Risk Factors and Prognostic Scale for CMV Reactivation in CMV Seropositive Patients after Allogeneic Hematopoietic Cell Transplantation – a Single Center Cohort Study

Background: Despite the progress of antiviral therapy in recent years, CMV infection continues to be a major complication after allogeneic hematopoietic cell transplantation (HCT). We aimed to study the risk factors for first and subsequent CMV infections among patients who are CMV seropositive. Methods: we analyzed all sequential CMV seropositive patients that were given allogeneic HCT in a single center. We tested the impact of a variety of patients and transplantation's characteristics on both first and subsequent CMV reactivations. Significant factors identified on multivariate analyses were entered into models to predict first and subsequent CMV reactivation. Results: Between May 2007 and December 2012, 121 CMV seropositive patients were given allograft. Multivariate model identified myeloablative preparative regimen (HR=4.297, p=.033) and acute GVHD prior to infection (HR=5.091, p=.021) as risk factors for first CMV infection. The cumulative incidences of first CMV infection for patients with 0, 1 and 2 risk factors were 52%, 71% and 91%, respectively, Figure. Receiver operating curves for the model showed for one risk factor a sensitivity of 84% and specificity of 34% and for 2 risk factors 41% and 91%, respectively. Multivariate analysis identified the diagnosis of lymphoma/myeloma (HR=3.5, p=.049) and GVHD (HR=1.280, p=.045) as risk factors for subsequent CMV infection.  High graft CD3 stem cell dose was protective (HR=0.543, p=.056). The cumulative incidences for subsequent CMV reactivation in patients with 0, 1, and 2-3 risk factors were 11%, 43% and 77%, respectively. Receiver operating curves for the model showed for one risk factor a sensitivity of 67% and specificity of 90% and for more than 2 risk factors 93% and 47%, respectively. Conclusions: In CMV serospotive patients, myeloabaltive conditioning and acute GVHD are risk factors for first CMV infection and lymphoma /myeloma, ongoing GVHD and low CD3 graft content are risk factors for a subsequent infection.