Long-Lasting HHV-6 Reactivation and Immune Recovery In Adult Long-Survivors After Umbilical Cord Blood (UCB) Allo-SCT: A Comparison With PBSC As Stem-Cell Source

HHV-6 reactivation and HHV-6 encephalitis have been identified as significant complications in the post allo-SCT setting, especially in patients receiving UCB as the stem cell source (Scheurer et al, BMT, 2012). It is known that HHV-6 reactivations occur mainly within the first month post-transplant and may persist few months after allo-SCT (Chevallier et al, BMT, 2010). At our knowledge, no study has evaluated the long-term persistence of HHV-6 infection and its consequences in patients after allo-SCT.

Here we have compared long-term HHV-6 reactivation and immune reconstitution (T, B and NK cells, CD3+, CD4+ and CD8+ T cells, gammaglobulin) between two cohorts of patients who received either double UCB units (n=23) or PBSC (n=25) as stem cells source for allo-SCT between February 2006 and January 2012. Patients were collected prospectively between October 2012 and June 2013. The median time between the graft and the time of analysis were 4 years for the UCB group vs 3.8 years for the PBSC group (p=NS). All patients were fit and in persistent complete remission at time of analyses.

There were no differences between UCB vs PBSC groups in term of sex (male: 56% vs 55%), type of disease (myeloid: 52% vs 55%), disease status at diagnosis (high-risk: 89% vs 71%), conditioning regimen (RIC: 83% vs 84%) or median year of transplant (2008 vs 2009). The use of ATG was significantly higher in the PBSC group: 93% of cases vs 10%, p<0.0001.

Half of the patients (52%, n=11) showed long-lasting HHV-6 reactivation in the UCB group (median viral load: 2.7 log₁₀copies/mL (range: 2-3.4) compared to only 4% of the patients (n=1, viral load: 2 log₁₀copies/mL) in the PBSC group (p<0.0001). Except a significant higher long-lasting B lymphocytes recovery in the UCB group (median: 740 vs 490 Giga/L, normal range: 100-400 Giga/L, p=0.03), there were no significant differences regarding immune reconstitution between both groups, where total lymphocytes, CD3+, CD4+ and CD8+ T cells, NK cells counts and gammaglobulin rates were in the normal ranges. In the UCB group, patients with higher B lymphocytes count (>740 Giga/L) showed no higher incidence of HHV6 reactivation (56% v 67%, p=1). Furthermore no statistically significant correlation was observed between B lymphocyte count and HHV6 reactivation. The persistence of HHV-6 reactivation has no clinical impact in this cohort.

In conclusion, HHV-6 infection persists for a very long time in half of the patients after UCB allo-SCT but is not clinically relevant. Long-term immune reconstitution does not explain this event. The cause of long-lasting HHV-6 reactivation after CBT allo-SCT in adults remains to be elucidated.