This research article retrospectively analyzes interferon-gamma release assay (IGRA) test results (QuantiFERON-TB and T-SPOT.TB) from cancer patients to determine their effectiveness in diagnosing tuberculosis (TB). The study at a major US cancer center found T-SPOT.TB yielded significantly more actionable results than QFT-TB, with QFT-TB producing a high rate of indeterminate results. Several factors, including immunosuppressant use and low hemoglobin, were associated with IGRA test invalidity or indeterminacy. While T-SPOT.TB showed better diagnostic performance for latent TB infection, the low TB disease prevalence limited conclusions on its ability to predict progression to active disease. The findings highlight the need for improved diagnostic tools for TB in immunocompromised individuals.

Batista MV, Sassine J, Khawaja F, et al. The Utility of Interferon-γ Release Assays in the Diagnosis of Tuberculosis in Patients With Cancer. Transpl Infect Dis 2024;e14428.

PMID: 39731624

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This study investigates the antibody response to respiratory syncytial virus (RSV) vaccines in immunocompromised individuals. Researchers measured antibody levels in a cohort of immunocompromised adults after receiving either an adjuvanted or non-adjuvanted RSV vaccine. Results showed heterogeneous antibody responses, with a significant portion not achieving seroconversion or a high-titer neutralization threshold. The adjuvanted vaccine showed better results. Study limitations included a small sample size and lack of cellular data. The findings suggest a need for further investigation into optimizing RSV vaccination strategies for immunocompromised populations.

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PMID: 39786402

Karaba AH, Hage C, Sengsouk I, et al. Antibody Response to Respiratory Syncytial Virus Vaccination in Immunocompromised Persons. JAMA 2024.

This article presents a subgroup analysis of the phase 3 SOLSTICE clinical trial, focusing on solid organ transplant recipients treated with maribavir for refractory cytomegalovirus (CMV) infection. The study compared maribavir to investigator-assigned therapy, assessing efficacy in CMV viremia clearance and safety, including treatment-emergent adverse events and the development of maribavir resistance. Results showed maribavir's superiority in CMV clearance across various transplant types and fewer treatment discontinuations compared to standard treatments. The findings support maribavir's effectiveness and safety profile in this specific patient population. Limitations of the open-label design and sample size are acknowledged.

PMID: 39613120

Blumberg EA, Witzke O, Harber M, et al. Maribavir for refractory cytomegalovirus infection (with or without resistance) in solid organ transplant recipients: Subgroup analysis of the phase 3 randomized SOLSTICE study. J Heart Lung Transplant 2024;S1053-2498(24)01971-5.

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This study, published in Bone Marrow Transplantation, analyzes adenovirus (ADV) infections in children and adults after allogeneic hematopoietic cell transplantation (allo-HCT). Researchers examined 2529 patients from the EBMT database, identifying risk factors for mortality. Children demonstrated better short-term survival than adults, with different factors influencing mortality in each group. In children, pre-transplant factors like CMV serostatus and performance score were key, whereas in adults, factors directly related to ADV infection, such as the type of infection and time of onset, were more impactful. The study highlights the need for regular ADV screening in both children and adults post-allo-HCT.

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PMID: 38987308

Styczynski J, Tridello G, Knelange N, et al. Adenovirus infections after allogeneic hematopoietic cell transplantation in children and adults: a study from the Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation. Bone Marrow Transplant 2024;59(10):1402–12.

This research article reports on a randomized clinical trial (BEATLE) investigating the efficacy of extended-infusion versus intermittent-infusion β-lactam antibiotics in treating febrile neutropenia in hematological patients. The study, conducted across four Spanish hospitals, aimed to determine if extended infusion improved treatment success, defined as defervescence without antibiotic changes. Results showed no significant difference in treatment success between the two groups. However, extended infusion achieved higher pharmacokinetic/pharmacodynamic targets for susceptible Pseudomonas aeruginosa. The authors conclude that extended infusion isn't routinely warranted but may benefit patients with infections caused by less susceptible microorganisms.

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PMID: 39433124

Laporte-Amargos J, Carmona-Torre F, Huguet M, et al. Efficacy of extended infusion of β-lactam antibiotics for the treatment of febrile neutropenia in haematologic patients (BEATLE): a randomized, multicentre, open-label, superiority clinical trial. Clin Microbiol Infect 2024;S1198-743X(24)00488-9.

This research article from Nature Medicine examines the lung microbiome and its connection to mortality in pediatric patients post-hematopoietic cell transplantation (HCT). The study identified four distinct lung microenvironment clusters based on microbiome composition and gene expression, revealing that depletion of beneficial bacteria coupled with viral or fungal enrichment strongly predicted in-hospital death. Antibiotic use significantly contributed to this dysbiosis. The findings were validated in an independent cohort, suggesting potential for improved diagnostics and treatments targeting specific lung microenvironment profiles. The researchers propose that precision pulmonary phenotyping could improve HCT outcomes.

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PMID: 38783139
Zinter MS, Dvorak CC, Mayday MY, et al. Pathobiological signatures of dysbiotic lung injury in pediatric patients undergoing stem cell transplantation. Nat Med 2024;30(7):1982–93.

This multicenter study investigated the clinical utility of plasma microbial cell-free DNA (mcfDNA) sequencing as an adjunctive diagnostic tool for pneumonia in immunocompromised patients. Researchers compared the diagnostic yield of mcfDNA sequencing to standard clinical testing in a prospective observational trial. The results demonstrated that mcfDNA sequencing significantly increased the detection of pneumonia etiologies, particularly in cases where conventional methods failed. This non-invasive approach offers a potential improvement in the diagnosis and treatment of pneumonia in this vulnerable population. The study also noted some limitations, including incomplete standard testing in a subset of patients and the impact of prior antimicrobial therapy.

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PMID: 37815489

Bergin SP, Chemaly RF, Dadwal SS, et al. Plasma Microbial Cell-Free DNA Sequencing in Immunocompromised Patients With Pneumonia: A Prospective Observational Study. Clin Infect Dis 2024;78(3):775–84.

We review the findings of the HOPE in Action study published in the New England Journal of Medicine (Durand et al., 2024). The study addresses the safety and efficacy of transplanting kidneys from deceased donors with HIV to recipients with HIV, a practice made legal for research in the U.S. following the 2013 HIV Organ Policy Equity (HOPE) Act.

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PMID: 39413376

Durand CM, Massie A, Florman S, et al. Safety of Kidney Transplantation from Donors with HIV. N Engl J Med 2024;391(15):1390–401.

This prospective, multi-center study investigated the role of human herpesvirus 6B (HHV-6B) in post-transplant pneumonia. Researchers found HHV-6B DNA and mRNA in a significant portion of bronchoalveolar lavage samples, establishing viral load thresholds predictive of active infection and increased mortality risk. Analysis of host gene expression revealed distinct transcriptional signatures associated with HHV-6B detection, particularly in patients with idiopathic pneumonia syndrome. These findings strongly implicate HHV-6B as a pulmonary pathogen following allogeneic hematopoietic cell transplantation, warranting further clinical consideration. The study utilized multiple molecular diagnostic techniques and RNA sequencing to analyze paired blood and BALF samples.

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PMID: 38228644

Hill JA, Lee YJ, Vande Vusse LK, et al. HHV-6B detection and host gene expression implicate HHV-6B as pulmonary pathogen after hematopoietic cell transplant. Nat Commun 2024;15(1):542.