Reactivation Of Human Herpesvirus Research Articles

Long-Lasting HHV-6 Reactivation in Long-Term Adult Survivors After Double Umbilical Cord Blood Allogeneic Stem Cell Transplantation

Higher incidence of human herpesvirus 6 (HHV-6) infection has been documented after umbilical cord blood allo-transplant in adults. Here we demonstrate that HHV-6 reactivation persists for a very long time in half of the patients after this type of graft. Long-term immune reconstitution does not explain this event, which remains to be explained.

The Clinical Significance of Human Herpes Virus 6 (HHV-6) Dnaemia in 68 Hematopoietic Cell Transplant Recipients (HSCT)

s / Biol Blood Marrow Transplant 20 (2014) S211eS256 S219 regimen, immunosuppressive regimen, stem cell source, time to engraftment, and underlying disease) predicted for HHV-6 reactivation. Comparing HSCTs with HHV-6 reactivation and those without, survival at 100 days (77% v. 73%, p1⁄40.706) and development of aGVHD (57% v. 32%, p1⁄40.062) were not significantly different. HHV-6 reactivation with > 1000 copies/mL trended towards increased development of aGVHD (63% v. 36%, p1⁄40.051). Notably, aGVHD developed significantly less often in Haplo-Cord HSCTs compared to HSCTs only using UCB (31% v. 61%, p1⁄40.022). Based on preliminary analysis, early HHV-6 reactivation after UCB HSCT occurs indiscriminately and does not influence survival or incidence of aGVHD at 100 days post-transplantation.

Analysis of human herpes virus 6 infections with a quantitative, standardized, commercial kit in pediatric stem cell transplant recipients after transplantation.

BACKGROUND AND OBJECTIVESThe aim of the study was to assess the incidence and clinical relevance of active Human Herpes Virus 6 (HHV6) infections in pediatric patients after allogeneic stem cell transplantation.DESIGN AND SETTINGSRetrospective analysis of samples prospectively collected at Akdeniz University Medical Faculty Hospital, Antalya, Turkey, between May 2006 and July 2007 from 15 pediatric patients with allogeneic hematopoietic stem cell transplantation (HSCT).SUBJECTS AND METHODSA commercial quantitative real-time polymerase chain reaction kit was used to analyze plasma samples collected from 15 pediatric allogeneic HSCT recipients.RESULTSHHV6 DNA was found positive in 8 (53%) patients. HHV6 DNA levels above 1000 copies/mL were found only in 2 patients and they were also consecutively positive for HHV6 DNA. Age at transplantation, use of ATG, and receiving grafts other than HLA identical siblings increased the risk, with a statistically significant difference, of having HHV6 reactivation with levels exceeding 1000 copies/mL (P values, respectively, P=.03, .001, .025). Active HHV6 infections with HHV6 viremia levels higher than 1000 copies/mL were associated with subsequent delayed platelet engraftment (P=.001), acute graft versus host disease (P=.001), skin rash, and fever of unknown origin.CONCLUSIONMore than half of pediatric allogeneic HSCT patients develop active HHV6 infection, and especially in patients with high viremic loads, the infection can result in serious clinical situations. A clinically significant cutoff value for viremia seems to be necessary to predict serious clinical complications.

Fever, Rash, and Systemic Symptoms: Understanding the Role of Virus and HLA in Severe Cutaneous Drug Allergy

Drug hypersensitivity syndromes such as abacavir hypersensitivity and the severe cutaneous adverse drug reactions have been associated with significant short- and long-term morbidity and mortality. More recently, these immunologically mediated and previously unpredictable diseases have been shown to be associated with primarily class I but also class II HLA alleles. The case of the association of HLA-B*57:01 and abacavir hypersensitivity has created a translational roadmap for how this knowledge can be used in the clinic to prevent severe reactions. Although many hurdles exist to the widespread translation of such HLA screening approaches, our understanding of how drugs interact with the major histocompatibility complex has contributed to the discovery of new models that have provided considerable insights into the immunopathogenesis of severe cutaneous adverse drug reactions and other T-cell-mediated drug hypersensitivity syndromes. Future translation of this knowledge will facilitate the development of preclinical toxicity screening to significantly improve efficacy and safety of drug development and design.

