I looked up the three small melphalan-prednisone studies on SMM patients mentioned in the abstract. Here are the links: 2009 abstract: http://tinyurl.com/ygnlwr5; 2000 full study: http://tinyurl.com/yjfneba, and 1996 full study: http://tinyurl.com/yhogw2y). A cursory glance shows that there was no difference in survival…indeed, a couple of patients in the first study developed acute leukemia during treatment. Unfortunately, I don’t have time now to read the studies in great detail, but the upshot seems clear: there is absolutely no benefit in administering early treatment to SMM patients. Case closed…as far as I am concerned, anyway.

The study goes on to discuss the administration of thalidomide to SMM patients and concludes that this drug cannot be recommended for the treatment of SMM until a benefit is shown in prospective randomized trials. Caution happens to be my middle name (well, okay…not really! ;-)). Personal note: in 2007, when my hematologist suggested that I take some thalidomide to zap the cancer cells lurking in my bone marrow (=50% at the end of 2005…down to less than 40% at the beginning of 2007 after one year on curcumin), I said no. She tried to insist, but I was adamant. I want my “tiger” to remain dormant for as long as possible…so, no CRAB, no treatment. Period.

As for bisphosphonates, the study states that data from a few SMM trials shows that they might be beneficial for those who have early bone disease, but the potential toxicities of bisphosphonates, such as renal injury and osteonecrosis of the jaw, should be taken into account […]. Wait a sec. I read something recently about bisphosphonates, but can’t recall what, exactly…hmmm…was it good or bad? Oh I know, I read about it on the MMA patient list. I don’t think list members will mind if I post the link, provided by a list friend (thanks!), to this “USA Today” article: http://tinyurl.com/ykguaxm If you are currently taking bisphosphonates, please read this article and ask your doctor about it…

Another thing that we should all keep in mind if some day we face the choice of undergoing conventional treatment: In patients with SMM who then evolve into symptomatic MM the response rate to chemotherapy has ranged from 52% to 64%. I was actually surprised to read that there was such a low response…

Well, okay, so what do we, SMM folks, need to do? The study offers a useful Table outlining the tests that should be done right after we have been diagnosed with smoldering myeloma:

• Medical history and physical examination
• Complete blood count
• Serum calcium and creatinine
• Protein studies
• Total serum protein and serum electrophoresis (serum M-protein quantitation)
• 24-h urine protein electrophoresis (urine M-protein quantitation)
• Serum and urine immunofixation
• Serum free light chain measurement (FLC ratio)
• Beta-2 microglobulin
• Bone marrow aspirate
• Skeletal survey
• MRI of thoracic-lumbar spine and pelvis

After three months, we should have our blood and urine tests repeated…then, if our markers remain stable, we should continue to be checked every 3 months for the first year in order to establish the pattern of evolution (evolving vs nonevolving). If the markers do not remain stable, however, then a full evaluation should be done again, including a bone marrow biopsy. However, SMM folks should not be treated, the authors repeat, until progressive disease with end-organ damage is evident. Especially those who are in the nonevolving category! I couldn’t agree more…

IMPORTANT: A progressive decrease in the Hb level is the most frequent and reliable indicator of progression. Other indicators of progression that mandate treatment are the development of soft-tissue plasmactyotmas or significant skeletal involvement as well as increased serum calcium or a rise in the serum creatinine level.

So please keep an eye on your hemoglobin, in particular…and take action immediately if that number shows any signs of decreasing!

I have to split this post into two parts, since it’s soooo long (I will publish part II tomorrow). It concerns a study on smoldering (asymptomatic) multiple myeloma published last month in the “Journal of Clinical Oncology”…Sherlock, grazie!, sent me the full text…

In the abstract (see: http://tinyurl.com/ybwtzke), there is a list of some of the risk factors for progression to full-blown myeloma, nothing new, here—M-protein size, percentage of bone marrow neoplastic cells, etc.

Interesting excerpt: Immediate therapy with cytotoxic agents, such as melphalan/prednisone has not resulted in improved outcome = this bit is explained more in detail in the full study, so we will get to it later. The following excerpt simply confirms what we already know: Patients should not be treated until progressive disease with end-organ damage occurs. There are so many things to keep in mind with myeloma…but this one is certainly NUMERO UNO: no CRAB, no treatment.

