Dr. Steven Pavletic in the NIH Clinical Center Atrium, his favorite place to have many brainstorming conversations that took place over the course of his career at NCI. This photo was taken on February 6, 2025, the day he announced his retirement.
Steven Z. Pavletic, M.D., Ph.D., is a renowned expert in chronic graft-versus-host disease (cGVHD), a serious late complication that can occur after allogeneic hematopoietic stem cell transplantation (HSCT). He has led national and international efforts to develop consensus guidelines for cGVHD clinical trials. After serving at the NCI for over 20 years, he is now announcing his retirement.
Pavletic received his M.D. from the University of Zagreb School of Medicine in Croatia in 1979. In 1992, he completed a clinical fellowship in bone marrow transplantation at the Fred Hutchinson Cancer Research Center and University of Washington Medical School in Seattle, WA. He completed his internal medicine residency and a hematology and oncology fellowship at the University of Nebraska Medical Center (UNMC) in Omaha, Nebraska. Pavletic then served as the Director of the Allogeneic Stem Cell Transplantation Program at UNMC for several years.
When Pavletic was in Seattle and Nebraska, cGVHD was a relatively new complication that arose with the increase of treatments for blood cancers that involved allogeneic stem cell transplants. HSCT, the process of transplanting a healthy donor’s bone marrow into a patient to give them a new immune system, could eliminate cancers like leukemia and lymphoma. But researchers increasingly observed the cGVHD complication occurring a few years after transplantation: the immune system would begin to attack the recipient’s body, and patients could be disabled for life. At that time, there was little clinical research or trials because there were no tools to study or diagnose the disease.
In 2002, Dr. Pavletic received an appointment at the NCI CCR and an adjunct appointment at the National Institute for Arthritis and Musculoskeletal and Skin Diseases at NIH. Here, he assembled a team to develop methods to conduct clinical trials and measure response to cGVHD treatments over the next two decades. He later joined the Immune Deficiency Cellular Therapy Program as a senior clinician, in which he also directs the intramural NIH cGVHD study group and the NIH Myeloid Malignancies Clinical Program, which is investigating myelodysplastic syndromes (MDS) and secondary or therapy-related acute myelogenous leukemia (AML).
In 2006, Pavletic received the NCI Director's Individual Merit Award for his achievements in developing national and international consensus guidelines for clinical trials in cGVHD. He has also received the Clinical Research Forum “Top 10 Research Achievement Award,” the CCR Myeloid Malignancy Program Group Special Act Award, and the Lukas D. Wartman Award for his work. He was a U.S. Department of State Embassy Science Fellow in Zagreb, Croatia, and is a corresponding member of the Croatian Academy of Sciences and Arts.
“To say that Dr. Pavletic is a giant in his field is not an exaggeration,” says Sung-Yun Pai, M.D., Chief of the Immune Deficiency Cellular Therapy Program. “As I got to know him as a colleague and friend, I grew to appreciate not only his incisive thinking, organization, productivity and infectious enthusiasm, but also his exceptional people skills and deep humanity. For someone so famous in the field of cGVHD and transplantation, he is humble and approachable, and I will miss the daily contact with him that I have enjoyed since coming to CCR in 2020.”
In the Q&A that follows, Pavletic discusses some reflections on his career and advice for the next generation of scientists.
Which scientific achievement(s) are you most proud of?
Defining, describing, and, for the most part, conquering chronic graft-versus-host disease (cGVHD) is certainly an achievement I proudly share with all my colleagues in this field. cGVHD is essentially a manmade complication: the consequence of very successful cancer immunotherapy for treating leukemia and lymphoma. When we first started examining the disease, it affected more than 50% of survivors that had received allogeneic hematopoietic stem cell transplantation (HSCT). Today, we are starting to consider that this whole disease may be eliminated as a significant problem in the near future. It took us about 20 years to get to that. And there's still much work to be done, but it's been extraordinarily gratifying.
Another accomplishment I’m quite proud of is the establishment of the Myeloid Malignancies Research Program at CCR, with the National Heart, Lung, and Blood Institute and the Clinical Center. We started this in 2019, and we were able to put all the intramural research resources together and organize a team to address how we can better treat some of the most recalcitrant and aggressive types of myeloid leukemias. This group has gone beyond any expectations, and it’s now really up and going.
How did the intramural environment of CCR and NIH facilitate your research, and what is the future of cGVHD?
Because cGVHD was such a new challenge in the early 2000s, we were essentially trying to treat a rare multiorgan disease, and such work can be resource demanding. It was also quite high urgency, almost to an epidemic proportion among HSCT patients, due to the rising prominence of successful bone marrow transplants for patients with blood cancers. So, we were facing this situation where we needed to mobilize resources in a relatively short time around a very complex problem. We needed to understand all the interconnected ways in which the disease was affecting the body — the skin, eyes, mouth, joints, lungs, liver, immune system, brain, you name it — and to find a solution quickly.
In this way, I would say cGVHD is a prime example of a problem that CCR was designed to address. The clinicians could collect information on the biological and clinical presentations of the disease, and laboratory scientists in the same place could analyze samples quickly to develop new therapeutic approaches. We were able to undertake almost all the work to define the disease, develop tools and standards for diagnosis and therapeutic response measures, and ultimately produce new treatments.
Over the last eight years, there have been four FDA drug approvals to treat refractory cGVHD, all of which used the NIH response criteria that we defined and the pathways we created for conducting clinical trials. The FDA approval of belumosudil for cGVHD in 2021 was led by CCR team members.
We organized three NIH consensus conferences between 2005 and 2020, out of which we published 19 papers, some of which are the most referenced papers in transplant literature. And our team, brought together with the resources CCR provides, was the force that was propelling this international research activity.
The next phase is creating more effective prevention methods. And we have made huge progress in bringing awareness and providing effective treatments. There’s still room for improvement, but we hope cGVHD won’t be a major problem for HSCT patients in the future.
Do you have any advice for future generations of cancer researchers?
First, you should strive to get the best possible education and training you can get in life, and once you get to that point, then do something meaningful with it. Something that's going to make a difference, you know?
Second, always persevere, because challenges are everywhere, and they’re a normal part of life. There have never been times without challenges of some kind, but you should never give up. Move forward and focus on what you can do to make a difference in a big-picture way.
What are you looking forward to most in your retirement?
Probably freedom. I’ve had plenty of freedom throughout my academic and research career to do what I wanted, but now I’m looking forward to having the luxury of more free time. I definitely plan to stay engaged in academic medicine and continue to serve my colleagues and other faculty in an advisory manner. But I'm certainly looking forward to doing some traveling, visiting family in Europe, on my own schedule. It’s been the opportunity of a lifetime to work at NIH, and I am fortunate to have been a part of something that really made a difference, and I think it’s okay to move on and enjoy this new phase in my life.
Dr. Steven Pavletic will retire from CCR on April 30, 2025.