Dr. David Miklos
Video: Dr. Miklos on Allogeneic Transplants & GVHD
Role of allogeneic bone marrow transplants
Some of your patients may have had an allogeneic transplant which is truly the immune therapy of some else’s immune system.
Maybe it’s a brother or sister or HLA-identical donor whose blood destroys the white cells, red cells, and regrows and reconstitutes the normal blood system.
In the process of getting rid of the patient’s blood system, it gets rid of the white cells, the lymphocytes, the b-cells, and the mantle cell lymphoma.
The allogeneic transplant is an immune therapy. I am an allogeneic transplanter and will talk about the major side effect of allogeneic transplant which is graft-versus-host disease (GVHD).
That means the immune response is not only attacking the blood and cancer, but it’s also sometimes attacking the skin, the gut, the liver, causing detrimental, inflammatory problems that can be the real bane of the existence of the patient.
The quality of life and the difficulties with organ involvements across the whole body has been seen. Those patients are really dependent on immune suppression.
So where’s the home run? The home run is, again, CAR T.
The original immunological therapy
Allogeneic transplant therapy is the original immunological therapy. As we take a histocompatible blood stem cell, we can call it the seed, and we bring some of the lymphocytes from that donor who is HLA-identical, put them into our patient’s body and let them regrow the immune system.
There’s a civil war that occurs between the North and the South, with the donor cells and the recipient’s cells.
We’re giving chemo to handicap the recipient’s lymphocytes, so we expect the North to win. We expect the donor’s cells are going to eliminate the recipient’s blood and immune cells.
It’s that elimination by an immune therapy, by the immune cells, by the lymphocytes, that are going to eliminate the red cells, white cells, platelets.
If you have myelogenous leukemia, that’s the therapy. If you have lymphoblastic leukemia, that’s the therapy. If you have aplastic anemia, you just need to grow blood, that’s the therapy. It’s one therapy for all.
But the problem is the donor’s immune cells may attack normal tissues in the body: the skin, gut, liver especially. That is a problem called graft-versus-host disease (GVHD).
That’s the North against the South, but now we’re hitting the central parts of the body. That detrimental immune response needs to be stopped because left alone, the immune response is very damaging.
It can cause liver failure, it can cause the GI/bowel to have profound diarrhea and infection, all kinds of problems.