Guidelines from the 2017 European Conference on Infections in Leukaemia for management of HHV-6 infection in patients with hematologic malignancies and after hematopoietic stem cell transplantation

Ward, Katherine N.; Hill, Joshua A.; Hubáček, Petr; Cámara, Rafael de la; Crocchiolo, Roberto; Einsele, Hermann; Navarro, David; Robin, Christine; Cordonnier, Catherine; Ljungman, Per

doi:10.3324/haematol.2019.223073

Cited by 98 publications

(157 citation statements)

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“…Future studies will possibly clarify the nature of these neurologic manifestations and their causal relationship with HHV-6 reactivation, as well as the need for preemptive antiviral treatment. 20,21 In conclusion, our study reinforces the evidence that (1) in immunocompetent hosts, CNS involvement from HHV-6 is limited to infants younger than 3 years presenting with primary infection; (2) HSCT recipients can develop HHV-6 encephalitis as a consequence of viral reactivation, although typical clinical imaging features of limbic encephalitis might be lacking, especially when brain MRI is performed shortly after symptoms onset; and (3) the CSF/blood replication ratio can be of great help to interpret the results of PCR testing and establish an accurate diagnosis of HHV-6 encephalitis in HSCT recipients.…”

Section: Discussionmentioning

confidence: 99%

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Human Herpesvirus 6 Encephalitis in Immunocompetent and Immunocompromised Hosts

Berzero

Campanini

Vegezzi

et al. 2021

Neurol Neuroimmunol Neuroinflamm

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ObjectiveThe aim of this study was to analyze the clinical, radiologic, and biological features associated with human herpesvirus 6 (HHV-6) encephalitis in immunocompetent and immunocompromised hosts to establish which clinical settings should prompt HHV-6 testing.MethodsWe performed a retrospective research in the virology database of Fondazione IRCCS Policlinico San Matteo (Pavia, Italy) for all patients who tested positive for HHV-6 DNA in the CSF and/or in blood from January 2008 to September 2018 and separately assessed the number of patients meeting the criteria for HHV-6 encephalitis in the group of immunocompetent and immunocompromised hosts.ResultsOf the 926 patients tested for HHV-6 during the period of interest, 45 met the study criteria. Among immunocompetent hosts (n = 17), HHV-6 encephalitis was diagnosed to 4 infants or children presenting with seizures or mild encephalopathy during primary HHV-6 infection (CSF/blood replication ratio <<1 in all cases). Among immunocompromised hosts (n = 28), HHV-6 encephalitis was diagnosed to 7 adolescents/adults with hematologic conditions presenting with altered mental status (7/7), seizures (3/7), vigilance impairment (3/7), behavioral changes (2/7), hyponatremia (2/7), and anterograde amnesia (1/7). Initial brain MRI was altered only in 2 patients, but 6 of the 7 had a CSF/blood replication ratio >1.ConclusionsThe detection of a CSF/blood replication ratio >1 represented a specific feature of immunocompromised patients with HHV-6 encephalitis and could be of special help to establish a diagnosis of HHV-6 encephalitis in hematopoietic stem cell transplant recipients lacking radiologic evidence of limbic involvement.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Human Herpesvirus 6 Encephalitis in Immunocompetent and Immunocompromised Hosts

Berzero

Campanini

Vegezzi

et al. 2021

Neurol Neuroimmunol Neuroinflamm

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“…Where viral infections are suspected, local or international guidelines for management should be followed. [58][59][60][61][62][63] The paediatric oncology patients who are most at risk of invasive fungal infections (IFI) are those with severe and prolonged neutropenia, often those with acute leukaemias or receiving HSCT. Additional factors associated with IFI include high-dose steroid exposure, acute and chronic GvHD and increasing age.…”

Section: Viral and Fungal Infectionsmentioning

confidence: 99%

Optimising Antimicrobial Selection and Duration in the Treatment of Febrile Neutropenia in Children

