“The bone-marrow niche in MDS and MGUS: implications for AML and MM.” Part 2.

Back to the Dana-Farber study that I wrote about a couple of days ago.

The section titled “Therapeutic opportunities” is interesting. How to prevent progression, that is. As you can imagine, the chef’s daily special consists only of conventional treatments. For example, the authors make a reference to the Spanish study (Mateos et al) that I have repeatedly condemned here on the blog. The Spanish researchers–some with strong ties to the big pharmaceutical companies (hello???)–tested lenalidomide and dexamethasone on a group of SMM patients. The study claims to have prolonged progression-free survival and even overall survival in those patients…without ever taking into consideration QUALITY OF LIFE. Sorry, but I have no patience for statistical studies that play with people’s lives…

That said, the trend toward early intervention is clearly taking off, as the Dana-Farber study points out. Very unfortunate, IMO.

And there is no way to stop it, except that we, the patients, can say just say NO. Of course, if you have CRAB symptoms, that’s another matter. But, in the absence of the CRABs, WHY TAKE THE CHANCE OF WORSENING YOUR QUALITY OF LIFE?

Makes zero sense.

And there’s another thing that bothers me: where’s the proof that the overall survival of someone with SMM was extended thanks to these conventional treatments? Do the Spanish researchers have crystal balls that give them the exact times of death for their patients, both with AND without treatment? Oh, right, no, that’s what their STATISTICS tell them. Based on the patients’ “high-risk” data (see yesterday’s post).

I’m not saying that statistics can’t be useful in certain circumstances, mind you. But in these cases, when someone with no CRABs is deciding on whether to agree to early treatment, or not!, they can be harmful. If I had agreed to begin conventional treatments in 2005, I don’t know where I would be today (according to my former hematologist, I’d be dead…would have died in 2010…didn’t happen, OBVIOUSLY!!!…I’m still here, still splendid 😉 , still no CRABs, still no conventional treatments…).

Sorry for the rant. Okay, let’s calm down and try to understand the rationale of early intervention from the Dana-Farber study perspective. The researchers say that if the number of osteoblasts (bone-forming cells) can be increased in the early stages of myeloma, myeloma cells cannot proliferate. That’s good to know. There are non-toxic ways to do that, btw, but let’s keep to the study…

Mice that were injected with nanoparticles loaded with bortezomib before being contaminated with MM cells lived longer than non-injected mice. The researchers give another example in which early treatment of an antiangiogenic antibody was used on mice. Okay, but we’re talking about mouse models here. The reality, as the researchers themselves admit at the end of this paragraph, is that “…the use of antiangiogenic agents other than thalidomide and other immunomodulatory agents has not been shown to be successful in patients with MM.”

Not successful in patients.

So much for that.

Then there’s immunotherapy, which we have heard and read a lot about in the last few years. You may have heard about the anti-CD38 antibody known as daratumumab, which activates the immune system.

Anyway, it’s in this paragraph that I found a remarkable admission.

But first, let me say that ever since I joined online myeloma support groups, one of the key issues we discussed was what how to deal with our immune system. Should we stimulate it, thereby possibly stimulating our myeloma cells, too? Or should we avoid anything that stimulates the immune system? The consensus usually drifted toward the former approach. I wrote a post about this in 2013: http://margaret.healthblogs.org/2013/10/20/long-term-survival-in-myeloma-is-finally-linked-to-a-robust-immune-system-and-my-new-discovery/

I’ve had mixed feelings about it throughout the years, but my gut has always told me that it makes no sense to keep our immune system weak.

And here, in this paragraph, I finally have my answer (vindication!!!): “Indeed, trials involving these antibodies provide the first proof of concept that activation of the immune system has therapeutic benefits in patients with MM.”

After years of not knowing what to do, we finally know that having a strong immune system is GOOD.

Quelle surprise…not.

Has “high risk” become a new disease?

As I was working on the post I published yesterday, I ran into a very interesting 2015 editorial by a Finnish professor on the issue of HIGH RISK and decided it was worth a post of its own, before I go on and finnish, I mean, finish! the bone microenvironment post.  😉 

Here’s the link: goo.gl/CWAexK

Prof. Järvinen argues that “high risk” has become a disease today. That is, relatively healthy people can start seeing themselves as no longer relatively healthy. AND, he adds, “almost every treatment has inherent risks.”

