Risk Factors for Graft-vs-Host Disease



Corey S. Cutler, MD, MPH, FRCPC: Zach, please share the risk factors for these 2 syndromes. Are they the same, or are they different? What are the most important things to try to modulate or change to prevent this from happening?

Zachariah DeFilipp, MD: There are a number of clinical risk factors that have been identified for acute and chronic graft-vs-host disease [GVHD]. For both syndromes, the most important risk factor is going to be HLA [human leukocyte antigen] matching. Patients who get transplants performed from HLA-mismatched donors have a higher risk for graft-vs-host disease. When thinking about acute graft-vs-host disease in addition to HLA matching, other clinical factors to consider are the intensity of the conditioning regimen and the use of total-body irradiation. Thinking about other factors related to the donor, transplants performed in male recipients from female donors have been shown to have a higher risk for graft-vs-host disease. With chronic graft-vs-host disease, some of the other clinical risk factors are the use of peripheral blood stem cells as a graft source, compared with bone marrow. Additionally, older patients and the development of previous acute graft-vs-host disease in their transplant course. The incidence—not necessarily the risk but the incidence—of GVHD after transplant is also influenced by the choice of GVHD prophylaxis.

Corey S. Cutler, MD, MPH, FRCPC: What is the standard of care for GVHD prevention, since this is a changing field?

Zachariah DeFilipp, MD: The standard of care at most transplant centers is to use a combination of immunosuppressive agents to help prevent the development of graft-vs-host disease. At many centers this consists of the combination of the inhibitor tacrolimus and methotrexate, which are what we use at MGH [Massachusetts General Hospital] for our fully matched transplants. Another popular combination is the combination of tacrolimus and the MTOR inhibitor sirolimus. For our HLA-mismatched transplants, there’s no agreed-upon approach to GVHD prophylaxis, but most centers consider some type of alternative regimen because of the higher risk of GVHD that we were discussing before. For some, this is through the addition of antithymocyte globulin, or ATG. Currently at MGH, we’ve been using post-transplant cyclophosphamide in this setting.

Transcript Edited for Clarity

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