corey cutler, md MPH FRCP(C)

Research Goal: Eliminating Graft-vs-Host Disease in Stem Cell Transplantation

The use of stem cell transplantation (also known as bone marrow transplantation) as a therapy for blood-derived cancers (such as the leukemias and lymphomas) has grown steadily over the last 20 years. During this time, there have been tremendous advances in the medical technology of transplantation that have improved outcomes, however, this procedure remains as one of the riskiest procedures in modern medicine, and substantial room for improvement still exists.

I study one of the most common and devastating complications of stem cell transplantation, a condition known as Graft-versus-Host Disease (GVHD). When we transplant stem cells, the immune system of the recipient is replaced by that of the donor. GVHD occurs when the transplanted immune system (the Graft), recognizes tissues of the recipient (the Host), as ‘foreign’ or non-self, and tries to reject them (the Disease). An analogous process occurs after kidney, liver or heart transplantation, where the condition is simply known as ‘rejection’, (the recipient’s immune system rejects the transplanted organ). In stem cell transplantation, the transplanted immune system finds itself in a new environment and tries to reject everything around it. The ensuing results can be devastating.

GVHD can be divided into two broad categories, that which occurs early after transplantation (Acute GVHD), and that which occurs later in time (Chronic GVHD). All stem cell transplant recipients receive a combination of medications to prevent Acute GVHD – these medications are termed immunosuppressants, since they suppress the immune system. However, despite these medications, Acute GVHD occurs in 35% - 50% of transplant recipients. Thus, there is a desperate need for better options in GVHD prevention.

Chronic GVHD occurs in over half of all long-term transplant survivors. There are no accepted approaches to prevent chronic GVHD, and once established, chronic GVHD is difficult to treat, and can require years of immunosuppressive therapy.

Over the past 5 years, I have been examining the potential of sirolimus, a novel immunosuppressant not previously tested in stem cell transplantation. At the Dana-Farber Cancer Institute, my colleagues and I have now completed three clinical studies in which sirolimus was been incorporated into our Acute GVHD prevention regimen. The results are quite promising. Across the four studies, patients displayed better GVHD control and have had improved long-term outcomes. As a result of these preliminary trials, we have now embarked upon a national, randomized, trial to examine the role of this medication in GVHD prevention. I am the Principal Investigator of this trial, which will enroll over 300 transplant patients nation-wide, and if successful, will herald the first major change in GVHD prevention in over 20 years.

Similarly, we have several new and exciting approaches to the treatment and prevention of Chronic GVHD, and many of the trials in this field are at an earlier stage of development. With close collaboration with my laboratory colleagues, we have identified an entirely new approach to the biology of chronic GVHD and are testing new agents to prove our new theories.

I firmly believe that my research efforts one day will make a difference. I look forward to the time that GVHD can be referred to as a problem of the past, and hope that I can say that I helped contribute to this change.