The association of cytomegalovirus infection and cytomegalovirus serostatus with invasive fungal infections in allogeneic haematopoietic stem cell transplant recipients: a systematic review and meta-analysis

Chuleerarux, Nipat; Nematollahi, Saman; Thongkam, Achitpol; Dioverti, M. Veronica; Manothummetha, Kasama; Torvorapanit, Pattama; Langsiri, Nattapong; Worasilchai, Navaporn; Plongla, Rongpong; Chindamporn, Ariya; Sanguankeo, Anawin; Permpalung, Nitipong

doi:10.1016/j.cmi.2021.10.008

Cited by 13 publications

(12 citation statements)

References 51 publications

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“…A total of 429 relevant reports were retrieved for SRs, with 3 SRs [ 12 – 14 ] included after the screening. Furthermore, a total of 2983 relevant reports were retrieved for clinical primary studies, and 22 clinical studies [ 15 – 36 ] were ultimately included after screening (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Results of the AMSTAR 2 assessment are shown in Online Resource 2 . For each AMSTAR 2 item, among the 16 items, nine items were rated as “Yes” (items 1, 3, 5, 6, 11, 13, 14, 15, and 16) for Giménez 2019 [ 13 ], nine items were rated as “Yes” (items 1, 3, 5, 9, 11, 13, 14, 15, and 16) for Chuleerarux 2021 [ 14 ], eight items were rated as “Yes” (items 1, 5, 6, 9, 11, 14, 15, and 16) for Zhang 2019 [ 12 ]. In addition, included primary clinical studies whose overall risk bias was all assessed with “Moderate” are shown in Online Resource 3 .…”

Section: Resultsmentioning

confidence: 99%

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The indirect effects of CMV reactivation on patients following allogeneic hematopoietic stem cell transplantation: an evidence mapping

Wu,

Ma,

Song

et al. 2024

Ann Hematol

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Cytomegalovirus (CMV) reactivation following allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a challenging problem, and the impact on the risk of overall mortality (OM) and non-relapse mortality (NRM) in patients following allo-HSCT is still controversial. Utilizing the evidence mapping method, we aimed to assess the effect of CMV infection on outcomes of patients post-transplantation and identify research gaps through systematic reviews (SRs) and clinical studies. PubMed, EMBASE, Web of Science, and Cochrane library databases were searched from inception until 5 July 2022 to identify relevant literature. After systematic literature screening and data extraction, evidence mapping of the effects of CMV reactivation on patients post-allo-HSCT was conducted. Three SRs and 22 clinical studies were included. In one SR, CMV reactivation was associated with an increased risk of mortality (HR 1.46; 95% CI, 1.24–1.72; P ≤ 0.001). In two SRs, CMV reactivation was associated with NRM. One SR reported CMV reactivation was potentially associated with significant protection against relapse in patients with acute myelocytic leukemia (AML), but no significant correlation with graft-versus-host disease (GVHD) was found. Lastly, in one SR CMV reactivation significantly increased the risk of invasive fungal disease (IFD). Most clinical articles reported that CMV reactivation increased the risk of renal dysfunction, poor graft function, re-hospitalization, and bacterial infections. CMV reactivation following allo-HSCT is associated with an increased risk of OM, NRM, IFD, and renal dysfunction, as well as a reduced risk of relapse in patients with AML.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

The indirect effects of CMV reactivation on patients following allogeneic hematopoietic stem cell transplantation: an evidence mapping

Wu,

Ma,

Song

et al. 2024

Ann Hematol

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“…Human cytomegalovirus (HCMV) reactivation is a common complication causing morbidity and mortality after allogeneic haematopoietic stem cell transplantation (allo‐HSCT). Opportunistic HCMV reactivation occurs in up to two‐thirds of seropositive allo‐HSCT patients and is associated with negative impacts including the development of end‐organ HCMV disease (seen in ~10% of patients), toxicities from antiviral drugs and increased risks of acute graft‐ vs .‐host disease (aGvHD) and microbial infections 1–5 . Despite the availability of prophylactic and pre‐emptive antiviral therapies, 6 HCMV reactivation continues to have a significant negative impact on transplant outcomes, 7,8 underlining the need for improved understanding of the immune parameters associated with HCMV reactivation and its impacts on immune recovery after allo‐HSCT.…”

Section: Introductionmentioning

confidence: 99%

Circulating cytokine and chemokine patterns associated with cytomegalovirus reactivation after stem cell transplantation

