Hospitalizations and Mortality Associated with dsDNA Viral Infections Among Hematopoietic Cell Transplant Recipients

Introduction: Hematopoietic cell transplant (HCT) recipients who experience reactivation or primary infections with double-stranded DNA (dsDNA) viruses such as cytomegalovirus (CMV), varicella zoster (VZV), Epstein-Barr virus (EBV) and BK virus (BKV) suffer substantial morbidity and mortality. The objective of this study was to examine the frequency of dsDNA viral infections during the index hospitalization for HCT. In addition, hospital length of stay (LOS) and the frequency of hospital readmission and mortality were assessed among HCT recipients who had dsDNA viral infections during hospitalization for HCT in comparison those who did not.

Methods: Patients who underwent HCT between January 2009 and September 2013 were identified from the hospital discharge records of the Premier Hospital database based on ICD-9-CM diagnosis codes. The hospitalization with the HCT procedure was defined as the index hospitalization. HCT recipients were grouped into two study cohorts: patients with a dsDNA viral infection during the index hospitalization and those without. Demographics, clinical characteristics, and hospital LOS during the index hospitalization were evaluated. Mortality during the index hospitalization was evaluated, as well as readmission mortality and hospital readmission frequency during a 12-month period following the index HCT hospitalization.

Results: Among the overall study population of HCT recipients (n=4,495; mean age: 50.4 years), 58% were male and 91% were ≥18 years of age. Of the overall study population, 2,798 patients received autologous HCT (62%) and 1,697 patients received allogeneic HCT (38%). Most patients received HCT in urban (94%), large (≥600 beds: 66%), teaching hospitals (88%). As identified by ICD-9-CM coding, 7.4% (n=332; mean age: 41 years) of the study population had a dsDNA viral infection during their index hospitalization and 92.6% (n=4,163; mean age: 51 years) did not. Among patients with a dsDNA viral infection, the most frequent virus infections were CMV (41%), herpes simplex virus (HSV, 28%), VZV (15%), BKV (11%), and human herpes virus (7%). LOS during the index HCT hospitalization was significantly greater for patients with a dsDNA viral infection vs. those without (43 vs. 23 days, p<0.001). A significantly higher proportion of patients died among those who had a dsDNA viral infection during the index hospitalization (12.1%, n=40) compared with 2.8% (n=117, p<0.001) of patients who did not have a clinically recorded dsDNA viral infection. Among the patients who survived the index hospitalization, mortality was also significantly higher over the subsequent 12 months among patients who had a dsDNA viral infection reported during the index hospitalization vs. those who did not have a reported viral infection (15% vs. 9%, p=0.002). In addition, a greater proportion of patients who had a dsDNA viral infection during the index hospitalization were readmitted over the next 12 months for a dsDNA viral infection (18% with vs. 9% without a dsDNA infection during the index hospitalization, p<0.001); specific infections cited among the two patient groups were CMV (11% vs. 6%, p<0.001) and BKV (4% vs. 1%, p<0.001).

Conclusions: Patients who had a dsDNA viral infection during their initial HCT hospitalization had significantly higher rates of hospital readmission and mortality in comparison to patients who did not have a dsDNA viral infection during their HCT hospitalization. Therapeutic strategies that can decrease the risk of reactivation or primary dsDNA viral infections have the potential to significantly impact mortality and morbidity, as well as healthcare resource use associated with hospital readmissions.