Cytomegalovirus reactivation is associated with an increased risk of late-onset invasive aspergillosis independently of grade II–IV acute graft-versus-host disease in allogeneic hematopoietic stem cell transplantation: JSTCT Transplant Complications Working Group

Kimura, Shun‐ichi; Tamaki, Masaharu; Okinaka, Keiji; Seo, Sachiko; Uchida, Naoyuki; Igarashi, Aiko; Ozawa, Yukiyasu; Ikegame, Kazuhiro; Eto, Tetsuya; Tanaka, Masatsugu; Shiratori, Souichi; Nakamae, Hirohisa; Sawa, Masashi; Kawakita, Toshiro; Onizuka, Makoto; Fukuda, Takahiro; Atsuta, Yoshiko; Kanda, Yoshinobu; Nakasone, Hideki

doi:10.1007/s00277-021-04660-3

Cited by 8 publications

(5 citation statements)

References 29 publications

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“…These results might reflect impaired immunity in the recipients. However, CMV reactivation is associated with modified immunity 25–28 and variable infections 29–31 . In addition, CMV reactivation has been reported to be associated with a poor response after vaccination against hepatitis B virus in SCT recipients 32 .…”

Section: Discussionmentioning

confidence: 99%

“…However, CMV reactivation is associated with modified immunity [25][26][27][28] and variable infections. [29][30][31] In addition,…”

Section: Discussionmentioning

confidence: 99%

“…We noted that the number of collected samples, particularly those after the first vaccination dose, was small because the epidemic and the unstable medical systems prevented frequent hospital visits. The median interval (with first and third quartiles) between the first and second vaccination doses was 21 days (21,22) for BNT162b2 and 28 days (28)(29)(30)(31) for mRNA-1273. The median interval (with first and third quartiles) from the first vaccination dose to each sampling was 14.5 (13.0- Ab test result for these two patients was negative, we included these patients in subsequent analyses for SARS-CoV-2 S1 Ab titers after vaccination.…”

Section: Patient Characteristicsmentioning

confidence: 99%

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Attenuated humoral response against SARS‐CoV‐2 mRNA vaccination in allogeneic stem cell transplantation recipients

et al. 2022

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Antibody persistence several months after SARS‐CoV‐2 mRNA vaccination in allogeneic stem cell transplantation recipients remains largely unknown. We sequentially evaluated the humoral response to two doses of mRNA vaccines in 128 adult recipients and identified the risk factors involved in a poor response. The median interval between stem cell transplantation and vaccination was 2.7 years. The SARS‐CoV‐2 S1 antibody became positive after the second vaccination dose in 87.6% of the recipients, and the median titer was 1,235.4 arbitrary units (AU)/mL. In patients on corticosteroid treatment, the corticosteroid dose inversely correlated with antibody titer. Multivariate analysis identified risk factors for poor peak response such as an interval from stem cell transplantation ≤ 1 year, history of clinically significant cytomegalovirus infection, and use of > 5 mg/day prednisolone at vaccination. Six months after vaccination, the median titer decreased to 185.15 AU/mL, and use of > 5 mg/day prednisolone at vaccination was significantly associated with a poor response. These results indicate that early vaccination after stem cell transplantation (<12 months) and cytomegalovirus infection are risk factors for poor peak response, while steroid use is important for a peak as well as a persistent response. In conclusion, although humoral response is observed in many stem cell transplantation recipients after two doses of vaccination, antibody titers diminish with time, and factors associated with persistence and a peak immunity should be considered separately.

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Section: Discussionmentioning

confidence: 99%

“…However, CMV reactivation is associated with modified immunity [25][26][27][28] and variable infections. [29][30][31] In addition,…”

Section: Discussionmentioning

confidence: 99%

Section: Patient Characteristicsmentioning

confidence: 99%

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Attenuated humoral response against SARS‐CoV‐2 mRNA vaccination in allogeneic stem cell transplantation recipients

et al. 2022

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“…Cytomegalovirus reactivation during this period is associated with IA. Whether this is due to viral immunomodulation or reflects broader immune status remains unclear [27]. Beyond 100 days, patients may remain at risk of IFRI if chronic GVHD is present.…”

