Genetic Test for Progression.

So recently they have delineated genetic markers for precursor conditions... 

Whole-Genome Sequencing Identifies 2 Distinct Myeloma Precursor Conditions

"Whole-genome sequencing (WGS) has the potential to accurately differentiate between stable and progressive precursor conditions to multiple myeloma in low disease burden clinical states and the use of this technology in the clinic may result in a significant shift in the management of these patients, according to data from a study published in Nature Communications.

The distribution of genetic events reveals striking differences and the existence of 2 biologically and clinically distinct entities of asymptomatic monoclonal gammopathies: (i) one entity characterized by a sufficient number of myeloma genomic defining events to confer malignant potential and which is associated with progressive disease, and (ii) another entity with a lower burden of genetic events characterized by high likelihood of a prolonged, indolent, and clinically stable course

Going forward, improved and biology-oriented strategies to accurately identify patients with progressive myeloma precursor condition before clonal expansion (i) will allow earlier initiation of therapy before onset of end-organ damage to avoid severe clinical complications, (ii) will prevent patients with precursor conditions from being overtreated."

This is all over the place in blood cancer journals so I feel like this is important.   If we can identify with a simple test who is in danger of progression and who isn't... we can treat someone BEFORE THEY GET A LOT OF CLONES.  Right now, the danger of treating someone is what if the condition never gets any worse... 

Imagine then if we could avoid the development of blood cancer for 20 to 30 years with just a simple treatment every 5 years or so? IMHO that would effectively end blood cancer. 

Currently I have sent a lot of blood and data to the PC Crowd and Impact studies. I hope they are using it to test some of these theories out. 

Results of Blood Donation

 So, two weeks after blood donation I got some lab tests - amazing results on Iron:

• My Ferritin went from 211 to 108;
• My Iron total went from 120 to 57
• My Iron Binding Capacity went from 360 to 340
• My Saturation % went from 31 to 16. 

All within range and a major drop from where I was before.  Yeh!

But, my number one concern is inflammation so I got HS-CRP done again and:

• My HS-CRP went from 4.2 to 3.8. 

STILL MASSIVELY HIGH. 

I am frustrated beyond measure. So I went and looked at my prior HS-CRP and only once was it as elevated as it is now. When I was doing a liquid diet of about 800 calories per day. 

When I was doing that my body went haywire. My brother had a similar reaction when he did a juicing fast. My cholesterol went up very high. All of it only went down when I started eating more.

So I looked it up... could "starvation" cause high inflammation? Yes... yes... I found several studies showing that people with Anorexia have higher inflammation even though, due to their weight, they should have less.

Wow, so frustrating. They tell you that losing weight will reduce inflammation but... eating too little will increase it.

You know what this means for my dieting right? I will have to increase my calories and attempt to lose a lot more slowly. Given the fact that I have about 50 lbs to lose, this is very depressing. 

Blood Donation: Part Five

So I went and donated blood again.  I think I am lucky. I live in an area with great medical facilities and that applies to blood donation.  I go to this company called RBC (Research Blood Components).  Basically they take your blood and sell it to various researchers. There really aren't too many companies like this around so I am lucky to have them close enough to me to make it practical. They seem very competent. The guy who takes my blood does it very well. Before starting they have me fill out an evaluation. Then they take my blood pressure (by hand not with a machine), they take my temperature, and the prick my finger to ensure I have enough iron / hemoglobin. A little mini check up. 

Of course, when I first signed up... they did blood tests on me to ensure I had none of several viruses... I didn't. 

Then, there is the pay.  They pay you $25 to come in and get evaluated and then they pay you $50 for whole blood. Plasma is much more money but I am mostly interested in blood. 

There is another company that pays slightly more but they are further away and also seem to want a lot of information before they will even clear you as someone who should get an evaluation. 

But the big reason imho to do it is that several studies have hinted that blood donation is good for you.  Or imho, evolutionarily we were made to lose blood more often than we do for modern life.  An evolutionary perspective explains the danger of iron overload as the result of a mismatch between our ancient bodies and our modern environment. The current thinking is that the mechanism is that  reduction in blood reduces iron but at this point we simply do not know the mechanism because there are not a lot of studies on the issue.  

• Before humans had reliable ways of purifying food and water, humans had to live with constant parasitical infection, which drained the body’s iron stores. To make sure our own bodies got enough iron, we evolved to store more than we needed. Now, when modern hygiene has all but eliminated the parasitic load on our bodies, we’re storing too much iron.

