Early Post-Transplant Viral Infections and the Incidence of Acute and Chronic Noninfectious Pulmonary Complications Following Hematopoietic Stem Cell Transplantation (HSCT)

Background: Non-infectious pulmonary complications, including Idiopathic Pneumonia Syndrome (IPS) and Bronchiolitis Obliterans Syndrome (BOS) are associated with significant morbidity and mortality following HSCT. Both preclinical and clinical models suggest that IPS and/or BOS may develop following a prior viral infection, upon clearance of the primary lytic infection. We now investigate the association of “early-onset” viral infections and the occurrence of IPS and/or BOS at a single center. Patients: Case records from 741 consecutive allogeneic transplants were reviewed, with IPS and/or BOS identified using NIH Consensus criteria. Community and non-community acquired viral infections occurring within the first 100 days post-HSCT were defined as “early-onset”. Only viral infections that developed prior to IPS were included in the IPS analysis. Results: Overall, early-onset viral infections (EOVI) occurred in 242 patients (33%). EOVI were associated with an increased risk of developing IPS (P = .04), and trended towards significance for the development of BOS (P = .08). Nineteen of 41(46%) patients with IPS, and 22 of 49(45%) patients with BOS had a preceding EOVI (Table 1, Table 2). Early-onset HHV6 infections occurred in 7 of 41 (17%) patients with IPS versus 47 of 700 (7%) patients without IPS respectively, P = .02. There was no association between early-onset CMV or community acquired viral (CAV) infections and IPS. In contrast, early-onset CMV infections were associated with an increased risk of developing BOS post-HSCT (P = .03), with no association between early-onset EBV, HHV6, HSV, CAV infections and BOS noted. The median duration from viral infection to the onset of IPS was 25 days (range, 1-335 days) and the median duration from viral infection to the onset of BOS was 465 days (range, 76-1168).Table 1Early-onset viral infections and IPS*Viral infections(excluding BK virus) within first 100 days post-HSCT.Total Patients n = 741IPS (%) n = 41No IPS (%) n = 700PAny viral22919(46)210(30).04CMV1164(10)112(16)0.38EBV274(10)23(3).06HHV-6547(17)47(7).02HSV62(5)4(1).04CAV262(5)24(3)0.65* Viral infections(excluding BK virus) within first 100 days post-HSCT. Open table in a new tab Table 2Early onset viral infection and BOS*Viral infections(excluding BK virus) within first 100 days post-HSCT.Total Patients n = 741BOS (%) n = 49No BOS (%) n = 692PAny viral24222(45)220(32).08CMV12614(29)112(16).03EBV272(4)25(4)0.70HHV-6565(10)51(7)0.41HSV71(2)6(1)0.21CAV260(0)26(4)0.17* Viral infections(excluding BK virus) within first 100 days post-HSCT. Open table in a new tab Conclusion: HHV-6 infections within the first 100 days post-HSCT are associated with an increased risk of developing IPS, whereas CMV infections occurring during this ‘early” post-HSCT period are associated with an increased risk for the development of BOS.