Now for the full study. Something I didn’t know (or didn’t remember…) is that smoldering myeloma was first described in 1980 by Drs. Kyle and Greipp, as follows: a distinct clinical entity characterized by the presence of a serum M-protein value higher than 3 g/dL, bone marrow clonal plasma cells (BMPC) involvement of 10% or higher, and no bone lytic lesions or clinical manifestations attributable to the monoclonal plasma-cell proliferative disorder. A distinct…er… “entity”? I’m walking around with an entity inside of me??? Hehe, that gave me a bit of a chuckle…

Problem: the diagnostic criteria have not been uniform, thus resulting in important differences in time to progression and in a lack of consistent predictors of outcome between the different series. (The “different series” bit refers to the different classifications of asymptomatic myeloma: SMM, indolent myeloma, asymptomatic myeloma or low tumor mass myeloma.)

Before 2003, there was no real consensus on how to define smoldering myeloma, or SMM. In 2003, the International Myeloma Working Group agreed on a new definition of SMM consisting of a serum M-protein of > 3 g/dL and/or > 10% bone marrow plasma cells with no evidence of end-organ damage (hypercalcemia, renal insufficiency, anemia or bone lesions [CRAB]).

The study then spells out the differences between MGUS and SMM, but I won’t focus on that, since we know them, or should know them! ;-), by now. The following, however, was new to me: When the M-protein size and the proportion of bone marrow plasma cells are consistent with MGUS but there is substantial albuminuria, congestive heart failure, renal failure, peripheral neuropathy, orthostatic hypotension, carpal tunnel syndrome, massive hepatomegaly, malabsorption syndrome, or any combination of the above, the most likely diagnosis is primary systemic amyloidosis (AL) […]. Something to keep in mind…

…as well as a few other things: elderly folks can have diseases that mimic myeloma, for instance an increase in serum creatinine, anemia, diffuse osteoporosis and so on. Even patients with a single asymptomatic lytic bone lesion, the possibility of an associated benign bone cyst or a bone angioma should be considered […]. So ONE bone lesion doesn’t necessarily mean that you have developed active myeloma…interesting…my notes are filling up my…mental pad!

Risk factors for progression: M protein > 30 g/L, bone marrow plasma cells > 20%, haemoglobin > 12 g/L, light chain proteinuria (Bence Jones) > 50 mg/24 hours and an IgA monoclonal heavy chain. And lytic bone lesions. And, going down the list, also the presence of MRI abnormalities. A personal note: at times, my M protein has gone above 30 g/L, in fact in May 2009 it went as high as 39.9 g/L (eek!)…then it went back down to 29.7 g/L in September 2009…so I am still smoldering…what I mean to say is: please don’t freak out if your M protein surpasses the 30 g/L limit…first look at the context and the trends…

An interesting paragraph is titled “Pattern of evolution.” According to a group of researchers, there are two kinds of SMM: 1 evolving and 2 non-evolving. Patients who fall into group 1 had an increase in M-protein levels in two follow-up consecutive visits. Group 2 was instead stable and had a longer time to progression (3.9 years versus 1.3 years).

And here we get to a very useful item that was mentioned in the abstract, too: Most patients with SMM progress with increasing anemia and/or skeletal involvement consisting of bone lytic lesions and/or diffuse osteoporosis. Anemia is defined as having a haemoglobin lower than 10g/dL…but hey, read this and breathe a sigh of relief: the authors of this review have seen patients with SMM with a Hb level between 9 and 10 g/dL with no need for cytotoxic therapy for several years. It must be considered that in patients with a high serum M-protein there is also a component of hemodilution, and so the severity of anemia may be overestimated.

