Insights From: Roy Chemaly, MD, The University of Texas MD Anderson Cancer Center
Roy Chemaly, MD: We know that it depends on the time period from transplant—you may have different risk factors or different stratification factors for identifying patients with cytomegalovirus reactivation or any other kind of infection. The highest risk period for this specific viral infection—CMV—is early on, probably between the period of peri-engraftment until day 60 or day 90. These patients still did not recover their immunity the way we wanted. They’re still probably lacking CMV-specific T-cell response and may have complications from the transplant that will put them at risk for reactivation as well as CMV end-organ disease, which we worry about the most. That’s how people try to stratify patients. From the get-go, we identify patients who are at risk through CMV serology of the recipient. Sometimes, we look at the CMV serology of the donor, as well. If they are CMV-seropositive, we know that they are at risk for CMV reactivation, as compared to recipients who are CMV-seronegative, with no prior exposure to CMV. After that, you have other stratifying risk factors, like I mentioned earlier: graft-versus-host disease, the type of transplant, T-cell depleted versus not, and the treatment of graft-versus-host disease with corticosteroids and other immunosuppressive therapy.
Donor serostatus for CMV is also important. Through a few published studies, we’ve found that if the donor is seropositive for CMV, some protection may be provided for the recipient, down the line, with a potentially quicker recovery of T-cell responses for CMV. This is one of the factors that we’ve looked at, and there [are] good data from large databases that look into the impact of donor CMV seropositivity and the outcome of CMV reactivation or CMV disease. But, what is more interesting, at least in my mind, are the recent data from the Fred Hutchinson Cancer Research Center and the CIBMTR [Center for International Blood and Marrow Transplant Research] database. They looked to see if any level of CMV viremia or detection in the blood would put a patient at higher risk or at a disadvantage for survival compared to a patient who never reactivated their CMV. It actually turned out to be true. In these 2 major studies, when we look at the data, in any level of CMV reactivation, or viremia—because they did a viral load in these studies, or antigenemia—the mortality is much higher than in the patient who never had CMV reactivation, or viremia, and antigenemia.
So, CMV reactivation puts patients at a disadvantage for survival, as compared to patients who never reactivated their CMV. I think this is an interesting observation. Now, we take CMV reactivation much more seriously. We’ve been treating and addressing this in the past, but now we have some evidence showing that CMV reactivation, or viremia, is usually bad news for patients.