Graft versus host disease (GVHD) used to present such a risk to transplant patients, an estimated 10-15% of patients would develop a fatal case of it. However, thanks to new treatments and approaches to transplant, the risk of death is down to about 0.1%, says Shernan Holtan, MD, Chief of Blood and Bone Marrow Transplantation at Roswell Park Comprehensive Cancer Center.
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Hi, I'm Shanan Holton, Chief of Blood and Marrow Transplant at Roswell Park Comprehensive Cancer Center. One of the biggest concerns historically has been a complication called graft versus host disease. This is where the donor's immune system attacks the patient. It used to be that somewhere around 10 to 15% of our patients would die of graft versus host disease after a transplant that risk today with newer technologies in terms of prevention and treatment, take the risk of death due to graft versus host disease down to less than 0.1%. It's a big difference what changed. Well, the main thing is prophylaxis. I was lucky to have a front row seat to some of the clinical trials where we saw that a treatment called post transplant cyclophosphamide. Combined with other immunomodulators drastically reduced the risk of graft versus host disease, both acute and chronic forms of it so much so that now HL A match is maybe not even our highest priority for finding a donor anymore. This effective graft versus host disease prophylaxis means that about 99% of patients will have a suitable donor and we can have excellent outcomes even without a perfect match. Another concern was just generalized toxicities of the conditioning chemotherapy, sometimes radiation and the toll that could take on the body. We used to basically only be able to take the youngest and healthiest to transplant while we still want people to be in good general condition. Currently, our upper age limit for transplants is 85 that must be higher than what you expected to hear. But it's true because of our better supportive care, our less toxic conditioning regimens and the support that we provide here at Roswell Park Corts of Cancer Center, in terms of diet, in terms of exercise, um excellent teams to help with antibiotics and other toxicities. We can really be pretty aggressive in giving people that chance at cure. Whereas before, it was just felt to be an unattainable goal and maybe patients weren't even referred in the first place. Brian Betts and I have collaborated on some research where we've discovered that a protein called CD 83 is expressed on top of the cells that cause both acute and chronic graft versus host disease. So it's on T cells during acute graft versus host disease and on B cells during chronic graft versus host disease. This means we have a brand new target to help mitigate those risks even further. So, if someone might develop graft versus host disease, despite our prophylaxis, we have this new target that we can go after with our research. Now, even better than that. We've discovered that this protein is expressed on top of leukemia cells. So now we not only have the opportunity to prevent and treat graft versus host disease, but also hopefully prevent and treat relapse with the very same target. This is very unique. There used to be a trade off. If we reduce GB HD risk, we increase the risk of relapse. Now we have research where we can target the exact same molecule and hopefully mitigate both gvhd and relapse risks really making transplant, very successful betts. And I have been working on this project for several years, but I'm excited to say that this spring, we should be able to open the first car T cell therapy for AM L targeting CD 83. So our first step is to make sure that this therapy is safe and effective in the context of AM L. If we're able to show that, then we can go into additional diseases such as graft versus host disease targeting CD 83 we hope to see that there's little time toxicity because this is not expressed on normal cells otherwise. And so we're really excited to take that first step in AM L and see where targeting CD 83 goes with all of the changes in the field of transplantation and cellular therapy. I encourage you to refer your patients to us. It used to be that we were seeing only a fraction of patients with a new diagnosis of acute leukemia or other serious hematologic malignancies, out of concern of toxicities of the transplant. It is a different era. I can't emphasize this enough. Through some of our research, we've been able to mitigate some of the most life threatening toxicities of transplant. It is much safer today than it used to be. So, we're happy to see them and evaluate them for transplant. And if their disease isn't under control, potentially we'll have a car t therapy for them as well.
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