Peripheral Blood Leukocyte Counts in Cytomegalovirus Infected Heart Transplant Patients: Impact of Acute Disease Versus Subclinical Infection

Cooke, Margaret E.; Potena, Luciano; Luikart, Helen; Valantine, Hannah A.

doi:10.1097/01.tp.0000242139.13197.7f

Cited by 5 publications

(5 citation statements)

References 15 publications

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“…Finally, CMV infection usually decreases the WBC. Therefore, GCV‐induced neutropaenia could in part be caused by CMV infection . Addressing these limitations in the future will allow the construction more reliable DT models.…”

Section: Discussionmentioning

confidence: 99%

Construction of a flow chart–like risk prediction model of ganciclovir‐induced neutropaenia including severity grade: A data mining approach using decision tree

et al. 2019

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What is known and objective Haematological toxicities such as neutropaenia are a common side effect of ganciclovir (GCV); however, risk factors for GCV‐induced neutropaenia have not been well established. Decision tree (DT) analysis is a typical technique of data mining consisting of a flow chart–like framework that shows various outcomes from a series of decisions. By following the flow chart, users can estimate combinations of risk factors that may increase the probability of certain events. In our previous study, we demonstrated the usefulness of this approach in the evaluation of adverse drug reactions. Therefore, we aimed to construct a risk prediction model of GCV‐induced neutropaenia including severity grade. Methods We performed a retrospective study at the Hokkaido University Hospital and enrolled patients who received GCV between April 2008 and March 2018. Neutropaenia was defined as an absolute neutrophil count (ANC) <1500 cells/mm3 and a decrease to <75% relative to baseline. We classified the patients who developed neutropaenia in three groups (Grades 2‐4) based on the National Cancer Institute‐Common Terminology Criteria for Adverse Events. Data collection was achieved through the retrieval of medical records. We employed a chi‐squared automatic interaction detection algorithm to construct the DT model and compared the accuracies to the logistic regression model (a conventional statistical method) to evaluate the established model. Results and discussion In total, 396 adult patients were included in the study; 61 (15.4%) developed neutropaenia. Three predictive factors (hematopoietic stem cell transplantation, baseline ANC <3854 cells/mm3 and duration of therapy ≥15 days) were extracted using the DT analysis to produce five subgroups, the incidence of neutropaenia ranged between 1.7% and 52.8%. In each subgroup, patients who developed neutropaenia were categorized based on the severity. The accuracies of each model were the same (84.6%), which indicated precision. What is new and conclusion We successfully built a risk prediction model of GCV‐induced neutropaenia including severity grade. This model is expected to assist decision‐making in the clinical setting.

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Section: Discussionmentioning

confidence: 99%

Construction of a flow chart–like risk prediction model of ganciclovir‐induced neutropaenia including severity grade: A data mining approach using decision tree

et al. 2019

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“…The major findings of the study were that leukopenia developed mostly before the diagnosis of CMV disease, neutrophils and monocytes were most affected by CMV disease, and the reduction of leukocytes during CMV disease was independent of immunosuppression. 27 Finally, a recent study evaluated the risk for development of leukopenia in relation to immunosuppressive medications. In the study, 2 groups were identified.…”

Section: Discussionmentioning

confidence: 99%

Increase in short-term risk of rejection in heart transplant patients receiving granulocyte colony-stimulating factor

