The Truth and Facts about GVHD

Today we will cover something that is coming up quite a bit in my posting these days, especially my weekly updates, GVHD.  Doesn't it sound like a such a scary acronym?  The definition for this acronym is actually Graft Versus Host Disease.  Which probably sounds even scarier to you now. If you were to do just a quick search on the internet about this, you would probably come away whiter than a ghost ;)  Unfortunately it is one of those topics that can't be skimmed over, because it really does have a lot of scary pieces of information related to it. 

The scariest being that it can actually kill me.  What's that you say, I underwent a procedure to get rid of a disease that could kill me, only to have the thing that saved me give me another disease that can kill me?  Confused yet?  Well read on and I will dispel all your confusion regarding this disease.  Hopefully I will also alleviate some of the angst and worrying you get everytime I talk about how my GVHD has gotten worse.

INTRO - Let me start by saying that GVHD is a frequent complication when undergoing an Allogenic Stem Cell Transplant (means my stem cells came from someone else) .  You see when I receive the bag of stem cells, it is also filled with millions of the donor's T Cells as well.  What are T Cells you ask, we will get to that.

The quick intto/coles notes version on GVHD is that the donor's immune cells see my body as being  foreign and are attacking me.  So you are probably asking what are the doctors not trying to stop it?  Well the funny thing is the doctors actually want GVHD to occur inside their patients, because it brings about a positive side effect called GVME (Graft versus Malignancy Effect).  Basically what this means is the donors cells also see any remaining cancer cells that the chemotherapy and radiation may have missed, and attack those as well.  This is something that we really want to happen, and is why the doctors allow the GVHD to be present. 

The trick for them is they have to control it so it doesn't get out of hand and do a bunch of damage to my body.  Additionally, the presence of GVHD gives the doctors a good measure of how strong the donor's immune system is inside you, before the aspiration at day 60 is done to determine the actual results.

TWO TYPES -  It is often discussed as one disease but GVHD is actually two different types, Acute and Chronic.  Acute usually occurs and flares up in the first 100 days post transplant and Chronic can flare up at any point for the remainder of my life.  Because we are so early in the process I am just going to focus on Acute GVHD for today.

T-Cells - I told you I would come back to these ;)  T-Cells are special white blood cells that recognize foreign cells in the body and orchestrate attacks on them.  These foreign cells could be bacteria, viruses or  other foreign substances.  T-Cells are so impressive that they can distinguish between body cells that are "self" (part of their body) and "non-self" (body cells from another body).  How can they do this do you ask? Well they have a little help from a thing called HLA markers.

HLA Markers - HLA Markers is shortform for Human Leukocyte Antigens.  Don't focus on the name, just know that they exist on every cell in our body and are like a fingerprint, no two people have the same set of HLA markers (except identical twins of course). 

So How on Earth can they do a Transplant? - So if all my cells have a different fingerprint than the donor cells, and I don't have an identical twin, how on earth did they do a transplant?  And how are the T-Cells not operating a full fledged war against me?  o prevent this war from taking place inside my body the doctor's have a couple prepatory steps they do:

First, they kick the crap out of me with chemotherapy and full body radiation.  This is intended to suppress and kill my own bone marrow. 

Second, they find the best genetic match possible for me in a donor.  You see in the HLA antigens there are 10 major or dominant markers that they look at.  In my case I had a 10/10 match.  So although I had a great match there are many another antigens that don't match, and thus the GVHD. 

Finally, post transplant they put me on a lot immunosuppressants to keep the T-Cells in check while they get used to their new home.  Eventually the donor's T-Cells will die off and my body will make its own T-Cells using the donor's stem cells.  These will still be a HLA than my body but the theory is they should be more comfortable in my body because they were made there. 

With all those steps why are there flare ups -  Administering the immunosuppressants is the least scientific part of the whole process.  One of the drugs, cyclosporine, requires very specific theurapeutic dose ranges based on body mass.  That is where the science ends and the guessing game begins.

There additional immunosuppressants that are used in conjuction with the cyclosporine to control the GVHD and keep T-Cells attacks on my body getting too serious.  The doses of these drugs are continually being changed based on how whether the GVHD is flaring up or subsiding in your body.

The fine balance is that they want the T-Cells attacking in my body to remove any remaining cancer cells but don't want the T-Cclls attacking my good cells. So if they suppress the T-Cells too much,  I can become very susceptible to all illnesses from bacteria, viruses and fungii. 

This is why the doctors are continually adjusting the levels.  They want me on the least amount of immunosuppressant as possible to keep the GVHD mild.  As it flares up they adjust my doses to get it quickly back in control and then slowly taper them back off.  It is just a game of waiting for the T-Cells to get comfy :)

Stages of Acute GVHD - So I have talked about a lot of the background stuff but not really gotten to the meat of GVHD. Physicians grade the severity of th GVHD based on the number of organs being affected and their severity.  The main organs affected with Acute GVHD are the skin, GI tract and Stomach, and Liver. It can be broken down into 4 different stages:

• Mild (Stage 1)  -a skin rash over less than 25% of the body
• Moderate (Stage 2) -and intestinal disorders.a skin rash over a more than 25% of the body accompanied by mild liver or stomach problems
• Severe (Stage 3) - redness of the skin, similar to a severe sunburn, and moderate liver, stomach and intestinal problems.
• Life Threatening (Stage 4) -blistering, peeling skin, and severe liver, stomach, and intestinal problems

 Each organ can individually range in severity as well.  Confused? I will go over each organ to clear it up a bit

GI Tract - this can range from mild cramping (mild), nausea (moderate), watery or bloody diarrhea (severe and/or life threatening).

Liver -  this they monitor through biweekly blood results checking all my liver enzymes to ensure they do not get to elevated.  If the liver is affected by GVHD too much I could develop yellow eyes or full on jaundice.

Skin - this is monitored visually. It usually starts as a small rash less than 25% of the body (mild), over 25% of the body (moderate).  The rash can become like a sunburn (severe) and finally blister and peel the skin which is life threatening

It can affect other area of the body as well but these are the ones the doctors are most concerned about. 

So What type of GVHD do I have - up until this point my gvhd has been classified as mild because only my skin has been affected.  Thankfully it has not really spread to my other organs yet. 

Unfortunately my skin hasn't been mild though. It has been moving back and forth between moderate and mild.  For the most part I just have a rash on my face, back, and shoulders, but recently my face flared up into being the sunburned level.  This is mainly just really uncomfortable as it feels like a bad sunburn. 

The doctors sprung into action with this flare up, by upping the doses of immunosuppresants.  When it comes to the skin they don't want it to blister and break. because this provides access points for infection. 

Well I hope this post has dispelled some of the mystery and fear surrounding GVHD. I really think that unless you are fully educated on a topic it is impossible to stay positive when symptoms are changing and you will worry more than you should. Now you have a reference guide for my weekly updates, so you can decide for yourself whether what I tell really is that scary and worth worrying about ;)

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