Human Herpesvirus 6 Infection Following Haploidentical Transplantation: Immune Recovery and Outcome

Abstract

Human herpesvirus 6 (HHV-6) is increasingly recognized as a potentially life-threatening pathogen in allogeneic hematopoietic stem cell transplantation (alloSCT). We retrospectively evaluated 54 adult patients who developed positivity to HHV-6 after alloSCT. The median time from alloSCT to HHV-6 reactivation was 34 days. HHV-6 was present in plasma samples from 31 patients, in bone marrow (BM) of 9 patients, in bronchoalveolar lavage fluid and liver or gut biopsy specimens from 33 patients, and in cerebrospinal fluid of 7 patients. Twenty-nine patients developed acute graft-versus-host disease (GVHD), mainly grade III-IV, and 15 had concomitant cytomegalovirus reactivation. The median absolute CD3 lymphocyte count was 207 cells/µL. We reported the following clinical manifestations: fever in 43 patients, skin rash in 22, hepatitis in 19, diarrhea in 24, encephalitis in 10, BM suppression in 18, and delayed engraftment in 11. Antiviral pharmacologic treatment was administered to 37 patients; nonetheless, the mortality rate was relatively high in this population (overall survival [OS] at 1 year, 38% ± 7%). A better OS was significantly associated with a CD3 cell count ≥200/µL at the time of HHV-6 reactivation (P = .0002). OS was also positively affected by the absence of acute GVHD grade III-IV (P = .03) and by complete disease remission (P = .03), but was not significantly influenced by steroid administration, time after alloSCT, type of antiviral prophylaxis, plasma viral load, or organ involvement. Although HHV-6 detection typically occurred early after alloSCT, better T cell immune reconstitution seems to have the potential to improve clinical outcomes. Our findings provide new insight into the interplay between HHV-6 and the transplanted immune system.

High human herpesvirus 6 viral load in pediatric allogeneic hematopoietic stem cell transplant patients is associated with detection in end organs and high mortality

“…Six of fourteen patients had more than one site that tested positive for HHV-6, while the remainder had single organ involvement. Interestingly, at the time of tissue detection of HHV-6, with the exception of one patient, the virus was only detectable at very low copy numbers or not at all in blood, as has also been described by Greco et al 36 We conclude that while preemptive antiviral treatment may enable clearance of the virus from blood, HHV-6 seems to persist in tissues.…”

High Incidence of Early Human Herpesvirus-6 Infection in Children Undergoing Haploidentical Manipulated Stem Cell Transplantation for Hematologic Malignancies

“…Despite the high mortality rate associated with HHV-6 infection, all our patients responded to treatment, and none died directly of infection, [8À11,35]. Treatment of choice was foscarnet in most cases as widely reported [34,35], followed by ganciclovir or a combination of both drugs, especially in patients with encephalitis. All patients reactivated HHV-6, and this fact may in part be explained by the active surveillance performed twice a week for HHV-6 infection by PCR from the start of conditioning regimen to the achievement of immune reconstitution to drive a preemptive or an early antiviral therapy.…”

“…D 3 1 X XMoreover, they reported a relatively high mortality rate, with an OS of 38% § 7% at 1 year after HHV-6 reactivation. Conversely, patients with CD3 + T cell counts > .2 £ 10 9 /L at the time of HHV-6 reactivation has a better OS (63% versus 11% for patients with CD3 < 200/mL) [35].…”

Unexpected High Incidence of Human Herpesvirus-6 Encephalitis after Naive T Cell–Depleted Graft of Haploidentical Stem Cell Transplantation in Pediatric Patients

“…Therefore, despite HHV-6 infection usually being self-limiting, patients who experienced symptomatic HHV-6 infections showed poorer long-term survival [48]. Immune reconstitution has been considered 1 of the most important factors for controlling HHV-6 reactivation and infection, with a better OS in patients with CD3 + 200 cells/mL at the time of infection [49].…”