Disclosures: NCI funded this study. The authors report no relevant financial disclosures.
November 09, 2020
2 min read

Early cytomegalovirus reactivation after allogeneic HSCT may help prevent future infection

Disclosures: NCI funded this study. The authors report no relevant financial disclosures.
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Early cytomegalovirus reactivation after allogeneic stem cell transplantation induced cytomegalovirus antigen-specific T cells that may better prevent future infection, according to results of a retrospective study.

The findings, published in Biology of Blood and Marrow Transplantation, suggest that low-level cytomegalovirus (CMV) infection within 100 days of transplantation may be beneficial and may not require treatment until progression of CMV reactivation, researchers noted.

Bone marrow transplant operation.
Source: Adobe Stock.

“Low-level antigenemia might be protective, because it may provoke the patient’s immune system to develop anti-CMV immunity,” Philip McCarthy, MD, professor of oncology and internal medicine and director of the Transplant and Cellular Therapy Center at Roswell Park Comprehensive Cancer Center, said in a press release. “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.”

CMV reactivation, defined as a viral replication in the blood, and CMV disease, defined as end-organ damage related to the virus, are causes of morbidity and mortality after allogeneic HSCT. About 11% to 32% of CMV-seropositive recipient/donor pairs experience CMV reactivation after transplantation.

Patients with CMV reactivation usually receive early treatment with valganciclovir, ganciclovir or foscarnet at the time of CMV detection. These treatments, however, have been associated with considerable morbidity.

Previous studies have suggested CMV reactivation after allogeneic HSCT may have a beneficial effect on immune reconstitution.

Philip L. McCarthy, MD
Philip McCarthy

McCarthy and colleagues analyzed 775 CMV antigen-specific T cell (CAST) measurements collected before transplant and 30, 100 and 365 days after transplant from 327 patients who underwent treatment between 2008 and 2016.

The researchers evaluated CMV reactivation with CMV antigenemia and CASTs to determine a CMV antigenemia threshold associated with improved CAST reconstitution and decreased incidence of CMV infection from day 100 to day 365 after transplant.

Results showed associations of detectable CASTs with recipient (P < .0001) and donor (P < .0001) CMV seropositivity prior to allogeneic HSCT.

Additionally, CMV reactivation within 100 days of transplant appeared associated with a higher rate of patients who achieved three or more CASTs/µL by day 100 (61% with reactivation vs. 39% without reactivation; P < .001).

Among transplant recipients at a high risk for CMV reactivation with a maximum of grade 2 acute graft-versus-host disease, reactivating CMV before day 100 and achieving three or greater vs. fewer than three CASTs/µL by day 100 appeared associated with reduced CMV reactivation from day 100 to day 365 after transplant (27% vs. 62%; P = .04).

Researchers observed this protective effect with low-level CMV reactivation, but not with high-level CMV reactivation.

Using CMV antigenemia rather than quantitative CMV polymerase chain reaction to measure viral load served as a limitation to this study.

“Some patients are always reactivating CMV because they haven’t developed an immunity and need to continue taking anti-CMV drugs,” George Chen, MD, associate professor of oncology at Roswell Park Comprehensive Cancer Center, said in a press release. “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.”