Graft-versus-Host Disease

Leukemia and certain related conditions are often treated with radiation and chemotherapy to eliminate cancerous or diseased cells, but this process also severely compromises the native blood forming and immune system in the patient, leaving them susceptible to infection and other complications. To address this, a patient will often receive radiation and chemotherapy, followed by an allogeneic hematopoietic stem cell transplant (HSCT) or peripheral blood stem cell transplant.  Using these procedures, a patient's blood stem cells are replaced with a transplant of blood and immune forming stem cells, also referred to as hematopoietic stem cells, obtained from the bone marrow or peripheral blood of a healthy donor. Stem cell donors may be related or unrelated to the patient, but are matched according to tissue type in order to minimize the potential for graft-versus-host disease (GvHD), a common complication of such procedures where donor immune cells transplanted with the donor HSCT attack the tissue and organs of the patient. Following the transplant, the patient will often remain hospitalized in specialized units until successful engraftment provides a sufficiently functional immune system. 

According to the Center for International Blood and Marrow Transplant Research, there are approximately 25,000 allogeneic HSCTs performed annually globally, although this number is projected to increase due to the anticipated growth in incidence of hematologic malignancies associated with an aging population. While this treatment approach can be an effective medical therapy for these types of cancer, it is often associated with substantial tissue damage and side effects, such as GvHD.

GvHD is a frequent complication associated with allogeneic HSCT, affecting approximately half or more of transplant recipients, and advanced GvHD can be severely debilitating or even fatal. Several factors affect a patient's likelihood of having GvHD and GvHD severity, including the treatment protocol used, the degree of tissue match between donor and recipient (with lower GvHD rates and severity associated with related donors and better tissue matches), and the condition of the patient among other factors. In addition, higher GvHD rates are typically observed in patients receiving peripheral blood stem cell transplants, as compared to patients receiving bone marrow-derived stem cell transplants. Current treatment approaches involve the prophylactic use of agents such as methotrexate, cyclosporine, or tacrolimus, but these are also associated with various risks and side effects. Treatment of GvHD relies on the use of immunosuppressive agents such as corticosteroids (e.g., prednisone), but these may be transiently effective or ineffective in many patients, and even where effective, these treatments may have other side effects (e.g., infection, organ damage).