Outcomes of Haploidentical Stem Cell Transplant Recipients with HHV-6 Reactivation Receiving Antiviral Therapy

Background Human herpesvirus 6 (HHV-6) frequently reactivates following allogeneic hematopoietic stem cell transplant (alloHCT) with spontaneous resolution in most patients. HHV-6 related encephalitis may occur; however, other clinical syndromes are less well defined. Previous antiviral pre-emptive and prophylactic studies have not demonstrated clinical efficacy in preventing HHV-6 related encephalitis or improving transplant related outcomes and is not routinely recommended by clinical guidelines. Less is known about the clinical impact of HHV-6 reactivation and antiviral treatment following haploidentical alloHCT. Objective To evaluate baseline characteristics and outcomes of patients with HHV-6 reactivation following haploidentical alloHCT treated with antiviral agents for HHV-6 compared to those who were clinically observed. Methods All patients at Moffitt Cancer Center undergoing haploidentical alloHCT from 11/2014 – 11/2020 with HHV-6 reactivation were retrospectively identified. Patients were not uniformly prospectively monitored, and treatment was determined by treating physician with institutional guidance. Baseline characteristics and clinical outcomes were compared between patients who received antiviral therapy for HHV-6 or were clinically observed. Results Of 188 patients undergoing haploidentical alloHCT, 58 (30.9%) were found to have HHV-6 reactivation. Median onset of reactivation was 25 days (range 3 – 94). Patients who received antiviral therapy were more likely to have high level reactivation, defined as ≥ 10,000 copies/mL (85.7% vs 40.5%, p<0.001) and had higher peak viral quantitative measurements (p=0.004). Central nervous system symptoms were present in 7 (33.3%) of treated patients compared to 4 (10.8%) of observed patients (p=0.077) with no difference in time to onset of symptoms. No definite cases of HHV-6 encephalitis were diagnosed. Not all patients received lumbar punctures but treated patients were more likely to have CSF assessment (76.2% vs 27.0%, p<0.001). Median time to clearance of plasma HHV-6 DNA and incidence of grade III or IV acute graft-versus-host disease did not differ between groups. Median time to neutrophil engraftment tended to be longer in treated patients (20 days vs 17 days) though this was not clinically significant (p=0.054). Day 100 mortality was higher in patients receiving antiviral therapy (38.1% vs 10.8%, p=0.020). Conclusions/Discussion Receipt of HHV-6 targeted antiviral therapy was not associated with improved transplant related outcomes in this retrospective study. Further controlled prospective studies are needed to evaluate if some populations may benefit from pre-emptive therapy.