Human Herpesvirus 6 Infection in Febrile Children: Frequency in an Iranian Referral Hospital

Polymerase chain reaction (PCR) tests for virus in blood and saliva are frequently positive in persons with past infection, re-infection with new strains or latency with or without repeated reactivation of human herpesvirus 6 (HHV6). The aim of this study is to determine the frequency of HHV6 infections in children aged two years or under with an initial diagnosis of fever during an evaluation in the paediatric emergency department of the Children’s Medical Center, an Iranian referral hospital, using PCR methodology. In all children, the clinical characteristics noted at the initial evaluation as well as demographic and laboratory findings were obtained. Among 150 patients (91 male, 59 female) admitted to the paediatric emergency department, HHV6 was found in 49 (33%; 14 female [29%] and 35 male [71%]). Rash was seen in 14/49 (29%) of HHV6-positive cases, while 35 cases without rash had a positive PCR test (71%). Seizures were found in 78/150 (52%) patients. There was no significant association between seizures and positive HHV6 results (43% in patients without seizure; 57% in cases that developed seizure). Although standard PCR on samples including blood cannot discriminate between latent and active HHV6 infection, nearly a third of patients (mainly children less than one year old) had HHV6 infection.

Status Epilepticus Due to Severe HHV-6 Encephalitis in an Allogeneic Stem Cell Transplant Recipient

Reactivation of human herpes virus-6 (HHV-6) after stem cell transplantation occurs frequently. It is associated with clinical manifestations varying from nonspecific symptoms such as fevers or rash, to severe life threatening complications including post-transplantation limbic encephalitis. We report a case of severe HHV-6 encephalitis with viremia in an allogeneic peripheral stem cell transplant recipient who presented with status epilepticus unresponsive to antiepileptic therapy. With intravenous ganciclovir and supportive care, the patient’s condition improved. Awareness of HHV-6 infection in stem cell transplant recipients may help with early diagnosis and improved outcome.

Detection of Herpes Viruses by Multiplex and Real-Time Polymerase Chain Reaction in Bronchoalveolar Lavage Fluid of Patients with Acute Lung Injury or Acute Respiratory Distress Syndrome

Background: Human herpes viruses (HHVs) are important pathogens in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Rapid and efficient diagnostic tools are needed to detect HHVs in the lung in ALI/ARDS patients. Objectives: This study aimed to evaluate the usefulness of multiplex and real-time polymerase chain reaction (PCR) analysis of bronchoalveolar lavage fluid (BALF) for detecting HHV reactivation in ALI/ARDS patients. Methods: Between August 2008 and July 2012, eighty-seven BALF samples were obtained from ALI/ARDS patients with unknown etiology and analyzed for HHVs. The types of HHVs in the BALF samples were determined using qualitative multiplex PCR followed by quantitative real-time PCR. Results: Multiplex PCR identified herpes simplex virus type 1 (HSV-1) (n = 11), Epstein-Barr virus (EBV) (n = 16), cytomegalovirus (CMV) (n = 21), HHV type 6 (HHV-6) (n = 2), and HHV-7 (n = 1) genomic DNA in 35 (40%) of the BALF samples, including 14 (16%) samples containing 2 or 3 HHV types. CMV and EBV reactivation was rare in immunocompetent patients, whereas reactivation of HSV-1 was predominantly observed in intubated patients regardless of their immune status. Overall, HHVs were almost exclusively found in patients with immunosuppression or endotracheal intubation. Real-time PCR detected 0.95-1.59 × 10⁶ copies of viral DNA/μg human genome DNA, and HSV-1 (n = 4), CMV (n = 9), and HHV-6 (n = 1) were identified as potentially pathogenic agents. Conclusions: The implementation of multiplex and real-time PCR of BALF was feasible in ALI/ARDS patients, which allowed efficient detection and quantification of HHV DNA.

