Graft Versus Host Disease (GVHD)

GVHD is the medical shorthand for Graft Versus Host Disease. 

Today a quick, non-geeky look at the phenomenon of GVHD, and how it differs from Transplanted Organ Rejection as seen in the previous cartoons noir post.(click here )

     For those of you just joining us, the procedure I have undergone here at Duke Med is technically an Allogenic Myleoablative Stem Cell Transplant or Bone Marrow Transplant. 

Allogenic: Taken from a donor (as opposed to autogenic, where they take your own cells out, hit you with some chemo, then put your own cells back in, or the syngeneic using stem cells donated by an identical twin)

Myleoablative: High-dose chemotherapy designed to completely wipe out the diseased blood-forming cells in the bone marrow. This chemo can cause side effects, often severe.

SCT: Stem Cell Transplant 

BMT: Bone Marrow Transplant, often used interchangeably with SCT 

As part of this I volunteered to participate in a clinical trial, A Randomized, Multi-Center, Phase III Study of Allogeneic Stem Cell Transplantation Comparing Regimen Intensity in Patients with Myelodysplastic Syndrome or Acute Myeloid Leukemia.  The regimen intensity refers to the pre-transplant chemo. I was randomized into the High Dose group, read about it in this post from March 27th. .

Let's Jump right in for it is pretty fascinating...

The fundamental difference between a conventional transplant & a Stem Cell Transplant:

    In a conventional organ transplant your body's immune system which is designed to protect against anything that is foreign, alien, or "not of you" will try to reject the donor's organ.

    In a stem cell transplant you, the host, get a new immune system grafted into your bones. This new immune system "sees" your whole body as being foreign, alien, "not of us" and wants to reject it.

Here is a recap in pictures, for you visual learners:

Lets use a Heart Transplant as an example again.

Your new heart faces

and attack from your immune system's

Warrior White Cells

that are on Patrol 24/7,

fighting against the swarms of  invading pathogens, germs, viruses, and orcs,

and are looking for any alien matter that does not carry their unique genetic papers.

And of course your newly transplanted heart cells don't have the right genetic papers, because you are you, the host, and your new heart is of your donor. So your immune system's attitude about the donor's heart is to get rid of it, send it back.

How a Stem Cell Transplant is Different:

      My immune system was totally wiped out by the pre-transplant chemotherapy, which was designed and administered to kill the rogue, mutated marrow cells which were spawning my MDS,  and all my white storm troopers were collateral damage.  Even though my donor/sister Laurie's stem cells were a so called "perfect match", there are still many, many types of my cells that are not 100% compatible, and none of her white cells were briefed on their mission - to  protect their new host, me.  

Fighting forces: American parachutists land between Nice and Marseille, in southern France, in August 1944

      All my sister/donor Laurie's warrior cells know is that they woke up one morning to find themselves dropped  behind the lines, into enemy territory.They don't recognize any of their surroundings and their rules of engagement are "shoot first, ask questions later". And none of my cells know the password.

     These new T-Cell Troopers are bivouacked in my marrow bones, and must have their innate rules of engagement modified and re-programmed or they will digest every host cell they encounter - hence the name Graft v.s. Host disease  An uneasy detente or truce is mediated by a delicate balance of immunosuppresive drugs. And for prophylaxis, since  the new white cells can't be trusted to fight infections, I have had to take many drugs. 

Anti fungals, antibiotics,and  antiviruals. Mouthwashes and gastric acid blockers, analgesics, lotions and unguents, Steroids, cortisoids, and the dreaded prednisone. I have been slowly tapering off these drugs.

      You don't want to totally suppress the new T Cells, just rein them in. They must be allowed to function against real threats and pathogens, and start building a new acquired immune system, that library of  how to destroy anything that is not "of you".  But too low a dosage of immunosuppressives, and you start digesting yourself.

     I am not just vulnerable to self digestion, but to any little (or big) germ, bug, or virus that I may encounter; hence the hand washing, gowns, masks and gloves, and other precautions in the hospital. This is a regimen to which I must adhere until such time as full engraftment  has taken place and I can begin to rebuild that library that is the acquired immune system.  Then I can get reinoculated for all the childhood diseases.*  

When was my last tetanus shot? 
Ummm, Never! 

And no, I can't get one just now.  It may well be a year or so before that happens.

Got the picture? I have to be real careful around edge tools and sawdust, no gardening, no crowds.

      When I get to go home, it is not because I am all better, it is because we will have my meds balanced to control my GVHD.  I will still need to monitor this balance with weekly or biweekly blood labs and tinker with the drug dosages. And there will be trips to Duke Med in the future for tests and evaluations, and for the reunion banquets that are held each year for the survivors.

 I will still be in self imposed quarantine for a while, so no hugs or handshakes yet.

All this is designated Acute GVHD , the initial post transplant reactions. 

There is also Chronic GVHD  which can show up anytime from now on and take the form of skin rashes, gut bleeding, renal and liver problems, loss of eyesight, and some other rarer conditions that can show up in some hosts. I hope Chronic GVHD will not be the subject of a future post, as this drama plays out for me.

 * List of vaccine-preventable child diseases:
I need to watch out for these plus all the other kid diseases like pink eye, scarlet fever, etc. until I can get reinoculated in a year or so.

Diphtheria

Haemophilus influenzae type b (Hib)

Hepatitis A

Hepatitis B

Influenza

Measles

Meningococcal

Mumps

Pertussis (whooping cough)

Pneumococcal disease

Polio

Rotavirus (severe diarrhea)

Rubella (German measles)

Tetanus (lockjaw)

Varicella (chickenpox)

OK, enough of that, lighter posts to come as we approach our going home day.

Chris