The newest member of the cellular therapy research team and Chief of the Bone Marrow and Transplantation Service at Roswell Park Comprehensive Cancer Center is eager to continue advancing the field.
Shernan Holtan, MD, joined Roswell Park from the University of Minnesota, where her initial research focused on finding ways to treat, and prevent, graft vs host disease.
“I watched too many patients die from graft versus host disease and really dedicated my career to solving that," she says. "I've developed a number of clinical trials through translational studies that have helped move the needle,” something that hadn’t happened much for nearly 40 years.
Now she can shift her focus to other areas of improving patient care and quality of life during treatment. “Can we get away from just immunosuppression and can we actually use medications that improve immune function? Can we incorporate medications that actually have direct anti-leukemia effects that can target relapse as well as graft vs host disease with the same drug? That’s what we’re testing now. We have to keep the health and quality of life of patients in mind.”
I'm Shanan Holton, professor of Medicine and Chief of the Blood and marrow transplant Service at Roswell Park Comprehensive Cancer Center. I went to medical school at the University of Nebraska in Omaha Nebraska. I chose blood marrow transplantation sort of by accident. I found a lot of specialties that I liked in medical school, infectious diseases, rheumatology, oncology, hematology, intensive care. I found out during an elective rotation that you could actually have all of those specialties in one and that's blood marrow transplantation. That was the late nineties, early two thousands. And I've been in love with the field ever since my focus in research has been on reducing toxicities of allogeneic transplantation for about the past 20 years. I've been focusing on this in my training. I've watched too many patients die from graft versus host disease and really dedicated my career to solving that I've developed a number of clinical trials through translational studies that have helped to move the needle. The more exciting research honestly is in prevention. I've been able to write and conduct a couple of clinical trials in collaboration with others to completely transform the landscape of graft versus host disease, prophylaxis the last time that our field made a change in GVHD prophylaxis was 1986. But I'm happy to report that that has changed as of 2023 with two clinical trials that we've conducted using a prophylaxis regimen including post transplant cyclophosphamide. So, when I was in training and in the early years of transplantation, around 50% of people would develop graft versus host disease. And now with the use of post transplant cyclophosphamide, the safety has improved so much. It's only now five, maybe 10% of people developing significant graft versus host disease. That's both acute and chronic gvhd. So I've been, you know, excited about the treatments I've been developing. But honestly, the prevention is where it's at now that we have so little severe graft versus host disease, we can focus on some of the bigger issues which remain such as relapse. These new approaches are available at Roswell Park now. Really, it's transforming care all around the world. What we're doing now though is we're taking it a step further variations on the theme of post transplant cyclophosphamide. What are other partners that we can use? Can we get away from just immunosuppression? And can we actually use medications that improve immune function? Can we operate medications that actually have direct anti leukemia effects so that we can target relapse as well as graft versus host disease with literally the same drug? That's what we're testing now. But beyond that, we're looking at ways to help patients through the procedure itself that don't necessarily involve drugs or radiation chemotherapy. We need to pay better attention to nutrition and exercise. If patients can't eat, if they can't walk, we haven't really done our jobs right. We have to keep the health and the quality of life of patients in mind. How will we improve patient care at Roswell Park? We're working on medical innovation, but we also need to pay attention to supportive care. Most patients are told that when they go in for an allergenic transplant, they need to be monitored very closely for 100 days. They usually need to stay off work for about six months, maybe a year and they have to have a full time caregiver throughout that 1st 100 days, maybe longer. If there are complications, we wanna change that. So we're gonna leverage our research, our medical innovations, but also our better supportive care to substantially reduce the burdens and that will really change the field here and around the world. This approach where we want to reduce the time to recovery by 50% is only happening here at Roswell Park. Our whole field has been transformed in the past few years. What I'm hoping is that we'll be seeing as I had mentioned, improved burdens but but fewer drugs. So right now when we're taking patients through a transplant, they might be on 30 medications or more. What I'm really excited to see if we can streamline this process and have a minimum of medications with a minimum of side effects. So what could that be, that might be cell therapies to reduce relapse? And in fact that that is really our highest priority. Now, can we use cells instead of pills to reduce the risk of relapse? Can we use cells instead of pills or IV medications to reduce the risk of infection? Can we help the immune system function better? So that infection risk is less of an issue? And then can we address nutrition, strength training, exercise, quality of life, so that patients are feeling healthy and resilient without us having to give so many prescriptions for a multitude of G I and other side effects. I'm really excited to see how we simplify the field and make treatments better using our novel therapies. The team that has been assembled at Roswell Park is the team that will be bringing these new therapies into the future with Dr Betts, Doctor Dawla, Doctor Brechin and others. We really have a unique vision and we have all of the facilities that we need. We have an incredible team surrounding us that will be able to make these transformations that I've been discussing. This is the right place. We have all of the ingredients, we have the energy, we have the vision. I can't wait to see how the field has been transformed by our work in the next couple of years.
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