Shock State

Some patients with drug reaction with eosinophilia and systemic symptoms (DRESS) are probably admitted in intensive care unit (ICU), but data concerning their clinical features at admission are scarce. Therefore, in the present study, we used a clinical network of French intensivists to study the clinical features and evolution of DRESS patients hospitalized in ICU. A national, retrospective, multicenter study collected DRESS cases hospitalized in ICU for DRESS from 2000 to end of 2011. All files were analyzed through the RegiSCAR scoring system as "no," "possible," "probable," or "definite" DRESS. Patients were included only if they had a probable or definite DRESS. Demographic, hemodynamic, biological, and infectious data were recorded. Twenty-one patients were included. Hospital mortality was 10 (47%) of 21, and 16 of 21 patients had on admission a shock state necessitating vasopressor agents. Echocardiographic ejection fraction in shock patients was depressed (47% ± 13%). Mechanical ventilation was required in 13 of 21 cases. Hepatic failure was observed in 11 of 21 cases, acute renal failure in 18 of 20 cases, and lactic acidosis in 12 of 20 patients. Initial bacteriology was negative in all patients. Human herpesvirus reactivations were found in five of 15 cases. In conclusion, shock without bacteriological documentation associated with multiple organ failure is the most common presentation of DRESS at admission in ICU and is associated with a higher mortality than previously described.

Sarcoma de Kaposi por virus del herpes humano de tipo 8 en un receptor de trasplante hepático pediátrico. Caso clínico

Patients under immunosuppressive treatment are at risk of developing malignant tumors. Primary infection or reactivation of human herpesvirus 8 (HHV-8) may predispose to Kaposi's sarcoma (KS) after solid organ transplantation. KS in pediatric liver transplant recipients has low incidence and poor prognosis. We report the clinical presentation of a KS in lymph node following HHV-8 infection in a pediatric patient presenting four months after liver transplantation. He had a good outcome with suspension of tacrolimus and conversion to sirolimus one month after diagnosis. To our knowledge, this is the frst KS reported case in our country after liver transplant in a pediatric recipient and we believe that this entity should be taken into consideration in the differential diagnosis of post-transplant complications.

DRESS syndrome

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, initially recognized as a serious form of cutaneous drug adverse reaction, is now viewed as a drug-related syndrome that can cause life-threatening organ dysfunctions. Characteristic features include a long time interval from first drug exposure to symptom onset and a prolonged course, often with flares, even after discontinuation of the causal drug. The pathophysiology of DRESS syndrome remains incompletely understood but involves reactivation of herpes viruses (HHV-6, HHV-7, EBV, and CMV), against which the body mounts a strong immune response. The culprit drugs may not only affect epigenetic control mechanisms, thereby promoting viral reactivation, but also induce an antiviral T-cell response by interacting with the major histocompatibility complex receptor in individuals with genetic susceptibility factors. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome is a potentially life-threatening form of cutaneous drug adverse reaction. The severity of this syndrome is related to the systemic manifestations, which can result in multiorgan failure. DRESS syndrome is characterized by highly specific features, most notably regarding the timing of the manifestations. New insights into the underlying pathophysiological mechanisms indicate a role for immunogenetic susceptibility factors and for reactivation of human herpes viruses (HHVs), chiefly HHV-6. We report a typical case of DRESS syndrome and discuss recent data about this condition.

