Cytomegalovirus retinitis after allogeneic hematopoietic stem cell transplantation under cytomegalovirus antigenemia-guided active screening

Mori, Takehiko; Kikuchi, Taku; Koh, Miki; Koda, Yuya; Yamazaki, Rie; Sakurai, Masatoshi; Tomita, Yohei; Ozawa, Yoko; Kohashi, Sumiko; Abe, Ryohei; Saburi, Masuho; Kato, Jun

doi:10.1038/s41409-020-01176-8

Cited by 10 publications

(11 citation statements)

References 20 publications

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“…The criteria for starting preemptive treatment are basically ≥1 CMV antigen‐positive cells in total on two slides in CB recipients or patients receiving systemic corticosteroid or anti‐thymocyte globulin as GVHD treatment or prophylaxis, or ≥10 CMV antigen‐positive cells in the other low‐risk patients 3 . CMV pneumonitis was defined as interstitial infiltration accompanied by histologic demonstration of CMV in a lung biopsy specimen or a positive CMV culture from bronchoalveolar lavage fluid; CMV gastroenteritis was defined as gastrointestinal symptoms accompanied by histologic demonstration of CMV obtained by endoscopy; and CMV retinitis was diagnosed based on characteristic retinal changes or the detection of CMV‐DNA by PCR in the vitreous fluid or aqueous humor 12,13 . An anti‐CMV agent, ganciclovir or foscarnet, was started immediately after a diagnosis of CS‐CMVi.…”

Section: Methodsmentioning

confidence: 99%

“…CMV gastroenteritis was defined as gastrointestinal symptoms accompanied by histologic demonstration of CMV obtained by endoscopy; and CMV retinitis was diagnosed based on characteristic retinal changes or the detection of CMV-DNA by PCR in the vitreous fluid or aqueous humor. 12,13 An anti-CMV agent, ganciclovir or foscarnet, was started immediately after a diagnosis of CS-CMVi. The choices of anti-CMV agent and dosage were at the discretion of each physician.…”

Section: Definitions Of and Intervention Against CMV Reactivation/dis...mentioning

confidence: 99%

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Risk factor analysis for cytomegalovirus reactivation under prophylaxis with letermovir after allogeneic hematopoietic stem cell transplantation

Mizuno

Sakurai

Kato

et al. 2022

Transplant Infectious Dis

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Background Letermovir has been approved as a novel cytomegalovirus (CMV) prophylactic agent after allogeneic hematopoietic stem cell transplantation (HSCT). However, there are still insufficient data to properly evaluate the real‐world role of letermovir, and the risk factors for CMV reactivation under letermovir prophylaxis have not been clarified. Methods We performed a single‐institution retrospective analysis of patients under prophylaxis with or without letermovir who underwent allogeneic HSCT between March 2012 and December 2019. In August 2018, letermovir was added to the clinical practice at our institution for the prophylaxis of CMV reactivation in allogeneic HSCT recipients. Patients who underwent HSCT without prophylactic letermovir from March 2012 until September 2018 served as a historical control. Results The cumulative incidence of clinically significant CMV infection (CS‐CMVi) was significantly lower in the letermovir group than in the historical control group not receiving letermovir (30.2% vs. 71.6%, p < .05, at 100 days). In addition, the cumulative incidence of non‐relapse mortality (NRM) at day 500 was significantly lower in the letermovir group (4.7% vs. 19.8%, p < .05). We then performed a risk factor analysis for developing CS‐CMVi in the letermovir group. The only significant factor identified by this multivariable analysis was transplantation from a CMV seronegative donor to a seropositive recipient (Hazard ratio = 2.76, 95% confidence interval 1.14–6.68, p < .05). Conclusion Our study showed that letermovir prophylaxis significantly reduced the incidence of CS‐CMVi and NRM in a real‐world setting and that the CMV serostatus of the donor remained as a risk factor for CS‐CMVi even under letermovir prophylaxis.

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Section: Methodsmentioning

confidence: 99%

Section: Definitions Of and Intervention Against CMV Reactivation/dis...mentioning

confidence: 99%

Risk factor analysis for cytomegalovirus reactivation under prophylaxis with letermovir after allogeneic hematopoietic stem cell transplantation

Mizuno

Sakurai

Kato

et al. 2022

Transplant Infectious Dis

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“…CMV retinitis (CMVR) after HCT is rare, but can cause potential devastating visual consequences. The median onset of CMV following HCT is Day +34, and the median time of diagnosis of CMVR is Day+ 251 post-HCT 4,5 . The minimal symptoms in the early stages of CMVR and its suboptimal response to systemic and intra-vitreal antiviral therapy, make CMVR a very challenging condition to diagnose and treat.…”

