Prospective Comparison Of Five Viral Infections (HHV6, CMV, EBV, ADV, BKv) After Umbilical Cord Blood (UCB) Vs PBSC Reduced-Intensity Conditioning Allogeneic Stem Cell Transplantation (allo-SCT) In Adults

Viral infections are well-known complications after allo-SCT and are responsible for morbidity and mortality in patients. Previous retrospective studies have reported a strong association between HHV6 infection and the use of umbilical cord blood (UCB) as stem cell source for allo-SCT. To better define the characteristics and consequences of HHV6 infection after UCB allo-SCT, we conducted the first prospective study comparing the frequencies of HHV6 infections and of 4 other viral reactivations (cytomegalovirus (CMV), Epstein Barr virus (EBV), adenovirus (ADV) and BK virus (BKv)) in 65 adults receiving either UCB allo-SCT (n=31) or unrelated PBSC allo-SCT (n= 34) after a reduced intensity conditioning regimen. Except graft source, characteristics of patients were similar between UCB vs PBSC groups in terms of sex, age at transplant, type of disease and disease status at transplant.

Viral loads were measured in whole blood (608 samples) before the graft and at least once a month up to six months post-graft. Data were analysed for correlation with various clinical/biological events occurring after the graft (engraftment, hematopoietic and immune reconstitutions, GVHD, deaths or the five considered viral infections).

Frequency of HHV-6 infections was significantly higher in the UCB group (83.9% vs 21.2%; p<0.0001). In this context, HHV-6 reactivations were observed mainly during the first month post-transplant occurring earlier (p<0.0001) and with a longer duration (median: 148 days vs 31 days) in the UCB group. However, there was no difference regarding viral loads between both groups. Neutrophils and platelets recoveries were significantly delayed in HHV-6 positive patients (median: 20 days vs 15 days, p=0.002; and 40 days vs 12 days; p=0.0001, respectively), especially when HHV-6 reactivations occurred before the end of aplasia (median: 28 days vs 17 days; p=0.0054 and 56 days vs 15 days; p=0.0006). The delayed recoveries was accordingly associated with a higher need for units of red blood cells and platelet packs in infected patients (median number of transfused units per patient: 8 vs 2; p=0.006 and 11 vs 1; p<0.0001, respectively). Moreover, HHV-6 infection was not associated with higher incidence of acute GHVD, CMV reactivations, relapses or death.

Regarding the four other viral infections, we observed a significant higher frequency of EBV reactivations in PBSC allo-SCT recipients (70.6% vs 25.8%; p=0.0003) but similar incidence of CMV infections between both groups. ADV infections were observed only in 4 UCB allo-SCT cases. Finally, BKv reactivations studied up to 2 months post-graft were significantly more frequent in the UCB group (51.6% vs 23.5%; p=0.019).

In conclusion, we prospectively confirm here a specific relationship between HHV6 and BKv infections and UCB allo-SCT. The pattern of immune reconstitution and the multivariate analyses are on-going and will be presented at the meeting.