Human herpes virus 6 reactivation: important predictor for poor outcome after myeloablative, but not non-myeloablative allo-SCT

Hematopoietic SCT (HSCT) is often complicated by viral reactivations. In this retrospective cohort study (January 2004-August 2008), predictors for human herpes virus 6 (HHV6)-reactivation and associations between HHV6-reactivation and clinical outcomes after allogeneic HSCT were studied. HHV6 DNA load in plasma was monitored weekly by quantitative real-time PCR. Associations between the main end point HHV6-reactivation and other end points, that is, acute GVHD (aGVHD) and NRM were analyzed using Cox proportional hazard models. In total, 108 patients receiving either a myeloablative (MA; n=60) or non-myeloablative (NMA; n=48) conditioning regimen were included. Median age was 40 years (range 17-65); median follow-up was 20 months (range 3-36). In 16/60 (27%) patients with MA conditioning regimen, a HHV6 reactivation was observed (mean viral load 50 323 cp/mL) compared with 2/48 (4%) patients with a NMA conditioning regimen with low viral load (mean 1100 cp/mL). In multivariate analysis, MA conditioning was the only predictor for HHV6 reactivation (P=0.02). In addition, HHV6 reactivation was associated with grades 2-4 aGVHD (P<0.001) and NRM (P=0.03). Regular monitoring of HHV6 reactivation after HSCT might be important in MA HSCT patients to enable early initiation of antiviral treatment or to anticipate aGVHD, all of which may improve clinical outcome.

Human Herpesvirus 6 (HHV-6) Reactivation and HHV-6 Encephalitis After Allogeneic Hematopoietic Cell Transplantation: A Multicenter, Prospective Study

The epidemiology of human herpesvirus 6 (HHV-6) encephalitis after allogeneic hematopoietic cell transplantation (HCT) and its relationship with HHV-6 reactivation have not been sufficiently characterized. This prospective, multicenter study of 230 allogeneic HCT recipients investigated the epidemiology of HHV-6 reactivation and HHV-6 encephalitis. Plasma HHV-6 DNA load was prospectively evaluated twice weekly until 70 days after HCT. Cumulative incidence of positive HHV-6 DNA and high-level HHV-6 reactivation (plasma HHV-6 DNA ≥10(4) copies/mL) at day 70 after HCT was 72.2% and 37.0%, respectively. Multivariate analysis identified myeloablative conditioning (hazard ratio [HR], 1.9; P = .004), umbilical cord blood transplantation (UCBT) (HR, 2.0; P = .003), and male sex (HR, 1.6; P = .04) as risk factors for displaying high-level HHV-6 reactivation. HHV-6 encephalitis occurred in 7 patients, and cumulative incidence at day 70 was 3.0%. None of the144 patients without high-level HHV-6 reactivation and 7 of 86 patients (8.1%) with high-level HHV-6 reactivation developed HHV-6 encephalitis (P = .0009). Prevalence of HHV-6 encephalitis was significantly higher among patients receiving UCBT than in patients with other sources (cumulative incidence at day 70, 7.9% vs 1.2%, P = .008). In each of 7 patients with HHV-6 encephalitis, central nervous system (CNS) symptoms developed concomitant with peak plasma HHV-6 DNA (range, 21 656-433 639 copies/mL). High levels of plasma HHV-6 DNA are associated with higher risk of HHV-6 encephalitis. UCBT is a significant risk factor for HHV-6 encephalitis. HHV-6 encephalitis should be considered if CNS dysfunction develops concomitant to high-level plasma HHV-6 DNA after allogeneic HCT.

Saliva Polymerase Chain Reaction Assay for Detection and Follow-up of Herpesvirus Reactivation in Patients With Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS)

