Antiviral Combination Therapy for Cytomegalovirus Infection in High-Risk Infants

Vora, Surabhi B; Waghmare, Alpana; Englund, Janet A.

doi:10.3851/imp3238

Cited by 10 publications

(7 citation statements)

References 18 publications

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“…In our retrospective study, the use of several drugs in different national reference units reflects the clinicians’ difficulties to treat CMV disease in immunocompromised patients. Vora et al have recently suggested that combined antiviral therapy could be a safe option for high-risk children with primary immunodeficiencies in pre-transplantation settings, especially for those with high viral loads [ 28 ]. Although these data have to be considered with caution and further studies are needed, dual therapy could be an option in infants with PID and severe CMV disease without viral load control.…”

Section: Discussionmentioning

confidence: 99%

“…Adoptive immunotherapy with virus-specific T-cells appears to have limited efficacy for treating disseminated cytomegalovirus infections in pre-transplantation settings [ 19 , 22 ]. Given that the presence of active cytomegalovirus infection adversely affects survival [ 1 , 6 , 28 ], adoptive immunotherapy could be administered as a rapid salvage therapy to reduce viremia until immunity is reestablished with an HSCT [ 19 , 22 ]. Lastly, adjuvant therapy with intravenous immunoglobulin or with cytomegalovirus-specific hyperimmune globulin may be considered in cases of severe disease associated with hypogammaglobulinemia [ 6 ], although its effect remains controversial [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

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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“…In general, antiviral prophylaxis is established with acyclovir or valacyclovir at least up to one year after CAR-T infusion, or until a CD4+ T lymphocyte level greater than 0.2 x 10 9 /L is documented ( 134 ). In paediatrics, nonspecific immunoglobulins are also frequently used to maintain total IgG levels above 0.4 g/L ( 135 ). With respect to monitoring, the EBMT guidelines recommend that PCR be performed when clinically indicated ( 133 ).…”

Section: In the Haematological Settingmentioning

confidence: 99%

Cytomegalovirus in Haematological Tumours

et al. 2021

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The exquisite coupling between herpesvirus and human beings is the result of millions of years of relationship, coexistence, adaptation, and divergence. It is probably based on the ability to generate a latency that keeps viral activity at a very low level, thereby apparently minimising harm to its host. However, this evolutionary success disappears in immunosuppressed patients, especially in haematological patients. The relevance of infection and reactivation in haematological patients has been a matter of interest, although one fundamentally focused on reactivation in the post-allogeneic stem cell transplant (SCT) patient cohort. Newer transplant modalities have been progressively introduced in clinical settings, with successively more drugs being used to manipulate graft composition and functionality. In addition, new antiviral drugs are available to treat CMV infection. We review the immunological architecture that is key to a favourable outcome in this subset of patients. Less is known about the effects of herpesvirus in terms of mortality or disease progression in patients with other malignant haematological diseases who are treated with immuno-chemotherapy or new molecules, or in patients who receive autologous SCT. The absence of serious consequences in these groups has probably limited the motivation to deepen our knowledge of this aspect. However, the introduction of new therapeutic agents for haematological malignancies has led to a better understanding of how natural killer (NK) cells, CD4+ and CD8+ T lymphocytes, and B lymphocytes interact, and of the role of CMV infection in the context of recently introduced drugs such as Bruton tyrosine kinase (BTK) inhibitors, phosphoinosytol-3-kinase inhibitors, anti-BCL2 drugs, and even CAR-T cells. We analyse the immunological basis and recommendations regarding these scenarios.

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“…Viruses were able to interfere with the reproductive function in both sexes. The CMV virus is transmission by close contacts among infected subjects, via such as blood or blood products, congenital, sexual intercourse (8). Infections for congenital HCMV are mostly noted as causes of hearing loss and mental retardation; latent CMV infections can be activated in immune compromised patients, e.g.…”

Section: Introductionmentioning

confidence: 99%

Immunological and Molecular Diagnosis of Cytomegalovirus Infection between Aborted & Pregnant Women in Babylon City

Al-Mousawi

AL-Hajjar²

2021

Baghdad Sci.J

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Human cytomegalovirus (CMV) is the globally highly prevalent herpesvirus worldwide. CMV infects populations of all ages according to the Center for Disease Control and Prevention (CDC) and World Health Organization (WHO). CMV infections remain the most common viral complication potentially multiple in humans and are a major cause of congenital normality in women, which is why they are critical for diagnosis in several times when it happens during pregnancy. Pregnant women with CMV infection can be in charge of abortion or congenital expandaedby. This study involves the collection a total of (90) samples taken from each aborted and pregnant woman (70 with abortion cases and 20 of pregnant without history of abortion as control subjects) referring to Babylon teaching hospital for Maternity and Children, covering a period from (October 2018 to March 2019) to investigate the occurrence of Cytomegalovirus (CMV) in Babylon city. Patients and controls were evaluated for IgG, IgM antibodies and anti-HCMV IgG, IgM for (90) subjects were controlled in this study using the Enzyme Immunoassay Test Kit and read by enzyme - linked immunosorbent analyze (ELISA). In addition the polymerase chain reaction (PCR) DNA detection for CMV are based on the amplification of pathogen genomes in a particular region using different primers. The Chi-square test was used to analyze the data. The results show among 90 samples, women were evaluated for CMV infection, the seroprevalence titer was significantly higher at P <0.05 in seropositive cases ranging from 62(89%) toward positive CMV IgG, while the 65 (93%) of patients were positive CMV IgM from (70) women with abortions. By contrast, the results obtained from the controls were 9 (45%) subjects seropositive for IgG and all of them were seronegative with IgM. The anti – HCMV IgG finding showed high positivity that represents the furthermost of CMV infections among females through ages ranging between 20-29 years. Furthermore, the outcomes of molecular detection showed that a small number of samples 13 (19%) were HCMV DNA detectable in aborted women less than in pregnant women 3 (15%).

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Antiviral Combination Therapy for Cytomegalovirus Infection in High-Risk Infants

Abstract: Combination GCV + FOS therapy may be a safe alternative to monotherapy in high-risk infants, especially those who are pre-transplant with primary immune deficiency syndromes and high viral loads.

Cited by 10 publications

References 18 publications

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

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

Cytomegalovirus in Haematological Tumours

Immunological and Molecular Diagnosis of Cytomegalovirus Infection between Aborted & Pregnant Women in Babylon City

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