Title fight: Graft vs. Host!

 "Faith is a living, daring confidence in God's grace, so sure and certain that a man could stake his life on it a thousand times." - Martin Luther

Below:  The 1965 heavyweight boxing title fight, featuring Muhammad Ali and Sonny Liston

In the previous post, I had undergone an Allogeneic Bone Marrow (or stem cell) transplant from an unrelated donor.  You would think that all my problems would be over at that point.  Unfortunately, this was not the case.

Both the donor and I were a 12/12 HLA match, which is as close as you can hope for in a transplant situation - but since we were unrelated, this was not a perfect match.  Because it's not a perfect match, there are going to be issues with tissue rejection - but interestingly, it's not the kind of rejection you get with a lung or kidney transplant, where a patient rejects an organ.  The reason?  Graft vs. Host Disease (GvHD in the medical business).

GvHD is a condition that arises when the bone marrow provided by the donor (the Graft) produces white blood cells that decide that they don't recognize the recipient (the Host), and decide to attack the host as an invading foreign object - which it is, but also is is not!  In effect, a foreign immune system has been transplanted into the patient, and this new immune system decides that it doesn't know or like the new surroundings very much.

The first 100 days after transplant is the most dangerous and difficult period, when Acute Graft vs. Host Disease can take place.  Acute GvHD can be life-threatening, because the new immune system tends to aggressively attack the host's vital organs.  For this reason, new transplant patients are instructed not to travel more than 30 minutes away from the clinic - including any potential traffic delays.  This rule applies for 100 days post-transplant, because 33-50% of Allogeneic transplant patients will experience acute GvHD.

After 100 days, the danger of Acute GvHD is mostly past, and then the concern turns to Chronic GvHD. Chronic GvHD is much less severe, and is typically less time-critical than the acute version.  Chronic GvHD can still attack the skin, intestines, eyes, and lungs, causing a great deal of damage, but this occurs over longer periods of time.  The patient is in charge of monitoring for these symptoms, and is  responsible for notifying the Long-Term Care Team at Fred Hutchinson in the event of a flare-up.

Back to the process though:  The chemotherapy, Alpha treatment, and radiation had destroyed my diseased native bone marrow.  That dead bone marrow had produced all the body's different blood cells - platelets, red cells and white cells.  Once the transplant was complete, the donor marrow cells migrated to the center of the long bones and hips, and after 2-4 weeks, began producing brand-new blood cells.  I received irradiated blood (to kill potential pathogens) in the interim to keep me alive.

At the +28 day point, they took another bone marrow sample for analysis.  This particular sample was of great importance.  The results determined that I was "engrafted", meaning that the donor's bone marrow had set up shop and was producing new blood cells.  The sample was also sent out to pathology to analyze it for any surviving leukemia and for "chimerism", pronounced "K eye mur izm".

The term "chimerism" derives from the Chimera, a creature in Greek mythology that has a lion's body with a goat's head protruding from its back, and a tail that has the head of a snake at the end - a veritable smorgasbord of animal parts, so to speak.

In the world of bone marrow, "chimerism" measures how much bone marrow contains the host's DNA, and how much of it contains the donor's DNA.  Given how much effort had been previously expended to destroy my diseased bone marrow, one would hope that it was mostly donor at this point!  To recap those earlier efforts:  Two rounds of chemotherapy in Idaho, a Phase IIb trial involving Astatine-221 Alpha therapy, three days of "conditioning" chemotherapy, and two grays of total body irradiation.  

The "chimerism" report came back indicating 100% of the bone marrow belonged to the donor.  Amen!!  None of the original diseased bone marrow had survived.  Furthermore, there was no detectable leukemia, down to the lower limit of the testing.  Great news then!!!  We still had a ways to go in Seattle, and the reason was the Chronic GvHD, as explained above.