Reactivations of human herpesviruses (HHVs) contribute to the development of drug reaction with eosinophilia and systemic symptoms (DRESS). Diagnosis of HHV reactivation is conventionally based on quantitative real-time polymerase chain reaction (PCR) analysis of blood samples, but these viruses are present in the oropharynx and are shed in saliva. To evaluate the use of a saliva PCR assay for demonstrating HHV shedding in patients with DRESS. Shedding of HHV in saliva was prospectively studied in patients with DRESS. Reactivations of HHV, including HHV-6, HHV-7, cytomegalovirus (CMV), and Epstein-Barr virus (EBV), were studied by performing quantitative real-time PCR analysis of blood samples obtained at admission) and serial samples of saliva obtained within the first 2 weeks of DRESS; saliva samples from controls were compared. The study included 5 patients who met definite criteria for DRESS and 15 controls (5 immunosuppressed patients and 10 healthy adults). DNA viral loads of HHV, including HHV-6, HHV-7, CMV, and EBV as measured with real-time PCR in blood and saliva samples from patients with DRESS and saliva samples from immunosuppressed and healthy controls. The PCR assay demonstrated shedding of HHV-7, EBV, HHV-6, and CMV, listed by order of magnitude. The DNA viral loads in blood and saliva samples, also measured with real-time PCR, were found to be close. In 1 patient, reactivations in saliva preceded clinical manifestations of CMV disease. Significant production of HHV-7 and EBV was demonstrated in saliva samples from the controls, but neither HHV-6 nor CMV were detected. The saliva PCR assay is a useful tool for demonstration and follow-up of HHV reactivation. The interpretation of HHV viral loads in saliva differs according to HHV type.

Skin recruitment of monomyeloid precursors involves human herpesvirus‐6 reactivation in drug allergy

In drug-induced hypersensitivity syndrome (DIHS), latent human herpesvirus (HHV)-6 is frequently reactivated in association with flaring of symptoms such as fever and hepatitis. We recently demonstrated an emergence of monomyeloid precursors expressing HHV-6 antigen in the circulation during this clinical course. To clarify the mechanism of HHV-6 reactivation, we immunologically investigated peripheral blood mononuclear cells (PBMCs), skin-infiltrating cells, and lymphocytes expanded from skin lesions of patients with DIHS. The circulating monomyeloid precursors in the patients with DIHS were mostly CD11b(+) CD13(+) CD14(-) CD16(high) and showed substantial expression of skin-associated molecules, such as CCR4. CD13(+) CD14(-) cells were also found in the DIHS skin lesions, suggesting skin recruitment of this cell population. We detected high levels of high-mobility group box (HMGB)-1 in blood and skin lesions in the active phase of patients with DIHS and showed that recombinant HMGB-1 had functional chemoattractant activity for monocytes/monomyeloid precursors in vitro. HHV-6 infection of the skin-resident CD4(+) T cells was confirmed by the presence of its genome and antigen. This infection was likely to be mediated by monomyeloid precursors recruited to the skin, because normal CD4(+) T cells gained HHV-6 antigen after in vitro coculture with highly virus-loaded monomyeloid precursors from the patients. Our results suggest that monomyeloid precursors harboring HHV-6 are navigated by HMGB-1 released from damaged skin and probably cause HHV-6 transmission to skin-infiltrating CD4(+) T cells, which is an indispensable event for HHV-6 replication. These findings implicate the skin as a cryptic and primary site for initiating HHV-6 reactivation.

Human Herpesvirus 6, 7 and 8 in Solid Organ Transplantation

Human Herpesvirus 6, 7 and 8 in Solid Organ Transplantation

Human Endogenous Retrovirus-K18 Superantigen Expression and Human Herpesvirus-6 and Human Herpesvirus-7 Viral Loads in Chronic Fatigue Patients

