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CMV Reactivation during Pre-Transplantation Evaluation: A Novel Risk Factor for Post-Transplantation CMV Reactivation.

Danniel ZamoraHu XieAlicja Sadowska-KlasaEleftheria KampouriMelinda A BiernackiMasumi Ueda OshimaElizabeth R DukeMargaret L GreenLouise KimballLeona A HolmbergAlpana WaghmareAlexander L GreningerKeith R JeromeGeoffrey R HillJoshua A HillWendy M LeisenringMichael J Boeckh
Published in: Blood advances (2024)
Cytomegalovirus (CMV) disease occurs occasionally before allogeneic hematopoietic cell transplantation (HCT) and is associated with poor post-HCT outcomes; however, the impact of pre-HCT CMV reactivation is unknown. Pre-HCT CMV reactivation was assessed in HCT candidates from the preemptive antiviral therapy (2007-17) and letermovir prophylaxis (2018-21) eras. CMV DNA PCR surveillance was routinely performed during the pre-HCT work-up period, and antiviral therapy was recommended according to risk for progression to CMV disease. Risk factors for pre-HCT CMV reactivation were characterized and the associations of pre-HCT CMV reactivation with post-HCT outcomes were examined using logistic regression and Cox proportional hazard models, respectively. A total of 1694 patients were identified and 11% had pre-HCT CMV reactivation 14 days (median; IQR 6-23 days) before HCT. Lymphopenia (≤300 cells/uL) was the strongest risk factor for pre-HCT CMV reactivation at multiple PCR levels. In the preemptive therapy era, patients with pre-HCT CMV reactivation had a significantly increased risk of CMV reactivation by day 100 as well as CMV disease and death by 1 year post-HCT. Clearance of pre-HCT CMV reactivation was associated with a lower risk of post-HCT CMV reactivation. Similar associations with post-HCT CMV endpoints were observed in a cohort of patients receiving letermovir prophylaxis. Pre-HCT CMV reactivation can be routinely detected in high-risk HCT candidates and is a significant risk factor for post-HCT CMV reactivation and disease. Pre-HCT CMV DNA PCR surveillance is recommended in high-risk HCT candidates and antiviral therapy may be indicated to prevent post-HCT CMV reactivation.
Keyphrases
  • cell cycle arrest
  • cell death
  • pi k akt
  • oxidative stress
  • stem cells
  • signaling pathway
  • metabolic syndrome
  • low dose
  • insulin resistance
  • skeletal muscle
  • adipose tissue
  • high dose
  • cell therapy
  • patient reported