Mortimer M. Bortin Lecture

The Mortimer M. Bortin Lecture commemorates the Founding Scientific Director of the International Bone Marrow Transplant Registry, now the CIBMTR. Dr. Bortin’s foresight and dedication were critical to the development of the CIBMTR as a global resource for HCT research.

In Search of the Holy Grail: Uncoupling GVL and GVH – Déjà Vu All Over Again?
Friday, February 23 | 5:10 PM - 5:40 PM CT

I am honored to be given the opportunity to speak at this year’s Mortimer M. Bortin Lecture. Over 30 years ago, Dr. Bortin was the senior author on one of the most recognized manuscripts in field of transplantation, the CIBMTR’s registry analysis linking the development of chronic GVH to a reduction in leukemia relapse. Generations of transplant investigators since have sought strategies to decouple GVH and GVL. Indeed, the very first Bortin lecture, delivered by Robert Truitt in 2004, dealt with this very topic. In some respects, we have succeeded, in part, in the context of acute leukemia. Trials of post-transplant cyclophosphamide, anti T lymphocyte globulin (ATLG), and even ex vivo T cell depletion have all demonstrated that the rates of chronic GVHD can be substantially reduced without compromising leukemia control. While we have perhaps reduced leukemia relapse a bit by recognizing the value of conditioning intensity and post-transplant maintenance therapy, we have made little to no progress in understanding and harnessing GVL activity itself. We know GVL exists as evidenced by the activity of donor lymphocyte infusions (DLI) for post-transplant relapse. particularly for relapsed CML. However, we have yet to identify what specific cell or cells in the graft mediate GVL, nor the targets (e.g., specific tumor associated antigens or minor histocompatibility antigens) against which those cells are directed. As such, we have been stymied in our attempts to rationally design approaches with sufficient precision that could reliably and safely promote alloreactivity against tumor targets. Yet, with the development of new technologies to identify both GVL effectors and antigens, we may be on the precipice of succeeding in this quest so that 20 years from now at the Bortin lecture we are not wrestling with the same issues as had Dr. Truitt two decades ago.

In the video below, Dr. Robert Soiffer introduces his lecture and welcomes you to the 2024 Tandem Meetings. Click on the video to watch. 

About Dr. Soiffer
Robert J. Soiffer, MD, is Chief of the Division of Hematologic Malignancies, Chair of the Executive Committee for Clinical Programs, Vice Chair of the Department of Medical Oncology at Dana-Farber Cancer Institute, and Worthington and Margaret Collette Professor of Medicine in the Field of Hematologic Oncology, Harvard Medical School.

Dr. Soiffer conducts research focused on modulation of immune responses in the setting of hematopoietic stem cell transplantation. The ultimate goal for his clinical trials and research grants is to optimize graft versus leukemia activity without inducing graft versus host disease. Dr. Soiffer is a former President of the American Society for Blood and Marrow Transplantation and Immediate Past-Chair of the Advisory Board for the Center for International Blood and Marrow Transplant Research. He serves on the Executive Steering Committees for Blood and Marrow Transplant Clinical Trials Network. Dr. Soiffer is a member of the Board of Directors for the National Marrow Donor Program and served as Chair of the Board from 2020 until 2022. Dr. Soiffer serves on the National Cancer Institute's Leukemia Steering Committee.

Dr. Soiffer has co-authored more than 400 peer-reviewed manuscripts and numerous book chapters, review articles, editorials, and monographs. Dr. Soiffer has received several honors and awards including the Casty Family Achievement in Mentoring Award from Dana-Farber, the Brian O’Dell Memorial Research Award from the Leukemia and Lymphoma Society, the George Thorn Award for Outstanding Teaching at Brigham and Women’s Hospital, and the Claire W. and Richard P. Morse Research Award.

E. Donnall Thomas Lecture

The E. Donnall Thomas Lecture recognizes an eminent physician or scientist, either a clinician or an investigator, who has contributed meritoriously to the advancement of knowledge in blood and marrow transplantation.

Is Transplantation Only Copacetic? A Personal Tale of Mentors, Trainees and Colleagues
Friday, February 23 | 5:50 PM - 6:20 PM CT

My research focuses on fundamental and translational aspects of leukemia, lymphoma and stem cell biology. These studies include identification of genetic abnormalities in human leukemias, understanding processes involving stem cell and leukemia cell trafficking and clinical and translational programs in both leukemia/MDS, lymphoma/myeloma and stem cell transplantation. I have also focused on the role of stem cell transplantation and novel targeted interventions including cellular therapies to alter the natural history of AML and other hematological malignancies. These include targeting key elements of the hematopoietic niche for optimal stem cell mobilization and chemo-sensitization, mitigating GvHD in T replete transplants, understanding the genomic alterations in de novo and relapsed AML especially after allogeneic stem cell transplantation and developing and testing in the clinic novel therapeutics and immuno-therapeutics for the treatment of AML before and after stem cell transplantation. This work has resulted in the FDA approval of two CXCR4 inhibitors (plerixafor in 2008 and motixafortide in 2023) for patients undergoing autologous transplantation for myeloma and lymphoma and the first drug approved by the FDA for the treatment of steroid refractory acute GvHD (ruxolitinib in 2019).

