Assessment of the association between cytomegalovirus DNAemia and subsequent acute graft‐versus‐host disease in allogeneic peripheral blood stem cell transplantation: A multicenter study from the Spanish hematopoietic transplantation and cell therapy group

Bueno, Felipe; Solano, Carlos; Vázquez, Lourdes; Giménez, Estela; Cámara, Rafael de la; Albert, Eliseo; Rovira, Montserrat; Espigado, Ildefonso; Calvo, Carmen; López‐Jiménez, Javier; Suárez‐Lledó, María; Chinea, Anabella; Esquirol, Albert; Pérez, Ariadna; Bermúdez, Aránzazu; Saldaña, Raquel; Heras, Inmaculada; González-Huerta, Ana Julia; Torrado, Tamara; Batlle, Montserrat; Jiménez, Santiago; Vallejo, Carlos; Barba, Pere; Cuesta, María Ángeles; Duarte, Rafael F.; Piñana, José Luís; Navarro, David

doi:10.1111/tid.13627

Cited by 6 publications

(7 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In turn, a large number of nonessential CMV genes (around one‐third of the CMV genome) encode proteins with proinflammatory (human homologs of cytokines, chemokines, or chemokine receptors) or immunosuppressive (i.e., inhibitors of natural killer [NK]‐cell activation or antigen presentation to CD4 + and CD8 + T cells) properties 4,5 . The proinflammatory and immunosuppressive nature of CMV mechanistically supports the association reported in some series between CMV infection and the occurrence of acute graft versus host disease (aGvHD) or virus superinfections (i.e., due to Epstein–Barr virus), 7,8 both among the so‐called “indirect effects.” Moreover, CMV DNAemia was suggested to be associated in a positive dose–response manner with an increased risk of overall mortality (OM) and nonrelapse mortality (NRM) in the first year after allo‐SCT, independent of the use of PET 9 . The link between CMV DNAemia, most notably that requiring PET, and OM/NRM has also been observed in other studies, 10,11 including a meta‐analysis and meta‐regression analysis 12 .…”

Section: Clinical Relevance Of CMV Infection In the Allo‐sct Settingmentioning

confidence: 63%

Immunovirology of cytomegalovirus infection in allogeneic stem cell transplant recipients undergoing prophylaxis with letermovir: A narrative review

Solano

Giménez

Albert

et al. 2023

Journal of Medical Virology

Self Cite

View full text Add to dashboard Cite

On November 7, 2017, the US Food and Drug Administration approved the use of letermovir (LMV) for prophylaxis of cytomegalovirus (CMV) infection in adult CMV‐seropositive allogeneic stem cell transplant recipients. After 6 years of use, a large body of real‐world experience has been accumulated that validates the Phase III clinical trial results, in which LMV was shown to significantly reduce the risk of clinically significant CMV infection—defined as CMV end‐organ disease or CMV DNAemia requiring pre‐emptive antiviral therapy (PET)—and increase survival up to Week 24 after treatment inception. Notwithstanding, several issues still need to be settled, thus further investigation is required. First, since viral DNA may accumulate as a result of LMV‐driven abortive CMV infection, what is the optimal viral load threshold in the blood that would prompt LMV prophylaxis interruption and PET inception? Should this be adapted to the patient's risk? Second, what is the impact of LMV prophylaxis on the reconstitution of functional CMV‐specific T‐cell responses? Would it be a wise approach to individually tailor the duration of LMV treatment according to the number of peripheral blood CMV‐specific T cells at the end of regular prophylaxis? Third, how frequently do LMV‐resistant strains arise while patients are on LMV prophylaxis and how could this be minimized? Here, we discuss the literature addressing these topics.

show abstract

Section: Clinical Relevance Of CMV Infection In the Allo‐sct Settingmentioning

confidence: 63%

Immunovirology of cytomegalovirus infection in allogeneic stem cell transplant recipients undergoing prophylaxis with letermovir: A narrative review

Solano

Giménez

Albert

et al. 2023

Journal of Medical Virology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Several studies have reported either a higher incidence of CMV DNAemia 4–9 or faster plasma CMV DNA duplication times 10 in PT/Cy‐haplo compared to HLA‐matched allo‐HSCT; nevertheless, these observations could not be explained by differences in the kinetics of CMV‐specific T‐cell reconstitution early after allo‐SCT 11 . The impact of the overall degree of HLA class I and II mismatching on the frequency of CMV DNAemia has been documented in cord blood transplantation, 30 in which setting a significant effect on the incidence of CMV reactivation was noted for HLA disparity (HR: 0.54 for 8/8 match compared with 3‐allele mismatch).…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3] Several studies have shown that Cytomegalovirus (CMV) DNAemia occurs at an exceedingly high frequency in PT/Cy-haplo compared to other allo-SCT modalities. [4][5][6][7][8][9] Moreover, subtle dissimilarities between PT/Cy-haplo and human leukocyte antigen (HLA)-matched allotransplants have been reported, namely shorter CMV DNA doubling times in plasma and higher CMV DNA peak levels in the former. 10,11 Robust reconstitution of functional CMV-specific CD8 + T cells has been shown to contribute crucially in preventing and resolving CMV DNAemia episodes in the allo-SCT setting.…”