Weekly checks with the oncologists went quite well for about five weeks.  The attending physician would look me over, state that I looked amazing for someone this far along after transplant, and we would be on our way again.  This is not to say that I felt great - I was very low on energy, and most days didn't feel like doing anything at all.  We were visiting the clinic daily for IVs, because they had to keep up on Potassium, Magnesium, platelets, and red blood cells.  I kept telling the wife that things were going a bit too smoothly, and wondering when the other shoe would drop...

The other shoe dropped around day +40 post-transplant.  I developed vicious diarrhea that was ongoing, day and night - more times per day than I could keep track of.  The team at the clinic decided that there were a few potential causes for the diarrhea: An infection in the intestines, lack of dietary fiber, GvHD attacking the bowels, or some of the recently prescribed oral medicines.

To rule out infection, I had to provide a stool sample - which came back positive for Norovirus.  Something I picked up at the clinic, since you can't give it to yourself.  I was given anti-diarrheal medicine and fiber supplements to ensure the issue wasn't dietary.  I was given a colonoscopy to determine if my bowels were under attack by the new immune system - which turned out to be positive after review by a pathologist.  I was also switched off the new oral medicines and returned to IV meds to ensure it wasn't inflammation caused by those.

I was put on large doses of antiviral drugs to clear the Norovirus, which seemed to work fairly quickly.  However, the GvHD required that I take massive doses of the steroid Prednisone, and my life became insanely miserable at that point.  Prednisone may reduce inflammation, but it has so many awful side-effects that it's almost not worth the trouble.

The worst side effects of the Prednisone were:

• A relentless ravenous appetite - it suppresses the hormone Leptin, which tells you when you are full, and to stop eating.
• Insomnia - the most horrific side-effect of this drug.  Any time I laid down and tried to relax, I felt an unbearable urge to move.  It felt like I was vibrating, and my hands shook constantly.  I nearly cried one night after weeks of very poor sleep.  I just laid there and thought "I can go another 10 minutes", after which I would repeat it over and over as the night progressed.  Eventually as the dose was reduced, and we found a decent sleep aid drug that worked, insomnia became less of an issue.  But it was awful.
• Drug-induced diabetes - Yep, I temporarily had to stick my fingers, sample for blood glucose, and inject insulin, thanks to this awful drug.
• Hypertension - I had to go on blood pressure medicine to counter this Prednisone side-effect.
• Irritability - No shortage of that...
• Water weight gain - they put me on Lasix pills to help shed water.  I still became bloated and also developed cankles.

Below:  One side effect of Prednisone - cankles, where your calf blends seamlessly with your ankle.  Note the ear plugs at the upper right, to drown out the racket of both Seattle and the air conditioning unit.

The diarrhea became less awful, but it didn't go away.  This led to the diagnosis that the GvHD was "refractory to Prednisone", meaning that the Prednisone wasn't having much effect.  This is fairly common with Prednisone treatment of GvHD.  About 40% of the time, Prednisone treatment fails to work.  At that point they began slowly tapering the Prednisone, while putting me on a secondary drug called Jakafi.

Jakafi (Ruxolitnib) is a chemotherapy type of drug.  It's toxic and requires special handling.  It makes your urine, feces, saliva and semen toxic as well.  I loved it though, because it allowed me to stop the Prednisone.  Anything - up to and including death, would have been welcome after experiencing the side effects of Prednisone. 

This is not in any way to intended to discourage someone who may need Predisone to resolve a medical issue!!!  It's just a recount of what happened to me while on a temporary high-level dose of the stuff.

After a while - about 43 days - the symptoms of GvHD had subsided.  I was at the clinic 1-2 times per week for blood work and the occasional IV for mineral upkeep, usually magnesium or potassium.  

Finally at the day 100 point, we were allowed to return home, released to our local oncology team - who were of course cognizant of my condition and needs. In many ways, my retirement was simply an exchange of a corporate boss with an oncologist boss - my life was directed by a different individual was the only change :)

Please don't misunderstand this.  I greatly loved and enjoyed the people that I worked with - both above and below me on the company totem pole.  They were unfortunately replaced by a different guy and woman from the medical/healthcare totem pole that I was previously not part of.  I came to love them as well! :)