UNASSIGNED: Cytomegalovirus (CMV) infection is a common complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT) and in patients receiving novel hematological therapies. Its impact on morbidity and mortality necessitates effective management strategies. Despite recent advances in diagnostics and treatment, unresolved questions persist regarding monitoring and treatment, prompting the need for updated recommendations.
UNASSIGNED: A consensus was reached among a panel of experts selected for their expertise in CMV research and clinical practice. Key clinical areas and questions were identified based on previous surveys and literature reviews. Recommendations were formulated through consensus and graded using established guidelines.
UNASSIGNED: Recommendations were provided for virological monitoring, including the timing and frequency of CMV DNAemia surveillance, especially during letermovir (LMV) prophylaxis. We evaluated the role of CMV DNA load quantification in diagnosing CMV disease, particularly pneumonia and gastrointestinal involvement, along with the utility of specific CMV immune monitoring in identifying at-risk patients. Strategies for tailoring LMV prophylaxis, managing breakthrough DNAemia, and implementing secondary prophylaxis in refractory cases were outlined. Additionally, criteria for initiating early antiviral treatment based on viral load dynamics were discussed.
UNASSIGNED: The consensus provides updated recommendations for managing CMV infection in hematological patients, focusing on unresolved issues in monitoring, prophylaxis, treatment, and resistance. These recommendations aim to guide clinical practice and improve outcomes in this high-risk population. Further research is warranted to validate these recommendations and address ongoing challenges in CMV management with emerging antiviral combinations, particularly in pediatric populations.

BACKGROUND: Care home residents are at high risk from outbreaks of respiratory infections, such as influenza and COVID-19. We conducted a systematic review of randomized controlled trials, to determine which interventions (apart from vaccines) are effective at reducing transmission of acute respiratory illnesses (ARIs) in care homes.
METHODS: We searched CINAHL, Medline, Embase and Cochrane for randomized controlled trials (RCTs) of interventions to prevent transmission of ARIs in care homes (excluding vaccines), to April 2023.
RESULTS: A total of 21 articles met inclusion criteria. Two infection control interventions significantly reduced respiratory infections. Oseltamivir significantly reduced risk of symptomatic laboratory-confirmed influenza (OR 0.39, 95%CI 0.16-0.94, three trials), and influenza-like illness (OR 0.50, 95%CI 0.36-0.69), even in a vaccinated population. High dose vitamin D supplementation reduced incidence of ARIs (incidence rate ratio 0.60; 95%CI 0.38-0.94, one trial). Nine other RCTs of vitamin, mineral, probiotic and herbal supplements showed no significant effect.
CONCLUSIONS: Transmission of respiratory infections in care homes can be reduced by educational interventions to improve infection control procedures and compliance by staff, by antiviral prophylaxis soon after a case of influenza has been detected, and by supplementation with high-dose Vitamin D3. Further research is needed to confirm the effect of high-dose Vitamin D3.

暂无摘要。

Herpes simplex virus (HSV) infections in allogeneic haematopoietic stem cell transplantation (HSCT) recipients pose significant challenges, with higher incidence, severity, and risk of emergence of resistance to antivirals due to impaired T-cell mediated immunity. This literature review focuses on acyclovir-refractory/resistant HSV infections in HSCT recipients. The review addresses the efficacy of antiviral prophylaxis, the incidence of acyclovir-refractory/resistant HSV infections, and the identification of risk factors and potential prognostic impact associated with those infections. Additionally, alternative therapeutic options are discussed. While acyclovir prophylaxis demonstrates a significant benefit in reducing HSV infections in HSCT recipients and, in some cases, overall mortality, concerns arise about the emergence of drug-resistant HSV strains. Our systematic review reports a median incidence of acyclovir-resistant HSV infections of 16.1%, with an increasing trend in recent years. Despite limitations in available studies, potential risk factors of emergence of HSV resistance to acyclovir include human leucocyte antigen (HLA) mismatches, myeloid neoplasms and acute leukaemias, and graft-versus-host disease (GVHD). Limited evidences suggest a potentially poorer prognosis for allogeneic HSCT recipients with acyclovir-refractory/resistant HSV infection. Alternative therapeutic approaches, such as foscarnet, cidofovir, topical cidofovir, optimised acyclovir dosing, and helicase-primase inhibitors offer promising options but require further investigations. Overall, larger studies are needed to refine preventive and therapeutic strategies for acyclovir-refractory/resistant HSV infections in allogeneic HSCT recipients and to identify those at higher risk.

We report a fatal case of disseminated herpes zoster in a patient with multiple myeloma, illustrating the severe risks immunocompromised individuals face from viral infections. By combining a detailed case report with an extensive literature review, the paper seeks to shed light on the underlying susceptibility factors for varicella-zoster virus infection in multiple myeloma patients. We further evaluate effective prophylactic protocols for herpes zoster, aiming to equip clinicians with improved therapeutic strategies. The case underscores the critical need for vigilant clinical assessments and tailored patient management to mitigate infection risks and enhance patient outcomes.