Stern,

McGuire,

Avdic

et al. 2023

Clin & Trans Imm

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ObjectivesHuman cytomegalovirus (HCMV) reactivation is the leading viral complication after allogeneic haematopoietic stem cell transplantation (allo‐HSCT). Understanding of circulating cytokine/chemokine patterns which accompany HCMV reactivation and correlate with HCMV DNAemia magnitude is limited. We aimed to characterise plasma cytokine/chemokine profiles in 36 allo‐HSCT patients (21 with HCMV reactivation and 15 without HCMV reactivation) at four time‐points in the first 100‐day post‐transplant.MethodsThe concentrations of 31 cytokines/chemokines in plasma samples were analysed using a multiplex bead‐based immunoassay. Cytokine/chemokine concentrations were compared in patients with high‐level HCMV DNAemia, low‐level HCMV DNAemia or no HCMV reactivation, and correlated with immune cell frequencies measured using mass cytometry.ResultsIncreased plasma levels of T helper 1‐type cytokines/chemokines (TNF, IL‐18, IP‐10, MIG) were detected in patients with HCMV reactivation at the peak of HCMV DNAemia, relative to non‐reactivators. Stem cell factor (SCF) levels were significantly higher before the detection of HCMV reactivation in patients who went on to develop high‐level HCMV DNAemia (810–52 740 copies/mL) vs. low‐level HCMV DNAemia (< 250 copies/mL). High‐level HCMV reactivators, but not low‐level reactivators, developed an elevated inflammatory cytokine/chemokine profile (MIP‐1α, MIP‐1β, TNF, LT‐α, IL‐13, IL‐9, SCF, HGF) at the peak of reactivation. Plasma cytokine concentrations displayed unique correlations with circulating immune cell frequencies in patients with HCMV reactivation.ConclusionThis study identifies distinct circulating cytokine/chemokine signatures associated with the magnitude of HCMV DNAemia and the progression of HCMV reactivation after allo‐HSCT, providing important insight into immune recovery patterns associated with HCMV reactivation and viral control.

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“…4 The early, intermediate, and late phases of transplantation are all potential times for CMV infection, and the median time to CMV infection was 41 d. 4 Moreover, CMV infection is likely to proceed to CMV disease, which has a high mortality rate and increases the risk of secondary opportunistic infection and graft-versus-host disease (GVHD). [5][6][7] Pretransplantation recipient and donor CMV serostatuses are the most important risk factor of CMV infection after allo-HSCT, especially recipients who are CMV-seropositive, who will be at increased risk of CMV infection and disease. 8,9 Approximately 80% of CMVseropositive recipients experience CMV infection after allo-HSCT without antiviral prophylaxis.…”

Section: Introductionmentioning

confidence: 99%

Efficacy, Safety, and Cost-effectiveness Analysis of Antiviral Agents for Cytomegalovirus Prophylaxis in Allogeneic Hematopoietic Stem Cell Transplantation Recipients

Qiu,

Zhang,

Teng

et al. 2023

Transplantation

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Background. Cytomegalovirus (CMV) infection is associated with higher non-relapse mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). But the preferred drug for preventing cytomegalovirus infection is still controversial. We evaluate the efficacy, safety, and cost-effectiveness of antiviral agents based on the most recent studies. Methods. A pairwise and network meta-analysis was conducted to obtain direct and indirect evidence of antivirals. The cost of allo-HSCT recipients in a teaching hospital was collected, and a cost-effectiveness analysis using a decision tree combined with Markov model was completed from the perspective of allo-HSCT recipients over a lifetime horizon. Results. A total of 19 RCTs involving 3565 patients (8 antivirals) were included. In the network meta-analysis, relative to placebo, letermovir, valacyclovir, and ganciclovir significantly reduced CMV infection incidence; ganciclovir significantly reduced CMV disease incidence; ganciclovir significantly increased the incidence of serious adverse event; none of antivirals significantly reduced all-cause mortality. Based on meta-analysis and Chinese medical data, the incremental cost-effectiveness ratios (ICER) per quality-adjusted life year (QALY) saved for maribavir, acyclovir, valacyclovir, ganciclovir, and letermovir relative to placebo corresponded to US$216 635.70, US$11 590.20, US$11 816.40, US$13 049.90, and US$12 189.40, respectively. One-way sensitivity analysis showed the most influential parameter was discount rate. The probabilistic sensitivity analysis indicated a 53.0% probability of letermovir producing an ICER below the willingness-to-pay threshold of US$38 824.23/QALY. The scenario analysis demonstrated prophylaxis with letermovir is considered cost-effective in the United States. Conclusions. Currently, letermovir is an effective and well-tolerated treatment for preventing CMV infection, and it might be a cost-effective choice in allo-HSCT recipients in China.

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The association of cytomegalovirus infection and cytomegalovirus serostatus with invasive fungal infections in allogeneic haematopoietic stem cell transplant recipients: a systematic review and meta-analysis

Cited by 13 publications

References 51 publications

The indirect effects of CMV reactivation on patients following allogeneic hematopoietic stem cell transplantation: an evidence mapping

The indirect effects of CMV reactivation on patients following allogeneic hematopoietic stem cell transplantation: an evidence mapping

Circulating cytokine and chemokine patterns associated with cytomegalovirus reactivation after stem cell transplantation

Efficacy, Safety, and Cost-effectiveness Analysis of Antiviral Agents for Cytomegalovirus Prophylaxis in Allogeneic Hematopoietic Stem Cell Transplantation Recipients

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