• When we were hunter gatherers we likely would have far more losses of blood over our life time. Hunters may be injured frequently and women likely gave birth and lost blood giving birth. 

• The fact is for over 3000 years bloodletting was a common treatment for everything. It has only recently—in the late 19th century—been discredited as a treatment for most ailments. It was given up due to more effective treatments but, it seems to me that something that was a common treatment for over 3000 years must be good for your body. To just disregard it seems unwise.

• There is even a theory that bread and agriculture has made the problem worse. Over the last 2000 years we have increased our consumption of foods other than meat. When humans started to rely on grains for a majority of daily calories, we adapted to deal with less iron, and now people in the Western world (who have switched back to a much more meat-based diet since approximately the Second World War) are feeling the drawbacks of a once-advantageous adaptation.

• May help stave off illnesses.  Worried about covid-19?  You need to donate blood. Not only will donating blood reduce chances of clotting....infectious agents require iron to survive and thrive.  Does it now make some sense that men, who are likely to have more iron than women get more sick from covid 19.

• May reduce risk for cancer. A few studies suggest there’s a connection between reducing iron through blood donation and reducing cancer risks.  The studies are inconclusive but given studies on blood thinners and cancer I think it is possible.

• Reduces hardening of the arteries and heart attack risk.  There is a lot of evidence for this but, with regard to MGUS -- particularly IGM - donating blood on a regular basis also reduces blood viscosity, or thickness. I don't care what anyone says, if I have an illness that could increase blood viscosity -- even if not to dangerous levels.. I will be better off if I routinely keep it in check. 

• Our redblood cells last for about 120 days. During this time they may collect sugar on them (glycation) and the older they are... the more rough and less flexible they are. This leads to more possibly of damage to the vascular system. The way that diabetics lose their legs and feet is that glycated red blood cells flow through the small capillaries in the feet and legs and literally destroy the capillaries. Eventually your body will just start cutting them off and eventually you will need to have your feet ampuated. Donating blood causes your body to produce new - more flexible - blood cells; with reduced levels of glycation. FYI, you should notice a reduction in your Ha1c if you donate blood. Mine dropped from 5.7 to 5.2.

This is just a small listing of the reasons to donate blood.  Benefits of Bloodletting; And this one Donating Blood: healthy or hype?

If you are interested what really convinced me was reading the book... "The Blood Thinner Cure"  by Carol Turkington and Kenneth R. Kensey. Not only does it go over the many ways blood donation can help but it also provides a way for you to know if you have too much blood. Hemocrit shouldn't be over 40%. 

Iron, Inflammation, and MGUS.

So I had to go get some blood taken for the Dana Farber - IMPACT - study. So I decided to get a few more limited blood tests. I retested Ferritin, tested Vitamin D and, TSH. 

For the last two weeks I have not had any red meat and I am happy to say that my Ferritin dropped down, from 245 to 211.  That is still higher than I would like but I think shows a clear issue with iron and red meat.  Both my Vitamin D and TSH were great.  Mainly, not having red meat really dropped the value in a short time period. 

There is great controversy about red meat for health. And I happen to find results all over the map. Based on those I was pretty confident that red meat would not be an issue and, since I was alternate day fasting, I assumed I would not over do it.  But thank god I tested it and it was an issue. Now I know. 

I was overdoing it. Primarily because of changes to the food supply. 

• Recently I have been having trouble finding veggies.  What ended up happening is I tended to eat either "cauliflower" or "creamed spinach".   Cauliflower has a ton of Vitamin C which allows absorption of iron and Spinach has iron. I was eating the entire bag, not just a serving.  In addition at one point I was told that the oxalates in the Spinach stop the iron from absorbing, but that only applies to raw Spinach, not cooked. 

• Recently I got into a nasty habit of having a burger for lunch (no bun) this is not my normal but, McDonalds no longer has grilled chicken food wraps and I was doing keto.  Typically I don't even eat at McDonalds but it was a nice ride every day in the pandemic.

• I have added red meat to my listing of food that I can eat and I switched to having red meat more frequently than chicken. And I would have like a 5 oz serving. In addition, I think I was having cuts that were more muscle (which has a lot of iron). 

