The Current Field of Graft Versus Host Disease - Episode 2
Dr Zeiser outlines the differences between acute and chronic GVHD and also reviews factors that put transplant patients at greater risk of GVHD.
Robert Zeiser, MD: Acute graft-vs-host disease [GVHD] primarily manifests as a maculopapular rash, weight loss, diarrhea, and hepatitis that typically occurs within the first 100 days after transplantations. It’s a clinical syndrome characterized by the kinetics of onset and the symptoms rather than by time point. There’s also acute graft-vs-host disease beyond day 100 and even at late time points, when patients receive donor lymphocyte infusions, which are donor T cells. They can also develop acute graft-vs-host disease several years after transplant. In contrast with acute graft-vs-host disease, the primary manifestations of chronic graft-vs-host disease are skin involvement resembling lichen planus, cutaneous scleroderma, dry or mucosa iterations, sclerosis of the intestinal tract, and elevated bilirubin levels and bronchiolitis obliterans-like syndromes. The disease is much slower compared with acute graft-vs-host disease. The symptoms are different, and virtually all organs can be affected by chronic graft-vs-host disease.
Factors known to increase a patient’s risk to develop acute graft-vs-host disease include the donor type, and the question is if it’s a matched related donor, matched unrelated donor, or a haploidentical donor, and the degree of mismatching increasing the risk of graft-vs-host disease. The stem cell source is peripheral blood stem cells, donor derived, or umbilical cord blood transplants. Peripheral blood-derived stem cell transplants are connected to the highest risk for acute graft-vs-host disease.
Sex mismatch is also a risk factor. If the donor is a woman and the recipient is a man, there’s a risk that the T cells recognize the Y chromosome of the recipient as foreign, and that can induce graft-vs-host disease. The age of the donor and recipient are important for the risk, because a higher age increases the risk for graft-vs-host disease. Conditioning regimen intensity, high-risk GVHD is connected to myeloablative intensive conditioning while reduced-intensity conditioning is connected to a lower risk for acute graft-vs-host disease.
Also, the underlying malignancies and prior treatment are connected to the risk of graft-vs-host disease. T-cell depletion and antithymocyte globulin, alemtuzumab, or post-transplant cyclophosphamide reduces the risk of acute graft-vs-host disease and the infection history of the patient, particularly CMV [cytomegalovirus] and EBV [Epstein-Barr virus]. Those are connected with more infections and higher CMV in the recipient but not in the donor, which increases the risk for reactivation and for graft-vs-host disease.
Transcript edited for clarity.