Chronic fatigue syndrome (CFS) is a complex, heterogeneous disease characterized by debilitating fatigue that is not improved with bed rest and worsens after physical activity or mental exertion. Despite extensive research into a cause of CFS, no definitive etiology has been determined; however, a large percentage of CFS patients note an acute infectious event that triggers their fatigue. Blood and saliva were collected from 39 CFS cases and 9 healthy control subjects. Peripheral blood mononuclear cells (PBMCs) were tested for human endogenous retrovirus-K18 (HERV-K18) env transcripts using a TaqMan quantitative polymerase chain reaction (qPCR). In addition, viral copy number of human herpesvirus-6 (HHV-6) and human herpesvirus-7 (HHV-7) were measured in both saliva and PBMCs using TaqMan qPCRs. Transcript levels and viral copy number were compared to patient CFS symptom severity. HERV-K18 env transcripts were not significantly different between healthy control subjects and CFS patients. Also, HERV-K18 env transcripts did not correlate with HHV-6 viral copy number or HHV-7 viral copy number in either PBMCs or saliva. HHV-6 viral copy number and HHV-7 viral copy number in both PBMCs and saliva were not significantly different between healthy control subjects and CFS patients. HERV-K18 env transcripts, HHV-6 viral copy number, and HHV-7 viral copy number did not correlate with CFS symptom severity. We fail to demonstrate a difference in HERV-K18 env transcripts, HHV-6 viral copy number, and HHV-7 viral copy number between CFS patients and healthy controls. Our data do not support the hypothesis of reactivation of HHV-6 or HHV-7 in CFS.

Human herpesvirus‐6 encephalitis during hematopoietic stem cell transplantation leads to poor prognosis

Indications for the application of hematopoietic stem cell transplantation (HSCT) from alternative donors have remarkably broadened in scope; however, the incidence of infections that lead to failure of HSCT, such as human herpesvirus-6 (HHV-6) encephalitis, has also increased. We analyzed risk factors for symptomatic HHV-6 reactivation and the development of HHV-6 encephalitis in 140 consecutive adult patients who received allogeneic HSCT at our institution. Stem cell sources for the recipients were as follows: related-donor bone marrow in 40, related-donor peripheral blood in 5, unrelated bone marrow in 67, and unrelated cord blood in 28. Symptomatic HHV-6 reactivation occurred in 22 patients (16%), and 11 patients manifested encephalitis. Multivariate Cox proportional hazards regression analysis identified cord blood cell transplantation (CBT) as an independent predictor of HHV-6 reactivation (P=0.008). Hyponatremia or hypernatremia at the time of HHV-6 reactivation was detected before the development of HHV-6 encephalitis in 2 or 4 patients, respectively. Two patients died of HHV-6 encephalitis and 6 patients died of relapse of underlying diseases. Survival analysis identified higher risk of the disease (P=0.021) and HHV-6 encephalitis (P=0.003) as independent risk factors for reduced overall survival. In cases involving CBT or unrelated-donor transplantation, patients should be carefully monitored for the symptomatic reactivation of HHV-6.

Drug-induced severe adverse reaction enhanced by human herpes virus-6 reactivation

Reactivation of certain latent viruses has been linked with a more severe course of drug-induced hypersensitivity reaction (HSR). For example, reactivation of human herpes virus (HHV)-6 is associated with severe organ involvement and a prolonged course of disease. The present study discusses an HSR developed in a previously healthy male exposed to ceftriaxone, doxycycline, vancomycin, and trimethoprim/sulfamethoxazole (co-trimoxazole; TMP/SMX). Initially, the patient presented clinical manifestations of HSR, as well as clinical and laboratory measurements compatible with liver and renal failure. Moreover, the patient presented skin desquamation compatible with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis. During the reaction, it was observed HHV-6 reactivation. The severity of clinical symptoms is correlated with HHV-6 titer, as well as with results of the invitro lymphocyte toxicity assay (LTA). Serum levels of a large panel of cytokines are compared between the patient, a large population of SJS patients, and a cohort of healthy controls, using data collected by our laboratory over the years. HHV-6 was measured in the cell culture media from lymphocytes incubated with each of the 4 drugs. Moreover, we describe a new assay using cytokines released by patient lymphocytes following invitro exposure to the incriminated drugs as biomarkers of HSR. Based on LTA results, HHV-6 reactivation and cytokine measurements, we establish that only doxycycline and TMP/SMX were involved in the HSR. As result of this analysis, the patient could continue to use the other 2 antibiotics safely.

