HHV-6 linked to neutropenia, thrombocytopenia, longer hospital stays and a 5X increased risk of serious complications after autologous transplant

In a prospective study, patients with active HHV-6 infection took 25% longer to recover from neutropenia, and platelet recovery took 7-10 days longer than in patients without active infection. Those with active infections also spent significantly more time in the hospital with complications.

Active HHV-6 infection was detected in 11.2% of 196 adult patients undergoing peripheral blood autologous stem cell transplantation (SCT). Those with active HHV-6 reactivation spent a median of 30.5 days in the hospital vs 22 days for patients without infection, and the median time between transplant and last transfusion was longer for infected patients (17 days vs 12.5 days). Active HHV-6 infection was also associated with an increased number, and severity, of serious complications, including liver enzyme elevation and acute kidney injury.

Thrombocytopenia (Tokimasa 2002) and neutropenia (Chitlur 2005, Nash 2004) in association with HHV-6 infection have been reported in SCT and solid organ recipients.

Source: Journal of Infection, Balsat 2019

Compared to platelet and neutrophil levels, T cell changes have been more extensively explored in SCT recipients with HHV-6 infection (Phan 2018). HHV-6B appears to affect T cell reconstitution (Wang 1999), although this may be cell subtype specific and time dependent (de Koning 2018), with CD4+ lymphocytes particularly affected. One previous report has found HHV-6 reactivation to be associated with rapid expansion of total lymphocytes (Watanabe 2018). A higher incidence of grade 2-4 acute graft vs host disease has also been observed among HSCT recipients with HHV-6 reactivation and impaired CD4+ lymphocyte reconstitution compared to those without HHV-6 reactivation. Patients with HHV-6 reactivation and satisfactory immune reconstitution were more likely to develop GVHD than those without HHV-6, but less likely than those with both HHV-6 and impaired immune reconstitution (Admiraal 2017). CD3+ lymphocyte reconstitution has also been found to be affected by HHV-6 (Comar 2005), and delayed reconstitution of CD3+ cells in HHV-6+ SCT recipients was associated with lower survival in one study (Greco 2016).

Further prospective studies using antiviral treatment are needed to confirm a causative role for HHV-6 in poor hematologic reconstitution post-transplantation.

A significantly higher percentage of patients who developed active HHV-6 infections underwent the BEAM conditioning regimen and had non-Hodgkin lymphoma as an underlying condition compared to patients without active HHV-6; the significance of these findings remains to be seen.

Find the full paper here: Balsat 2019.