Assessment of a cytomegalovirus serology dual‐testing strategy in hematopoietic stem cell transplant recipients

Perry, D. Alexander; Hakki, Morgan

doi:10.1111/tid.12591

Cited by 3 publications

(2 citation statements)

References 21 publications

(38 reference statements)

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“…However, it is worth noting that in polytransfused patients (as exemplified by many haematological patients awaiting an allogeneic transplant), the serological status may be an artefact of a passive immunization mechanism. Discrepancies in CMV have been observed in up to 29%-33% of patients when this has been analysed ( 86 , 87 ). Routinely determined serostatus is still currently used as a criterion for estimating CMV reactivation risk before transplant.…”

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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Section: In the Haematological Settingmentioning

confidence: 99%

Cytomegalovirus in Haematological Tumours

et al. 2021

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“…In any case, the accurate determination of D/R CMV serostatus prior to allo‐HSCT is of major relevance. In a recent study, Perry and Hakki noted that allo‐HSCT recipients may be miscategorized as being CMV seropositive if serological testing is performed after receipt of blood transfusions or when employing assays with suboptimal specificity . Recently, Loeth et al found CD4 + and/or CD8 + pp65‐specific T‐cell responses in five out of 44 seronegative individuals.…”

Section: Introductionmentioning

confidence: 99%

Going beyond serology for stratifying the risk of CMV infection in transplant recipients

Navarro

Fernández‐Ruiz

Aguado

et al. 2018

Reviews in Medical Virology

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Summary Knowledge of donor and recipient (D/R) cytomegalovirus (CMV) serostatus is critical for risk stratification of CMV infection and disease in transplant recipients, particularly in the solid organ transplantation (SOT) setting. Despite its broad availability and the success of it use, the risk stratification based on the D/R serostatus is not free of limitations since there are a nondepreciable number of patients that are not accurately categorized by this approach. In fact, up to 20% of seropositive SOT recipients, classically considered at intermediate risk, develop episodes of CMV infection and disease after transplantation. Here, we provide an overview of additional donor and recipient factors that may have utility in identifying patients at risk for post‐transplant CMV infection. Specifically, we summarize our current understanding regarding the potential use of use CMV‐specific T‐cell‐mediated immunity, neutralizing antibodies and host genetics that may influence the risk of CMV infection and disease. We provide an overview of the benefits and limitations associated with using these immunological factors in risk stratification and propose specific variables that could be analyzed at the pretransplant evaluation to improve the identification of patients with increased individual susceptibility.

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Impact of cytomegalovirus (CMV) seroconversion pre‐allogeneic hematopoietic cell transplantation on posttransplant outcomes

Sayyed,

Wilson,

Stavi

et al. 2024

European J of Haematology

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Cytomegalovirus (CMV) reactivation post‐allogeneic hematopoietic cell transplantation (post‐alloHCT) increases morbidity and mortality. We sought to determine the frequency of CMV seroconversion in patients pre‐alloHCT and to investigate the impact on posttransplant outcomes. We retrospectively investigated 752 adult patients who underwent alloHCT at our center from January 2015 to February 2020 before the adoption of letermovir prophylaxis. CMV serology was assessed at consult and pretransplant. The cohort was divided into four groups based on pretransplant CMV seroconversion: negative to positive (Group 1), positive to negative (Group 2), consistently negative (Group 3), and consistently positive (Group 4). Eighty‐nine patients (12%) had seroconverted from negative to positive, 17 (2%) from positive to negative, 151 (20%) were consistently seronegative, and 495 (66%) were consistently seropositive pretransplant. For the four CMV serostatus groups, cumulative incidence of CMV reactivation at 6 months posttransplant was 4.5%, 47.1%, 6.6%, and 76.6% for Groups 1, 2, 3, and 4, respectively (p < .0001). No differences between groups were seen regarding Grade III–IV acute graft‐versus‐host disease (GVHD) (p = .91), moderate/severe chronic GVHD (p = .41), or graft failure (p = .28). On multivariable analysis, there was no impact of CMV serostatus group on overall survival (p = .67), cumulative incidence of relapse (p = .83) or non‐relapse mortality. alloHCT patients who demonstrate CMV seroconversion pretransplant from negative to positive have a very low risk of CMV reactivation posttransplant. The observed seroconversion may be due to passive CMV immunity acquired through blood products. Quantitative CMV immunoglobulin G/immunoglobulin M pretransplant may help differentiate between true seroconversion and passively transmitted CMV immunoglobulin.

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Assessment of a cytomegalovirus serology dual‐testing strategy in hematopoietic stem cell transplant recipients

Cited by 3 publications

References 21 publications

Cytomegalovirus in Haematological Tumours

Cytomegalovirus in Haematological Tumours

Going beyond serology for stratifying the risk of CMV infection in transplant recipients

Impact of cytomegalovirus (CMV) seroconversion pre‐allogeneic hematopoietic cell transplantation on posttransplant outcomes

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