BACKGROUND: The risk of hepatitis B virus (HBV) reactivation remains unclear in people with multiple sclerosis (MS) receiving ocrelizumab. We aimed to assess HBV seroprevalence and reactivation risk in MS patients on ocrelizumab and to evaluate the effectiveness of antiviral prophylaxis against HBV reactivation.
METHODS: In this single-center, cross-sectional study, 400 people with MS receiving ocrelizumab were screened for HBV at baseline and antiviral prophylaxis was implemented based on serological results. Patients were monitored for HBV reactivation, and outcomes were analyzed.
RESULTS: Among 56 (14%) patients who had serology compatible with occult or resolved HBV infection, 49 (85.7%) received antiviral prophylaxis regularly and had no HBV reactivation during the follow-up. Reactivation of HBV occurred in 2 out of 7 (28.6%) patients who did not receive antiviral prophylaxis and in one patient who did not adhere to the prophylaxis regimen. All patients with reactivation had anti-HBs levels below 100 mIU/mL and the median titer was significantly lower than the patients with no HBV reactivation (p = 0.034).
CONCLUSIONS: This study highlights a 14% anti-HBc positivity, indicating a potential risk for HBV reactivation in people with MS receiving ocrelizumab. This suggests the importance of vigilant monitoring and the implementation of prophylactic measures. Our recommendation emphasizes antiviral prophylaxis, particularly for patients with low anti-HBs, and a pre-emptive strategy for others.

The risk of reactivation in patients with chronic or past/resolved hepatitis B virus (HBV) infection receiving chemotherapy or immunosuppressive drugs is a well-known possibility. The indication of antiviral prophylaxis with nucleo(t)side analogue is given according to the risk of HBV reactivation of the prescribed therapy. Though the advent of new drugs is occurring in all the field of medicine, in the setting of hematologic malignancies the last few years have been characterized by several drug classes and innovative cellular treatment. As novel therapies, there are few data about the rate of HBV reactivation and the decision of starting or not an antiviral prophylaxis could be challenging. Moreover, patients are often treated with a combination of different drugs, so evaluating the actual role of these new therapies in increasing the risk of HBV reactivation is difficult. First results are now available, but further studies are still needed. Patients with chronic HBV infection [hepatitis B surface antigen (HBsAg) positive] are reasonably all treated. Past/resolved HBV patients (HBsAg negative) are the actual area of uncertainty where it could be difficult choosing between prophylaxis and pre-emptive strategy.

