Community-acquired respiratory virus infections in patients with haematological malignancies or undergoing haematopoietic cell transplantation: updated recommendations from the 10th European Conference on Infections in Leukaemia.

To update recommendations of the 4th European Conference on Infections in Leukaemia (ECIL-4) on community-acquired respiratory virus (CARV) infections published in 2013, we reviewed publications from between Jan 1, 2014, and June 30, 2024 on adenovirus, bocavirus, coronavirus, influenzavirus, metapneumovirus, parainfluenzavirus, respiratory syncytial virus (RSV), and rhinovirus in patients with haematological malignancies or undergoing haematopoietic cell transplantation (HCT), or both. In the current ECIL recommendations (ECIL-10), we outline a common approach to infection control, laboratory testing, and diagnosis for all CARVs (including SARS-CoV-2) and specific management and deferral strategies for CARVs other than SARS-CoV-2. For influenzavirus, seasonal inactivated-vaccines and early antivirals are recommended, whereas routine antiviral prophylaxis is discouraged for immunocompromised patients.

Adenovirus Burden in Allogeneic Hematopoietic Stem Cell Transplantation: Monitoring Versus Symptoms-Based Testing-A Cost-Effectiveness Analysis.

Background: Adenovirus infection (AdVi) causes significant morbidity and mortality in allogeneic hematopoietic stem cell transplantation (allo-HCT) recipients.

Methods: This retrospective study of 131 patients (2020-2024) compared systematic monitoring in high-risk patients versus symptom-based testing in standard-risk patients.

Results: The 1-year incidence of AdV DNAemia was 19.

Co-infections during SARS-CoV-2 infection in hematologic patients and cell therapy recipients in the omicron era: a Spanish hematopoietic stem cell transplantation and cell therapy group study.

Background: Although SARS-Cov-2 outcomes have improved in the Omicron era, the synergistic or additive effects between SARS-CoV-2 Omicron variants and other microbiological agents in adult hematologic patients have been little explored. We aimed to characterize co-infection types, identify risk factors for co-infection and determine co-infection-related mortality in hematologic patients and recipients of cellular therapy with a first episode of SARS-CoV-2 infection in the Omicron era.

Methods: Retrospective national Spanish registry analysis of 692 consecutive patients with hematological disease including receptors of cellular therapy from December 2021 to May 2023.

Natural Killer (NK) Cell Alloreactivity in Haploidentical Stem Cell Transplantation.

This paper conducts a literature review on the role of natural killer cells in haploidentical hematopoietic stem cell transplantation. Theoretical concepts related to genes are introduced regarding their structure, nomenclature, genetic organization, polymorphism, and inheritance pattern, types of KIR proteins and receptors, HLA ligands for KIR receptors, and the definition of different NK alloreactivity prediction models for the donor of haploidentical hematopoietic stem cell transplantation and the recipient. These models include the following and consider incompatibility: ligand-ligand, receptor-ligand, gene-gene, and KIR haplotype models or the donor group.

Defining bloodstream and central venous catheter-related infections in patients following haematopoietic cell transplantation: position paper of the European Blood and Marrow Transplantation Society Infectious Diseases Working Party and Practice Harmonization and Guidelines Committee.

Scope: This position paper is intended for clinicians and data managers involved in the diagnosis, management, and reporting of bloodstream infection (BSI) and central venous catheter (CVC)-related BSI and CVC-related local skin/soft-tissue infections (lSSTI) in haematopoietic cell transplant (HCT) recipients.

Methods: The panel reviewed the relevant guidelines on BSI and CVC-related lSSTI definitions, and their applicability to HCT recipients. We developed practical recommendations aiming to establish their standardized reporting considering the unique features of HCT recipients.

Cytomegalovirus DNA Doubling Time for Early Identification of Clinically Significant Infection Episodes in Allogeneic Hematopoietic Stem Cell Transplant Recipients Undergoing Primary Letermovir Prophylaxis: A Multicenter Study.

Background: Letermovir (LMV) prophylaxis currently represents the first-line strategy for preventing clinically significant cytomegalovirus (CMV) infection (CsCMVi) in CMV-seropositive recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT). A wide variety of CMV DNA thresholds for LMV interruption and preemptive antiviral therapy (PET) inception are in place across transplantation centers.

Methods: We evaluated the potential of CMV DNA doubling time (dt) in plasma to distinguish between CsCMVi and abortive CMV infection in allo-HSCT recipients on primary LMV prophylaxis.

