Impact of CMV reactivation on relapse of acute myeloid leukemia after HCT is dependent on disease stage and ATG

Turki, Amin T.; Tsachakis‐Mück, Nikolaos; Leserer, Saskia; Crivello, Pietro; Liebregts, Tobias; Betke, L; Alashkar, Ferras; Leimkühler, Nils B.; Trilling, Mirko; Fleischhauer, Katharina; Beelen, Dietrich W.

doi:10.1182/bloodadvances.2021005509

Cited by 22 publications

(7 citation statements)

References 46 publications

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“…On the other hand, a multicenter study showed that the incidence of CMV viremia was lower in non-T-cell depleted haplo-HSCT ALL patients ( Nagler et al., 2021 ). An interesting study found that the administration of ATG abrogated relapse protection following CMV reactivation in AML patients which we previously discussed ( Turki et al., 2022 ). In our study, only I-II aGVHD was linked to a significantly high incidence of CMV infection in univariate analysis.…”

Section: Discussionmentioning

confidence: 79%

Features of cytomegalovirus infection and evaluation of cytomegalovirus-specific T cells therapy in children’s patients following allogeneic hematopoietic stem cell transplantation: A retrospective single-center study

Ruan

Luo²,

Liu³

et al. 2022

Front. Cell. Infect. Microbiol.

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Cytomegalovirus (CMV) infection remains a critical cause of mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT), despite improvement by pre-emptive antivirus treatment. CMV-specific cytotoxic T lymphocytes (CMV-CTL) are universally used and proven well-tolerance after allo-HSCT in adult clinical trials. However, it is not comprehensively evaluated in children’s patients. Herein, we conducted a retrospective study to determine the risk factors of CMV infection and evaluation of CMV-CTL in children patients who underwent allo-HSCT. As result, a significantly poor 5-year overall survival was found in the CMV infection group (87.3 vs. 94.6%, p=0.01). Haploidentical HSCT (haplo-HSCT) was identified as an independent risk factor for CMV infection through both univariate and multivariate analyses (p<0.001, p=0.027, respectively). Furthermore, the cumulative incidence of CMV infection was statistically higher in the haplo-HSCT group compared to the HLA-matched donor group (44.2% vs. 21.6%, p<0.001). Finally, the overall response rate of CMV-CTL was 89.7% (26/29 patients) in CMV infection after allo-HSCT. We concluded that CMV infection following allo-HSCT correlated with increased mortality in children’s patients, and haplo-HSCT was an independent risk factor for CMV infection. Adoptive CMV-CTL cell therapy was safe and effective in pediatric patients with CMV infection.

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Section: Discussionmentioning

confidence: 79%

Features of cytomegalovirus infection and evaluation of cytomegalovirus-specific T cells therapy in children’s patients following allogeneic hematopoietic stem cell transplantation: A retrospective single-center study

Ruan

Luo²,

Liu³

et al. 2022

Front. Cell. Infect. Microbiol.

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“…The interplay between CMV infection and primary disease relapse in patients with hematological malignancies after allo-HSCT has been an area of interest and controversy for several years. Increased evidence and our recent meta-analysis ( 20 ) implied that CMV reactivation is associated with a decreased risk of leukemia relapse in AML patients ( 21 – 25 ), although registry data from both the EBMT ( 26 ) and the CIBMTR ( 27 ) do not support the protective effect of CMV serology or reactivation against relapse.…”

Section: Introductionmentioning

confidence: 96%

Different recovery patterns of CMV-specific and WT1-specific T cells in patients with acute myeloid leukemia undergoing allogeneic hematopoietic cell transplantation: Impact of CMV infection and leukemia relapse