Section: Introductionmentioning

confidence: 99%

“…The minimal symptoms in the early stages of CMVR and its suboptimal response to systemic and intra-vitreal antiviral therapy, make CMVR a very challenging condition to diagnose and treat. 4 Recently, virus-specific T lymphocytes (VSTs) have been used to treat systemic CMV, as they were found to be effective in 83% of subjects treated for CMV infection 6 .…”

Section: Introductionmentioning

confidence: 99%

Persistent Cytomegalovirus Retinitis following Hematopoietic Stem Cell Transplantation Treated with Viral-Specific T Cells

Montiel-Esparza

Michalak

et al. 2023

Preprint

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Cytomegalovirus retinitis (CMVR) following hematopoietic stem cell transplantation (HCT) for a primary immunodeficiency is a rare but highly morbid condition with potential irreversible consequences despite optimal antiviral pharmacotherapy. Viral-specific T cells (VSTs) pose a promising and safe approach eradicating intractable viral disease. We describe the case of a 21-month-old male with Wiskott-Aldrich syndrome (WAS) and CMVR post-HCT with sustained long-term virologic and clinical response after CMV-specific T cell therapy. This case highlights the need to consider VSTs as an adjunct upfront strategy in refractory CMVR and for routine ophthalmologic screening and surveillance in high-risk patients post-HCT.

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“…Human cytomegalovirus (HCMV) seroprevalence is high worldwide ( Manicklal et al., 2013 ; Zuhair et al., 2019 ), and HCMV reactivation is a frequent issue in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) ( Kaito et al., 2020 ), in whom it causes direct and indirect harmful effects ( Hancock et al., 2020 ; Mori et al., 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Early immune surveillance to predict cytomegalovirus outcomes after allogeneic hematopoietic stem cell transplantation

Xia

Li²,

Gui³

et al. 2022

Front. Cell. Infect. Microbiol.

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BackgroundThere is no method of predicting human cytomegalovirus (HCMV) outcomes in allogeneic hematopoietic stem cell transplant recipients clinically, leading in some cases to excessive or insufficient antiviral therapy. We evaluated the early immune response of recipients with disparate HCMV outcomes.MethodsThe HCMV outcomes of recipients were determined by long-term monitoring of HCMV DNA levels posttransplant. HCMV IgG and IgM concentrations at 1 week before and 1 week after transplantation, absolute lymphocyte counts, and HCMV-specific IFN-γ secreting cells at 1 month posttransplant were evaluated based on HCMV outcome.ResultsAll recipients were negative for HCMV IgM. Significant differences between recipients with and without HCMV reactivation were observed in pre- and post-transplant HCMV IgG antibody levels, absolute lymphocyte counts, and HCMV-specific IFN-γ secreting cells (P < 0.05). HCMV IgG antibody levels significantly increased after transplantation in recipients with HCMV reactivation (P = 0.032), but not in those without reactivation. Multivariate analysis revealed that except for the absolute lymphocyte count these biomarkers were related to HCMV reactivation, independent of other clinical factors. In time-to-event analyses, lower levels of these biomarkers were associated with an increased 150-day cumulative incidence of HCMV reactivation (log-rank P < 0.05). In recipients with HCMV reactivation, the duration of HCMV DNAemia had negative correlation with HCMV-specific IFN-γ-secreting cells (P = 0.015, r = -0.372). The relationships between the peak HCMV DNA load and absolute lymphocyte count and HCMV-specific IFN-γ-secreting cells followed the same trends (P = 0.026, r = -0.181 and P = 0.010, r = -0.317).ConclusionsHCMV IgG, absolute lymphocyte count, and HCMV-specific IFN-γ secreting cells represent the humoral and cellular immune response. Early monitoring of these immune markers could enable prediction of HCMV outcomes posttransplant and assessment of the severity of HCMV DNAemia.

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Cytomegalovirus retinitis after allogeneic hematopoietic stem cell transplantation under cytomegalovirus antigenemia-guided active screening

Cited by 10 publications

References 20 publications

Risk factor analysis for cytomegalovirus reactivation under prophylaxis with letermovir after allogeneic hematopoietic stem cell transplantation

Risk factor analysis for cytomegalovirus reactivation under prophylaxis with letermovir after allogeneic hematopoietic stem cell transplantation

Persistent Cytomegalovirus Retinitis following Hematopoietic Stem Cell Transplantation Treated with Viral-Specific T Cells

Early immune surveillance to predict cytomegalovirus outcomes after allogeneic hematopoietic stem cell transplantation

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