Researchers around the world are exploring ways that they can minimise the risk of graft vs host disease (GVHD) occurring in patients who have received a bone marrow or stem cell transplantation.
The disease tends to develop as a result of differences in the tissue between the donated and the host cells. The cells from the graft (i.e. donation) view the host (i.e. recipient) cells as foreign and begin to attack them. Doctors are ideally looking for a match across five pairs of HLA antigens.
There are two manifestations of the disease, acute GVHD, which tends to develop in the first 100 days after a transplant, and chronic GVHD, which a patient tends to develop beyond the 100-day period. The chronic presentation can continue for more than a year in some people. Researchers are looking at ways of fighting both forms of the disease. Some recent projects in the fight against GVHD include focusing on reducing ocular symptoms, identifying early signs of chronic GVHD, identifying the role gut bacterium play against the effects of the disease and the use of high dose cytoreductive agents in severe cases of GVHD.
Reducing ocular GVHD symptoms
Ocular GVHD can be a symptom of chronic GVHD, the manifestation of the disease that can affect organs beyond the skin, liver and gut. In the condition, the eyes can become dry and irritable and the patient can experience blurred vision.
Researchers at the Massachusetts Eye and Ear and Harvard Medical School in the US have studied the effect of the immunosuppressant drug tacrolimus on ocular symptoms. They compared it to the steroid methylprednisolone. They observed the effect in 40 GVHD patients over ten weeks, treating 24 of them with topical tacrolimus and the other 16 of them with topical methylprednisolone.
The patients appeared to have reduced ocular symptoms with tacrolimus and without the side effects associated with the other treatment. Further research will be continued to decide whether this compound is a potential medicine for the condition.
Identifying early signs of chronic GVHD
A method for quickly identifying whether a patient is developing chronic GVHD would be useful for medical staff. An international research team including Canadian and American institutes, the University Hospital Regensburg in German and the King Faisal Specialist Hospital and Research Centre in Saudi Arabia have been researching this area.
Their research suggests that measuring the protein CXCL10 in the blood can provide an early signal of the development of chronic GVHD. To do this they took blood samples 36 chronic GVHD patients in two different populations. They also analysed samples from 134 patients in another group for eleven specific markers. CXCL10 was detected in the patients with early chronic GVHD.
How bacterium in the gut affects GVHD
GVHD can have a severe impact on the gut of patients affected. Researchers from the University of Michigan decided to investigate what happens to the lining of the gut during the disease by using mice as a model. They gave mice allogenic bone marrow transplants and noticed that the bacterial chemical butyrate was reduced in the cells lining the intestines and histone acetylation was also lowered. When they increased the butyrate, histone acetylation returned to its usual levels and GVHD symptoms improved.
The researchers then added 17 different strains of high butyrate producing bacteria, Clostridia, to alter the bacteria production and this resulted in a reduction of GVHD. The research suggests that decreasing butyrate levels increases GVHD and reversal of that has the opposite effect.
High dose cyclophosphamide may reduce severe GVHD
Nasheed Mohammad Hossain, MD and fellow researchers at the Fox Chase Cancer Center in Philadelphia analysed the effect of high-dose cyclophosphamide on severe graft versus host disease and found that it seems to improve the mortality rate in patients who have undergone hematopoietic stem cell transplants. The treatment appears to reduce the chance of the acute manifestation of the disease occurring.
The team carried out their study on 105 patients between 2010 and 2014 with 35 patients receiving the high-dose cyclophosphamide and 70 patients having treatment with tacrolimus and methotrexate. The patients with the cyclophosphamide had lower neutrophil counts and platelet recovery than with the other treatment. Research is ongoing.