et al. 2023

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In allogeneic hematopoietic cell transplantation (allo-HSCT), both virus-specific T cells and leukemia-specific T cells need to be reconstituted to protect patients from virus infections and primary disease relapse. Cytomegalovirus (CMV) infection remains an important cause of morbidity and mortality after allo-HSCT. Emerging data indicate that CMV reactivation is associated with reduced risk of leukemia relapse in patients with acute myeloid leukemia (AML) undergoing allo-HSCT. In a cohort of 24 WT1+ AML patients during the first year following HSCT, CMV specific CD8+ T cells (CMV-CTL) reconstituted much faster than WT1-specific CD8+ T cell (WT1-CTL) after allo-SCT. Moreover, CMV-CTL expressed lower levels of exhaustion markers and were more functional as identified by production of IFN-γ/TNF-α and expression of Eomes/T-bet. Interestingly, our patients with CMV reactivation presented higher frequency of CMV-CTL, lower levels of Eomes+T-bet- and higher levels of Eomes+T-bet+ expression in response to WT1 and CMV pp65 antigen during the first year after transplantation as compared to patients without CMV reactivation. Kinetics of CMV-CTL and WT1-CTL after transplantation might be associated with measurable residual disease and later leukemia relapse. Our results support that CMV reactivation, aside from the CMV-CTL reconstitution, could influence WT1-CTL reconstitution after allo-HSCT, thus potentially contributing to the remission/relapse of AML.

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“…Our study has several limitations due to its retrospective design, small sample size, and relatively short follow-up duration. Although CMV reactivation is a signi cant contributor to non-relapse mortality in allo-HSCT, numerous studies have also highlighted a protective aspect of CMV reactivation against relapse in AML and ALL (37)(38)(39). Owing to the small cohort and limited follow-up, we could not evaluate the protective effect of CMV reactivation against relapse.…”

Section: Discussionmentioning

confidence: 96%

Cytomegalovirus-specific T cell immunity reconstitution following allogeneic hematopoietic stem cell transplantation: a pilot stduy

Wang,

Li,

Huang

et al. 2023

Preprint

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Purpose Reactivation of cytomegalovirus (CMV) leads to significant morbidity and mortality following allogeneic hematopoietic stem cell transplantation (allo-HSCT). The reconstitution of CMV-specific T cells plays a crucial role in the antiviral response after allo-HSCT. However, the impact of CMV reactivation on the recovery of CMV-specific T cells in the early stages after allo-HSCT, particularly haploidentical HSCT, remains undisclosed. Methods We retrospectively examined CMV-specific T-cell recovery in 78 allo-HSCT recipients to assess the influence of clinically significant CMV infection (CS-CMVi) on CMV-specific T-cell restoration. Results Patients in CS-CMVi group displayed higher absolute quantities of CMV-specific IFN-γ+ T cells on day 30 (CD4+ T cells: 1.40 vs. 0.07 cells/µL, p = 0.02; CD8+ T cells: 1.64 vs. 0.15 cells/µL, p = 0.11), but lower counts on day 180 (CD4+ T cells: 1.06 vs. 5.95 cells/µL, p < 0.01; CD8+ T cells: 3.70 vs. 55.36 cells/µL, p = 0.04). Among patients receiving letermovir prophylaxis (LTV group), the recovery of CMV-specific CD8+ T cells was significantly delayed compared to those receiving preemptive therapy (PET group) from day 60. The LTV group was more likely to experience late-onset CMV reactivation if their absolute counts of polyfunctional CMV-specific CD4+ T cells or CD8+ T cells was below 2.01 (AUC = 0.78, p = 0.003) or 0.90 cells/µL (AUC = 0.89, p < 0.001). Conclusions In conclusion, our pilot study provides direct evidence that early episodes of CS-CMVi impair the recovery of CMV-specific T cells after allo-HSCT. Additionally, insufficient polyfunctional restoration would lead to late-onset CMV reactivation in LTV group.

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Impact of CMV reactivation on relapse of acute myeloid leukemia after HCT is dependent on disease stage and ATG

Cited by 22 publications

References 46 publications

Features of cytomegalovirus infection and evaluation of cytomegalovirus-specific T cells therapy in children’s patients following allogeneic hematopoietic stem cell transplantation: A retrospective single-center study

Features of cytomegalovirus infection and evaluation of cytomegalovirus-specific T cells therapy in children’s patients following allogeneic hematopoietic stem cell transplantation: A retrospective single-center study

Different recovery patterns of CMV-specific and WT1-specific T cells in patients with acute myeloid leukemia undergoing allogeneic hematopoietic cell transplantation: Impact of CMV infection and leukemia relapse

Cytomegalovirus-specific T cell immunity reconstitution following allogeneic hematopoietic stem cell transplantation: a pilot stduy

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