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Cytomegalovirus Viral Load Kinetics Predict Cytomegalovirus End-Organ Disease and Mortality After Hematopoietic Cell Transplant

Anat Stern, Yiqi Su, Henry Dumke, Jiaqi Fang, Roni Tamari, Ann A. Jakubowski, Christina Cho, Sergio Giralt, Miguel‐Angel Perales, Genovefa A. Papanicolaou

2021The Journal of Infectious Diseases21 citationsDOIOpen Access PDF

Abstract

BACKGROUND: We investigatedthe association between time-averaged area under the curve (AAUC) of cytomegalovirus (CMV) viral load (VL) by day 100 and overall survival (OS) at 1-year after hematopoietic cell transplantation (HCT). METHODS: In a retrospective cohort study, including patients receiving HCT between June 2010 and December 2017 from Memorial Sloan Kettering Cancer Center, AAUC was calculated for patients with detected VL. Patients were categorized into non-controllers (Q4) and controllers (Q1-Q3) using the highest AAUC quartile as cutoff. Cox models were used to estimate the association between AAUC and OS. Patients with non-detected CMV VL were categorized into elite-controllers (recipient+ [R+] or R-/donor+ [D+]) and R-/D-. RESULTS: The study (N = 952) included 282 controllers, 93 non-controllers, 275 elite-controllers, and 302 R-/D-. OS was 80.1% and 58.1% for controllers and non-controllers, respectively. In multivariable models, non-controllers had worse OS versus controllers (adjusted hazard ratio [HR] = 2.65; 95% confidence interval [CI], 1.71-4.12). In landmark analyses, controllers had similar OS as elite-controllers (HR = 1.26; 95% CI, .83-1.91) or R-/D- (HR = 0.98; 95% CI, .64-1.5). CONCLUSIONS: Non-controllers had worse OS 1-year post-HCT. Controllers had similar OS as elite-controllers or R-/D-. Future studies are needed to validate our AAUC cutoff across different cohorts and CMV management strategies.

Topics & Concepts

Hazard ratioCytomegalovirusMedicineViral loadHematopoietic cellConfidence intervalCytomegalovirus infectionInternal medicineProportional hazards modelRetrospective cohort studyQuartileCohortHematopoietic stem cell transplantationTransplantationHuman cytomegalovirusOncologyImmunologyBiologyViral diseaseHuman immunodeficiency virus (HIV)VirusHaematopoiesisHerpesviridaeStem cellGeneticsCytomegalovirus and herpesvirus researchImmune Cell Function and InteractionViral-associated cancers and disorders