New treatment for GVHD could benefit some COVID-19 patients

Image credit – UC Davis Health

CANCER DIGEST – Dec. 26, 2021 – New research shows promise of significantly limiting one of the most severe complications of stem cell transplants for cancer, called graft vs host disease.

In a mouse study led by researchers at the University of California Davis Health and published in the Dec. 16, 2021 journal Blood, the researchers found that blocking two immune system substances can significantly reduce graft vs. host disease.

Graft vs Host Disease (GVHD) has been one of the most significant complications of bone marrow and stem cell transplants and is one of the biggest challenges in managing transplant therapies for blood cancers and other diseases. Some inflammation from GVHD is a good sign that the donor cells are working to attack the cancer, too much inflammation is caused by the grafted stem cells attacking the patient’s healthy tissues.

There are two forms of GVHD. Acute GVHD targets skin, gut and liver and occurs usually within the first six weeks of the transplant. It can cause abdominal pain or cramps, nausea, vomiting, and diarrhea. It occurs in 30 to 40 percent of patients who receive stem cells from a related donor and 50 percent of patients whose donor is unrelated, according to GVHD Now a patient support website sponsored by biopharmaceutical company Incyte Dermatology.

Chronic GVHD develops more slowly within the first year of transplant. It affects skin and internal tissues in ways similar to autoimmune diseases like psoriasis, scleroderma, and rheumatoid arthritis. It affects 30 to 70 percent of patients who receive donor stem cells.

Earlier research by the UC Davis team had shown that GVHD was exacerbated by obesity, which has since been shown to play a role in excessive reactions to SARS-CoV2 the virus that causes COVID-19 to be more severe in obese patients.

The chief way doctors have managed GVHD is to block one of two cytokines IL-6 and TNF, which are substances released by the immune system that attack "foreign" invaders in the body, such as cancer or viruses.

The idea was to allow the donated stem cells to attack the cancer, but modify the attacks on healthy tissues. Until now, it was thought that blocking both cytokines would blunt the attack on the cancer.

In their study, the UC Davis researchers blocked both TNF and IL-6 in obese mice. The result was improved protection against GVHD, particularly reducing the gastrointestinal effects, without reducing the anti-tumor effects of the transplanted stem cells.

If the same effect is shown in human patients it could lead to better treatments for GVHD as well as inflammatory diseases such as COVID-19 an autoimmune diseases.

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Sources UC Davis Health press release and the journal Blood