Birgitta Versluijs

54 Discussion Discussion Our cohort of 110 patients had a high incidence (50%) of early RV infection, occurring at a median of 16 days after HSCT. Rhinovirus infection was the most common RV detec- ted. The RV infections usually had a mild clinical course, and most patients experienced spontaneous recovery within 2 weeks. RV infection occurring during the first 100 days after HSCT appeared to be the sole predictor for the development of acute and chronic allo-LS, which was found in 27.3% of the patients. All patients had recovered from their initial URTI symptoms before a new episode of respiratory symptoms occurred, leading to the diagnosis of allo-LS. The presence of a single RV or multiple RVs, or the presence of rhinovirus and other (non-rhinovirus) RVs, was not associated with the development of allo-LS. Paradoxically, aGVHD had a protective effect against the development of allo- LS, likely resulting from the prolonged immunosuppressive therapy in the patients with aGVHD. All of the patients with allo-LS initially exhibited good clinical response to MP pulse therapy. The development of allo-LS was associated with high mortality, however. A possible weakness of our study is that we changed our policy on testing for RV during the study period. In the early phase of the study, we tested NPA samples for RV only in those patients exhibiting symptoms. Later in the study period, once the significance of RV was recognized, weekly surveillance assays were done in all patients. These surveil- lance assays identified 7 RV-positive patients without symptoms at the time of sampling; however, all of these patients developed URTI symptoms within 14 days after positive sampling, and so these RVs would ultimately have been detected regardless of the testing policy. Thus, we believe that we did not miss any RV-positive patients in the presurveil- lance period, and that the change in testing policy had no major impact on our results (data not shown), the only difference being that the median time to RV positivity would have been shorter had we monitored the whole group routinely. Three patients with symptoms and a clinical course typical of viral URTI were considered RV-positive despite negative RV-PCR results. In these patients, symptoms might have resulted from a virus not detectable by our PCR panel. It would be interesting to test these for more recently identified viruses, such Boca and Wu/KI. Because of the obvious symptoms and the fact that other study groups have included similar patients in their analyses, we decided to do so as well. 10 Had we considered these patients RV-negative in our analysis, the results would have been the same (only 1 of the 3 patients developed allo-LS). We realize that we may well have missed some mild URTI symptoms in the period between discharge and day 1100 and so do not have full data on RV positivity after discharge from the hospital. No patient who was RV-PCR–negative on discharge developed allo-LS, however. Acquisition of RV very early after HSCT appears to be im- portant for the development of allo-LS; the patients who were RV-positive within 16 days of HSCT tended to be more susceptible to allo-LS. 3

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