Management of infection in patients with haematological malignancies and after cellular therapy: guidelines from 10th European Conference on Infections in Leukaemia (ECIL-10).

infection (CDI) poses a significant challenge in patients with haematological malignancies (HM) and those undergoing cellular therapy such as haematopoietic cell transplantation (HCT) or CAR T-cell therapy. These patients have high rates of both colonization with and diarrhoea due to non-infectious causes, leading to challenges with establishing diagnosis and optimal management of CDI, especially in the setting of molecular detection of toxin genes alone. Current severity criteria are of limited usefulness since underlying haematological disease and its treatment impact white blood count and inflammatory manifestations of severe CDI.

Innovation in active and passive immunisation of people who are immunocompromised: a call to action.

The proportion of the population with immunocompromising conditions, who are at increased risk for complications from infectious diseases, continues to grow. Concurrently, outbreaks due to known and emerging pathogens are increasing. Vaccines are the foundation of infection prevention; however, attenuated immune responses in people who are immunocompromised necessitates innovation in design and delivery strategies.

Elucidating novel immune profiles for predicting infection in high-risk cohorts: a pilot study in patients with relapsed and refractory chronic lymphocytic leukaemia.

Objectives: Chronic lymphocytic leukaemia (CLL) patients are at increased risk for infection, with the risk even higher for relapsed and refractory patients. Clinical assessment of infection risk is increasingly challenging in the era of immune-based therapies, such as Bruton's tyrosine kinase inhibitors. A pilot study was conducted to elucidate possible predictive immune markers.

Recommendations for innovation in vaccination services for adults with haematological malignancies: an Australian cross-sectional survey study.

Introduction: People affected by haematological malignancies are at high risk of vaccine-preventable diseases due to the immunosuppressive effects of their cancer, treatment and reduced immunogenicity. However, evidence suggests that members of this population suboptimally complete suggested vaccination schedules during and after treatment. This study was undertaken to identify barriers, enablers, and preferences to vaccination to inform service innovation.

Influenza-Specific T-Cell Responses to Vaccination Are Independent of Underlying Hematological Malignancy: Analysis of a Randomized Influenza Vaccination Trial.

Background: There are few in-depth immunogenicity analyses of novel influenza vaccination strategies in high-risk patients with hematological malignancy (HM).

Methods: Participants receiving treatment for active HM (multiple myeloma [MM], chronic lymphocytic leukemia [CLL], or non-Hodgkin lymphoma [NHL]) in a randomized controlled trial of 2 doses of adjuvanted quadrivalent inactivated influenza vaccine (QIV) versus 2 doses of standard-dose QIV during 2022 were included. Hemagglutination (HA) inhibition assay and HA probe-specific B-cells were compared at baseline and 1, 2, and 6 months after the first vaccine dose (visits 1-4).

The DESTINIES Study: an online Delphi study to build international consensus on the medical conditions and procedures that confer immunosuppression and their respective COVID-19 risk profiles.

Background: The lack of international consensus on defining and categorising immunosuppression has undermined disease surveillance and patient care, particularly during the COVID-19 pandemic. To address this, a global expert panel was recruited to join the eDElphi STudy to fully defiINe and COVID-risk stratify ImmunosupprESsion (DESTINIES) and develop a COVID risk-stratified digital phenotype for 'adult immunosuppression' (the DESTINIES phenotype).

Methods: Panellists were presented with all medical diagnoses and procedures cited in prevailing immunosuppressed definitions; they evaluated their appropriateness for the DESTINIES phenotype and their risks for severe COVID-19 outcomes through anonymous online questionnaires and discussion.

"It's a risk-benefit analysis": Qualitative perspectives on barriers and enablers to post-treatment vaccination from adults affected by a haematological malignancy in Australia.

Background: People affected by haematological malignancies are at high risk of morbidity and mortality caused by vaccine-preventable infections. However, vaccination commencement and completion following anti-cancer treatment is sub-optimal for this population. Innovation relating to vaccination delivery and schedules, informed by the needs and preferences of the target population, may improve uptake of vaccinations.

Management, Outcomes, and Predictors of Mortality of Cryptococcus Infection in Patients Without HIV: A Multicenter Study in 46 Hospitals in Australia and New Zealand.

Background: Limited data exist regarding outcomes of cryptococcosis in patients without human immunodeficiency virus (HIV), and few studies have compared outcomes of Cryptococcus gattii versus Cryptococcus neoformans infection.

Methods: We conducted a retrospective study in 46 Australian and New Zealand hospitals to determine the outcomes of cryptococcosis in patients without HIV diagnosed between 2015 and 2019 and compared outcomes of C. gattii versus C.

Infections during novel myeloma therapies.

