Impact of HHV-6 in Recipients of Ex Vivo T-Cell Depleted Hematopoietic Cell Transplant

Abstract

<h3>Introduction</h3> Recipients of ex-vivo T-cell depleted (TCD) (CD34⁺ selected) hematopoietic cell transplant (HCT) are at increased risk for infections by double-stranded DNA viruses. TCD HCT recipients at Memorial Sloan Kettering Cancer Center were routinely screened for HHV-6 by plasma PCR between 2012 and 2016. The objectives of our study were to 1) report the incidence of persistent HHV-6 viremia and disease 2) identify risk factors of persistent HHV-6 viremia; 3) examine the association between persistent HHV-6 viremia and overall survival (OS) at 1-year post-HCT. <h3>Methods</h3> Recipients with TCD HCT between 2012 and 2016 routinely screened for HHV-6 by plasma PCR were reviewed retrospectively. CD34⁺ selection was performed by the CliniMACS CD34 Reagent system (Miltenyi Biotec, Germany). HHV-6 viremia was defined as ≥1 HHV-6 viral load (VL) >limit of quantification. Persistent HHV-6 viremia was defined as ≥2 consecutive measurements of VL ≥500 copies/mL through day+100 post-HCT, death, relapse, and second transplant whichever occurred first. Cox proportional model was used to examine the risk factors of persistent HHV-6 viremia. One-year OS was estimated by Kaplan-Meier method. <h3>Results</h3> Of 312 patients, 59% were male and median age was 55 years (range, 22-73). 67% had acute leukemia and myelodysplastic syndrome and 18% had mismatched donors. 55% developed HHV-6 viremia. Eighty-three (27%) had persistent HHV-6 viremia with a median duration of 67 days (interquartile range [IQR], 56-75) (Figure 1). Mismatched donor (P=0.04) and recipient CMV seronegativity (R-) (P=0.04) were associated with persistent HHV-6 viremia. Of 83 patients with persistent HHV6 viremia, 23 (28%) had max VL ≥10,000 copies/mL and 7 (8%) developed HHV-6 disease (encephalitis 1, pneumonitis 4, and organizing pneumonia 2). Maximum VL with HHV-6 disease was a median VL 71,700 copies/mL (IQR, 8,211-123,500). Persistent HHV-6 viremia was associated with lower absolute lymphocyte counts (ALCs) up to 1-year post-HCT (figure 2) and lower 1-year OS (P=0.02) (figure 3). <h3>Conclusion</h3> 27% of TCD HCT recipients developed persistent HHV-6 viremia. Mismatched donor and CMV R- were associated with persistent HHV-6 viremia. Among patients with persistent HHV-6 viremia, 8% developed HHV-6 disease. Persistent HHV-6 viremia was associated with lower ALCs and OS at 1-year post-HCT.