Human herpesvirus-6 reactivation and disease after allogeneic haematopoietic cell transplantation in the era of letermovir for cytomegalovirus prophylaxis

Kampouri, Eleftheria; Zamora, Danniel; Kiem, Erika S.; Liu, Winnie; Ibrahimi, Sarah; Blazevic, Rachel L.; Lovas, Erika A.; Kimball, Louise E.; Huang, Meei-Li; Jerome, Keith R.; Ueda Oshima, Masumi; Mielcarek, Marco; Zerr, Danielle M.; Boeckh, Michael J.; Krantz, Elizabeth M.; Hill, Joshua A.

doi:10.1016/j.cmi.2023.07.026

Cited by 7 publications

(4 citation statements)

References 34 publications

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“…Since these broad-spectrum antivirals have a prophylactic effect against HHV-6B, an increase in HHV-6B reactivation could be possible [ 21 , 31 , 32 , 33 ]. A large retrospective study among 738 HCT recipients compared the incidence of HHV-6B reactivation and disease (by clinical testing) in two cohorts: before and after the routine use of letermovir [ 34 ]. Reassuringly, the cumulative incidence of HHV-6B detection was similar in the two cohorts (3%), as was the incidence of HHV-6B encephalitis (0.5% and 0.6% pre- and post-letermovir, respectively), despite a decrease of approximately 40% in the use of broad-spectrum antivirals [ 34 ].…”

Section: Epidemiology Of Hhv-6b After Allogeneic Hctmentioning

confidence: 99%

“…A large retrospective study among 738 HCT recipients compared the incidence of HHV-6B reactivation and disease (by clinical testing) in two cohorts: before and after the routine use of letermovir [ 34 ]. Reassuringly, the cumulative incidence of HHV-6B detection was similar in the two cohorts (3%), as was the incidence of HHV-6B encephalitis (0.5% and 0.6% pre- and post-letermovir, respectively), despite a decrease of approximately 40% in the use of broad-spectrum antivirals [ 34 ]. Some differences in viral kinetics were observed;HHV-6B detection shifted to earlier after HCT by a median of 10 days in the post-letermovir cohort [ 34 ].…”

Section: Epidemiology Of Hhv-6b After Allogeneic Hctmentioning

confidence: 99%

“…Reassuringly, the cumulative incidence of HHV-6B detection was similar in the two cohorts (3%), as was the incidence of HHV-6B encephalitis (0.5% and 0.6% pre- and post-letermovir, respectively), despite a decrease of approximately 40% in the use of broad-spectrum antivirals [ 34 ]. Some differences in viral kinetics were observed;HHV-6B detection shifted to earlier after HCT by a median of 10 days in the post-letermovir cohort [ 34 ]. Given that immune reconstitution improves with time after HCT, this earlier timeline could be associated with reduced immunological control [ 35 ].…”

Section: Epidemiology Of Hhv-6b After Allogeneic Hctmentioning

confidence: 99%

“…Given that immune reconstitution improves with time after HCT, this earlier timeline could be associated with reduced immunological control [ 35 ]. Further, the peak plasma and CSF HHV-6B viral load tended to be higher by nearly 1 log 10 copies/mL in the post-letermovir cohort compared to the pre-letermovir cohort [ 34 ]. Whether these changes are clinically relevant remains to be determined.…”

Section: Epidemiology Of Hhv-6b After Allogeneic Hctmentioning

confidence: 99%

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Human Herpes Virus-6 (HHV-6) Reactivation after Hematopoietic Cell Transplant and Chimeric Antigen Receptor (CAR)- T Cell Therapy: A Shifting Landscape

Kampouri,

Handley,

Hill

2024

Viruses

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HHV-6B reactivation affects approximately half of all allogeneic hematopoietic cell transplant (HCT) recipients. HHV-6B is the most frequent infectious cause of encephalitis following HCT and is associated with pleiotropic manifestations in this setting, including graft-versus-host disease, myelosuppression, pneumonitis, and CMV reactivation, although the causal link is not always clear. When the virus inserts its genome in chromosomes of germ cells, the chromosomally integrated form (ciHHV6) is inherited by offspring. The condition of ciHHV6 is characterized by the persistent detection of HHV-6 DNA, often confounding diagnosis of reactivation and disease—this has also been associated with adverse outcomes. Recent changes in clinical practice in the field of cellular therapies, including a wider use of post-HCT cyclophosphamide, the advent of letermovir for CMV prophylaxis, and the rapid expansion of novel cellular therapies require contemporary epidemiological studies to determine the pathogenic role and spectrum of disease of HHV-6B in the current era. Research into the epidemiology and clinical significance of HHV-6B in chimeric antigen receptor T cell (CAR-T cell) therapy recipients is in its infancy. No controlled trials have determined the optimal treatment for HHV-6B. Treatment is reserved for end-organ disease, and the choice of antiviral agent is influenced by expected toxicities. Virus-specific T cells may provide a novel, less toxic therapeutic modality but is more logistically challenging. Preventive strategies are hindered by the high toxicity of current antivirals. Ongoing study is needed to keep up with the evolving epidemiology and impact of HHV-6 in diverse and expanding immunocompromised patient populations.

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