Recovery of CMV immunity after allogeneic haematopoietic stem cell transplant - Insight from an in-depth analysis of a small cohort of patients with clinical correlation.

BACKGROUND

We conducted an evaluation of the IFN-g ELISpot assay with the primary objective of exploring its clinical use after allogeneic haematopoietic stem cell transplant (allo-HSCT). Here we analysed its correlation with occurrence of clinically-significant CMV infection (cs-CMVi) and risk factors.

METHOD: Frozen mononuclear cells collected at 2, 3, 4 and 5 months after allo-HSCT were tested against CMV pooled peptide pp65 and IE1 in an IFN-g ELISpot assay. Spot forming cells (SFC) per 250,000 cells were correlated with clinical course.

RESULTS

Amongst the 18 CMV seropositive recipients including 3 with seronegative donors, 11 of the 14 low responders (< 50 SFC) developed cs-CMVi while all the 4 high responders with >50 SFC were protected. High dose glucocorticoids (1 mg/kg or higher) predisposed to a second episode of cs-CMVi even after acquisition of more than 50 SFC after the first episode, while low dose (20 mg/day or lower) did not matter. Low level CMV viremia resolved spontaneously in 2 of the 4 high responders but progressed to cs-CMVi in the other 11 low responders. Consistent with literature, recipients of T-depleting regimen and cord blood were at a higher risk of cs-CMVi. The median time to first acquisition of more than 50 SFC was 118 days. The 3 recipients of seronegative donors did not recover immunity beyond the monitoring period and 2 had recurrent cs-CMVi.

CONCLUSION

This small series provides in-depth insight into the recovery of CMV immunity and cs-CMVi post allo-HSCT for each recipient and supplements knowledge provided by large series.