Frequent Human Herpesvirus-6 Viremia But Low Incidence of Encephalitis in Double-Unit Cord Blood Recipients Transplanted Without Antithymocyte Globulin

Abstract

Cord blood transplantation (CBT) is a known risk factor for human herpesvirus-6 (HHV-6) infection. We analyzed the nature of HHV-6 infections in 125 double-unit CBT recipients (median age 42 years) transplanted for hematologic malignancies with calcineurin-inhibitor/ mycophenolate mofetil prophylaxis and no anti-thymocyte globulin (ATG). One-hundred and seventeen (94%) patients reactivated HHV-6 by quantitative plasma PCR (median peak 7,600 copies/mL, range 100-160,000) at a median of 20 days (range 10-59) after transplantation. HHV-6 encephalitis occurred in 2 patients (1.6%), of whom one died and the other recovered with therapy. There was no association between high level HHV-6 viremia (≥ 10,000 or ≥ 25,000 copies/mL) and age, diagnosis, conditioning intensity, or dominant unit characteristics, or between high level viremia and transplant outcomes (engraftment, cytomegalovirus reactivation, day 100 grade II-IV acute graft-versus-host disease, day 100 transplant-related mortality, or 1-year disease-free survival). HHV-6 therapy delayed the onset of cytomegalovirus reactivation. Interestingly, HHV-6 resolution was observed in untreated patients, and resolution of viremia correlated with absolute lymphocyte count recovery. We observed a low incidence of encephalitis and no association with CBT outcomes. Our data suggests therapy in uncomplicated viremia may not be warranted. However, further investigation of the risk-benefit of HHV-6 viremia treatment and standardization of PCR testing is required.

Clinical characteristics and outcome of human herpesvirus-6 encephalitis after allogeneic hematopoietic stem cell transplantation

“…11,27 Methods of GvHD prophylaxis were shown to be associated with the development of HHV-6 encephalitis in CBT; previous reports have supported the clinical plausibility of such a relationship. An inflammatory milieu early after allo-HSCT, such as pre-engraftment immune reaction, 11 engraftment syndrome 28 and GvHD, 12,28 represents risk factors for subsequent development of HHV-6 encephalitis.…”

Human herpesvirus-6 encephalitis after allogeneic hematopoietic cell transplantation: What we do and do not know

“…4,5 HHV-6 encephalitis develops concomitant to peak blood HHV-6 DNA. 3,5,7,8 Some studies in which blood levels of HHV-6 DNA have been monitored have shown a correlation between HHV-6 reactivation and the development of HHV-6 encephalitis, 1,[3][4][5][6][7][8]56 but others have failed to demonstrate such associations. 2,57,58 The reasons for these divergent results may be because of the low incidence of HHV-6 encephalitis even in patients with HHV-6 reactivation.…”

Roseoloviruses in transplant recipients: clinical consequences and prospects for treatment and prevention trials

“…A recent meta-analysis of 19 papers found that HHV-6B encephalitis was significantly higher in CBT recipients (8.3%) than other allogeneic HCT recipients (0.5%) [19 •• ]. In a prospective cohort of CBT recipients transplanted without antithymocyte globulin, reactivation was documented in 94% of patients [29]. The authors reported a low level (1.6%) of encephalitis and no association with clinical outcomes, but almost 1/3 of patients received preemptive antiviral therapy.…”