Association between the kinetics of cytomegalovirus reactivation evaluated in terms of the area under the curve of cytomegalovirus antigenemia and invasive mold infection during the post‐engraftment phase after allogeneic hematopoietic stem cell transplantation

Background We evaluated the clinical impact of cytomegalovirus (CMV) reactivation calculated in terms of the area under the curve of CMV antigenemia (CMV‐AUC) on the development of invasive mold infection (IMI) in the post‐engraftment phase after allogeneic hematopoietic stem cell transplantation (HSCT). Methods Among 394 consecutive patients who underwent their first allogeneic HSCT at our center between 2007 and 2018, 335 were included after excluding patients with a past history of invasive fungal disease (IFD), the development of IFD before engraftment, engraftment failure, or early death within 30 days. CMV antigenemia (CMV‐AG) was monitored weekly after engraftment and 3 or more cells/2 slides were regarded as positive. CMV‐AUC was calculated by the trapezoidal method using the number of CMV‐AG after logarithmic transformation and the duration in weeks and was added until negative conversion. Patients with CMV reactivation were divided into low and high CMV‐AUC groups using the median value of CMV‐AUC as a threshold. Results There were 17 proven/probable IMIs including one mucormycosis and 16 probable invasive aspergillosis, and the 2‐year cumulative incidence was 1.0% in the negative CMV‐AUC group (n = 136), 3.3% in the low CMV‐AUC group (n = 98) and 13.8% in the high CMV‐AUC group (n = 101) (P = .001). In a multivariate analysis, grade II‐IV acute GVHD (HR 3.74) and CMV‐AUC (HR low 1.25, high 5.91) were identified as independent significant factors associated with a higher incidence of IMI. Conclusions Cytomegalovirus kinetics evaluated in terms of CMV‐AUC were significantly associated with the development of IMI in the post‐engraftment phase after allogeneic HSCT.