Most recent post first:
April 14 2013 post. Epstein Barr, or infectious mononucleosis. Here we go again.
It’s been ages since I last wrote about a possible viral connection to the insurgence of MGUS…At one point, a few years ago, I even had the brilliant (?) idea of asking you all to let me know if you had had a similar experience to mine. What happened to me is that I began having what I now know were possible symptoms of MGUS (mainly, fatigue fatigue fatigue) while I was in grad school, right after I had recovered from a bad case of Epstein-Barr (= EBV, from now on)…This would have been April of 1995 (I’ve written about this before on the blog…just do a search for “Epstein Barr”).
After my appeal on the blog, I received a number of messages and comments, but I just couldn’t detect a trend or anything that might be useful. Not at that time, anyway. So I just put all that data away and, well, eventually, forgot about it. After all, I reasoned, even if I discovered that my MGUS, now SMM, is connected to my bout with Epstein Barr, how would that help me/us now? I mean, it’s a bit too late for prevention, right?
However, in the past few days I’ve renewed my interest in EBV. What happened is that I came across a Mexican case report about an 11-year-old girl diagnosed with myeloma (!) associated with, yes, EBV: http://goo.gl/othmW
I was able to read the full report, so I’ll be able to give you a bit more information. What we know from the abstract is that the above-mentioned girl was 9 years old (!!!!!!) when a plasmacytoma was found at the base of her skull. She tested positive for EBV but had no cancer cells in her bone marrow at that time. She was given steroids/local radiotherapy, and her symptoms disappeared. For a while.
Two years later she went back to the doctors because of generalized bone pain. Unfortunately, bone lesions were found in several areas of her body, including the skull, ribs, humerus and spine (and various other bones, too). By this time she had 95% plasma cells in her bone marrow. Incidentally, the full study mentions that gadolinium was used as a contrast agent in her imaging tests…Uhm.
Anyway, this was her diagnosis: plasma cell myeloma with kappa chain restriction/IgA+ at a Durie/Salmon clinical stage of IIIA.
One good thing: she didn’t have any kidney damage. She began treatment with dex, thalidomide and zoledronic acid….and, in February 2012 (at the time the study was written), she was awaiting a stem cell transplant.
An important bit of information: EBV was found in the nuclei of 70% of the little girl’s myeloma cells (= two different BMB specimens). 70%!
According to the authors, EBV can cause a polyclonal B-cell expansion, which can eventually develop into a monoclonal malignancy. Eh??? What the haystacks does that mean? Okay, step by step:
- B-cells or B lymphocytes, as we know, are the cells that become malignant in myeloma. They get damaged and start proliferating like mad, totally out of control.
- I thought precursor cells were stem cells, but I checked, just in case. No, they aren’t. While precursor cells are similar to stem cells, they’re more specific. The simple difference between stem and precursor cells is that the former can “reproduce” themselves forever and ever, but the latter can’t.
Simply put: the EBV virus appears to be able to infect (and hide inside the nucleus of) these B-cell precursor cells, which activates a whole series of unfortunate events that eventually lead to the development of myeloma.
Now, the authors note that the association between multiple myeloma and EBV seems to be a rare occurrence. Yes, that may well be true…but then, how many people newly diagnosed with MM or MGUS or SMM get routinely tested for EBV? Were you tested for EBV at the time of your diagnosis? Probably not. I certainly wasn’t.
Here’s some more food for thought:
- EBV frequently doesn’t cause any symptoms. That is, most people are EBV carriers but don’t know it.
- Something like 95% of the world adult population has been infected with the EBV virus. Yes, that’s right. 95%.
- However, 95 % of the world’s population does not have myeloma or MGUS or SMM….otherwise it wouldn’t be considered a rare type of cancer, right?
That said, why couldn’t some of us have gotten this icky thing after a bout with EBV…I mean, why couldn’t EBV possibly be at least one of the causes? After all, I read somewhere that it only takes one wacky cell…and bam!, eventually we have myeloma (or MGUS or SMM).
It all begins with just one wacky, abnormal cell.
So here are my final questions of the day:
- what if the EBV test were part of the routine tests we have to have when we are first diagnosed with MGUS, SMM or MM?
- What if an association could be established, at least for some of us?
If (again, for some of us) an association were found, then perhaps our myeloma researchers could devote a bit of their time to studying this issue. See:https://margaret.healthblogs.org/2010/10/28/pieces-of-the-viral-puzzle/
Well, I’m intrigued (again!)…and I want to do some more digging. I’ve found a few, recently published studies on this topic. Furthermore, as I mentioned earlier, when I have a bit of time (SIGH!) I’ll go back and look at the data you have already sent to me. This time, I might be able to put the puzzle together, in spite of the missing pieces…
And that is precisely why I’d very much welcome your thoughts and experiences and help…again!!! Thank you!!!
