the history of myeloma.” And there it was, my 2008 post! Gave me a good chuckle…

Useful links for figuring out Freelite test results

A blog reader who was recently diagnosed with smoldering myeloma wrote to me about his rather high serum free light chain (Freelite) test results. Our exchange reminded me of how puzzled I was back in May when I read my first (ever) Freelite results. At the time, my blog reader Rudi very kindly helped me decipher them, but I neglected to post the link to “The Binding Site, Inc.” Here it is: http://tinyurl.com/ydf78tj So, if you are as confused about your Freelite results as I was, all you have to do is have a look at the chart on this page. Very very helpful. 

If you have no idea what I’m talking about (and if you are a MGUS, SMM or even MM patient and have never had a Freelite test), go have a look at the exhaustive Freelite brochure published in May 2009 by the IMF, International Myeloma Foundation: http://tinyurl.com/ya8qabq Here you will find everything you ever wanted to know about serum free light chains and more…much more! The Freelite test is an important one–and here I must pause for a second to thank my friend Sherlock for suggesting that I have this test in the first place–so, if you belong to the above-mentioned categories, please add it to your list of blood tests. The IMF brochure, by the way, is available in five different languages, including Italian.

And finally, here is an interesting excerpt from a 2008 interview with Guido Tricot, MD, Ph.D. (see page 3 of the Binding Site’s newsletter: http://tinyurl.com/yz7djs6): If you entertain the diagnosis of MGUS or smoldering myeloma and you see a Freelite kappa that’s over 100 mg/L, usually you know this is not MGUS. Hmmm, I don’t find anything “entertaining” about a MGUS or SMM diagnosis 😉 , but (okay, seriously, now) my Freelite kappa result is less than half that number. And, in fact, it went down a bit further in October. Based on my results, I fall into the “MGUS with BM suppression” category. Needless to say, I am very pleased…!