New generation therapies such as bispecific antibodies (BsAb), chimeric antigen receptor T-cell therapy (CAR T) and antibody-drug conjugates (ADC) have revolutionized the treatment of relapsed/refractory multiple myeloma (RRMM). However, there is emerging evidence of increased infection risk associated with these treatments in clinical trials and observational settings. This infection risk may be mediated by on-target, off-tumor side effects such as cytokine release syndrome, hypogammaglobulinaemia and cytopenias, disease-related humoral impairment and the consequences of multiple previous lines of treatment.

High Rates of Seroprotection and Seroconversion to Vaccine-Preventable Infections in the Early Post-Autologous Stem Cell Transplant Period.

In patients early post-autologous stem cell transplant, seroprotection rates were high for type B and tetanus toxoid (70%-90%) but lower for (30%-50%) including after revaccination. There were high rates of seropositivity (67%-86%) to measles, mumps, and rubella and varicella zoster virus. Durability of protection requires assessment.

Infections in haematology patients treated with CAR-T therapies: A systematic review and meta-analysis.

A registered (PROSPERO - CRD42022346462) systematic review and meta-analysis was conducted of all-grade infections amongst adult patients receiving CAR-T therapy for haematological malignancy. Meta-analysis of pooled incidence, using random effects model, was conducted. Cochran's Q test examined heterogeneity.

Recommendations on prevention of infections in patients with T-cell lymphomas: a narrative review and synthesis.

T/Natural killer (NK) cell lymphomas (TCL) represent a heterogenous subgroup of non-Hodgkin lymphoma, associated with poorer prognosis and higher treatment toxicity. A cohesive synthesis of infection outcomes among TCL patients is lacking. International guidelines offer no specific recommendations regarding prophylaxis or supportive infection care for TCL patients.

Consensus position statement on advancing the standardised reporting of infection events in immunocompromised patients.

Patients can be immunocompromised from a diverse range of disease and treatment factors, including malignancies, autoimmune disorders and their treatments, and organ and stem-cell transplantation. Infections are a leading cause of morbidity and mortality in immunocompromised patients, and the disease treatment landscape is continually evolving. Despite being a critical but preventable and curable adverse event, the reporting of infection events in randomised trials lacks sufficient detail while inconsistency of categorisation and definition of infections in observational and registry studies limits comparability and future pooling of data.

COVID-19 Vaccination in Patients With Cancer and Patients Receiving HSCT or CAR-T Therapy: Immune Response, Real-World Effectiveness, and Implications for the Future.

Patients with cancer demonstrate an increased vulnerability for infection and severe disease by SARS-CoV-2, the causative agent of COVID-19. Risk factors for severe COVID-19 include comorbidities, uncontrolled disease, and current line of treatment. Although COVID-19 vaccines have afforded some level of protection against infection and severe disease among patients with solid tumors and hematologic malignancies, decreased immunogenicity and real-world effectiveness have been observed among this population compared with healthy individuals.

Vaccine schedule recommendations and updates for patients with hematologic malignancy post-hematopoietic cell transplant or CAR T-cell therapy.

Revaccination after receipt of a hematopoietic cell transplant (HCT) or cellular therapies is a pillar of patient supportive care, with the potential to reduce morbidity and mortality linked to vaccine-preventable infections. This review synthesizes national, international, and expert consensus vaccination schedules post-HCT and presents evidence regarding the efficacy of newer vaccine formulations for pneumococcus, recombinant zoster vaccine, and coronavirus disease 2019 in patients with hematological malignancy. Revaccination post-cellular therapies are less well defined.

Drivers and barriers to COVID-19 vaccination in Australians with cancer.

Purpose: To understand the drivers and barriers for COVID-19 vaccination in people with cancer in Australia.

Methods: A cross-sectional, online survey, distributed nationally following the establishment of community vaccination programs, wider availability of COVID-19 vaccines and emergence of new variants. Consisting of 21 questions, the survey was designed to determine the behavioural and social drivers of vaccination, participant demographics, underlying disease and treatment, and vaccination status.

Infections following bispecific antibodies in myeloma: a systematic review and meta-analysis.

Bispecific antibodies, a novel immunotherapy with promising efficacy against multiple myeloma, form immune synapses between T-cell surface marker CD3 and malignant cell markers, including B-cell maturation antigen (BCMA), FcRH5, and G protein-coupled receptor GPRC5D. These bispecific antibodies so effectively deplete plasma cells (and to some extent T-cells) that patients are at increased risk of developing infections. A systematic review and meta-analysis of infections in published studies of patients with myeloma treated with bispecific antibodies was conducted to better characterize the infection risks.

COVID-19 infection among patients with cancer in Australia from 2020 to 2022: a national multicentre cohort study.

Background: The global COVID-19 pandemic disproportionately affected certain populations and its management differed between countries. This national study describes characteristics and outcomes of COVID-19 in patients with cancer in Australia.

Methods: We performed a multicentre cohort study of patients with cancer and COVID-19 from March 2020 to April 2022.