Morgan¹,

Phillips²,

Haeusler³

et al. 2021

IDR

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Febrile neutropenia (FN) is a frequent complication of cancer treatment in children. Owing to the potential for overwhelming bacterial sepsis, the recognition and management of FN requires rapid implementation of evidenced-based management protocols. Treatment paradigms have progressed from hospitalisation with broad spectrum antibiotics for all patients, through to risk adapted approaches to management. Such risk adapted approaches aim to provide safe care through incorporating antimicrobial stewardship (AMS) principles such as implementation of comprehensive clinical pathways incorporating deescalation strategies with the imperative to reduce hospital stay and antibiotic exposure where possible in order to improve patient experience, reduce costs and diminish the risk of nosocomial infection. This review summarises the principles of risk stratification in FN, the current key considerations for optimising empiric antimicrobial selection including knowledge of antimicrobial resistance patterns and emerging technologies for rapid diagnosis of specific infections and summarises existing evidence on time to treatment, investigations required and duration of treatment. To aid treating physicians we suggest the key features based on current evidence that should be part of any FN management guideline and highlight areas for future research. The focus is on treatment of bacterial infections although fungal and viral infections are also important in this patient group.

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“…If the clinical data raised a suspicion, DNAemia was determined by quantitative or qualitative polymerase chain reaction of the U67 target gene. HHV‐6 infection and encephalitis were defined according to the 2017 European Conference on Infections in Leukemia guidelines 26 …”

Section: Methodsmentioning

confidence: 99%

The role of early natural killer cell adoptive infusion before engraftment in protecting against human herpesvirus‐6B encephalitis after naïve T‐cell‐depleted allogeneic stem cell transplantation

et al. 2021

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Background Naïve T‐cell‐depleted grafts have been employed as an ex vivo T‐cell depletion (TCD) platform to prevent graft‐versus‐host disease (GvHD) and improve immune reconstitution by providing rapid donor memory T‐cell reconstitution after allogenic hematopoietic stem cell transplantation (allo‐HSCT). CD45RA− memory T cells confer protection against viruses such as cytomegalovirus, Epstein–Barr virus, and adenovirus; however, reports have shown an unexpectedly high incidence of human herpesvirus (HHV)‐6B encephalitis among pediatric allo‐HSCT patients. Methods We report the first 18 consecutive allo‐HSCT, 16 haplo‐HSCT, and two human leukocyte antigen‐matched related donors implanted with naïve TCD grafts. All donors were administered three cell products: first, a CD34+ stem cell product; second, a CD45RA+ TCD graft, followed by an adoptive natural killer (NK) cell infusion within 10 days after HSCT. The study's primary endpoint was the incidence of HHV‐6B encephalitis. Results Engraftment was achieved in 94.5% of cases; 2‐year overall survival, event‐free survival, and GvHD/relapse‐free survival were 87.2% (95% CI 78.6–95.8), 67.3% (95% CI 53.1–81.5), and 64% (95% CI 50.5–78.1), respectively. HHV‐6B reactivation occurred in 7 of the haplo‐HSCT patients, six of who received a cell infusion with an NK/CD4 ratio <2. None of the patients developed encephalitis. Conclusions In this clinical study, we show that early adoptive NK cell infusion after a 45RA+ TCD allo‐HSCT graft is safe and can prevent HHV‐6B encephalitis. We recommend infusing adoptive NK cells after allo‐HSCT using CD45RA+ TCD grafts.

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Guidelines from the 2017 European Conference on Infections in Leukaemia for management of HHV-6 infection in patients with hematologic malignancies and after hematopoietic stem cell transplantation

Cited by 98 publications

References 100 publications

Human Herpesvirus 6 Encephalitis in Immunocompetent and Immunocompromised Hosts

Human Herpesvirus 6 Encephalitis in Immunocompetent and Immunocompromised Hosts

Optimising Antimicrobial Selection and Duration in the Treatment of Febrile Neutropenia in Children

The role of early natural killer cell adoptive infusion before engraftment in protecting against human herpesvirus‐6B encephalitis after naïve T‐cell‐depleted allogeneic stem cell transplantation

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