Graft Versus Host Disease

Treating and preventing GVHD are two very different areas

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Despite all the clinical progress that's already been made in preventing graft-versus-host-disease (GVHD), the idea is still a scary concept overall. Before an effort was made to largely inhibit patient susceptibility, GVHD was a serious complication. Now that preventative measures have been put into place, the severity of GVHD has decreased significantly. Although there may only be a comparatively small number of exceptions in terms of the effectiveness of preemptive therapies, treating and preventing GVHD are two very different areas.

While there have been cases reported in solid organ transplants or blood transfusions, these are extremely rare. Because the affliction is the result of the immune system of the donor not recognizing -- and, subsequently, attacking -- the recipient, it mainly affects patients who have undergone bone marrow transplants. In a recent interview with ADVANCE, Javier Bolaños Meade, MD, associate professor of oncology at Johns Hopkins and director of both the graft versus host disease program and the marrow and apheresis collections facility, discussed the diagnosis, treatment and potential in addressing GVHD.

"Graft-versus-host-disease will occur when there are immune cells from a donor in an immune-suppressed environment," said Bolaños Meade. "So, this is mainly a complication of bone marrow transplants."

Preventative treatment for GVHD first took place in the late '60s and early '70s, when researchers started experimenting with immunosuppression therapies. By utilizing combinations of drugs to temporarily disable the immune system, the technique helped transplant patients more readily accept the donor's immune system -- and vice versa. These drug therapies and treatments have roughly cut the risk of developing either acute or chronic GVHD in half. Bolaños Meade noted that, with the currently available prevention drugs, the chances of GVHD not only become less likely, but the severity is also substantially limited.

"The majority of people who develop graft-versus-host-disease will develop very mild forms of the disease," he explained. "Essentially, a skin rash that sometimes doesn't even have to be treated or, if it's treated, it will go away."

There are now multiple proven methods in immunosuppression, including the most common methods, which combine methotrexate and either tacrolimus or cyclosporine. The use of cyclophosphamide and T-cell depletion have also been developed as promising new approaches in the prevention of GVHD.  The use of high-dose cyclophosphamide, a chemotherapy treatment, or other drugs in order to suppress the immune system is common and effective. T-cell depletion is also effective and well-tolerated, but requires more sophisticated equipment in order to remove the donor's T-cells from the graft. According to Bolaños Meade, T-cells play a major role in GVHD. By removing them, physicians limit the patient's susceptibility to the disease.

Looking past preventative options into treatment, the steroid and immunosuppressant prednisone is commonly used to treat both acute and chronic GVHD. Following the transplant, patients are typically kept on immunosuppressants and gradually weaned off. GVHD typically presents as a skin rash (for acute patients) and sometimes with an additional symptom like dry mouth or dry eye, etc (seen in chronic cases). Both are treated with prednisone until the disease is under control. For severe cases that have moved beyond treatment with prednisone and have led to visceral disease in the liver or bowel along with extreme skin involvement, however, secondary therapies do not have a particularly successful history.

"Now, once you have to move into secondary therapies, things are not so good because the track record of secondary therapies is actually very poor. And this has been published extensively," continued Bolaños Meade. "I mean, every single report ever published for patients with graft-versus-host-disease may yield high responses, but very, very high mortality."

Due to the somewhat unsuccessful results of secondary therapies, the industry has mainly been focused on finding the most efficient preventative therapy available. Bolaños Meade cited a recent movement in the field to compare and contrast T-cell depletion with cyclophosphamide-based therapies. While each produces similar results, they have never been compared head-to-head. The latest goal in the field is really just to find if one is better than the other for facilities across the country.

As the role of stem cell therapies continue to increase in an evolving healthcare industry, the ability to stop complications like GVHD in transplant patients is vital. The concept of GVHD prevention has thrived in producing real-world results and therapies such as immunosuppression since it was originally developed, but there remains a long way to go for physicians treating GVHD patients.  With a fruitless effort to develop post-GVHD treatments behind them, industry professionals are now completely focused on prevention, hoping to close the gap in narrowing patient chances for developing GVHD. 

Michael Jones is on staff at ADVANCE.

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