CMV Infection and CMV-Specific Immune Reconstitution Following Haploidentical Stem Cell Transplantation: An Update

Luo, Xiao‐Hua; Zhu, Yan; Chen, Yuting; Shui, Li-Ping; Liu, Lin

doi:10.3389/fimmu.2021.732826

Cited by 18 publications

(11 citation statements)

References 117 publications

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“…Identical) as an independent risk factor for CMV and EBV co-reactivation. Compared with HLA identical sibling transplantation, patients undergoing HLA-haploidentical stem cell transplantation(haploSCT) usually receive more intensive immunosuppressors to guarantee engraftment and later prevent graft-versus-host disease (GVHD) (Luo et al, 2021). Previous studies have shown that risk factors for CMV reactivation after HSCT include a donor or recipient seropositive for CMV, mismatched or unrelated donors, pre-allo-HSCT viremia, and use of alemtuzumab (Sousa et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Association Between Cytomegalovirus and Epstein-Barr Virus Co-Reactivation and Hematopoietic Stem Cell Transplantation

Zhang

Jia

et al. 2022

Front. Cell. Infect. Microbiol.

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The co-reactivation of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in patients undergoing hematopoietic stem cell transplantation (HSCT) has been found. Research has shown that the reactivation of CMV or EBV is closely related to poor HSCT outcomes. In this study, we describe the clinical characteristics of HSCT patients with co-reactivation of CMV and EBV. We retrospectively reviewed the medical records of 327 patients who underwent HSCT at the Peking University People’s Hospital Institute of Hematology. Co-reactivation of CMV and EBV was observed in a total of 75 patients (22.9%) who also had a higher incidence of hemorrhagic cystitis (P=0.000). HSCT patients with CMV and co-reactivation of CMV and EBV had a significantly lower 1-year overall survival (OS; P=0.050). Further, COX regression analysis showed that viral infection was a risk factor for 1-year OS (HR, 12.625 for co-reactivation vs. no reactivation, p=0.021, and HR 13.580 for CMV reactivation vs. no reactivation, P=0.013). In conclusion, the patients with CMV reactivation had poorer outcome after HSCT regardless of EBV reactivation.

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Section: Discussionmentioning

confidence: 99%

Association Between Cytomegalovirus and Epstein-Barr Virus Co-Reactivation and Hematopoietic Stem Cell Transplantation

Zhang

Jia

et al. 2022

Front. Cell. Infect. Microbiol.

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“…Cytomegalovirus (CMV) infection remains another challenging obstacle in transplant recipients ( 17 ). Prophylactic and preemptive antiviral treatment strategies has greatly reduced the morbidity and mortality of CMV infection post allo-HSCT, but the reconstitution of CMV-specific CTL (CMV-CTL) following transplantation is essential to confer long-term protection against CMV infection ( 18 , 19 ). 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.…”

Section: Introductionmentioning

confidence: 99%

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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“…The effect of donor serostatus on patients with IEI and cytomegalovirus infection is not yet clearly elucidated. In addition, we have to take into account that the conditioning regimen could also modify the immune reconstitution and the transferred T cell immunity of the donor, the rate of CMV reactivations, and, therefore, the long-term survival [ 33 ]. Other approaches such as the use of ATG, ex vivo T-cell depletion using CD34 + positive selection, or post-transplant cyclophosphamide could affect the control of viral replication, leading to a higher incidence of CMV infection [ 33 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

Impact of cytomegalovirus infection prior to hematopoietic stem cell transplantation in children with inborn errors of immunity

et al. 2022

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The presence of active viral infections has an impact on the prognosis of patients undergoing hematopoietic stem cell transplantation (HSCT). Nevertheless, the number of reports of cytomegalovirus infection in patients with inborn errors of immunity (IEI) who undergo HSCT is relatively low. To analyze the effect of cytomegalovirus infection acquired prior to curative treatment on patient survival in 123 children with IEI. An observational and retrospective study was performed with patients younger than 18 years diagnosed with IEI who were candidates for HSCT, gene therapy, or thymus transplantation at five hospitals in Spain between 2008 and 2019. We included 123 children, 25 infected by cytomegalovirus prior to undergoing curative treatment (20.3%). At IEI diagnosis, 24 of the patients were already infected, 21 of whom had symptomatic cytomegalovirus disease (87%), while the other three patients developed disease before undergoing curative treatment. The patients with cytomegalovirus infection had higher mortality than those without ( p = 0.006). Fourteen patients developed refractory cytomegalovirus infection (56%), all of whom died, while no patients with non-refractory infection died ( p = 0.001) All deaths that occurred before curative treatment and three of the five after the treatment were attributed to cytomegalovirus. Patients with refractory cytomegalovirus disease had the highest pre-HSCT mortality rate (64.3%), compared with the non-infected children and those with non-refractory cytomegalovirus disease (10.1%) ( p < 0.0001). Conclusion : Prevention and prompt control of cytomegalovirus infection, together with early HSCT/gene therapy, are crucial for improving the prognosis in children with IEI. What is Known: • Cytomegalovirus is the most frequent viral infection in children with inborn errors of immunity who are candidates to hematopoietic stem cell transplantation (HSCT). • Active viral infections at the time of HSCT lead to worse prognosis. What is New: • In children with inborn errors of immunity and indication of HSCT, refractory cytomegalovirus disease is associated with a very high mortality rate, compared with non-infected children and those with non-refractory cytomegalovirus disease. • In patients with novel transplantation indications, the presence and treatment response of CMV infection should be considered to decide the best possible moment for HSCT. Supplementary Information The online version contains supplementary material available at 10.1007/s00431-022-04614-5.

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CMV Infection and CMV-Specific Immune Reconstitution Following Haploidentical Stem Cell Transplantation: An Update

Cited by 18 publications

References 117 publications

Association Between Cytomegalovirus and Epstein-Barr Virus Co-Reactivation and Hematopoietic Stem Cell Transplantation

Association Between Cytomegalovirus and Epstein-Barr Virus Co-Reactivation and Hematopoietic Stem Cell Transplantation

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

Impact of cytomegalovirus infection prior to hematopoietic stem cell transplantation in children with inborn errors of immunity

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