No Evidence for Long-Term Persistence of HHV-6 Viremia after Cord Blood Transplantation

Abstract

HHV-6 reactivation is common after cord blood transplantation (CBT). However, the ability of the new immune system to clear HHV-6 viremias is unknown. A previous study of 23 CBT recipients suggested that ∼50% of patients had detectable HHV-6 by whole blood PCR over a year after transplant (Illiaquer et al. J Infect Dis 2014; 567-570). We studied HHV-6 persistence in a larger cohort using serum. We reviewed CBT recipients at the University of Minnesota (2011-2017) who reactivated HHV-6 (whole blood quantitative PCR > 500 copies/mL on at least 1 occasion) by 1 year post-transplant. A subset (n = 59) had an available research serum sample at 1 year (+/- 4 weeks) on an IRB-approved biorepository protocol; we tested these samples by quantitative PCR for HHV-6A and B (Rotor-Gene, Qiagen) in a CLIA-certified laboratory. Median (range) age was 44 (1-72) years; 40 (68%) were male. The most common underlying diseases were acute leukemia (n = 29), lymphomas (n = 10), and non-malignant disorders (n = 9). 33 patients were CMV seropositive. ATG or alemtuzumab were used in 16 patients. Conditioning was reduced-intensity in 31 patients. GVHD prophylaxis was cyclosporine/MMF in 41 and sirolimus/MMF in 18. Grade II-IV acute GVHD occurred in 25 patients and chronic GVHD by 1 year in 12. Twelve (20%) patients cleared viremia (based on whole blood PCR) before the research sample was collected. This clearance occurred at median (range) of 64 (13-244) days after HCT. One (2%) patient cleared HHV-6 at 538 days after HCT. 46 (78%) patients continued to have detectable whole blood PCR until a median (range) of 127 (15-1441) days after HCT with no subsequent negative sample. Among research serum samples collected at 1 year, only 1 had HHV-6A (14,556 copies/mL) and 1 had HHV-6B (below the lower limit of quantification). The patient with detectable HHV-6A had chromosomal integration. The patient with detectable HHV-6B had previous whole blood levels ranging 9,900-164,800 copies/mL. Late persisting HHV-6 viremia was rare in our 59 CBT recipients. Using serum in our study permitted exclusive detection of cell-free HHV-6 DNA, which is a more specific test for HHV-6 reactivation. We suggest no defect in cord blood allograft's ability to clear HHV-6 viremia.