The clinical impact of cytomegalovirus infection following allogeneic hematopoietic cell transplantation: Why the quest for meaningful prophylaxis still matters

Chan, Shawna T.; Logan, Aaron C.

doi:10.1016/j.blre.2017.01.002

Cited by 61 publications

(58 citation statements)

References 114 publications

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“…In light of current data, the relationship between CMV and GVHD can be best described as bidirectional. While GVHD and its treatment increase the risk of a CMV infection, based on current data, the presence of a CMV infection may in turn be connected to developing GVHD [24]. In our study, 30 allogeneic transplant patients manifested GVHD.…”

Section: Discussionmentioning

confidence: 58%

Cytomegalovirus Reactivation in Hematopoietic Stem cell Transplantation managed by Preemptive Treatment with lower dose Valganciclovir

Akyol¹,

Şahin²

2019

IJHBD

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Objective: The aim of this study was to investigate risk factors for cytomegalovirus (CMV) infection, effect of viral reactivation on hematopoietic stem cell transplantation (HSCT) and efficacy of preemptive treatment using a lower dose valganciclovir for the first time. Material and Method:The data of 447 patients who underwent HSCT for malignant and non-malignant hematological disorders at a single center from September 2009 to December 2016 were retrospectively evaluated in this study. DNA levels of CMV were routinely tested two days per week for the first 24 months following HSCT, and in case of clinical suspicion after 24 months using the Quantitative Real-Time quantitative polymerase chain reaction (RT-PCR).Results: Ninety (54.2%) allogeneic transplant patients, and forty one (14.6%) autologous transplant patients had CMV reactivation. There was a statistically significant increase in CMV reactivation in the non-myeloablative (NMA) allogeneic transplant group compared to the myeloablative (MA) group at a value of 150-1000 copies/mL CMV-PCR (p= 0.002). Acute/chronic Graft Versus Host Disease (GVHD) were observed in 30 of allogeneic HSCT patients. 29 of these patients (96.6%) had CMV antigenemia. There was a significant association between the development of acute/ chronic GVHD, and CMV viremia (p= 0.001). The patients without CMV antigenemia had a higher incidence of mortality at first 100-day, and 365-day in allogeneic transplant group (p= 0.022, p= 0.024, respectively). The 5-year overall survival (OS) rate was 61% in the viremia group, and 62% in the non-viremia group. There was no statistically significant difference between the two groups in terms of 5-year OS (p= 0.551). In patients receiving a lower dose of 900 mg/day valganciclovir treatment due to viremia, CMV disease did not develop and no adverse effect that required the drug to be discontinued was observed. Conclusion:The results conducted that development of GVHD was associated with CMV viremia. Early and late mortality rate were higher in the patients without CMV antigenemia. However; CMV reactivation had no impact on patients' survival post allogeneic and autologous HSCT. Also, this was the first study that conducted preemptive treatment approach in the CMV viremia using a lower dose valganciclovir is safe and effective in HSCT.

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Section: Discussionmentioning

confidence: 58%

Cytomegalovirus Reactivation in Hematopoietic Stem cell Transplantation managed by Preemptive Treatment with lower dose Valganciclovir

Akyol¹,

Şahin²

2019

IJHBD

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“…This viremia is linked to several negative outcomes, including increased mortality due to CMV disease, increased incidence of graft-versus-host disease (GVHD), an increased risk of posttransplant malignancy relapse, and mortality linked to the side effects of currently approved antiviral agents, notably myelosuppression and renal failure. 25…”

Section: Specific Patient Populationsmentioning

confidence: 99%

Antiviral Therapies for Herpesviruses: Current Agents and New Directions

Poole

James

2018

Clinical Therapeutics

108

125

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“…Reactivation of CMV is a common complication in immunosuppressed patients (2) and contributes to morbidity and mortality associated with allogeneic stem cell transplantation (allo-SCT) in patients with acute myeloid leukemia (AML; ref. 3). Preemptive antiviral therapy has made CMV reactivation manageable in most AML cases (3).…”

Section: Introductionmentioning

confidence: 99%

“…3). Preemptive antiviral therapy has made CMV reactivation manageable in most AML cases (3). Moreover, several studies suggest that CMV reactivation after allo-SCT in AML is associated with reduced relapse risk (4-6).…”

Section: Introductionmentioning

confidence: 99%

“…The mechanism underlying the purported protective effects of CMV infection on outcome of allo-SCT is unknown, but may involve effects of CMV infection on the distribution and function of the immune cells that eliminate AML cells (7)(8)(9). Individuals harboring IgG antibodies against CMV (CMV-seropositive individuals, CMV þ ) as a sign of past CMV infection show elevated numbers of differentiated adaptive CD57 þ NKG2C þ NK cells in blood (10)(11)(12)(13), and CMV-induced reactivation after allo-SCT is associated with rapid reconstitution of such differentiated NK cells (3,(14)(15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

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Cytomegalovirus Serostatus Affects Autoreactive NK Cells and Outcomes of IL2-Based Immunotherapy in Acute Myeloid Leukemia

Bernson

Hallner

Sander

et al. 2018

Cancer Immunology Research

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Human cytomegalovirus (CMV) infection is reported to promote NK cell differentiation and education. The CMV-induced generation of highly differentiated adaptive-like NK cells has been proposed to affect favorably on the maintenance of remission in patients with acute myeloid leukemia (AML) after allogeneic stem cell transplantation (allo-SCT). The impact of CMV infection and adaptive-like NK cells on relapse and survival of patients with AML not receiving allo-SCT remains unknown. We assayed CMV IgG serostatus to determine past CMV infection in 81 nontransplanted AML patients who were receiving relapse-prevention immunotherapy comprising histamine dihydrochloride and low-dose interleukin-2 (HDC/IL2; NCT01347996). CMV seropositivity correlated negatively with leukemia-free and overall survival of patients receiving HDC/IL2, but did not correlate with outcomes in a contemporary control cohort. Analysis of outcome after stratification of patients based on concordant or discordant killer immunoglobulin-like receptor (KIR) and HLA genotypes implied that the negative impact of CMV seropositivity was restricted to patients lacking a ligand to inhibitory KIRs (iKIR). Previous CMV infection was also associated with fewer NK cells expressing only nonself iKIRs (NS-iKIR). We propose that CMV-driven NK cell education depletes the population of NS-iKIR NK cells, which in turn reduces the clinical benefit of relapse-preventive immunotherapy in AML. .

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The clinical impact of cytomegalovirus infection following allogeneic hematopoietic cell transplantation: Why the quest for meaningful prophylaxis still matters

Cited by 61 publications

References 114 publications

Cytomegalovirus Reactivation in Hematopoietic Stem cell Transplantation managed by Preemptive Treatment with lower dose Valganciclovir

Cytomegalovirus Reactivation in Hematopoietic Stem cell Transplantation managed by Preemptive Treatment with lower dose Valganciclovir

Antiviral Therapies for Herpesviruses: Current Agents and New Directions

Cytomegalovirus Serostatus Affects Autoreactive NK Cells and Outcomes of IL2-Based Immunotherapy in Acute Myeloid Leukemia

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