Who can determine the threshold for “high risk”? Doctors? And what if patients disagree? Well, check out  what he says about that, in the section titled: “Understanding risk: are the blind leading the blind?”: “If we assume doctors are truly more competent in making value judgements about the lives of their patients than the patients sitting in front of them, should we not have proof that doctors can do the job? Sadly, despite medical education and clinical experience, doctors do not seem to possess the required skill.


Once again, we run into the issue of statistics, which tell you that you are at “high risk” of developing this or that if you fall into such and such a category. This has to have an impact on our mental health, among other things. Has to. And we know how much stress is related to a bunch of cancers, including myeloma.

Perhaps it’s time to re-evaluate the issue of “high risk”…?

Anyway, a very interesting editorial…

“The bone-marrow niche in MDS and MGUS: implications for AML and MM.”

Remember the post I wrote back in December 2014 about myeloma subpopulations and the bone marrow microenvironment? Probably not…so here’s the link: http://margaret.healthblogs.org/good-or-bad-for-myeloma/first-do-no-harm-myeloma-subpopulations/

The main point is that not much is known about the interactions between the myeloma subpopulations living in our bone marrow, how they compete for survival and so on…

Therefore, the only conclusion, in my opinion, is that going in with conventional bombs and blasting the heck out of this microenvironment doesn’t seem to be the best strategy for those of us with MGUS and SMM…certainly not until we know a LOT more about what goes on inside this complex and, I would add, delicate setting.

Luckily, there have been more studies on this topic since my 2014 post, including this recent Dana Farber one, titled “The bone-marrow niche in MDS and MGUS: implications for AML and MM.” A blog reader sent me the link (thanks!): goo.gl/Ew3K4A

The full study isn’t available for free online, but I was able to read it thanks to a good friend. Okay, let’s have a look at it…

We know that MM is preceded by MGUS and by an intermediate stage called SMM.

Progression, that is, the “clonal evolution” of myeloma, takes place between MGUS and MM. But, the researchers add, some of the characteristics of myeloma can be found, “at lower frequencies,” at the MGUS and SMM stages. For example, the gene deletions.

Therefore, they say, it is the development of neoplastic “subclones” in the earlier stages that probably leads to the progression to myeloma.

This development wouldn’t be able to take place without the help of the bone marrow microenvironment, which therefore must be targeted in order to prevent progression as well as increase the effectiveness of conventional treatments once the stage of MM has been reached.

As I was reading this study, full of technical jargon that I could barely grasp, I began imagining the bone marrow microenvironment as a marketplace where strong nasty myeloma hooligans live and operate in coexistence with other, not-so-harmful, silly myeloma characters, as well as a bunch of normal folks, our normal cells.

Problem: myeloma clones have the ability of turning the marketplace into a toxic environment that helps them grow and proliferate.

A lot depends on how the marketplace reacts to these attempted changes. If it is weak and yields to the MM hooligans, it will become full of “weeds.” If it resists, it will be full (well, perhaps not entirely!) of crowds of happy customers, what the researchers call a “physiologically useful crop of mature blood cells,” that is, normal blood cells.

Now, a NORMAL marketplace contains all sorts of custome…I mean, all sorts of cells, including osteoclasts, macrophages, endothelial cells and, don’t you love this one?, sympathetic neurons. Lots of different cells that live happily ever after in this lovely area of the body.

Too many details here…okay, we don’t need to know this stuff…skip skip skip.

Certain cells (the above-mentioned stromal cells, e.g., after they have gone over to the dark side) become responsible for helping myeloma develop. Furthermore, whenever myeloma cells initiate a disruption, things that should be sleeping (in technical terms: in a quiescent state) wake up (remember EBV?). Not good.

Disruptions also cause tumor suppressor genes, such as Rb1, to be…suppressed. Also not good!

The end result of all the disrupting and suppressing, without any reaction from the immune system, is that the BM microenvironment becomes myeloma-friendly, and MM stem cells can begin proliferating, helped along by processes such as angiogenesis (remember all my posts on VEGF?).

As you can imagine, the study doesn’t mention anything remotely non-conventional. But some of its findings are interesting, so let’s keep reading.

Ah, another thing occurs: immunosuppressive cells arrive in the marketplace and make such a ruckus that T cells and B cells are completely overwhelmed and can’t function properly. This means, of course, that myeloma cells are no longer being sought and destroyed by our immune system.