A lot of people tell me that food cannot make your iron stores go up. The truth is, they are just wrong.  It is often said that once iron goes into your body there is no way to get rid of it - that is even more true that one might know. Even though you supposedly need a lot of iron per day... just recently it was discovered that we already have a massive source of iron.... our own blood cells.  Our bodies recycle blood cells and the iron in them. Thus, the vast majority of iron that you get each day is from this recycling.  Like 80%. So, if you are eating a lot of iron and absorbing it, you are continuing the build up of iron - that basically - unless you donate blood - is hard to reduce.  This means it is VERY easy to over do it with iron. 

After looking into iron more I am horrified that it is so ignored as a health concern. I am rather furious that my doctor never ran this test.  Imagine if I hadn't?  I would have been unknowingly hurting myself? As it is, I have no idea if I did hurt myself.  I had an issue with this once. I started taking a multivitamin that had iron it it and I started turning brown. My iron was wayyyy high. I stopped taking the vitamin and all was well.  So I feel like my doctor should have been looking for that. 

But it is apparently well known as something that should be watched in women post menopause. Especially if they have had issues before.  Yet, even with my much higher RBC and hemoglobin counts being on the high side... nothing. I will have to be careful in the future. Keto without red meat is not easy. I can have things that block the absorption of iron but I don't fully trust them. 

I happened also to come upon some science in this area last night and our understanding of iron has radically changed in the last ten years.  In particular, they have discovered a hormone that controls the amount of iron in your body... and this hormone being high, is not necessarily a good thing.  Hepcidin helps to control the expression of iron in the body and recently it was shown to be unregulated in gastric cancer.  The cancer that took out my mother. Hepcidin is a key regulator of the entry of iron into the circulation in mammals. Hepcidin is typically elevated with inflammation. 

Blood Donation: Part Four

So what happened to me when I gave blood and then had my MGUS blood tests go out of wack. As we saw in the previous post: no plasma cells are usually in circulation. The only way to get a direct look at them is to do a bone marrow biopsy. But MGUS patients use markers in the blood to determine what is going on with those clonal cells. The clonal cells produce "excess junk" that shows up in our blood stream. From looking at the junk we can reverse engineer what is going on with the clonal cells. 

So it is my belief that my tests were thrown off by my having a reduction in the absolute value of the blood, but not necessarily the absolute value of the junk. The "junk" remained relatively stable... my blood volume did not. It is possible also that the absolute value of the junk changed slightly as well. 

The measurement of the M-protien is in grams per liter. So if your liters drop down... your measurement of protein per liter is going to go up. 1 liter = 2.11 pints. So losing a pint of blood means that you will be losing 1/2 a liter. Mine did hardly move, from .3 to .5 g/dl.

The measurement of light chains however is.. milligrams per liter so it would seem that this might have a larger absolute amount since the unit of measurement milligrams is smaller than grams. Losing 1/2 a liter of blood from the body may have had a slight effect.  My results seemed wrong since I am IGM-kappa, you would expect to see an increase in Kappa and a stable Lambda. Instead my Lambda went way down. That would seem to be wrong. Since this blood test it came up. 

Now of course I had these blood tests about six to eight weeks after the blood donation and frankly it is questionable as to whether, at that point, there would have been any real difference.  But the absolute minimum between blood donations is sixty days and that is right at the edge of when these tests were done. 

Blood Donation: Part Three

So what did we learn from this (and further research)

Your body is replacing blood cells all the time naturally.  In fact, I was curious and I looked it up - red blood cells are replaced every 120 days But white blood cells are replaced much more frequently - almost daily.  All white blood cells are derived from cells in the bone marrow known as hematopoietic stem cells. The bone marrow then stores an estimated 80–90% of white blood cells. But some still circulate in the blood. 

It is these hematopoietic stem cells that are damaged in the first instance. These stem cells have mutations that may not allow the stem cell to turn into a normal functioning b cell / plasma cell (differentiate). The stem cells work fine for every other kind of White Blood Cell. They only have a mutation that effects differentiation B/ Plasma Cells. When the body calls for new b cells / plasma cells it calls up damaged stem cells and these stem cells can become clonal cells. The particular type of White Blood Cells that we have issues with are B cells: also known as B-lymphocytes, also known as Plasma B cells, these cells produce antibodies to help the immune system mount a response to infection.  There are like 7 different white blood cell types but MGUS people only have a defect with regard to the WBCs that are B cells / Plasma cells. 

So Dr. Kyle did help me figure some of this out... when he said that he doubted that plasma cells would be in the blood with a small MGUS. That gave me the hint that the white blood cells in the blood would be less than red. 