September 30 2011 post. Today I got caught up with my Science Daily articles, one of which triggered my curiosity: http://goo.gl/Ogr7B Now this is really really REALLY interesting: if you TREAT cytomegalovirus, a really crappydappydangerous type of virus that 70-75% of us adults have inside of us (luckily, it remains dormant in most cases), you can REDUCE the growth of brain tumours. Note: 92% of brain tumours are infected with cytomegalovirus, or CMV. Wow…as soon as I read that, I rushed to consult PubMed, the main source I use in my research. Not surprisingly, when I did a search for CMV and myeloma, I found some interesting abstracts…
It turns out that myeloma patients who have received chemotherapy treatments and stem cell transplants are at risk of awakening this terrible virus. The consequences can be scary, even devastating…
Here follows a selection of some of these studies…
This one concerns patients who have received chemo treatments but not stem cell transplants:http://goo.gl/WXOO7
Infections in myeloma patients undergoing stem cell transplants are discussed here:http://goo.gl/IWfc9
This full study shows how different treatments put patients at risk for different infections:http://goo.gl/VTqWg
A fatal case of myeloma and CMV (full study): http://goo.gl/z2Npw Scary…
I’ll stop here, but you can find other studies on PubMed if you’re interested in the topic…
The viral connection pops up again…and again…When I get back to Florence, I have some work to do…
UPDATE: as I was fishing around on PubMed for natural ways to combat CMV, I found an abstract on the wonders of caprylic acid, which I’d never heard of before but apparently can be found in the milk of some mammals and in coconut oil…Here is the link: http://goo.gl/UNZsn Note: this stuff is used to treat candida (Paul, what do you think?)…Hmmm…
June 23 2011 post. As I announced last week, I’ve finally decided to tackle the possible virus connection topic that we began discussing seriously last fall (boy, time does fly, doesn’t it?!!!) here on the blog. Back then I received many ”viral” messages and comments…so many, in fact, that I simply felt too overwhelmed to do anything with them. I tried, but my brain kept going into shutdown mode. I had to give up finally and look at other topics…
Oh, it wasn’t just the messages, mind you…I was also overwhelmed by all the virus connection studies that are still sitting inside a file on my desktop. To be honest, I still feel a bit overwhelmed, but okay the time has come to stop procrastinating, to sift through this rather daunting mountain of information and try to figure out if there could be a pattern or something that might be useful to us…
I need to do this slowly, though, in order to retain my sanity. So it’ll take some time to get through all the material and organize my thoughts and your comments (Note: new virus connection comments are welcome…). Uhm…please put on your patience hat…
I’ll begin with a Hungarian study published in 2006. As luck would have it, the full shebang is available online: http://goo.gl/Ot37F This is great, since you can read it, too, and see if I’ve missed any important bits or misinterpreted the data etc.
These researchers tested 69 MM patients (48 in stage III, 21 in stage II) and a smaller number of MGUS folks (16 with MGUS and 10 with Waldenström’s macroglobulinemia) for the presence of four herpes-related viruses, as follows:
- Epstein-Barr, which I myself contracted toward the end of my grad school period (and, if my memory serves me right, I also had mononucleosis in my last year, undergrad, at Harvard; I don’t have those medical records anymore, unfortunately, but I remember being quite ill at one point and going to the student health service center…).
- Cytomegalovirus or CMV (I have a good story there, but that’s fodder for another post…).
- Two herpesviruses: HHV-6 and HHV-8, which (the latter only!) has been associated with the development of multiple myeloma.
More on HHV-8: this virus has also been implicated in the progression from MGUS to MM. Hmmm, I don’t think I knew that…
The control group consisted of 44 patients with non-Hodgkin’s lymphoma…Now, I confess that this part puzzled me…Why use NHL patients? There is no explanation for that. I can only surmise…I must admit that my lack of a scientific background irks me at times like these…
At any rate…these researchers discovered that the most common virus present in the bone marrow and blood both of the MGUS and MM group was, TA DAAA!!!!, Epstein-Barr or EBV. Yes, it turned out that more than half the patients had had EBV at some point (indeed, some were actually in the acute phase of the EBV infection at the time of the study). So they conclude (see abstract) that:
- since 13 of the HHV-8 positive MM patients also had an acute EBV infection and
- since there was nothing similar in the control group, then
- in addition to HHV-8, the transitional reactivation of EBV may also play a role in the pathogenesis of MM.