The study therefore gives us a lesson in progression. First and foremost, as we’ve just seen, myeloma cells learn how to avoid being annihilated by the immune system. They then create what the researchers call an “immunosuppressive environment” where the immune system defenders are no longer able to function normally. Other types of important cells present in this now-toxic environment are also affected, such as stromal cells.

When MGUS progresses to SMM and then MM, immunosuppression is one of the main culprits. In fact, I recently read a study that discussed this problem, concluding that patients with SMM whose other immunoglobulins—in my case, e.g., IgA and IgM—are suppressed are more at risk of developing myeloma. *

The questions are: can we stop this process? How? And…when?

In 2014 (and before), my opinion was to “watch and wait” for as long as possible. Until CRAB symptoms appear. My opinion hasn’t changed in all these years. Indeed, it hasn’t changed today.

“Watch and wait” doesn’t mean sitting around and moping and doing nothing but watch TV series all day long. It means being proactive, doing research, enjoying life, taking something that doesn’t have any toxic side effects and that has been shown at least in vitro to be anti-myeloma, such as curcumin. And so on. There’s lots of stuff we can do in this stage…

Okay, I think this is enough for one day. After almost falling asleepzzz myself, I decided to divide this post into three parts…or perhaps only two.

So…more on this topic tomorrow! Ciao!

P.S. The study also discusses the evolution from MDS to AML, but I didn’t really look at that part, of course, since it’s not my main focus…

* P.P.S.S. While it’s true that my IgA and IgM are suppressed (barely “alive,” in fact!), it’s also true that they’ve been pretty much at the same tiny level for years now. So yes, I am in the high risk category BUT I am still here, leading a normal life, no CRAB symptoms…

Living proof that being at “high risk” doesn’t have to be as scary as it sounds…right?  🙂 

EBV and myeloma stem cells. Chapter 3

Back to the Ph.D. thesis. Dr. Biswas tells us, on page 28, “that the tiny percentage of cells that harbor virus are [sic] stably maintained over months or years.” Years?

Could it be maintained for decades, too? Hmmm. At my request, I was tested a few years ago for EBV, but the only thing we found was that I had some anti-EBV antibodies…nothing at all useful…

Anyway, here’s something interesting on page 31: “EBV infects B cells both in vitro and in vivo.” In vitro, EBV makes these B cells immortal. What happens in vivo, however, isn’t that clear. In people who aren’t affected long-term by EBV, as mentioned previously, the virus doesn’t cause any real harm. What triggers it to wake up and initiate the development of different types of cancer?

On page 46 we find “that in myeloma, EBV persists in a latent form in the 47 CD19+CD138- B-cell progenitor population and undergoes lytic reactivation in tandem as the cell becomes a CD19-CD138+ plasma cell.” So something has to happen within the B cell, the CD19 positive cell that is, in order for EBV to wake up and jump into action.

It’s actually on page 46 where my brain almost exploded. Lytic reactivation? 😯  I had absolutely no idea what that meant, so I looked for an “easy” explanation, which I found, finally (if you are interested, have a look here: http://goo.gl/pg8Q6r ).

This study tells us there are two ways in which a virus, nothing more than a “parasite,” can infect its host cell: 1. actively, by causing “a lytic infection characterized by the release of new progeny virus particles, often upon the lysis of the host cell,” (lysis refers to the destruction of a cell, the host cell in this case), or 2. inactively, which occurs when the virus just sleeps, without reproducing itself.

Reactivation” occurs when a sleeping virus wakes up and reproduces, stimulated by internal or external factors…but that gets into too much detail, so let’s skip that part.

Here’s another clue: in order to be reactivated, EBV needs the help of a protein called Zta, as well as a transcription factor called Rta (remember NF-kappaB?). Not easy to describe a process that I barely comprehend myself, but, in a few words, a transcription factor (XBP-1) activates this pesky Zta, which then rushes over to hug its buddy Rta. The two of them, fortified by their love, then activate other genes, in what is called a “cascade.” (Phew…wiping the sweat off my brow…)

At the end of this process, EBV gets reactivated, which means it’s fully awake and ready to do its evil deeds. And in fact this is discussed in the Ph.D. thesis, too, on page 13, if you want to have a look. Yes, I’m jumping a bit back and forth, but it’s inevitable, especially when things aren’t too clear. [I just hope I’m not making any mistakes…Please correct me if I am! Thanks!]

