Characterization of Viral Infections after Antithymocyte Globulin–Based Conditioning in Adults Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

Antithymocyte globulin (ATG) has been shown to reduce the incidence of graft-versus-host-disease (GVHD) after matched related donor (MRD) and matched unrelated donor (MUD) hematopoietic stem cell transplantation (HCT); however, because of increased risks of infection and relapse, this use has not translated into a significant improvement in post-transplant survival. The goal of this single-center, retrospective cohort analysis was to quantify the incidence of viral reactivation and viral end-organ disease (EOD) within the first 100 days after MUD HCT with ATG-based conditioning compared with MRD HCT without ATG. Fifty-nine adult patients underwent ATGbased MUD HCT compared with 64 patients receiving MRD HCT without ATG. Cytomegalovirus reactivation was the most frequent event in both groups (65% MUD versus 61% MRD), followed by BK virus reactivation (26% versus 24%) and Epstein-Barr virus reactivation (20% versus 9%). A higher percentage of MUD patients experienced viral EOD by day +100 when compared with MRD patients (34% versus 16%, P = .022). This was most notable for EOD involving BK virus (15% versus 6%, P = .14) and Epstein-Barr virus (7% versus 0%, P = .050). Correspondingly, more patients in the MUD group experienced virus-related complications, including hospitalization (24% versus 3%, P < .001), intensive care unit admission (10% versus 6%, P = .19), and mortality (8% versus 4%, P = .44). There were no significant differences in either relapse-free survival (RFS; 62% versus 78%, P = .07) or overall survival (OS; 72% versus 86%, P = .07) at 6 months post-HCT. However, when using the final time point of 21 months in the MUD/ATG group and 23 months in the MRD/no ATG group, MUD patients who received ATG had inferior survival (OS: 27% versus 77%, P = .009; RFS: 40% versus 59%, P = .042). Our results add to and further quantify the infectious risks associated with the use of ATG in MUD transplants and promote the implementation of more intensive preemptive viral monitoring practices in patients receiving ATG-based MUD transplants. Published by Elsevier Inc. on behalf of the American Society for Transplantation and Cellular Therapy.

BRCC36 functions noncatalytically to promote antiviral response by maintaining STAT1 protein stability

“…Many diseases could result in attenuated host antiviral ability. For example, it has been reported that patients receiving HSC transplantation (HSCT) are more susceptible to viruses [36‐38]. Interestingly, we found that BRCC36 expression was significantly downregulated in the allo‐HSCT disease model.…”

“…After studying several models of human diseases, we noticed that BRCC36 expression could be largely downregulated during allogeneic HSC transplantation (allo‐HSCT), as compared with syngeneic HSCT (syn‐HSCT). Clinically, patients receiving allo‐HSCT are at high risk of viral infection [36‐38]. Thus, we questioned whether BRCC36 is one of the possible regulators that result in the fact that the patients after transplantation are more susceptible to viruses.…”

Monitoring of adenoviremia in pediatric patients undergoing hematopoietic stem cell transplantation: Is it alone sufficient to predict adenoviral disease?

“…A recent study including adult patients revealed that the use of ATG in conditioning resulted in virus-associated morbidity and mortality. 26 A higher percentage of patients who received ATG experienced virus-associated end-organ disease by day +100 when compared to patients who did not. In this study, the most common viral infections were CMV and EBV, however, some patients experienced AdV infection.…”

Updates in hematopoietic cell transplant and cellular therapies that enhance the risk for opportunistic infections

“…Patients who receive ATG are at significantly higher risk of DNA viral reactivation. 96 In most centers, weekly surveillance is conducted for both EBV and CMV using PCR assays. In many of these patients, prophylactic letermovir has been successfully used to reduce the risk of CMV infection.…”

“…Practice varies worldwide, with many American centers avoiding the use of ATG due to concerns about toxicity (particularly infectious), with increased use in Europe and Canada. Patients who receive ATG are at significantly higher risk of DNA viral reactivation 96 . In most centers, weekly surveillance is conducted for both EBV and CMV using PCR assays.…”