Impact of Human Herpesvirus-6 Reactivation on Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation

Aoki, Jun; Numata, Ayumi; Yamamoto, Eri; Fujii, Eriko; Tanaka, Masatsugu; Kanamori, Heiwa

doi:10.1016/j.bbmt.2015.07.022

Cited by 33 publications

(37 citation statements)

References 34 publications

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“…1). One of the most commonly reported complications of HHV-6 is encephalitis, which generally occurs in patients with high viral loads, although reports vary depending on the type of transplant (33,34). In some studies, early reactivation of HHV-6 posttransplantation was associated with delayed neutrophil and platelet engraftment, increased mortality, and the development of acute graft-versus-host disease (GVHD) (35,36).…”

Section: Cytomegalovirus Reactivation Of Latent Cytomegalovirus (Cmv)mentioning

confidence: 99%

Laboratory Diagnosis of Infections in Cancer Patients: Challenges and Opportunities

Babady

2016

J Clin Microbiol

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Infections remain a significant cause of morbidity and mortality in cancer patients. The differential diagnosis for these patients is often wide, and the timely selection of the right clinical tests can have a significant impact on their survival. However, laboratory findings with current methodologies are often negative, challenging clinicians and laboratorians to continue the search for the responsible pathogen. Novel methodologies are providing increased sensitivity and rapid turnaround time to results but also challenging our interpretation of what is a clinically significant pathogen in cancer patients. This minireview provides an overview of the most common infections in cancer patients and discusses some of the challenges and opportunities for the clinical microbiologist supporting the care of cancer patients. Cancer is the leading cause of death worldwide, with 8.2 million deaths reported worldwide in 2012 (1). Common treatment options for oncology patients include hematopoietic stem cell transplantation (HSCT), chemotherapeutic drugs, and surgical resection. The first successful HSCT was performed in 1959 by E. Donall Thomas in Cooperstown, NY, with infusion of two acute lymphocytic leukemia (ALL) patients with bone marrow from their disease-free identical twins. Although initially successful, their remission was short-lived, with recurrence of the disease occurring within a few months of the transplant (2). Today, HSCT is a curative therapy for many types of hematologic malignancies and immune deficiency diseases. E. Donall Thomas and Joseph E. Murray received the 1991 Nobel Prize in Physiology or Medicine for their discoveries concerning "organ and cell transplantation in the treatment of human disease."Of note for microbiologists, the history of cancer chemotherapy started as a history of antibiotics with Paul Ehrlich's discovery in 1909 of arsphenamine (Salvarsan), the first effective treatment against Treponema pallidum infection. Paul Ehrlich also evaluated early versions of alkylating agents to treat cancer but with little hope that these drugs would be curative. Decades of investigations and trials have resulted in the current modern chemotherapeutic agents that are curative for large groups of either hematologic malignancies or solid tumors when used in conjunction with surgical resection (3). CANCER AND INFECTIONSInfections remains a significant cause of death in cancer patients, particularly in HSCT recipients (1). Susceptibility to infections is related to a host's ability to reconstitute their immune system following HSCT and/or chemotherapy treatment. The longer it takes a patient to recover, the higher at risk they are of developing infections. In general, the highest risk of infections occurs in allogeneic HSCT recipients and leukemia patients, and the lowest risk occurs in solid-tumor patients on standard chemotherapy (Table 1) (4). The posttransplant period may be divided into three stages: preengraftment (less than 4 weeks), early postengraftment (3 weeks to 3 months), and late poste...

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Section: Cytomegalovirus Reactivation Of Latent Cytomegalovirus (Cmv)mentioning

confidence: 99%

Laboratory Diagnosis of Infections in Cancer Patients: Challenges and Opportunities

Babady

2016

J Clin Microbiol

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“…Almost all children have been infected with human herpesvirus 6 (HHV‐6), which causes exanthema subitum, and HHV‐6 remains latent in host cells lifelong. After allogeneic hematopoietic stem cell transplantation (allo‐HSCT), incidence of reactivation of HHV‐6 ranges from 35.0% to 72.2% . HHV‐6 encephalitis/myelitis is a devastating complication after allo‐HSCT in association with HHV‐6 reactivation.…”

Section: Introductionmentioning

confidence: 99%

Risk factors of human herpesvirus 6 encephalitis/myelitis after allogeneic hematopoietic stem cell transplantation

Miyashita

Endo

Onozawa

et al. 2017

Transplant Infectious Dis

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“…In the analysis of HHV-6 reactivation, high lymphocyte AUC was strongly associated with viral reactivation. Because early intervention with antiviral agents is necessary to reduce HHV-6 reactivation and subsequent virus-related complications [21][22][23][24], regular examination of the plasma level of HHV-6 viral load is strongly recommended for all patients, especially in those who show rapid growth of lymphocytes by day +15. In previous studies, HHV-6 reactivation was associated with a myeloablative conditioning regimen, cord blood transplantation, and immune reactions [21,25].…”

Section: Discussionmentioning

confidence: 99%

Lymphocyte Area Under the Curve as a Predictive Factor for Viral Infection after Allogenic Hematopoietic Stem Cell Transplantation

Watanabe

Kanda

Hishizawa

et al. 2019

Biology of Blood and Marrow Transplantation

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Viral infection is a serious complication that can greatly affect patient mortality and morbidity after allogenic hematopoietic stem cell transplantation (allo-HSCT). For the early identification of patients at high risk for viral infection, we evaluated the impact of lymphocyte area under the curve (AUC) value as a new predictive factor for early immune reconstitution after allo-HSCT against viral infection. This study included 286 patients who underwent their first allo-HSCT at Kyoto University Hospital between 2005 and 2017. Lymphocyte AUC from day 0 to day +15 was calculated in the analysis of human herpesvirus 6 (HHV-6), and lymphocyte AUC from day 0 to day +30 was calculated in the analysis of other viruses (cytomegalovirus [CMV], adenovirus, BK virus, JC virus, and varicella zoster virus). The risk factors for each viral reactivation/infection were assessed by multivariate analysis. The median age at transplantation was 51 years (range, 17 to 68 years). The median lymphocyte AUC was 63/mL (range, 0 to 5620/mL) at day +15 and 3880 (range, 0 to 118,260/mL) at day +30. An increase in lymphocyte AUC was significantly associated with a high frequency of HHV-6 reactivation (P = .033) and a low frequency of CMV antigenemia (P = .014). No apparent association was found between lymphocyte AUC and reactivation/infection of other viruses. Aplastic anemia as a primary disease (hazard ratio [HR], 5.34; P < .001) and cord blood as a donor source (HR, 3.05; P = .006) were other risk factors for HHV-6 reactivation. Other risk factors for CMV antigenemia included the occurrence of acute graft-versus-host disease (HR 2.21; P < .001) and recipient age (HR 1.55; P = .017). Higher lymphocyte AUC at day +30 was significantly associated with low treatment-related mortality (HR, .47; P = .045). Lymphocyte AUC may be a good predictive factor for immune reconstitution against CMV reactivation. It also provides valuable information for predicting HHV-6 reactivation and treatment-related mortality.

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Impact of Human Herpesvirus-6 Reactivation on Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation

Cited by 33 publications

References 34 publications

Laboratory Diagnosis of Infections in Cancer Patients: Challenges and Opportunities

Laboratory Diagnosis of Infections in Cancer Patients: Challenges and Opportunities

Risk factors of human herpesvirus 6 encephalitis/myelitis after allogeneic hematopoietic stem cell transplantation

Lymphocyte Area Under the Curve as a Predictive Factor for Viral Infection after Allogenic Hematopoietic Stem Cell Transplantation

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