631. CMV Reactivation in Hematopoietic Cell Transplant Candidates: A Novel Risk Factor for Post-transplant Reactivation
Authors: Zamora Danniel , Xie Hu , Hill Joshua A , Duke Elizabeth , Green Margaret , Kimball Louise E , Holmberg Leona , Waghmare Alpana , Greninger Alexander L , Jerome Keith R , Flowers Mary , Hill Geoffrey , Leisenring Wendy M , Boeckh Michael J 
Published: December 2022

Abstract

Background
CMV reactivation is occasionally detected during the work-up for hematopoietic cell transplantation (HCT) but its natural history and significance on posttransplant CMV risk is unknown.

Methods
CMV seropositive 1st HCT allograft recipients in the preemptive therapy era (2010-17) were analyzed. CMV PCR testing was routinely performed before and after HCT. Cumulative incidences of CMV reactivation after HCT were calculated at multiple PCR thresholds by pre-HCT viral loads (peak: &lt; or &gt;150 IU/mL; last prior to HCT positive vs positive to negative). Treatment of pre-HCT reactivation was recommended for viral loads &gt;50 IU/mL. Multivariable Cox proportional hazard models were used to determine the association of pre-transplant CMV reactivation on post-HCT CMV reactivation at different PCR thresholds.

Results
Among 1536 patients (median age 50 y, range 0.1-81), 155 (10%), 53 (3.5%) and 24 (1.6%) had pre-HCT reactivation in the month before HCT at any level, &gt;150 IU/mL, and &gt;500 IU/mL, respectively. Pre-transplant CMV reactivation was associated with a higher risk of post-HCT CMV reactivation at all examined PCR thresholds and with CMV disease after transplantation in cumulative incidence (Figure 1) and multivariable analyses (Figure 2A). Patients who had CMV DNA detected that subsequently became negative before HCT (with or without treatment) had a lower risk than those who proceeded to HCT with viremia (Figure 2B).
Cumulative Incidence of CMV Infection and Disease
Multivariable Cox Regression

Conclusion
CMV reactivation occurs pre-HCT in ∼10% of CMV seropositive HCT candidates and is a risk factor for post-HCT CMV events at all severity levels, placing a HCT recipient in a high-risk category. Thus, pre-HCT PCR testing and antiviral treatment as well as the use of optimized posttransplant antiviral or immunotherapy prevention strategies are recommended.

Disclosures
Joshua A. Hill, MD, Allovir: Advisor/Consultant|Allovir: Grant/Research Support|Covance/CSL: Advisor/Consultant|CRISPR: Advisor/Consultant|Deverra: Grant/Research Support|Gilead: Grant/Research Support|Karius: Advisor/Consultant|Karius: Grant/Research Support|Merck: Grant/Research Support|Octapharma: Advisor/Consultant|OptumHealth: Advisor/Consultant|Oxford Immunotec: Grant/Research Support|Pfizer: Advisor/Consultant|Symbio: Advisor/Consultant|Takeda: Advisor/Consultant Leona Holmberg, MD, PhD, Bristol Myers Squibb: Grant/Research Support|Janssen: Grant/Research Support|Merck: Grant/Research Support|Millennium-Takada: Grant/Research Support|Sanofi: Grant/Research Support|Seattle Genetics: Grant/Research Support|Up to Date: Royalty Alpana Waghmare, MD, Allovir: Grant/Research Support|Ansun Biopharma: Grant/Research Support|Devarra Therapeutics: DSMB|Kyorin Pharmaceutical: Advisor/Consultant|Pfizer: Grant/Research Support|Vir/GSK: Grant/Research Support Alexander L. Greninger, MD, PhD, Abbott: Contract Testing|Cepheid: Contract Testing|Gilead: Grant/Research Support|Gilead: Contract Testing|Hologic: Contract Testing|Merck: Grant/Research Support|Novavax: Contract Testing|Pfizer: Contract Testing Mary Flowers, MD, Incyte Corp.: Grant/Research Support|Janssen: Honoraria|Johnson & Johnson: Honoraria|Novartis: Honoraria|Pharmacyclics, Inc.: Grant/Research Support Geoffrey Hill, M.D., FRACP, FRCPA, Applied Molecular Transport: Grant/Research Support|Compass Therapeutics: Grant/Research Support|Generon Corporation: Advisor/Consultant|Heat Biologics: Grant/Research Support|iTeos Therapeutics: Advisor/Consultant|iTeos Therapeutics: Grant/Research Support|Laevoroc Oncology: Grant/Research Support|NapaJen Pharma: Advisor/Consultant|Neoleukin Therapeutics: Advisor/Consultant|Serplus Technology: Grant/Research Support|Syndax Pharmaceuticals: Grant/Research Support Michael J. Boeckh, MD PhD, Allovir: Advisor/Consultant|Amazon: Grant/Research Support|Ansun Biopharma: Grant/Research Support|EvrysBio: Advisor/Consultant|Gates Ventures: Grant/Research Support|Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|GlaxoSmithKline: Advisor/Consultant|GlaxoSmithKline: Grant/Research Support|Helocyte: Advisor/Consultant|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Kyorin Pharmaceuticals: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Regeneron: Grant/Research Support|ReViral: Advisor/Consultant|Symbio: Advisor/Consultant|Takeda: Grant/Research Support|Vir Biotechnology: Advisor/Consultant|Vir Biotechnology: Grant/Research Support.