Neutralizing Antibody and T-Cell Spike Targeted Responses Following Receipt of a Monovalent Omicron JN.1-Adapted mRNA COVID-19 Vaccine in Immunosuppressed and Healthy Individuals.

We evaluated homologous neutralizing antibody (NtAb) and T-cell responses after receipt of a JN.1-adapted mRNA vaccine in a mixed population comprising healthy controls (HC) (n = 15), end-stage chronic kidney disease (CKD) patients (n = 17), and allogeneic hematopoietic stem cell transplant recipients (allo-HCT) (n = 13). Most participants (42/45) were SARS-CoV-2-experienced at the time of immunological testing.

American Society for Transplantation and Cellular Therapy Series #10: Management of Parainfluenza and Human Metapneumovirus Infections in Hematopoietic Cell Transplantation and Cellular Therapy Recipients.

In 2019, The Practice Guidelines Committee of the American Society for Transplantation and Cellular Therapy partnered with its Transplant Infectious Diseases Special Interest Group to update the 2009 compendium-style infectious disease guidelines for hematopoietic cell transplantation (HCT). The new format is now structured around frequently asked questions (FAQs), concise tables, and figures to better support clinical providers. Here, a panel of experts in HCT and infectious diseases identified relevant FAQs, which they graded based on the strength of clinical practice recommendations and the level of supporting evidence, as described herein.

To proceed or delay? The dilemma of community-acquired respiratory viruses in adults and pediatrics before allogeneic stem cell transplantation and chimeric-antigen-receptor T-cell therapy.

Purpose Of Review: This review explores the impact of community-acquired respiratory virus (CARV) infections on outcomes before proceeding with hematopoietic cell transplantation (HCT) and chimeric-antigen-receptor T-cell (CAR-T) therapy recipients and which conditions should be considered to delay or proceed with cell therapy. It aims to assess current practices, the risks associated with early CARV infections in cell therapy recipients, and potential modifications to reduce complications and improve clinical outcomes if delay is not an option.

Recent Findings: Studies have shown that pretransplant CARV infections, particularly those with symptomatic lower respiratory tract disease (LRTD), are linked to increased mortality and prolonged hospitalization after hematopoietic stem cell transplant.

Post-pandemic recommendations for the management of COVID-19 in patients with haematological malignancies or undergoing cellular therapy, from the European Conference on Infections in Leukaemia (ECIL-10).

In the post-pandemic years, SARS-CoV-2 morbidity and mortality declined due to less pathogenic variants, active and passive immunization, and antiviral therapies. However, patients with hematological malignancies and/or undergoing hematopoietic cell transplantation (HCT) remain at increased risk for poor outcomes. Therefore, adherence to contact and droplet precautions is essential to avoid transmission, especially during epidemic waves.

Frequency and Distribution of KIR Genotypes of Donors-Recipient Pairs in the Haploidentical Haematopoietic Stem Cell Transplantation Setting: Collaborative Study by the Spanish Working Group in Histocompatibility and Transplant Immunology (GETHIT) and the Spanish Haematopoietic Transplantation and Cell Therapy Group (GETH-TC).

There is limited information regarding the influence of KIR genotype, compared to the HLA system, in haploidentical haematopoietic stem cell transplantation (haplo-HSCT). This study aimed to determine the frequencies of KIR genotypes in Spanish haematologic patients undergoing haplo-HSCT. A study was conducted on 113 oncohaematological patients and their donors, treated across five centres that are members of the Spanish Working Group in Histocompatibility and Transplant Immunology (GETHIT) and the Spanish Haematopoietic Transplantation and Cell Therapy Group (GETH-TC).

Evaluation of the VIDAS Cytomegalovirus (CMV)-IGRA for Assessing CMV-Specific T-Cell Responses in Immunocompetent and Immunosuppressed Individuals.

We compared the performance of the VIDAS Cytomegalovirus (CMV)-Interferon-gamma release assay (IGRA) with that of laboratory-developed flow cytometry for intracellular cytokine staining (FC-ICS) for the assessment of CMV-specific interferon-gamma (IFN-γ)-producing T-cell responses (CMV-CMI). A total of 147 blood specimens from 78 adult participants were collected: 11 healthy controls, 34 hematological patients (HP), of which 32 had undergone allogeneic hematopoietic cell transplantation (allo-HCT), and 33 Kidney transplant recipients. Of the 147 specimens, 96 tested positive, 24 negative, 25 indeterminate, and 2 were invalid by the VIDAS CMV IGRA.