Section: Introductionmentioning

confidence: 99%

“…Unmanipulated haploidentical hematopoietic stem cell transplantation (haplo‐SCT) with high‐dose posttransplant cyclophosphamide (PT/Cy‐haplo) has been consolidated as an effective allotransplant platform for treatment of a variety of hematological malignancies 1–3 . Several studies have shown that Cytomegalovirus (CMV) DNAemia occurs at an exceedingly high frequency in PT/Cy‐haplo compared to other allo‐SCT modalities 4–9 . Moreover, subtle dissimilarities between PT/Cy‐haplo and human leukocyte antigen (HLA)‐matched allotransplants have been reported, namely shorter CMV DNA doubling times in plasma and higher CMV DNA peak levels in the former 10,11 …”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Impact of cytomegalovirus immunodominant HLA‐I donor–recipient matching on the incidence and features of virus DNAemia and virus‐specific T‐cell immune reconstitution in unmanipulated haploidentical hematopoietic stem cell transplantation

Huntley

Giménez

Vázquez³

et al. 2023

Transplant Infectious Dis

Self Cite

View full text Add to dashboard Cite

Background:We investigated whether donor-recipient mismatch involving one or more cytomegalovirus (CMV) immunodominant (ID) human leukocyte antigen (HLA)-I alleles may impact on the degree of CMV pp65/immediate-early 1 (IE-1) T-cell reconstitution and the incidence of CMV DNAemia in patients undergoing unmanipulated haploidentical hematopoietic stem cell transplantation with high-dose posttransplant cyclophosphamide (PT/Cy-haplo).Methods: Multicenter observational study including 106 consecutive adult PT/Cyhaplo patients (34 CMV ID HLA-I matched and 72 mismatched). A real-time PCR was used for plasma CMV DNA load monitoring. Enumeration of CMV-specific (pp65/IE-1) interferon (IFN)-γ-producing T cells from several patients was performed by flow cytometry by days +30, +60, +90 and +180 after transplantation. Results:The cumulative incidence of CMV DNAemia, clinically significant CMV DNAemia episodes (cs-CMVi), and recurrent CMV DNAemia was comparable across CMV ID HLA-I matched and mismatched patients (71.8% vs. 80.9%, p = .95; 40.7% vs. 44.2%, p = .85; 16.4% vs. 28.1%; p = .43, respectively). The percentage of patients exhibiting detectable CMV-specific IFN-γ-producing T-cell responses (either CD8 + or CD4 + ) was similar across groups; nevertheless, significantly higher CMV-specific CD8 + T-cell counts were enumerated in the CMV ID HLA-I matched compared to mismatched patients by day +60 (p = .04) and +180 (p = .016) after transplantation. Conclusion:CMV ID HLA-I matching may impact on the magnitude of CMV-pp65/IE-1-specific CD8 + T-cell reconstitution; yet, this effect seemed not to have an impact on the incidence of initial, recurrent CMV DNAemia, or cs-CMVi.

show abstract

“…Up to 80% of CMV seropositive recipients can experience viral reactivation after allo-HSCT during the T-cell depletion phase. [3][4][5][6][7] CMV reactivation is reported to be associated with an increased risk for secondary bacterial and fungal infections, tissue-invasive CMV illness if neglected, 8 as well as graft-versus-host-disease (GvHD), [9][10][11] and increases mortality rates. 12 Pre-emptive therapy (PET) has been found to significantly lower the incidence of CMV infection in those who have undergone an HSCT.…”

Section: Introductionmentioning

confidence: 99%

QuantiFERON‐CMV and monitor predict cytomegalovirus, mortality, and graft‐versus‐host disease in transplant recipients

Souan,

Jazar,

Nashwan

et al. 2023

Journal of Medical Virology

View full text Add to dashboard Cite

Cytomegalovirus (CMV) is the most prevalent infection in recipients of hematopoietic stem cell transplant (HSCT). QuantiFERON‐CMV (QF‐CMV) and QuantiFERON‐Monitor (QFM) assays were used to test whether immune‐competent adult allogeneic HSCT recipients with CMV‐specific T cells can control CMV infection or reactivation. Our data demonstrated a significant correlation between CMV infection measured by CMV‐antigenemia test and QF‐CMV results, graft versus host disease (GvHD), and mortality rates. The QF‐CMV test revealed that CMV‐specific T cells with higher interferon‐γ (IFN‐γ) release were correlated with lower CMV infection rates. There was a significant negative association between QF‐CMV results, GvHD, and mortality rates. Data showed that a one‐unit rise in IFN‐γ was linked with a 12.7% reduction in GvHD and a 20.7% reduction in the mortality odds ratio. In addition, a negative correlation was found between QF‐M results and CMV infection, with the QFM test predicting protection against CMV infection by 1.9%. This is one of the few studies establishing the QF‐CMV test's predictive value for GvHD and mortality, its use to monitor HSCT patients for pre‐emptive therapy, and the use of the QFM test to predict CMV infection and mortality in HSCT patients. Thus, these assays could be utilized to optimize preventive and pre‐emptive therapy procedures to reduce transplant recipient adverse effects and posttransplant therapy costs.

show abstract

Assessment of the association between cytomegalovirus DNAemia and subsequent acute graft‐versus‐host disease in allogeneic peripheral blood stem cell transplantation: A multicenter study from the Spanish hematopoietic transplantation and cell therapy group

Cited by 6 publications

References 23 publications

Immunovirology of cytomegalovirus infection in allogeneic stem cell transplant recipients undergoing prophylaxis with letermovir: A narrative review

Immunovirology of cytomegalovirus infection in allogeneic stem cell transplant recipients undergoing prophylaxis with letermovir: A narrative review

Impact of cytomegalovirus immunodominant HLA‐I donor–recipient matching on the incidence and features of virus DNAemia and virus‐specific T‐cell immune reconstitution in unmanipulated haploidentical hematopoietic stem cell transplantation

QuantiFERON‐CMV and monitor predict cytomegalovirus, mortality, and graft‐versus‐host disease in transplant recipients

Contact Info

Product

Resources

About