Cytomegalovirus (CMV) reactivation is a life-threatening complication after allogeneic hematopoietic stem cell transplantation (HSCT). Introduction of letermovir (LMV) seems to improve post-transplant outcomes, but delayed-onset CMV reactivation still remains a challenge. In this study, we report on our first experience with LMV prophylaxis in 93 CMV-seropositive adult patients receiving HSCT in our center.
We retrospectively analyzed the data of 93 adult CMV-seropositive recipients receiving LMV as CMV prophylaxis after HSCT for hematological malignancies between 2019 and 2023. The starting LMV dose was 480 mg daily, reduced to 240 mg daily for those receiving cyclosporin A co-administration. CMV DNA in the blood was measured by real-time polymerase chain reaction weekly for the first 2 months after transplantation, then every other week until the end of immunosuppressive treatment. LMV was continued to day +100 or to CMV reactivation.
The median recipient age at the time of transplant was 51 (range: 20-71) years. All patients received grafts from peripheral blood, mostly for acute myeloid leukemia (60%). The median time from transplantation to LMV initiation was 3 (range: 0-24) days. While 55% of patients were transplanted from matched related donors, 32% had unrelated donors and 13% underwent haploidentical HSCT. Four patients (4%) had CMV “blips” while on LMV, but the drug was continued and repeated assays were negative. Only 2 patients (2%) experienced CMV reactivation while on LMV, on days 48 and 34 after HSCT, respectively. Seven patients (7%) developed late-onset CMV reactivation after a median of 124 days after HSCT (range: 118-152 days) and they were successfully treated with ganciclovir. CMV disease was not observed. Grade III-IV acute graft-versus-host disease occurred in 6 patients (6%) during LMV treatment. LMV treatment was free of side effects.
LMV prophylaxis was effective in preventing CMV reactivation with a favorable safety profile. CMV reactivation occurred mostly after LMV discontinuation; thus, extending the duration of prophylaxis beyond 100 days could be beneficial.
Sitomegalovirüs (CMV) reaktivasyonu allojenik hematopoetik kök hücre transplantasyonu (HKHT) sonrasında hayatı tehdit eden bir komplikasyondur. Letermovir (LMV) kullanımının nakil sonrası sonuçları iyileştirdiği görülmektedir, ancak gecikmiş başlangıçlı CMV reaktivasyonu hala bir sorun olmaya devam etmektedir. Bu çalışmada, merkezimizde HKHT olan 93 CMV-seropozitif yetişkin hastada LMV profilaksisi ile ilgili ilk deneyimimizi bildiriyoruz.
2019-2023 yılları arasında hematolojik maligniteler için HKHT sonrası CMV profilaksisi olarak LMV başlanan 93 yetişkin CMV-seropozitif alıcının verilerini retrospektif olarak analiz ettik. Başlangıç LMV dozu günde 480 mg olup siklosporin A ile birlikte uygulananlar için günde 240 mg’a düşürülmüştür. Kandaki CMV DNA’sı gerçek zamanlı polimeraz zincir reaksiyonu ile transplantasyondan sonraki ilk 2 ay boyunca haftada bir, daha sonra immünosupresif tedavinin sonuna kadar iki haftada bir ölçülmüştür. LMV profilaksisi +100. güne kadar veya CMV reaktivasyonuna kadar devam ettirilmiştir.
Nakil sırasındaki ortanca alıcı yaşı 51 (aralık: 20-71) idi. Tüm hastalar, çoğunlukla miyeloid akut lösemi (%60) nedeniyle periferik kandan nakil yapılmıştır. Transplantasyondan LMV başlangıcına kadar geçen medyan süre 3 (aralık: 0-24) gündü. Hastaların %55’ine doku tipi uyumlu akraba vericilerden nakil yapılırken, %32’sine akraba olmayan vericiler ve %13’üne haploidentik HKHT uygulanmıştır. Dört hastada (%4) LMV kullanırken CMV “blips” görüldü, ancak ilaca devam edildi ve tekrarlanan testler negatif çıktı. Sadece 2 hastada (%2) LMV kullanırken, sırasıyla HKHT’den sonraki 34. ve 48. günlerde CMV reaktivasyonu görülmüştür. Yedi hastada (%7) HKHT’den ortanca 124 gün sonra (aralık: 118-152 gün) geç başlangıçlı CMV reaktivasyonu gelişmiş ve bu hastalar gansiklovir ile başarılı bir şekilde tedavi edilmiştir. Bu hastalarda CMV hastalığı gözlenmemiştir. LMV tedavisi sırasında 6 hastada (%6) grade III-IV akut graft-versus-host hastalığı meydana gelmiştir. LMV tedavisi boyunca yan etki görülmemiştir.
LMV profilaksisi, olumlu bir güvenlik profili ile CMV reaktivasyonunu önlemede etkili olmuştur. CMV reaktivasyonu çoğunlukla LMV kesildikten sonra meydana gelmiştir; bu nedenle profilaksi süresinin 100 günün ötesine uzatılması faydalı olabilir.

Utilizing assays that assess specific T-cell-mediated immunity against cytomegalovirus (CMV) holds the potential to enhance personalized strategies aimed at preventing and treating CMV in organ transplantation. This includes improved risk stratification during transplantation compared to relying solely on CMV serostatus, as well as determining the optimal duration of antiviral prophylaxis, deciding on antiviral therapy when asymptomatic replication occurs, and estimating the risk of recurrence. In this review, we initially provide an overlook of the current concepts into the immune control of CMV after transplantation. We then summarize the existent literature on the clinical experience of the use of immune monitoring in organ transplantation, with a particular interest on the outcomes of interventional trials. Current evidence indicates that cell-mediated immune assays are helpful in identifying patients at low risk for replication for whom preventive measures against CMV can be safely withheld. As more data accumulates from these and other clinical scenarios, it is foreseeable that these assays will likely become part of the routine clinical practice in organ transplantation.

The use of Bcr-Abl TKI was found to be associated with hepatitis B (HBV) flares, with a more profound risk observed in females. This study was conducted to characterize the clinical features of patients with HBV flare among Bcr-Abl TKI users, to estimate sex-specific incidence rates of HBV flare, and to evaluate potential cumulative effect of Bcr-Abl TKI.
Bcr-Abl TKI users with chronic HBV infection were identified from Taiwan\'s National Health Insurance database. The HBV flare cases were identified within the cohort. Incidence rates of HBV flare between men and women were assessed. Nested case-control analysis was used to evaluate the cumulative effect of Bcr-Abl TKI use on HBV flare.
Among 415 patients with chronic HBV infection treated with Bcr-Abl TKI from 2005 through 2018, 45 flare cases (28 males and 17 females) were identified. Days between Bcr-Abl TKI initiation and HBV flare was 319 days in women compared to 610 days in men. 66.7% of the flares occurred during TKI therapy. Twelve of the 45 patients died, half of them died around 6 months after hepatitis B flare. Incidence rates of HBV flare were 2.34 and 3.33 per 100 person-years in males and females, respectively. Higher incidence was observed among patients with chronic myeloid leukemia. Cumulative effect of Bcr-Abl TKI on HBV flare was not observed.
Approximately 10% of HBV carriers who used Bcr-Abl TKI experienced HBV flare in Taiwan. The risk was higher in women and among patients with chronic myeloid leukemia.