Section: The Hostmentioning

confidence: 99%

Diagnosis of invasive respiratory mycoses in the immunocompromised host

Houston

Wilson

Stone

2023

Current Opinion in Pulmonary Medicine

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Purpose of reviewThe burden of invasive fungal infection is increasing worldwide, largely due to a growing population at-risk. Most serious human fungal pathogens enter the host via the respiratory tract. Early identification and treatment of invasive fungal respiratory infections (IFRIs) in the immunocompromised host saves lives. However, their accurate diagnosis is a difficult challenge for clinicians and mortality remains high.Recent findingsThis article reviews IFRIs, focussing on host susceptibility factors, clinical presentation, and mycological diagnosis. Several new diagnostic tools are coming of age including molecular diagnostics and point-of-care antigen tests. As diagnosis of IFRI relies heavily on invasive procedures like bronchoalveolar lavage and lung biopsy, several novel noninvasive diagnostic techniques are in development, such as metagenomics, ‘volatilomics’ and advanced imaging technologies.SummaryWhere IFRI cannot be proven, clinicians must employ a ‘weights-of-evidence’ approach to evaluate host factors, clinical and mycological data. Implementation studies are needed to understand how new diagnostic tools can be best applied within clinical pathways. Differentiating invasive infection from colonization and identifying antifungal resistance remain key challenges. As our diagnostic arsenal expands, centralized clinical mycology laboratories and efforts to ensure access to new diagnostics in low-resource settings will become increasingly important.

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“…While CMV infection typically remains asymptomatic in most healthy individuals, transplant recipients, due to their suppressed immune systems, lack CMV-specific cytotoxic cells and helper T cells, rendering them vulnerable to life-threatening cytomegalovirus disease. Moreover, CMV infection heightens the susceptibility to other pathogenic infections, such as bacteria, fungi, Epstein-Barr virus, varicella-zoster virus, and escalates the incidence of Graft-Versus-Host Disease (GvHD) in patients ( 3 ).…”

Section: Introductionmentioning

confidence: 99%

Expansion of effector memory Vδ2neg γδ T cells associates with cytomegalovirus reactivation in allogeneic stem cell transplant recipients

Huang,

Jiang,

Zhu

et al. 2024

Front. Immunol.

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BackgroundCytomegalovirus (CMV) reactivation is a significant concern following allogeneic stem cell transplantation. While previous research has highlighted the anti-CMV reactivation effect of γδ T cells in immunocompromised transplant patients, their characterization in recipients at high risk of CMV reactivation remains limited.MethodsThis study focused on D+/R+ recipients (where both donor and recipient are CMV seropositive) at high risk of CMV reactivation. We analyzed 28 patients who experienced CMV recurrence within 100 days post-allogeneic hematopoietic stem cell transplantation, along with 36 matched recipients who did not experience CMV recurrence. Clinical data from both groups were compared, and risk factors for CMV reactivation were identified. Additionally, CMV viral load was measured, and flow cytometric analysis was conducted to assess changes in peripheral blood γδ T cell proportions, subpopulation distribution, and differentiation status. We also analyzed the CDR3 repertoire of the TCR δ chain in different γδ T cell subsets. Functional analysis was performed by measuring the lysis of CMV-infected cells upon stimulation.ResultsCMV reactivation post-transplantation was associated with acute graft-versus-host disease (aGvHD) and reactivation of non-CMV herpesviruses. Notably, CMV reactivation led to sustained expansion of γδ T cells, primarily within the Vδ2neg γδ T cell subpopulation, with a trend toward differentiation from Naive to effector memory cells. Analysis of the δ chain CDR3 repertoire revealed a delay in the reconstitution of clonal diversity in Vδ2neg γδ T cells following CMV reactivation, while Vδ2pos T cells remained unaffected. Upon stimulation with CMV-infected MRC5 cells, the Vδ2neg γδ T cell subpopulation emerged as the primary effector cell group producing IFN-γ and capable of lysing CMV-infected cells. Moreover, our findings suggest that NKG2D is not necessary involved in Vδ2neg γδ T cell-mediated anti-CMV cytotoxicity.ConclusionThis study provides novel insights into the role of γδ T cells in the immune response to CMV reactivation in transplantation recipients at high risk of CMV infection. Specifically, the Vδ2neg γδ T cell subpopulation appears to be closely associated with CMV reactivation, underscoring their potential role in controlling infection and reflecting CMV reactivation in HSCT patients.

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Cytomegalovirus reactivation is associated with an increased risk of late-onset invasive aspergillosis independently of grade II–IV acute graft-versus-host disease in allogeneic hematopoietic stem cell transplantation: JSTCT Transplant Complications Working Group

Cited by 8 publications

References 29 publications

Attenuated humoral response against SARS‐CoV‐2 mRNA vaccination in allogeneic stem cell transplantation recipients

Attenuated humoral response against SARS‐CoV‐2 mRNA vaccination in allogeneic stem cell transplantation recipients

Diagnosis of invasive respiratory mycoses in the immunocompromised host

Expansion of effector memory Vδ2neg γδ T cells associates with cytomegalovirus reactivation in allogeneic stem cell transplant recipients

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