Pneumonia definition in allogeneic hematopoietic cell transplant recipients: Update and challenges in 2024. Recommendations from the EBMT Infectious Diseases Working Party and Practice Harmonization and Guidelines committee.

To optimize and homogenize data on infectious diseases complications, the Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation (IDWP EBMT) participated in the 2023 EBMT international workshop focusing on the standardization of the definition of specific infections, including respiratory infections [1]. This is pertinent considering that a new software for data collection, including data on post-transplant infectious disease complications, was launched in 2023 and which will remain the main tool for future epidemiological studies. In this report, we briefly discuss our proposals for pneumonia definition, predominately focusing on bacterial and fungal pneumonias.

Clinical Impact of CD19 Expression Assessed by Quantitative PCR in Lymphoma Patients Undergoing CAR-T Therapy.

Introduction: Current guidelines do not mandate CD19 tumor expression assessment before chimeric antigen receptor T-cell (CAR-T) therapy in large B-cell lymphoma (LBCL) patients due to limitations of immunohistochemistry (IHC) or flow cytometry. Quantitative polymerase chain reaction (qPCR) offers a more sensitive alternative for detecting CD19 expression, with the primary advantage that mRNA can be easily extracted from paraffin-embedded tissues.

Methods & Results: In our study, we included 51 adult patients with LBCL treated with axicabtagene ciloleucel.

Assessment of the Immunodeficiency Scoring Index for Predicting Outcomes After Respiratory Syncytial Virus Infection in Allogeneic Stem Cell Transplant Recipients.

Respiratory syncytial virus (RSV) is a common cause of respiratory infections in allogeneic hematopoietic stem cell transplant (allo-HCT) recipients. The immunodeficiency scoring index (ISI) has shown predictive value in assessing the risk of progression to lower respiratory tract disease (LRTD) and mortality in allo-HCT recipients developing RSV infection but requires further validation in external cohorts. This retrospective study examined RSV episodes in adult allo-HCT recipients from December 2013 to June 2023 at 2 Spanish hospitals.

Community-Acquired Respiratory Virus Infections: A Threat to Long-Term survivors after Allogeneic Stem Cell Transplant?

Background: Studies on late community-acquired respiratory virus (CARV) infections in long-term allogeneic hematopoietic stem cell transplantation (allo-HCT) survivors are scarce, creating knowledge gaps on the epidemiology, risk of progression to lower respiratory tract disease (LRTD), and conditions linked to poor outcomes.

Patients And Methods: We included consecutive CARV infection episodes occurring up to six months after allo-HCT registered in our database from December 2013 to June 2023 at two Spanish transplant centers.

Results: Among 426 allo-HCT recipients, 1070 CARV episodes were recorded, 791 (74%) with only upper respiratory tract disease (URTD) and 279 (15%) progressing to LRTD, at a median of 18.

Update on Cytomegalovirus Infection Management in Allogeneic Hematopoietic Stem Cell Transplant Recipients. A Consensus Document of the Spanish Group for Hematopoietic Transplantation and Cell Therapy (GETH-TC).

Background: 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.

The value of the reflective discussion in decision-making using multi-criteria decision analysis (MCDA): an example of determining the value contribution of tabelecleucel for the treatment of the Epstein Barr virus-positive post-transplant lymphoproliferative disease (EBV PTLD).

Background: The aim of this study was to assess the contribution of the reflective multidisciplinary discussion in determining the value contribution of innovative drugs through the multi-criteria decision analysis (MCDA). This methodology considers all relevant criteria for healthcare decision-making in a global, transparent, and systematic manner and from the perspective of relevant stakeholders. The determination of value contribution of tabelecleucel for the treatment of Epstein-Barr virus-positive post-transplant lymphoproliferative disease (EBV PTLD) compared to salvage therapy was used as an example.

Pitfalls in definitions on respiratory viruses and particularities of Adenovirus infection in hematopoietic cell transplantation patients: Recommendations from the EBMT practice harmonization and guidelines committee.

In 2023, the EBMT Practice harmonization and Guidelines Committee partnered with the EBMT Infection Diseases Working Party (IDWP) to undertake the task of delivering best practice recommendations, aiming to harmonize by expert consensus, the already existing definitions and future epidemiological and clinical studies among centers of the EBMT network. To attain this objective, a group of experts in the field was convened. The workgroup identified and discussed some critical aspects in definitions of community-acquired respiratory viruses (CARV) and adenovirus (ADV) infections in recipient of hematopoietic cell transplant (HCT).