My lab is developing chimeric antigen receptor T cell (CAR-T) therapies for the treatment of AML, multiple myeloma, T ALL and T/B-NHLs. To minimize the on-target/off-tumor toxicities of CAR-T, we engineer epitopes on CAR-T and/or the donor stem cells used in transplantation to provide selective resistance to CAR-T therapies. We couple these efforts to generate novel CAR-T in multiple malignancies with genome-wide discovery efforts to identify novel targets in hematoloic malignancies for immunotherapy. Finally, my laboratory is interested in developing novel conditioning regimens for both stem cell transplantation and gene therapy that are devoid of chemotherapy, radiation and even antibody drug conjugates. I am a previous recipient of the ASH Mentor Award in Clinical Investigation in 2014 and have been voted as “Teacher of the Year” on four different occasions in three different institutions (UCLA, U of Rochester and Wash U) consistent with my commitment to mentoring.

My lecture will focus on examples of progress in the fields of transplantation and cellular therapy, with a focus on our own limited contributions while acknowledging those others who have shaped my efforts and that of the field in general.

In the video below, Dr. John DiPersio introduces his lecture and welcomes you to the 2024 Tandem Meetings. Click on the video to watch. 

About Dr. DiPersio
Dr. John F. DiPersio is a Professor of Medicine and Pathology & Immunology, Director, Center for Gene and Cellular Immunotherapy at Washington University School of Medicine in St. Louis and the Virginia E. and Sam J. Golman Professor of Medicine.

His research focuses on mechanistic and translational aspects of leukemia and stem cell biology. He has played a key role in the clinical development of plerixafor as a mobilizing agent for stem cell transplantation. His recent studies have focused on the development of novel methods of targeting the hematopoietic niche through the development of highly active small molecule inhibitors of CXCR4 and VLA-4, and agonists of CXCR2, for both stem cell mobilization and chemosensitization. He was the first to implicate the role of JAK1/2 signaling in GvHD pathogenesis which led to FDA approval of Ruxolitinib for the treatment of steroid refractory acute GvHD. His recent studies have uncovered the mechanisms by which JAK inhibitors alter T cell biology, and have led to the identification of ‘best-in-class” JAK inhibitors for the prevention and treatment of GvHD in humans.

DiPersio has played a key leadership role in the team-science work at Washington University that has defined the genetic and epigenetic factors that contribute to clonal evolution and relapse in AML. His group was the first to use whole genome sequencing to define clonal evolution at relapse resulting from the expansion of very small genetically defined AML subclones. Recently, this group showed that epigenetic downregulation of HLA Class II antigens on AML blasts is associated with immune escape, often leading to relapse after allogeneic transplantation. Together, these studies have changed our understanding of AML relapse after chemotherapy and/or transplantation.

His group has recently developed a novel conditioning regimen for successfully engrafting donor cells across major allogeneic barriers, using chemotherapy- and radiation-free conditioning regimens which may significantly influence how patients are prepared for gene therapy for inherited diseases, such as sickle cell anemia. Finally, his lab has developed the first off-the-shelf, fratricide-resistant CAR-T cells for the treatment of patients with relapsed CD7+ T-ALL and have found ways to enhance the expansion, persistence and anti-tumor efficacy of CAR-T cells for multiple cancers using analogues of IL-7 and IL-15.

DiPersio is an internationally recognized leader in hematopoietic stem cell transplantation and acute leukemia. He has served in leadership roles for the American Society of Hematology (ASH), multiple NIH, CIRM, LLS, and CPRIT Study Sections, and has served on NCI’s Board of Scientific Counselors. He is an elected member of ASCI and AAP, and past president of the American Society of Transplantation and Cellular Therapy (2019). He has received the AACR Joseph H. Burchenal Memorial Award for Outstanding Achievement in Clinical Cancer Research in 2014, the ASH Mentor Award for Clinical Investigation in 2014, the 2022 American Italian Cancer Foundation Prize for Scientific Excellence in Medicine, 2022 American College of Physicians Harriet P. Dustan Award for Science as Related to Medicine and an NCI R35 Outstanding Investigator Award in 2017. His work has resulted in more than 450 publications, more than 20 patents, and the co-founding of two companies (Magenta Therapeutics, Cambridge MA and WUGEN, St Louis, MO).

Dr. DiPersio was the Chief of the Division of Oncology and Deputy Director of the NCI-CCC Siteman Cancer Center at Washington University School of Medicine from 1994-2022.