Wow, now this bit of news is very very important…it proves that treatment protocols should not be applied too rigidly, as happens all too often!!!, but that each case should be evaluated carefully…in its own context. In other words, just because your Hb has dipped below 10 g/dL doesn’t necessarily mean that you should undergo immediate treatment…that number could in fact remain stable or even go up…So this is another thing for us to keep in mind…

This morning I received a Google Alert that took me to a vet’s webpage discussing the possible benefits of administering curcumin to dogs with cancer. The vet’s name is Dr. Dressler, and he apparently is known as the “dog cancer vet.” Anyway, his post (see below link) and his readers’ comments were very interesting, but one of the comments really stuck out, the one about the 12-year-old dog diagnosed with multiple myeloma (=March 9 2010 comment), see: http://tinyurl.com/yzvqvkk

Now, have you ever heard of a dog or cat being diagnosed with multiple myeloma? No…I don’t think I have, either. Oh noooo, here it comes…another research topic…!!!

Okay, now back to being serious. Very serious. Ever since losing a beloved cat (the kitty I adopted at the Toronto Humane Society while I was doing my PhD at U of T) to some sort of horrible kidney disease or tumor, I have considered giving my cats some curcumin for preventive purposes. Well, after reading this web page, I think the time has come…I just have to figure out how to do it, and how much (not very much!) to give to them. Luckily, I have already written a post more or less on this topic, see: http://margaret.healthblogs.org/2007/10/11/curcumin-for-cats/ 

Stefano and I are both taking curcumin…now it’s our cats’ turn! Prevention…prevention…if only I had known years ago what I know now…

Remember my post on papaya and myeloma? If not, here is a reminder: http://margaret.healthblogs.org/2010/01/13/myeloma-papayas-and-papain/. Well, today I have a promising papaya (…promising papaya? hehe, sometimes my fingers type the darndest things!) update. According to a newly published University of Florida study, a papaya leaf extract had a dramatic anticancer effect against a broad range of lab-grown tumors, including cancers of the cervix, breast, liver, lung and pancreas.

You can read the UF press release here: http://news.ufl.edu/2010/03/09/papaya-2/ Interesting excerpt: Researchers exposed 10 different types of cancer cell cultures to four strengths of papaya leaf extract and measured the effect after 24 hours. Papaya slowed the growth of tumors in all the cultures. This extract attacked the cancer cells but left the healthy ones alone…

There was no mention of cancer cell apoptosis (=programmed cell death) in the press release, which talks “only” about slowing the growth of cancer cells, so I would like to read the full study at some point…I would be curious to see if myeloma cells were tested, too. The researchers tested ten different cancer cells, but only five types (=cervix, breast, liver, lung and pancreas, see above) are mentioned in the press release…

By the way, you can find the abstract here: http://tinyurl.com/y96k4z9. The papaya-cancer study is no. 27 (click on “Preview”) on the list of articles published in the Journal of Ethnopharmacology‘s February 17 issue…I must bookmark this journal! Just have a look at some of the other titles…fascinating…indeed.

Now, one thing that interested me about this papaya extract is that it increased the production of a certain class of cytokines: Th-1. Without going into too much detail, this is a very good thing…for myeloma patients, too, it would seem. As usual, you see, I immediately checked PubMed where I found several studies on the benefits of an increased Th-1  production in myeloma treatment, including this one showing that Th-1 suppresses the growth and function of myeloma cells: http://tinyurl.com/yd5bbfb

In conclusion, once again we have a non-toxic, anticancer extract that targets only cancer cells, not healthy ones…an extract that may affect myeloma cells, too (please note my use of the conditional tense…I need to study this topic a bit more…).

You know, I am getting a bit tired of repeating the same things over and over again…about how much funding goes into toxic drug research compared to non-toxic (mind-boggling, really!)…let me just say that this time I really really hope that Dr. Dang’s very promising research will receive a lot of attention…AND funding. 

In the meantime, I wonder…where does one find papaya leaves…??? Papaya leaf tea…well, why not?

I just learned that “The Cove,” a documentary on the incredibly cruel and senseless slaughter of dolphins in a secluded cove in southern Japan, won the Oscar for best feature documentary. Well done!

