Bone Marrow Transplant (BMT) Program Research
The vision of the U-M Bone Marrow Transplant Program is to create a future where transplantation is safer, more effective, and eventually, less common. Our program is patient-focused and research-driven. We know that in order to bring our patients the very latest advances in care, we must learn as much as we can, as quickly as we can, and that is only possible through a robust program of basic, clinical and translational research:
U-M investigators are conducting numerous laboratory studies of the biology and immunology of blood and marrow stem cells, to better understand how these cells behave at a molecular level, and how they respond to transplantation.
Our clinical research is dedicated largely to finding new and improved strategies to prevent relapse and complications after BMT. In particular, we are focused on reducing the incidence and severity of the common and dangerous complication graft-vs.-host disease (GVHD). U-M faculty members are recognized nationally and internationally for their expertise in treating chronic GVHD through our groundbreaking multidisciplinary chronic GVHD clinic and survivorship programs - programs that evolved from our research findings.
This area of study involves projects that rapidly move scientific findings from the laboratory into the clinical setting, where they can directly impact patients. Our translational studies are focused on developing new strategies to make allogeneic BMT safer and more effective.
Patients: Our Partners in ResearchU-M investigators and clinicians have made major contributions to science's understanding of how blood and marrow transplants combat cancers like leukemia and lymphoma, and how to lessen the toxicities that can occur with transplants. For the success of our research effort, we have our patients to thank. They support our vision through a very high level of participation in our research studies. Today, nearly half of our patients are enrolled in one of our therapeutic clinical trials, and virtually every patient is participating in a long-term follow up study or an observational trial.
Numerous ongoing clinical trials are now open at the University of Michigan for bone marrow transplant patients, including studies initiated by our own faculty, studies we participate in along with other leading academic institutions and studies sponsored by the pharmaceutical industry. Learn more about available clinical trials related to BMT, by visiting the Bone Marrow Transplant clinical studies web page.
Recent BMT Research Highlights:The biology of allogeneic BMT
Researchers at the Cancer Center are working to understand the fundamental biology of donor and patient cells involved in allogeneic BMT, to make the procedure even safer and more effective. Their goal is to reduce the impact of the most serious consequence of BMT, GVHD while at the same time leveraging one of the most positive byproducts of BMT, graft-vs.-leukemia effect (GVL). These studies fall into three categories:
- understanding the interaction between the cells that suppress GVHD, leading to the development of new drug therapies that can be rapidly translated into the clinic,
- learning more about the various proteins that produce antigens (substances that trigger the immune system to produce antibodies to neutralize foreign objects such as bacteria or viruses) with the potential to enhance GVL, and
- exploring the role of gene regulation and changes in specific proteins, and how these mechanisms impact the production of antigens after allogeneic BMT.
Developing lab tests to predict response to allogeneic BMT and to diagnose GVHD
Currently, there are no established biological indicators to forecast how well patients will respond to allogeneic BMT. U-M researchers have made major strides in this area, starting with the identification of eight potential biomarkers that may help determine which patients will develop GVHD. It is hoped that these ongoing lab studies will eventually lead to reliable tests to determine in advance a patient's GVHD risk.
A "reverse-translational" study of extracorporeal photopheresis
In one of many efforts to develop better strategies to fight GVHD, our BMT investigators are conducting a unique "reverse-translational" study - taking an observation made with patients in our clinic into the lab to find a molecular explanation for it. They are studying extracorporeal photopheresis (ECP), a therapeutic regimen that separates a patient's white blood cells from the bloodstream, treats the cells with chemotherapy and radiation, and returns them to the body. ECP has been used to treat GVHD, and is known to work in part by contributing to the death of the donor T-cells that attack the patient's immune system. But very little is known about the longer term impact of ECP. U-M investigators have developed a model for testing the ECP procedure in the lab, and based on what they have learned, have launched an innovative clinical trial to evaluate the effectiveness of ECP in reducing the severity of GVHD and steroid dependence in patients who receive high-risk grafts.
Developing a T-Cell vaccination
Scientists know that there is a trade-off between graft-vs.-leukemia effect (GVL, also known as graft-vs.-tumor effect or GVT), a beneficial consequence of allogeneic BMT, and the toxicity of GVHD. They also know that the donor's T-cells (T-lymphocytes) are responsible for the development of GVHD. But they know little about how T-cells might be targeted to relieve GVHD. Initial studies are underway at U-M to see if it is possible to exploit the abnormal development of T-cells to knock out GVHD without losing the protective effects of GVL.
Building a BMT patient database
U-M researchers have developed a comprehensive database containing information from every U-M Cancer Center patient who has received a transplant since 2000, and are in the process of expanding it to include patients transplanted since 1995. Currently, the database contains clinical data on more than 2,000 BMT patients, including some 850 recipients of allogeneic grafts. In total, more than 9,000 clinical research samples have been collected from patients and annotated with information about the patient, the donor, the stem cell source, the conditioning regimen, response to treatment over time, the incidence of complications such as GVHD and more. The establishment of such an extensive database has already made it possible to conduct several landmark biomarker studies and to develop clinical trials based on the findings of those studies.
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