Risk Factors for Cytomegalovirus Infection after Allogeneic Hematopoietic Cell Transplantation Using Rabbit...

Letermovir (LTV) prophylaxis has reduced clinically significant cytomegalovirus (CMV) infection (csCMVi) after allogeneic hematopoietic cell transplantation (allo-HCT). In vivo T-cell depletion is widely used for graft-versus-host disease (GVHD) prevention but is associated with increased risk of CMV infection. The risk heterogeneity and associated viral kinetics in this population remain poorly defined in the LTV era. We therefore evaluated risk factors and viral kinetics of csCMVi in this population.

We conducted a retrospective cohort study including 128 CMV-seropositive allo-HCT recipients who received in vivo T-cell depletion using rabbit anti-thymocyte globulin (r-ATG) or porcine anti-human T lymphocyte immunoglobulin (p-ATG). All patients received LTV prophylaxis. The primary endpoint was csCMVi. Competing-risk regression was used for risk factor analysis. Viral kinetics were assessed by the viral load area under the curve (AUC) within 180 days.

At a median follow-up of 342 days, csCMVi occurred in 43 patients (33.6%). Grade II-IV acute GVHD was independently associated with an increased risk of csCMVi (55.3% vs 21.0%; Subdistribution Hazard Ratio [SHR], 2.05; P=0.006). Compared with r-ATG, p-ATG was associated with a lower risk of csCMVi (28.2% vs 44.2%; SHR, 0.40; P = 0.012). Recipients in the r-ATG group also showed a higher early viral burden (median normalized AUC 0.106 vs 0.043; P < 0.001).

Despite LTV prophylaxis, csCMVi remains frequent in T-cell-depleted recipients. Acute GVHD is a key risk factor. Different anti-thymocyte globulin preparations are associated with distinct CMV risk profiles and early viral kinetics. These findings warrant further validation and investigation of their clinical implications in the LTV era.