An important aside (p. 48): EBV doesn’t become a target of T cells because it hides its “viral gene expression during latency.” Aha!!!

Another aside: the EBV myeloma lines are different from those of Burkitt lymphoma and lymphoblastoid cell lines, but are similar to chronic lymphocytic leukemia or CLL cell lines. The EBV-infected CLL B cells, however, do not become immortal and only grow for a short time. Bit of a difference there.

So, okay, back to us: in myeloma, B cells get activated and become plasma cells, thanks to the help of transcription factors (Blimp-1 and the above-mentioned XPB-1, etc.). In this process of transformation, in this cascade of events, EBV disappears. That is, it is no longer present in the newly-created plasma cell. Since plasma cells cannot reproduce themselves, it doesn’t have to be. It has already done its damage.

And now let’s get to something that I thought could be very useful, potentially at least: if you interfere with the cascade, with the process of transformation, EBV cannot reactivate itself.

This is important because, as we can see on page 93, “The investigations presented here show that although the cells that harbor EBV are only a tiny percentage of the cells in culture, EBV is an important driver for the proliferation of the cultured cell population considered as a whole.”

Margaret’s simple (simplistic) solution: we need to block the reactivation of EBV…keep it asleep, like Fluffy, the three-headed dog in Harry Potter. We need to block these transcription factors.

Shortly after I began this umpteenth EBV-MM journey (but, THIS TIME, with PROOF of the association!), I went to see our family doctor, who is a real genius. I’d sent him the main EBV-MM association studies, which we discussed briefly. Then I asked him to prescribe an anti-EBV drug for me.

My idea was:  block the EBV = block the MM.

Well (I should have known it), my doctor told me it’s not that simple. Sure, he could prescribe a cycle of acyclovir for me, but:

  1. For how long?
  2. What should the dose be?
  3. Would it work?
  4. What about the side effects?
  5. Did I really want to take the risk?

Of course I had no good answers, except to question e. (I’ve taken risks before, so, no biggie). And so I gave up, but only for the time being.

I just have to do some more research. There must be a way, a non-conventional way. Any ideas?

Hmmm, I just read that bortezomib (Velcade) kills EBV. Not that that gives me an incentive to start conventional treatments, mind you! But 1. if you are already on Velcade, AND 2. if EBV might have initiated your myeloma, well then, two birds with one stone, right?

Anyway, proteasome inhibitors in general have an effect against EBV, including, tada!, curcumin.

Food for thought.

Okay, I think I have enough fodder for a Chapter 4, then I’m done with the Ph.D. thesis. Take care, everyone! Ciao!

EBV and myeloma stem cells. Chapter 2.

One thing Dr. Biswas discovered is that the subset of EBV-positive (as opposed to the EBV-negative) myeloma cells are the blasted stem cells, which have CD19 on their surface. What does that mean? Simply that we’re not talking about plasma cells here, but about B-cells that have the ability to REPRODUCE themselves, turning into plasma cells (which do not have that ability, btw).

Confused? Well then, let’s have a look at something different.

On page 12, Dr. Biswas discusses the 90% percentage that I mentioned in my previous post. While EBV “is benign in acute stages and latent in chronic stages […], in some cases, EBV has been demonstrated to be involved in the development of many malignancies, both hematologic and epithelial.”

So EBV doesn’t normally cause any terrible mischief. but remains inactive (quiescent) once it gets inside its host cell. But, in some cases, EBV doesn’t keep sleeping like Fluffy (Harry Potter reference: Fluffy, the three-headed sleeping dog)…That is the case with myeloma, as we have seen, but it happens in other types of cancers, too, such as Burkitt lymphoma, Hodgkin and non-Hodgkin lymphomas.

Even though it’s difficult to keep up with the technical gobbledegook, what is clear is that other factors have to be present in order for EBV to initiate the development of cancer (the image in my brain is of Fluffy waking up when the music stops…the music would be the “other factors”…). Anyway, that will be fodder for my third chapter, methinks.

So, summing up: 1. in MOST cases, EBV causes no long-term harm but simply remains dormant inside its host cell; 2. In some cases, unfortunately, it is associated with the development of cancer; 3. In myeloma, EBV DNA is present only in a small subpopulation of MM cells = the myeloma stem cells; 4. EBV doesn’t cause just one type of cancer, but quite a few, and 5. As for other types of cancer, EBV is present in EVERY SINGLE tumor cell, so myeloma really stands out in this group of EBV-associated malignancies. Yaaay, we’re special! Um.  🙄

A question just popped into my head (actually, it’s been in my head for a while now): would it make a difference if you took antiviral drugs such as acyclovir as soon as you receive an EBV diagnosis? Hmmm.

