Graft vs Host Disease (GVHD)Graft vs Tumor (GVT)

At the request of a reader, I'm going to discuss Graft vs Host Disease (GVHD) and Graft vs Tumor (GVT) as they relate to allogeneic or mini-allo transplants. This is gonna be pretty dry. It's pretty difficult to be witty on these subjects.

I guess the first step is going to be defining what the words mean.

GRAFT - The graft is the stem cells I got from the donor.
HOST - The host is the patient. In this case, me.
TUMOR - The tumor is the cancer cells in our bone marrow.

Now that the definitions are clear, allow me to go back over the procedure(s) that lead to a mini-allo:

1) My bone marrow was ablated (significantly reduced) by chemotherapy and total body irradiation (TBI). This had the net effect of killing an estimated 90% of my bone marrow cells. (An autologous transplant kills 100% of the cells.)

2) Prior to #1 above, a kind volunteer went thru considerable discomfort to create a bunch of excess bone marrow stem cells. This graft was collected and shipped to my hospital.

3) The donor cells (the graft) were infused into my bloodstream.

4) The donor cells eventually engrafted, meaning that they began to grow and reproduce inside my bones. In other words, they took up residence in my body. As of my last test, 100% of the cells in my marrow belong to the donor. There are no "Andre cells" left in the marrow. (Note that this is 30 days into the process and I'm far from the end of the 120 day observation period.)

Now, I hope it's clear that the whole purpose of this is to make the donor cells combat the tumor(s). The donor cells are supposed to find the myeloma cells and kill them. The donor cells do this by recognizing the myeloma cells as foreign cells and launching one of many "kill" methods. (I asked Ed and the actual biology is pretty complex and not really relevant.)

When the graft kills the tumor, you have GVT with a positive outcome. GVT - Graft vs Tumor. It's the objective and a good thing.

But GVT and GVHD are a bit like love and marriage. "You can't have one without the other."

If the graft (donated cells) are able to recognize the myeloma cells as foreign, they'll also recognize every cell in my body as foreign! The same graft that is killing the tumors is also trying to kill me as if I were a giant infection it stumbled across. This is the nature of Graft vs Host Disease (GVHD).

In order to get the GVT we want, we have to accept there will be some GVHD.

Common symptoms of GVHD tend to appear first in the more sensitive parts of the body. This would be the upper and lower GI tract, the eyes, and the skin.

GVHD is managed by three major drugs. MMF (mycophenolate mofetil or CellCept), tacrolimus or cyclosporine, and steroids. These three drugs fall into the category of anti-rejection drugs and their purpose is to prevent the host from rejecting the graft, and prevent the graft from attacking the host.

Yes, I have GVHD and it's manageable. Will it remain so? We don't know, because while 100% of the cells in my marrow are the donors, this is not the case in my bloodstream yet. It takes some time for my cells to die of old age and be replaced with the donor cells. It's entirely possible that, as the quantity of graft cells increases and the host cells decrease, the attack on my body will increase.

On the other hand, the ultimate objective is to use the anti-rejection drugs to buy enough time for the graft and the host to learn to live with one another (immune tolerance). There are LOTS of mini-allo patients who have been alive for years after their transplant. Eventually, the GVHD seems to get easier.