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The article published in the British Journal of Haematology discusses the preservation of vaccine-associated antibodies in patients undergoing chimeric antigen receptor T-cell (CAR-T) therapy. The study evaluated seropositivity against vaccine-preventable infections (VPIs) in a lymphoma cohort during the early CAR-T period (0-6 months post-infusion). Results showed that a high proportion of patients maintained antibodies against viral VPIs and tetanus, with lower rates for bacterial VPIs like Streptococcus pneumoniae. The study highlights the need for further research on optimal revaccination strategies post CAR-T therapy. [Extracted from the article]

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. This systematic narrative review highlights infection outcomes in TCL patients treated with conventional, and novel therapies. Recommendations for infection screening, antimicrobial prophylaxis and vaccination strategies are outined. [ABSTRACT FROM AUTHOR]

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. This review highlights important considerations around poor vaccine response, seroprevalence preservation after cellular therapies, and the optimal timing of revaccination. Future research should assess the immunogenicity and real‐world effectiveness of new vaccine formulations and/or vaccine schedules in patients post‐HCT and cellular therapy, including analysis of vaccine response that relates to the target of cellular therapies. [ABSTRACT FROM AUTHOR]

In patients early post–autologous stem cell transplant, seroprotection rates were high for Hemophilus influenzae type B and tetanus toxoid (70%–90%) but lower for Streptococcus pneumoniae (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. [ABSTRACT FROM AUTHOR]

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. Characterizing and understanding the immune response to increasing doses or differing schedules of COVID-19 vaccines among patients with cancer is important to inform clinical and public health practices. In this article, we review SARS-CoV-2 susceptibility and immune responses to COVID-19 vaccination in patients with solid tumors, hematologic malignancies, and those receiving hematopoietic stem cell transplant or chimeric-antigen receptor T-cell therapy. [ABSTRACT FROM AUTHOR]

Infection remains a significant contributor to morbidity and mortality in patients with myeloma. This guideline was developed by a multidisciplinary group of clinicians who specialise in the management of patients with myeloma and infection from the medical and scientific advisory group from Myeloma Australia and the National Centre for Infections in Cancer. In addition to summarising the current epidemiology and risk factors for infection in patients with myeloma, this guideline provides recommendations that address three key areas in the prevention of infection: screening for latent infection, use of antimicrobial prophylaxis and immunoglobulin replacement and vaccination against leading respiratory infections (severe acute respiratory syndrome coronavirus 2, influenza and Streptococcus pneumoniae) and other preventable infections. This guideline provides a practical approach to the prevention of infection in patients with myeloma and harmonises the clinical approach to screening for infection, use of prophylaxis and vaccination to prevent infectious complications. [ABSTRACT FROM AUTHOR]

The article discusses the need for a standardized approach to reporting infection events in immunocompromised patients. The authors highlight the limitations in current reporting practices and emphasize the importance of accurate and comprehensive reporting in clinical trials and observational studies. They introduce a basic core reporting dataset called "SCORE," which consists of five components that describe an infection event. The authors also provide guidance on additional details that should be included in different types of studies. They recommend the use of a ready-built data collection instrument and established definitions for pathogens and infectious syndromes. The article concludes by emphasizing the importance of adopting the proposed reporting dataset to improve research collaboration and advance research in immunocompromised patients. [Extracted from the article]

Infection has a significant impact on patients with multiple myeloma (MM) [[1]]. Patients completed a median of 5 (IQR 2-11) cycles of BsAb therapy and CRS occurred in 28 (72%) and ICANS in 2 (5%) patients. Therefore this study was conducted to describe the epidemiology and outcomes of infections in BsAb treated MM patients to better guide antimicrobial prophylaxis and treatment in this emerging cohort. Methods All MM patients who received BsAb therapy on a range of clinical trials between 1st January 2018 and 30th May 2022 at Peter MacCallum Cancer Centre were included in this retrospective review of patients' electronic medical record. [Extracted from the article]