When my EBV infection was diagnosed, I was given nothing, e.g. Nothing. Just told to go home and rest…

But after going through all these new EBV-myeloma studies, I wonder if I would have ended up with MGUS (more than 18 years ago!) if I had immediately taken acyclovir or something similar? And I wonder this not just for myself but for all the people who have EBV-associated cancers.

Well, perhaps it’s because there wasn’t much research on this topic back then (the EBV-MM studies are quite recent, as we have seen). Perhaps EBV is too insidious to be targeted by any existing drug on the planet…even acyclovir has its limits, I have read. Perhaps it’s because nothing can be done once the process has begun, but I can tell you that I’d have been “relieved” (with lack of a better word) to have known the cause/s of my cancer. It would have eliminated all these years of wondering where I got this thing (well, not wondering obsessively…you know what I mean).

And another thing: with all we know about EBV now, it seems absolutely astounding that everyone diagnosed with MGUS, SMM, or MM doesn’t get immediately tested for EBV. I mean, NOW (not 20 years ago).

Or am I wrong? Was anyone here tested for EBV?

Okay, enough for today. I seem to have more questions than answers…

My next chapter is going to be a bit more technical. I’m sure you can’t wait, eh! 😉 I’ll try to tone it down…  😎 

More on EBV and myeloma stem cells

A few months ago, before all the kitten chaos began in our lives (read: when I had a bit more free time!), I came across a 2013 Johns Hopkins University Ph.D. thesis titled “Persistence of EBV in the cancer stem cells fraction of multiple myeloma,” by Sunetra Biswas. [Reminder: EBV is the acronym for Epstein-Barr Virus, about which I’ve written a bunch of posts, most recently in October 2017…A connection has finally been established between EBV and MM in SOME patients.]

I began reading, and drafting a post about, Dr. Biswas’ thesis, which is very interesting but also quite technical here and there…well, okay, it’s technical everywhere 😉 Now, I might repeat some stuff, but that’s because there are some repetitions in the thesis, as you will see if you are brave enough to go have a peek. I apologize for the repetitions…I just took one out, in fact, and I’ve only re-read this post at least five times! 😉

Here’s the link: goo.gl/fgANzE

In the abstract, Dr. Biswas states that “EBV is present in some multiple myeloma cell lines and patients and when present, it is detected in a subpopulation of cells.” This subpopulation has “a mature B cell phenotype.”

But EBV just doesn’t sit inside the cell and do nothing. Nope, it helps MM cells grow.

However, check this out: when EBV is taken out of the MM cells (using a viral inhibitor), their growth slows down. On page iii, she talks about the growth of myeloma STEM cells. Oh how I wish I’d known all this when I became infected with EBV, decades ago!!! This viral inhibitor business gets reiterated on Page 8, btw.

On Page 2 of the Introduction, she states something that I already knew (but reminders aren’t a bad thing, eh): some B-cells infected by EBV become IMMORTAL. Just like cancer cells.

On Page 8 she begins looking at multiple myeloma and at myeloma stem cells, and then states that her research “suggests that EBV persists in cancer stem cells in MM patients and in four out of seven commonly studied MM cell lines.” More than half…wow.

Further on, Dr. Biswas states what we already know: “Multiple myeloma is a neoplasm of the plasma cells that has not been previously shown to be associated with EBV.” Indeed, in the past, whenever I asked a MM expert about this possible connection, all I got were denials and eye rolls. Well, now we have more than one study showing that there IS a connection…for SOME of us, at least.

Can’t be denied now. No more eye rolls expected… 😉

Now, even though she “identified EBV in 4 out of 7 multiple myeloma cell lines, EBV wasn’t present in every single myeloma cell, but only in a subset of cells, that is, a small population of cells, which makes it different from other EBV-caused cancers. And yes, the subset of cells happen to be myeloma stem cells.