Pathogenesis (I had to look this up) means “the mechanism by which the disease is caused.” Aha. This was the most interesting part of the study for me, especially given what I mentioned above, i.e. that I almost certainly contracted mono in college and then, less than ten years later (while working toward my Ph.D. at the University of Toronto), I tested positive for EBV…I had a recurrence, it seems. So…could EBV have been my trigger or one of my triggers? Notice, in Table 2, that more than half the folks in the NHL control group also tested positive for EBV…Is this just a coincidence? Oh how I wish this study had had a healthy control group, too…
Well, it didn’t, so let’s fast forward to “Results.” As mentioned above, more than half the MM folks tested positive for EBV, also known as HHV-4; however, the difference between the MM and the control groups was only significant for HHV-8. Oh. Okay.
As for the MGUS folks, I thought it was interesting that nine (out of sixteen) had EBV antibodies. Again, more than 50%…
Interesting excerpt: In the history of HHV-8 research, it has been exceedingly difficult to obtain lymphoid cell lines (e.g. effusion lymphoma) devoid of the EBV genome (Renne et al., 1996; Said et al., 1997). This raises the issue of a possible interaction between these two lymphotropic herpesviruses, at least in diseases of the lymphoid system. Could that have been the reason for choosing the NHL control group?
So what’s the bottom line, here? Well, there certainly seems to be a potential association of MM and HHV-8. But there is more. The final sentence in the study reiterates the final sentence in the abstract: The data also indicate that in addition to HHV-8, the transitional reactivation of EBV may also play a role in the pathogenesis of MM.
Personally, I think there must be something to the EBV connection…perhaps not for all MGUS, SMM and MM folks, but for a subgroup, anyway…
October 28 2010 post. Pieces of the viral puzzle. This article, http://www.sciencedaily.com/releases/2010/10/101025161217.htm, is about (ta tata taratata, drum roll!!!) the relationship between microRNAs and the Epstein-Barr Virus (EBV). A new study shows that EBV uses its own viral microRNAs to evade the immune system. Incidentally, EBV is more common than I thought: up to 95% of U.S. citizens have it. Anyway, in most cases the virus falls into a deep slumber and never wakes up again…but some unfortunate EBV-infected folks, e.g. those with weak immune systems, can develop cancer (Hodgkin’s lymphoma, e.g.). One of the study authors concludes that microRNA activity has a real and potent effect on health. No kidding. I found this article absolutely fascinating and plan to re-read it more carefully ASAP.
October 25 2010 post (highlights only): In April of 1995 I came down with infectious mononucleosis. I don’t remember much from that period, except that I must have had enough symptoms to go to the doctor. Luckily, I still have my Canadian test results, which means that I can provide a few numbers. In mid April, my AST was 196, which is about ten times the high end of normal; my ALT was 458, and my alkaline phosphatase was 250, which is also way above the normal range (high end: 115 U/L).
But the main point is that I tested positive for “Heterophile AB” (=infectious mononucleosis, which is caused by the Epstein Barr virus, or EBV).
I don’t remember how long it took me to recover…I probably spent at least a couple of weeks, possibly a full month, locked inside my cosy (=tiny, but adorable) one-room Victorian attic apartment on Huron Street in Toronto…together with my beloved cat, Keshé. A very kind university friend did all my shopping, including cat food, of course!
As for the EBV aftermath, all I recall is that I was exhausted all the time and for a long time…so much so that my above-mentioned friend bought me a couple of books (which I still have) on the Chronic Fatigue Syndrome. Eh. Oh, and one more thing: at the end of May 2005, while Keshé and I were visiting my parents in the States, I came down with a nasty urinary tract infection. I was in such pain that my parents drove me to the Cape Cod Hospital emergency room, where, after a battery of unnecessary tests (I mean, hello?, even I knew that it was a UTI), I was finally diagnosed and treated. Well, I guess it is not surprising that my immune system was quite low at that point…
April 8 2010 post (highlights only): Here is my question: does anyone else have a similar story? I mean, a viral infection preceding a MGUS, SMM or even MM diagnosis?
Here is an excerpt from an IMF document dating to 2005: Recently, researchers have proposed infection, particularly viral infection, as a causal or trigger factor. Several studies have linked multiple myeloma to HIV, hepatitis, herpes virus infections (especially herpes virus 8), Epstein Barr Virus (EBV), as well as new “stealth adapted” viruses such as mutated cytomegalovirus (CMV). The significance of these viruses with regard to multiple myeloma remains to be fully explored.
As I mentioned, I have already discussed this topic, which you can find under “Myeloma Triggers” (see: https://margaret.healthblogs.org/life-with-myeloma/what-is-multiple-myeloma/mgus-to-mm-progression-sox2/myeloma-triggers/), but I would like to take another look at it…there might be a more recent study out there…interesting topic, yes…