Clinical Trial Details
— Status: Enrolling by invitation
Administrative data
| NCT number |
NCT05238155 |
| Other study ID # |
041.PHA.2021.D |
| Secondary ID |
|
| Status |
Enrolling by invitation |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
October 19, 2021 |
| Est. completion date |
October 19, 2024 |
Study information
| Verified date |
March 2024 |
| Source |
Methodist Health System |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Graft-versus-host disease (GVHD) is a life-threatening complication of transplantation. It
occurs when the donor graft contains immunologically competent T-cells that recognize the
recipient as foreign.
Description:
GVHD is commonly observed in allogeneic hematopoietic stem cell transplantation recipients
but can also occur in recipients of solid organ transplantation , with the first case of GVHD
in a SOT recipient described in 1984. While the exact incidence of SOT-associated GVHD has
not been determined due to challenges with identifying and diagnosing GVHD in SOT recipients,
the reported incidence of GVHD following orthotopic liver transplantation ranges from
0.1%-2%, one of the highest rates among SOT recipients. Although it occurs very rarely with
SOT, GVHD leads to poor patient outcomes, with a mortality rate exceeding 75%. Risk factors
for SOT-associated GVHD have not been clearly defined, but possible risk factors have been
identified, such as recipient age ≥65 years, donor-recipient age difference of ≥40 years,
degree of human leukocyte antigen matching, level of immunosuppression, and history of
hepatocellular carcinoma.
There are currently no guideline recommendations for treatment or prevention of GVHD in SOT
patients. Current treatment strategies include a combination of increasing immunosuppression,
decreasing immunosuppression, or changing immunosuppression agents, making it difficult to
definitively determine an effective treatment approach.
However, it has been postulated that decreasing immunosuppression may allow the transplant
recipient's native immune system to reject donor lymphocytes and would therefore act
protectively against GVHD in these patients. Since there is currently no clinical outcomes
data to support this and because GVHD is a very rare occurrence in this population, reducing
immunosuppression as a preventative measure for GVHD is not a commonplace practice amongst
SOT centers.
The Liver Institute at Methodist Dallas Medical Center (MDMC) is a comprehensive,
multidisciplinary disease management center. One of its services is OLT with life-long
outpatient follow-up. When OLT recipients are discharged following transplantation, they are
typically prescribed a triple immunosuppression maintenance regimen, consisting of a
calcineurin inhibitor, an antimetabolite, and a corticosteroid. Over the last several years,
there have been changes made to this protocol, and the current protocol now suggests
consideration for the omission of the antimetabolite at discharge if there is a
donor-recipient age discrepancy (DAD) that is greater than 30 years. This change was made
with the intention to reduce the risk of GVHD, given that a greater disparity in
donor-recipient age may put these patients at a higher risk for GVHD.
Since this protocol implementation, the exact clinical implications of this reduction in
immunosuppression are still unclear. While this approach may reduce the incidence of GVHD,
omission of the antimetabolite in maintenance immunosuppression regimens puts these OLT
recipients at risk for rejection of their graft, which can also be a life-threatening
complication. Evaluation of the clinical outcomes related to this protocol change is
warranted in order to appropriately weigh the risks versus benefits of reducing
immunosuppression to prevent GVHD.
