Cytomegalovirus gastroenteritis in patients with acute graft-versus-host disease

Abstract

A preemptive strategy has successfully decreased cytomegalovirus (CMV) disease after allogeneic hematopoietic cell transplantation (HCT). However, some recipients still develop CMV gastroenteritis, especially after acute graft-versus-host disease (aGVHD), and its incidence, risk factors, and prognostic impact remain to be elucidated. We retrospectively analyzed 3759 consecutive adult patients who developed grade II-IV aGVHD using a Japanese registry database. The cumulative incidence of CMV gastroenteritis was 5.7% by day 365 from the development of grade II-IV aGVHD. Advanced age (hazard ratio [HR], 1.60; 95% confidence interval [CI], 1.16-2.22; P = .004), GVHD prophylaxis with mycophenolate mofetil and calcineurin inhibitor (HR, 1.73; 95% CI, 1.08-2.77; P = .024), lower-gut aGVHD (HR, 2.17; 95% CI, 1.58-2.98; P < .001), and the use of systemic steroids (HR, 1.78; 95% CI, 1.16-2.74; P = .008) were independent risk factors for CMV gastroenteritis. Development of CMV gastroenteritis was associated with an increased risk of nonrelapse mortality (HR, 1.89; 95% CI, 1.50-2.39; P < .001). Moreover, letermovir prophylaxis significantly reduced both the incidence of CMV gastroenteritis (HR, 0.50; 95% CI, 0.25-0.99; P = .047) and the risk of nonrelapse mortality (HR, 0.72; 95% CI, 0.52-0.99; P = .043). In summary, CMV gastroenteritis is a life-threatening complication that sets the need for preventive strategies with letermovir and targeted surveillance.

Graphical abstract

Figure 1.

Cumulative incidence of CMV reactivation and gastroenteritis. The cumulative incidence of CMV reactivation (A), the adjusted cumulative incidence of CMV reactivation in patients with and without letermovir prophylaxis (B), the cumulative incidence of CMV gastroenteritis (C), and the adjusted cumulative incidence of CMV gastroenteritis in patients with and without letermovir prophylaxis (D). Adjusted curves were plotted with the following covariates: recipient’s age at HCT, sex mismatch, CMV serological status, disease, DRI, KPS, HCT-CI, donor source, conditioning intensity, GVHD prophylaxis, in vivo T-cell depletion, year of HCT, organ involvement sites of aGVHD, and use of systemic steroids.

Figure 2.

Impact of CMV gastroenteritis and letermovir on NRM. Simon-Makuch plots for the effect of CMV reactivation and gastroenteritis on NRM (A) and the adjusted cumulative incidence of NRM in patients with and without letermovir prophylaxis (B). Adjusted curves were plotted with the following covariates: recipient’s age at HCT, sex mismatch, CMV serological status, disease, DRI, KPS, HCT-CI, donor source, conditioning intensity, GVHD prophylaxis, in vivo T-cell depletion, year of HCT, organ involvement sites of aGVHD, and use of systemic steroids.