I found out about this massacre–which, incidentally, has been going on for years–when, months ago, I watched an Italian news broadcast showing a group of hysterical, sobbing surfers who had just returned from the cove after witnessing the brutal violent killing of the dolphins…the broadcast included footage of the carnage…the sea water turning a horrible shade of red…At first, I watched in unbelieving shock, then horror and anger took over…I will never forget those scenes…

I immediately looked up the story on Internet and signed this petition: http://www.thepetitionsite.com/4/ban-the-sale-of-dolphin-meat 

I have to confess that I will probably never have the heart to watch “The Cove” (what I saw on the Italian broadcast still makes me tear up as I write this post, months later…)…well, I guess it’s obvious that I feel very VERY strongly on this particular issue. And these massacres don’t just happen in Japan, I am very sad to report. Something similar happens right here in Europe, in fact (I just signed another petition…sigh…).

I just don’t understand…what’s the point??? Why???

Let’s stop these massacres of the dolphins (and whales, for that matter!)!!! Please sign the petition, it’s the least we can all do…

The Oscar story: http://tinyurl.com/y9833ml

On February 19th I wrote a post announcing that I had put my blog on Facebook. Today’s post gives a few more details on this…project (?).

Pinga, our cat # 5, got spayed on February 18 2010. While waiting for the vet to call (after the operation), I was too nervous and distracted to concentrate on anything useful…so, on a whim, I put my blog on Facebook.

Well, I must say that it has been really wonderful to connect with my blog readers on a more personal level…Indeed, until now I had no idea how much fun Facebook can be…

I also set up a personal profile on Facebook (=separate from the blog, that is). The difference between the two pages is that my blog can be seen by everyone on Facebook, but my personal profile is private (I have posted photos there, e.g.). Only my Facebook friends (and perhaps some hackers…) can see my personal profile.

Anyway, if you have a Facebook profile, please become a fan of my blog (see below link; my blog has 60 fans so far!) and/or send me a Facebook friendship request. I am always thrilled to connect with blog readers!

Here is the direct link to my blog’s Facebook page…you have to be a member of Facebook for this to work, by the way: http://www.facebook.com/#!/pages/Margarets-Corner-Living-with-smoldering-myeloma/312414599519 See you there! 😀

Update: actually, I am almost positive that anyone can view my blog’s FB page…even non-FB-members, just try clicking on the above link. I doubt, however, that you can become a fan of my FB blog without a FB membership…

Sherlock, grazie!, sent me the link to an abstract published in the March 2010 “Mayo Clinic Proceedings” (http://tinyurl.com/yc44yw7). Unfortunately, she didn’t have access to the full study…I would really love to have a look at the whole shebang, since, truth be told, the abstract left me with more questions than answers…

These are the main points that we can glean from the abstract:

1. the study concerns 773 patients diagnosed with myeloma between 1950 and 2005 in Malmö, the third most populous city in Sweden.

2. the number of cases of myeloma in all age groups did not increase between 1950 and 2005…did I read that correctly, or should I make myself another cup of coffee…? Seems quite odd, no? No increase over such a long period of time?

3. what did increase was the average age at diagnosis in some 10-year periods: between 1950 and 1959 AND between 2000 and 2005, e.g., it went from 70 to 74.

4. another thing that increased was the proportion of newly diagnosed patients aged 80 years or older (from 16 to 31%). Indeed, the proportion of patients with MM aged 80 years or older doubled between 1950-1959 and 2000-2005. DOUBLED…!

My main question: how does this study fit in with the recent reports showing that increasing numbers of younger people are being diagnosed with multiple myeloma? The Conclusion did not provide a satisfactory answer…indeed, the Conclusion seemed more of a Confusion than anything else. The answer may, or may not, lie in the full study……okay, I’d better stop here before I write something really really dumb…!

A friend, thank you!, sent me the following video. I solemnly promise that this story has a happy ending, so don’t worry!, but it certainly kept me on the edge of my seat for a few minutes, and it will probably do the same for you, too, in spite of the above-mentioned promise…! See: http://tinyurl.com/yj9cypq

Another friend, grazie!, sent me the link to one of the most popular videos on YouTube…entirely different subject (two adorable little brothers…love their expressions!): http://tinyurl.com/25evu3

I was actually going to publish something of a more serious nature today, but my best friend just called to see if I wanted to play cards this afternoon. Uhm, er, let me see…sit at home in front of the computer OR go have fun for a couple of hours with my best buddies? Gee…that’s a toughie! (Not!) The serious stuff can wait till tomorrow…take care, everyone! Ciao! 🙂