A Case of Toxic Epidermal Necrolysis Induced by Allopurinol with Human Herpesvirus-6 Reactivation

A Case of Toxic Epidermal Necrolysis Induced by Allopurinol with Human Herpesvirus-6 Reactivation

HHV-6 Viremia Is Frequent but the Incidence of Encephalitis Is Low in Double-Unit Cord Blood Transplant Recipients Transplanted without ATG

AbstractAbstract 459 Background:While cord blood transplantation is a known risk factor for Human Herpesvirus-6 (HHV-6) reactivation, recent studies have yielded inconsistent results in regard to the level of viremia which is associated with a high risk of HHV-6 encephalitis. Moreover, the association with graft failure or transplant-related mortality is controversial. Methods:We conducted a retrospective analysis of 125 patients who underwent double-unit cord blood transplantation (DCBT) for the treatment of hematologic malignancies from 2/2006-3/2012 who were monitored for HHV-6 reactivation to examine the incidence and severity of HHV-6 viremia, the incidence of encephalitis, and the association with DCBT outcome. HHV-6 viremia was measured by quantitive PCR of HHV-6 DNA from plasma (lower limit of detection 100 DNA copies/ml). Results:Of the 125 patients (median age 42, range 1–69), 93 (74%) received myeloablative conditioning and 32 (26%) received a non-myeloablative regimen followed by 4–6/6 HLA-A, B antigen, DRB1 allele matched DCBT for the treatment of AML (N = 43, 34%), ALL (N = 24, 19%), MDS/CML/other leukemia (N = 12, 10%), or lymphoma/CLL (N = 46, 37%). No patient received anti-thymocyte globulin (ATG). Of 125 monitored patients, 117 (94%) reactivated HHV-6 to a median peak of 7,600 (range 100–160,000) copies/ml at a median onset of 20 days (range 10–59) post-DCBT. The median time to peak viremia was 23 days (range 12–62) with a median viremia duration of 10 days (range 1–60 days). Fifty-one patients (41% of total, 44% of viremic patients) developed HHV-6 > 10,000 copies/ml (median peak viremia 31,200 copies/ml at 20 days, range 12–57). Only 6 patients (5% of total, 5% of viremic patients) developed HHV-6 > 100,000 copies/ml (median peak 130,000 copies/ml at 19 days, range 14–29). HHV-6 encephalitis occurred in 2 patients (1.6%, peak viremias 13,000 and 118,000, respectively). One patient died from encephalitis and the other had a complete recovery following therapy. Four additional viremic patients had HHV-6 isolated from bronchoalveolar lavage but did not meet criteria for HHV-6 pneumonia. Using a high level viremia definition of > 10,000 copies/ml from days 14–60 (a level reportedly associated with end-organ disease and decreased survival, Dulery, BBMT 2011), viremia was not associated with diagnosis or conditioning regimen. Engrafting unit-recipient HLA-match and TNC, CD34+ and CD3+ cell dose were not associated with high level viremia. Treating viremia as a time-dependent covariate in Cox regression analysis, no association was found between viremia and neutrophil or platelet engraftment. Specifically, there were two graft failures in patients with no or low level viremia and two in patients with high level viremia. There was also no association between viremia and CMV reactivation, day 100 grade II-IV aGVHD, day 100 TRM, relapse or overall survival. A second analysis was performed to examine effects of high level viremia defined as a level > 25,000 copies/ml (N = 31 patients, the highest peak viremia quartile during days 14–60) and no associations with DCBT outcomes were detected. Conclusions:In our DCBT population, nearly all patients have reactivated HHV-6. However, the incidence of end-organ disease is relatively low. We postulate the difference between our findings and other studies reporting higher rates of HHV-6 encephalitis in DCBT recipients could be due to our exclusion of ATG from the conditioning regimen. At this time our understanding of the significance of HHV-6 after CBT is incomplete. We are currently evaluating anti-viral treatment responses, and ultimately a prospective trial is needed to better define the causality between HHV-6 viremia and transplantation outcomes, and to investigate the risk-benefits of pre-emptive therapy. Disclosures:No relevant conflicts of interest to declare.