Ongoing evaluation of these therapies, and newer MAb as they are developed for the treatment of mild COVID-19, as well as pre-exposure prophylaxis, and investigational treatments are required. This is of interest, given the widespread availability of the messenger RNA vaccines and the Food and Drug Administration's recommendation for the third dose to immunocompromised patients, including HSCT patients, with the COVID-19 vaccine since mid-August 2021. Keywords: antiviral; COVID-19; monoclonal antibody; stem cell transplant; treatment; vaccination EN antiviral COVID-19 monoclonal antibody stem cell transplant treatment vaccination 1 4 4 02/23/23 20230201 NES 230201 Hematopoietic stem cell transplant (HSCT) recipients and patients with hematological malignancy (HM) are at high risk of significant morbidity and mortality from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, with an estimated at least 2.5-fold increased risk of death.[1] In HSCT patients, estimated mortality from centers of European Group for Blood and Marrow Transplantation was approximately 25%, and similar for autologous and allogeneic-HSCT patients.[2] Risk factors for severity include older age, higher immunodeficiency scoring index group (based on neutrophils <0.5 × 10 SP 9 sp /L, lymphocytes <0.2 × 10 SP 9 sp /L, age >=40 years, myeloablative conditioning, graft vs. host disease, use of steroids and HSCT < 30 days) and poor performance status.[[2]] The aims of treatment of SARS-CoV-2 infection are based on the pathogenesis of coronavirus disease 2019 (COVID-19), where there is an initial viral phase that may be followed by an inflammatory phase, the latter of which can be the cause of a high mortality rate. [Extracted from the article]

Acquired hypogammaglobulinemia or secondary immunodeficiency (SID) occurs commonly in hematological malignancies with increasing incidence and complexity in the era of modern therapies. Despite current practice of immunoglobulin replacement (IgRT) in SID, the evidence is lacking, especially for newer treatments. We discuss the current evidence for IgRT in various disease groups including issues, such as actual or ideal body weight (IBW)-based dosing, length of treatment, antibiotic prophylaxis, and vaccination. Incidence of SID with newer treatment is lacking. While there is a trend toward decreased respiratory infections and hospitalizations with IgRT, this is not consistent across all disease course or treatment groups. Dosing and indications for cessation of IgRT are also inadequately characterized. Further randomized controlled trials (RCTs) and observational studies are required to assess the optimal indications, timing, and duration of IgRT to improve the efficacy, safety, and cost-effectiveness. Assessment of alternative and adjunctive therapies, such as vaccination and antibiotic prophylaxis could also improve the outcomes and costs. [ABSTRACT FROM AUTHOR]

Background Seroprotection and seroconversion rates are not well understood for 2-dose inactivated influenza vaccination (IIV) schedules in autologous hematopoietic stem cell transplantation (autoHCT) patients. Methods A randomized, single-blind, controlled trial of IIV in autoHCT patients in their first year post-transplant was conducted. Patients were randomized 1:1 to high-dose (HD) IIV followed by standard dose (SD) vaccine (HD-SD arm) or 2 SD vaccines (SD-SD arm) 4 weeks apart. Hemagglutination inhibition (HI) assay for IIV strains was performed at baseline, 1, 2, and 6 months post–first dose. Evaluable primary outcomes were seroprotection (HI titer ≥40) and seroconversion (4-fold titer increase) rates and secondary outcomes were geometric mean titers (GMTs), GMT ratios (GMRs), adverse events, influenza-like illness (ILI), and laboratory-confirmed influenza (LCI) rates and factors associated with seroconversion. Results Sixty-eight patients were enrolled (34/arm) with median age of 61.5 years, majority male (68%) with myeloma (68%). Median time from autoHCT to vaccination was 2.3 months. For HD-SD and SD-SD arms, percentages of patients achieving seroprotection were 75.8% and 79.4% for H1N1, 84.9% and 88.2% for H3N2 (all P  > .05), and 78.8% and 97.1% for influenza-B/Yamagata (P  = .03), respectively. Seroconversion rates, GMTs and GMRs, and number of ILI or LCIs were not significantly different between arms. Adverse event rates were similar. Receipt of concurrent cancer therapy was independently associated with higher odds of seroconversion (OR, 4.3; 95% CI, 1.2–14.9; P  = .02). Conclusions High seroprotection and seroconversion rates against all influenza strains can be achieved with vaccination as early as 2 months post-autoHCT with either 2-dose vaccine schedules. Clinical Trials Registration Australian New Zealand Clinical Trials Registry: ACTRN12619000617167. [ABSTRACT FROM AUTHOR]