Nguyen

Lourenço

Chung

et al. 2018

The Journal of Heart and Lung Transplantation

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BACKGROUND: Neutropenia is a significant adverse event after heart transplantation (HT) and increases infection risk. Granulocyte colony-stimulating factor (G-CSF) is commonly used in patients with neutropenia. In this work, we assessed the adverse effects of G-CSF treatment in the setting of a university hospital. METHODS: Data on HT patients from January 2008 to July 2016 were reviewed. Patients who received G-CSF were identified and compared with patients without a history of therapy. Baseline characteristics, rejection episodes, and outcomes were collected. Data were analyzed by incidence rates, time to rejection and survival were analyzed using Kaplan–Meier curves, and odds ratios were generated using logistic regression analysis. RESULTS: Two hundred twenty-two HT patients were studied and 40 (18%) received G-CSF for a total of 85 total neutropenic events (0.79 event/patient year). There were no differences in baseline characteristics between the groups. In the 3 months after G-CSF, the incidence rate of rejection was 0.067 event/month. In all other time periods considered free of G-CSF effect, the incidence rate was 0.011 event/month. This rate was similar to the overall incidence rate in the non-GCSF group, which was 0.010 event/month. There was a significant difference between the incidence rates in the G-CSF group at 0 to 3 months after G-CSF administration and the non-GCSF group (p = 0.04), but not for the other time periods (p = 0.5). Freedom from rejection in the 3 months after G-CSF administration was 87.5% compared with 97.5% in the non-GCSF group (p = 0.006). CONCLUSIONS: G-CSF administration was found to be associated with significant short-term risk of rejection. This suggests the need for increased surveillance during this time period.

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“…17 However, in most patients, no prophylaxis is given, and CMV infection involving leukocytes remains common. 6 Evidence is accumulating that graft vasculopathy may be driven by the consequences of low-grade systemic infection and reduced by its suppression. 17 Pretransplantation CMV seropositivity (and consequent lack of aggressive prophylaxis) appears to be associated with coronary lumen loss.…”

Section: Discussionmentioning

confidence: 99%

“…3 Coronary endothelial dysfunction is associated with CMV infection 4 and the later development of transplant vasculopathy. 5 Recent work has shown that lowlevel systemic CMV infection is common after transplantation, 6 although infection of the heart itself is rare. 7 It is therefore possible that the coronary vascular disease attributed to CMV may be driven by the consequences of lowgrade systemic infection rather than infection of the transplant organ, which may have broader vascular consequences.…”

mentioning

confidence: 99%

Endothelial Dysfunction and Cytomegalovirus Replication in Pediatric Heart Transplantation

et al. 2008

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Background-Cardiac allograft vasculopathy is the major limiting factor to the long-term success of pediatric heart transplantation. Cytomegalovirus (CMV) has been shown to be a significant risk factor for the development of cardiac allograft vasculopathy. Recent work has demonstrated CMV DNA in leukocytes in the absence of direct allograft infection, suggesting that vascular changes may not be limited to the allograft. Method and Results-Systemic arterial endothelial function was assessed with high-resolution ultrasound to determine brachial artery flow-mediated dilation in 50 pediatric heart transplant recipients (8 to 17 years of age; 27 male). Patients were separated into 2 groups according to CMV status: those without evidence of CMV replication after transplantation (nϭ38; 19 male) and patients with evidence of viremia after transplantation (nϭ12; 8 male). No patient had detectable viremia at the time of study. Flow-mediated dilation was significantly impaired in patients with evidence of CMV replication after transplantation (6.64Ϯ1.12%, meanϮSE) compared with those without (9.48Ϯ0.56%; Pϭ0.02). This difference remained after adjustment for age, time since transplantation, and medication. Pretransplantation recipient and donor CMV status and traditional CMV risk were not associated with flow-mediated dilation. Conclusions-CMV replication after cardiac transplantation is associated with chronic endothelial dysfunction in the systemic circulation in children. The implication for both systemic and coronary vascular health requires prospective evaluation.

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Peripheral Blood Leukocyte Counts in Cytomegalovirus Infected Heart Transplant Patients: Impact of Acute Disease Versus Subclinical Infection

Abstract: Aside from implications for early diagnosis, CMV-associated decrease in monocytes is important because viral infections like Epstein-Barr virus cause monocytosis. The absence of leucopenia in subclinical late infections is a new important finding.

Cited by 5 publications

References 15 publications

Construction of a flow chart–like risk prediction model of ganciclovir‐induced neutropaenia including severity grade: A data mining approach using decision tree

Construction of a flow chart–like risk prediction model of ganciclovir‐induced neutropaenia including severity grade: A data mining approach using decision tree

Increase in short-term risk of rejection in heart transplant patients receiving granulocyte colony-stimulating factor

Endothelial Dysfunction and Cytomegalovirus Replication in Pediatric Heart Transplantation

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