Time for a mind-boggling statistic: the B-cells of 90% of the world’s population are infected with EBV. So here’s a good question: since Epstein-Barr is such a common viral infection, why don’t more people have myeloma or other types of cancer associated with an EBV infection? Clearly something else must be going on, otherwise practically everyone in the world would have some sort of EBV-associated cancer…

There must be other factors involved for an EBV infection to lead to MGUS and so on…

I hope to find the answer to that question by the end of this post (but I may not…there may be no answer as of yet), which I am going to divide into “chapters”…although if I skip a lot of the technical stuff, and the repetitions, I might end up with less material than originally planned… 😉 …

Oh, okay, drat, Pixie and Pandora have woken up from a nice cat nap and are becoming way too interested in what I’m doing at the computer, so I have to stop for today…Meeeeow! I mean, Ciao! 🙂

Holly Butcher: her letter goes viral after she dies at age 27

Many thanks to Cynthia for posting about a letter written by a young Australian woman, Holly Butcher, who died on January 4.  She had Ewing’s sarcoma, a rare type of bone cancer that usually affects young people and children.

I was quite touched by parts of it, so I decided to write a quick post. Before I forget, here’s the link to an Australian news article about Holly (and you can get to and read her full letter there, too): goo.gl/sLEYd8

In Holly’s letter, I recognized some of the feelings I myself have/have had…For instance, the irritation that I feel at times because my girlfriends don’t want to turn off their cellphones while we are playing cards. These weekly get-togethers, which last a couple of hours or so, are an important moment for all four of us. It’s therapeutic, too, for all of us. We chat up a storm, we laugh, we are silly, we eat homemade goodies, we make fun of one another, and so on. It’s OUR FUN TIME TOGETHER. But it can also be our serious time whenever one of us has a problem to talk about and try to solve. Before the cellphone era, there were no interruptions. But now the cellphones have to be turned on (not mine, by the way. Mine is always OFF).

It’s all the more annoying when I consider that, just a few years ago, those cellphones didn’t even exist…Our generation grew up with rotary dial phones, which then became cordless phones. Cellphones entered our lives in the late 1990s (if I am not mistaken). Before then, we weren’t connected to the world every single nanosecond of the day…but hey, we managed to survive anyway. So why is it that nowadays we are obsessively and almost physically attached to those little, annoying devices (useful in emergencies, I’ll grant you that)?

Anyway…Sorry for the rant. That was just a thought that popped into my head as I was reading the part about girlfriends having their hair done and so on.

Like Holly, I have always been frustrated that certain subjects are taboo. Death, she writes, is treated as a taboo subject, as though it will never happen to us, and that is certainly true.

Cancer is also taboo. Here in Italy people always die after “a long illness” or “an incurable illness” and similar euphemisms. Very rarely does someone mention the dreaded word, “cancro.” Even now, in the 21st century! Whenever I hear that a friend’s relative has died after a long illness, I always ask “was it cancer?” If the answer is yes, and it almost always is, then I ask, “what type of cancer was it?”

I’m not afraid to use that word anymore. But many years ago, the situation was quite different. When I was first told I had multiple myeloma, I thought I was going to die at any minute. But if cancer hadn’t been such a taboo subject throughout my life, I’m sure I would have had an easier time dealing with this terrible diagnosis.

And that’s my point here, really: we have to bring these topics out into the open. Of course, not ALL the time, duh!  I mean, who wants to talk about cancer and/or death all the time? Yikes! Not I, for sure!!!  🙂 

Anyway, I haven’t died (yet), and, as the  years have gone by with no great shake-ups, I have followed some of the suggestions mentioned in Holly’s letter…For example, Stefano and I have become birdwatchers (although we still say “hey, look, there’s a BIRD over there!” hehehe, still rather terrible at identifying birds, we are…), we travel as much as possible (not lately, but I hope that will change soon). And so on.

And then there’s the part about stopping to watch/listen to Nature…to cuddle with your pet (a dog, in her case…cats, in mine)…to listen, really listen to music…to eat the cake – zero guilt…to say no to things you really don’t want to do…

Oh yes, indeed. I do try…although life does get in the way sometimes, as it has recently when I’ve had to deal with a few stressful personal items. But…life goes on, and I’m certainly not a “whinger.” Uh-uh. No way. I deal with the stress, do my best, and get on with it!

In sum, there are a lot of really good suggestions in this letter, and that is why I decided to post this link, even though, yes, it’s always sad, very sad, to read about someone’s death, particularly that of a young person.

But her letter is actually very upbeat, as you will see, and that’s how she wants to be remembered…as will I, too, someday!