The Current Field of Graft Versus Host Disease - Episode 2

Differences Between Acute and Chronic GVHD and Risk Factors for GVHD

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.