Googling it, I found out 

Most people will produce around 100 billion white blood cells every day. There are normally between 4,000 and 11,000 cells in every microliter of blood, although this can vary according to race.

 And, in fact

Plasma cells are not normally found in the blood circulation. Notably, B cells, the precursors of plasma cells, also undergo much of their early development in the bone marrow.   

Ok so now we are getting someplace, it would seem that in the first place... that blood donation is likely to have zero effect on B /Plasma cells. As this particular type of WBC is not in circulation anyway.  But, even if they were... losing a pint of blood is not going to effect your white blood count very much.  You have about 7 to 10 pints of blood in your body. Looking it up.. since there are about 4000 WB cells in 1 milliliter of blood, and a pint of blood  is 473 or 568 milliliters.... you probably will loose about 1,892,000 white blood cells in one pint of blood.  If we produce about 100 billion white blood cells daily well, it would seem the body might hardly notice a million cell loss.

So finally I think I have an answer. Blood donation will not effect the plasma cells / clone cells because they are "walled off" from the blood stream.

It does make sense. If you want to get a count of your clonal cells you cannot just test the blood. The only thing that will be in the blood are after effects of clonal cells, M-Protien,  immunoglobulins, and Light Chains. To see what is going with clonal cells you need to get a bone marrow biopsy. 

The B / Plasma cells will not react to blood donation but, they will react to viral or bacterial infection - when bacteria or viruses enter the body, some of the B cells will change into plasma cells. The plasma cells make antibodies to fight bacteria and viruses, to stop infection and disease.  There is a great chart on this link that gives a good idea -- Chart

Blood Donation: Part Two.

So I went to a Myeloma foundation and the person there tried to answer my question on her own. She did advise me to bring this up with my doctor but, as we saw in part one... that is a non-starter.

She stated:

Our bone marrow is constantly producing new hematopoietic cells to replenish the cells that are currently in circulation, working at their various jobs; red cells carry oxygen in the blood stream, various white blood cells fight infection and platelets help our blood clot if we get cut. Each different cell type has a different life span, but they all need to be replaced whether they live days or weeks.

Ok so far so good. 

I have trouble understanding why donating a physiologically safe amount of blood would cause abnormal stress on the bone marrow. 

So here is the problem. I have trouble understanding why they can't understand my concern and they simply NEVER TELL ME WHY? So frustrating. Presumably losing a lot of blood cells at once is going to stress the factories that will need to make new ones in quick time and, under stress, I worry it would be more likely they would go for broken stem cells to make new WBCs that were lost. 

She continues:

I have not read any studies showing blood transfusions caused myeloma to become active. 

Here is the problem with this. People with MGUS will be advised not to donate blood to other persons. So it is very likely that no one with MGUS will donate blood and therefore no one will ever find out if it causes issues. Never mind that with the limited funds for MGUS research NO ONE is going to do a study on this.   

Later on, without my requesting her to she

I wrote to Dr Robert Kyle, who was with the Mayo Clinic for many many years and is most knowledgeable regarding MGUS. He responded to your questions as follows. 

Yeh that is right, Robert A. Kyle, MD, Luminary in Myeloma Research -- that guy, you know the FATHER of MGUS.  He stated:

There is no evidence to his knowledge that donating a sample of blood on an ongoing basis would cause the MGUS to progress.  In fact, he doubts that there is any harm to the recipient, but there is no data in this regard.  As a prospective blood donor, one should tell the Blood Bank that they do have a MGUS and the Blood Bank will probably turn them down as a donor. A larger MGUS could have circulating plasma cells, but that is unlikely to be a problem for the recipient.

Ok but here is the problem... of course there is no evidence. People with MGUS are advised not to donate blood - as he rightly states (and completely contradicts my hematologist /oncologist team).

He goes on to incorrectly state that there is no benefit to donating blood.

There is no benefit in giving a research sample other than “participating” in the research project. 

I have to disagree. There is a lot of benefits to blood donation, in particular with regard to cardiac issues. 

In closing he did provide another good nugget of information:

[he had] wondered if you were referring to the use of plasmapheresis if there is too high a protein level in the blood, thinking it would be similar to donating blood and might explain benefit. He explained that hyperviscosity does not occur in MGUS except for extremely rare situations.

That is good to know. At this point I figured I better just shut the heck up over it. My name was on the e-mails and I don't want to get a "reputation" - I had decided that maybe I just shouldn't donate blood at all.   More in Part 3.