Incidence and Outcome of Non-CMV Viral Infections in 202 Consecutive Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) Recipients.
Authors: Junghanss Christian , Rohde Sebastian , Haversath Max , Kundt Guenther , Wolff Daniel , Hilgendorf Inken , Andree Holger , Casper Jochen , Leithaeuser Malte , Kahl Christoph , Freund Mathias 
Published: April 2020

Abstract
Background: Viral infections contribute significantly to morbidity and mortality following allogeneic HSCT. Whereas incidences and risk factors for CMV infections are well studied data for other viral infections are more limited. Here, we present data on 202 alloHSCT recipients that received predominantly reduced intensity conditioning (RIC).
Patients and Methods: Data of 202 consecutive patients (pts) who received HSCT during 1/1999 to 12/2006 were retrospectively analysed with regards to viral infections caused by adenovirus (AdV), herpes simplex virus (HSV), varicella zoster virus (VZV), human herpesvirus 6 (HHV6), epstein-barr virus (EBV) and BK-virus (BKV). Other factors included were gender, age, underlying disease, disease status, year of diagnosis, year of HSCT, time from diagnosis to HSCT, donor type, gender-matching between donor and recipient, stem cell source, conditioning-regimen, T-cell-depletion, prior autologous HSCT, acute and chronic GvHD, prior fungal infection, and viral serostatus of the recipients.
Results: Median follow-up was 9.2mths (mean 21.7mths, range 8days to 95.3mths). Median pt. age was 45yrs (range 15 to 69yrs). Underlying diseases were ALL (n=20), AML (n=63), CLL (n=7), CML (n=32), MDS (n=21), MM (n=17), NHL (n=28), OMF (n=5), others (n=9). 137 pts received RIC most commonly based on treosulfan/fludarabine (n=112). 65 pts received myeloablative conditioning mainly based on 12Gy TBI containing regimen (n=48). GvHD-prophylaxis consisted of CSA/MTX (n=106), other CSA based regimen (n=83) or other (n=13). The overall infection incidences of AdV were 4.0%, of HSV 7.4%, of VZV 5.9%, of HHV6 8.9%, of EBV 4.5% and of BKV 5.4%. Median time of onset of AdV infections were 64 days after HSCT, of HSV 34 days, of VZV 542 days, of HHV6 97 days, of EBV 83 days, of BKV 50 days. Pts with AdV or HHV6 infections had a inferior survival compared to pts w/o the according viral infection (p=0.024 and p=0.048, respectively). 3/8 pts (37%) with AdV and 5/18 pts (28%) with HHV6 infections died within 30 days after infection diagnosis. Pts with EBV or BKV infections tended to have an inferior survival compared to pts w/o the according infection (p=0.084, p=0.152, respectively). 4/9 pts (44%) with EBV and 2/11 pts (18%) with BKV infection died within 30 days after infection diagnosis. Whereas pts with HSV infections had a similar survival compared to pts w/o infections, mean survival for pts with VZV infections was significantly better compared to pts w/o VZV infections (p=0.003). In multivariate analyses VZV infections remained to be associated with better survival (p=0.046, HR 0.132, CI 0.018–0.962). The other viral infections did not remain significant risk factors when analysed adjusted for competing risk factors. In order to determine the influence of late viral infections we performed an additional multivariate analyses solely including pts surviving beyond day 90. EBV infections (p=0.024, HR 2.807, CI 1.147–6.873) and HHV6 infections (p=0.013, HR 2.594, CI 1.227- 5.484) were significant risk factors for inferior survival besides unrelated donor HSCT (p=0.013), acute GvHD III/IV (p=0.001) and fungal infection prior to HSCT (p=0.005).
Conclusion: Non-CMV viral infections are commonly observed following myeloablative and RIC alloHSCT. Since they are associated with significant mortality early broad viral screening seems advisable if virus infections are clinically suspected.