Cytomegalovirus Immune reconstitution in cord blood transplant recipients on letermovir prophylaxis

Abstract

AbstractIntroductionCytomegalovirus (CMV) can cause significant morbidity and mortality in cord blood transplant (CBT) recipients. Development of CMV‐specific cell‐mediated immunity (CMV‐CMI) has been associated with protection against CMV clinically significant reactivation (CsCMV). In this study, we evaluated CMV‐CMI reconstitution during letermovir prophylactic therapy, which prevents CsCMV without complete suppression of CMV reactivation.MethodsWe measured CMV‐CMI in CMV‐seropositive CBT recipients pre‐transplant after Day+90 of letermovir prophylaxis and at Days +180, and +360‐ post‐transplant using a dual color CMV‐specific IFNγ/IL2 FLUOROSpot. CsCMV and nonCsCMV reactivations were abstracted from medical records. CsCMV was defined as CMV viral load ≥5,000 IU/ml using a whole blood assay.ResultsAmong 70 CBT recipients, 31 developed CMV‐CMI by Day+90 and an additional eight and five participants by Days +180 and +360, respectively. Thirty‐eight participants developed CMV reactivation, including nine with CsCMV. Most reactivations (33 of 38) occurred before Day+180. Early CMV‐CMI was present in six out of nine participants with CsCMV, indicating a lack of protection against CsCMV. Moreover, the magnitude of CMV‐CMI at Day+90 did not differ between participants with CsCMV and nonCsCMV.ConclusionApproximately 50% of CBT recipients reconstituted CMV‐CMI during letermovir prophylactic therapy. However, CMV‐CMI did not reach levels protective against CsCMV. Extension of CMV prophylaxis beyond Day+90 may be considered in CMV‐seropositive CBT recipients. image