Human herpesvirus‐6B infection in pediatric allogenic hematopoietic stem cell transplant patients: Risk factors and encephalitis

Abstract

Background Human herpesvirus‐6B (HHV‐6B) infection after allogenic hematopoietic stem cell transplantation (allo‐HSCT) is known to be associated with post‐transplant limbic encephalitis in adults. Meanwhile, the association between HHV‐6B infection and central nervous system complications remains unclear in pediatric allo‐HSCT patients. Methods In this study, HHV‐6B infection was monitored for more than 50 days after HSCT using virus isolation and real‐time PCR. Clinical information such as patient background and encephalitis status was collected retrospectively from medical records. Risk factors for HHV‐6B infection were determined by the Cox proportional hazards model, and the clinical features of HHV‐6B encephalitis in pediatric allo‐HSCT patients were elucidated. Results Human herpesvirus‐6B infection was observed in 74 (33.8%) of 219 patients at 3‐47 days (median 18, interquartile range 13‐20). Risk factors identified in multivariable analysis were hematological malignancy (hazards ratio [HR], 5.0; 95% confidence interval [CI], 2.3/12.5; P < .0001), solid tumor (HR, 4.8; CI, 1.5/16.3; P = .0104), unrelated donor (HR, 2.1; CI, 1.0/4.6; P = .0378), and sex‐mismatched donor (HR 1.8; CI, 1.1/3.0; P = .0257). HHV‐6B encephalitis occurred in only one of the 219 patients (0.46%); this patient demonstrated the typical clinical course of posterior reversible encephalopathy syndrome. Conclusion Hematological malignancy, solid tumor, unrelated donor, and sex‐mismatched donor were significant risk factors for HHV‐6B infection after pediatric allo‐HSCT. In pediatric allo‐HSCT patients, the incidence of HHV‐6B encephalitis was low and the clinical features differed from those in adult patients.

Epidemiology and outcome for viremia in children undergoing bone marrow transplant: A retrospective cohort study

“…Other proposed theories for variation in detection rates include different monitoring durations, variation in risk factors across different source populations, different PCR assay sensitivity or practices (eg, use of whole blood vs plasma), and differing viral load cut-offs. 12,13 Our detection rate of HHV-6 at 8.5% (38/445) is low compared to other similar cohorts 1,6,14,15 and likely reflects non-routine HHV-6 testing in our cohort.…”

“…Cord blood transplants are known to be at a high risk of HHV-6 reactivation due to the absence of HHV-6-specific T cells in cord blood. 15,20,28 We demonstrated a high percentage of cord transplants amongst episodes affected by HHV-6 compared to the other viruses. Given, however, that routine screening was not performed for HHV-6, this may also reflect a surveillance bias to test cord transplants for HHV-6 reactivation.…”

Hippocampal Atrophy in Pediatric Transplant Recipients with Human Herpesvirus 6B

“…By contrast, a limited number of pediatric patients with PALE have been reported to date [31]. Our recent retrospective study showed a low prevalence of HHV-6B encephalitis in pediatric HSCT recipients [32]. It has been suggested that HHV-6B infection is associated with mild cognitive impairment in pediatric HSCT recipients [33].…”

“…As described above, our recent retrospective study demonstrated that HHV-6B-associated CNS disease in pediatric HSCT recipients occurs less frequently than that in adult HSCT recipients. The clinical symptoms also differ between pediatric and adult HSCT recipients [32]. It is possible that mild cognitive impairment caused by HHV-6B infection may be missed in pediatric patients.…”

Pediatric Infectious Diseases Related to Transplantation: Insights From Japan

“…12 A low frequency (0.5%) of HHV-6 encephalitis despite a high rate (34%) of HHV-6 infection was reported with active monitoring in 219 pediatric HCT patients in Japan. 12,13…”