Allowing low-level CMV infection may boost immunity in stem cell transplant recipients

Patients who develop cytomegalovirus (CMV) infections after allogeneic stem cell transplantation may be able to develop an immunity against the virus, strengthen their immune system and reduce reliance on strong antiviral medications, a team of cellular-therapy specialists from Roswell Park Comprehensive Cancer Center has found. Their findings have been published in a new study in the journal Biology of Blood and Marrow Transplantation.

A Roswell Park team led by George Chen, MD, Theresa Hahn, PhD, and Philip McCarthy, MD, studied 315 patients who received hematopoietic stem cell transplants from an allogeneic donor between 2008 and 2015 to determine how many suffered from CMV reactivation and developed anti-CMV immune responses following their transplants.

Allogeneic stem cell transplant is a common treatment for many leukemias and other blood cancers. Many patients undergoing allogeneic BMT will experience CMV -; a viral infection that can lay dormant in a person's body for decades but can be reactivated after receiving immunosuppression. CMV reactivation, which can occur in about 25-30% of transplant patients, is associated with few clear symptoms. Unchecked, it can develop into a more serious infection that can damage the lungs, colon, liver or retina.

The research team studied the immune responses of patients to CMV reactivation in the first 365 days after transplantation. They found that those who reactivated CMV and developed three or more CMV-specific T cells per microliter of blood were less likely to subsequently reactivate CMV.

By testing patients for the presence of CMV antigen-specific T cells (CASTs), the authors conclude, medical teams can determine whether CMV could be controlled by the patient's immune system alone without medication.

"Some patients are always reactivating CMV because they haven't developed an immunity and need to continue taking anti-CMV drugs," says Dr. Chen, an Associate Professor of Oncology in the Department of Medicine at Roswell Park. "At some point, they have to come off the drug. To determine when they can come off, we can measure the number of CMV-specific T cells in the blood to establish whether they have CMV immunity. Once they develop immunity, they have a greater chance of not reactivating the virus again and can come off the drug."

Dr. McCarthy, Professor of Oncology and Internal Medicine and Director of the Transplant & Cellular Therapy Center at Roswell Park, says this research represents "a completely new look at immunity and immune reconstruction" after cell or organ transplants.

"We all see pathogens in the context of our own tissue antigens," Dr. McCarthy notes. "When we get a cold, we express viral antigens to T cells, and our T cells recognize that antigen. Everybody has different reactions to a virus."

Testing for antigen-specific T cells might help protect against other kinds of viral infections for people who receive stem cell or bone marrow transplants, he says.

While further research in this area is needed before clinical practice is routinely changed, the team's findings show that it may be beneficial to allow patients, under careful supervision, to develop a low-level viral infection without immediately providing medication.

"Low-level antigenemia might be protective, because it may provoke the patient's immune system to develop anti-CMV immunity," Dr. McCarthy says. "If the levels remain low and then go away, the patient's immune system has taken care of the CMV without requiring drug therapy, which can be associated with significant side effects."