Antifungal prophylaxis can reduce morbidity and mortality from invasive fungal disease (IFD). However, its use needs to be optimised and appropriately targeted to patients at highest risk to derive the most benefit. In addition to established risks for IFD, considerable recent progress in the treatment of malignancies has resulted in the development of new 'at‐risk' groups. The changing epidemiology of IFD and emergence of drug resistance continue to impact choice of prophylaxis, highlighting the importance of active surveillance and knowledge of local epidemiology. These guidelines aim to highlight emerging risk groups and review the evidence and limitations around new formulations of established agents and new antifungal drugs. It provides recommendations around use and choice of antifungal prophylaxis, discusses the potential impact of the changing epidemiology of IFD and emergence of drug resistance, and future directions for risk stratification to assist optimal management of highly vulnerable patients. [ABSTRACT FROM AUTHOR]

Objectives: Patients with multiple myeloma (MM) are at increased risk for infection. Clinical assessment of infection risk is increasingly challenging in the era of immune‐based therapy. A pilot systems‐level immune analysis study to identify predictive markers for infection was conducted. Methods: Patients with relapsed and/or refractory MM (RRMM) who participated in a treatment trial of lenalidomide and dexamethasone were evaluated. Data on patient demographics, disease and episodes of infection were extracted from clinical records. Peripheral blood mononuclear cells (PBMCs) collected at defined intervals were analysed, with or without mitogen re‐stimulation, using RNA sequencing and mass cytometry (CyTOF). CyTOF‐derived cell subsets and RNAseq gene expression profiles were compared between patients that did and did not develop infection to identify immune signatures that predict infection over a 3‐month period. Results: Twenty‐three patients participated in the original treatment trial, and we were able to access samples from 17 RRMM patients for further evaluation in our study. Nearly half the patients developed an infection (8/17) within 3 months of sample collection. Infections were mostly clinically diagnosed (62.5%), and the majority involved the respiratory tract (87.5%). We did not detect phenotypic or numerical differences in immune cell populations between patients that did and did not develop infections. Transcriptional profiling of stimulated PBMCs revealed distinct Th2 immune pathway signatures in patients that developed infection. Conclusion: Immune cell counts were not useful predictors of infection risk. Functional assessment of stimulated PBMCs has identified potential immune profiles that may predict future infection risk in patients with RRMM. [ABSTRACT FROM AUTHOR]

Introduction: A multi‐centre study to determine the outcomes and risks for invasive fungal disease (IFD) in myeloma (MM) patients treated with second‐generation immunomodulatory drugs, proteasome inhibitors and monoclonal antibodies was conducted. Methods: Clinical and microbiology records were reviewed to capture patient demographics, disease characteristics, treatment, IFD episodes and outcomes. Categorical and continuous variables between patients with IFD and without IFD were compared using chi‐square test, Fisher's exact test and Mann‐Whitney rank sum test, respectively, with P‐value <.05 considered statistically significant. Results: Five out of 148 (3.4%) MM patients were diagnosed with five episodes of IFI: 3 were proven, 1 probable and 1 possible. Median time from commencement of new generation therapy to IFD diagnosis was 4.0 months (Interquartile range [IQR]: 3.4‐5.7). In patients with IFD, median cumulative steroid dose over 60 days was 1119 mg (IQR: 1066‐1333 mg). None of the patients with IFD had prolonged neutropenia (neutrophil count < 0.5 × 109/L for more than 10 days). Common sites of infection were the respiratory tract (40.0%) and bloodstream (40.0%). Cryptococcus neoformans (n = 2) and Candida krusei (n = 1) were the fungal pathogens isolated in the three proven cases. 30‐day mortality rate was 40.0%. Patients with IFD were younger (median 58 versus 68 years, P =.52) and treated with more lines of therapy (median 5 vs 3, P =.04). Conclusion: IFD rate is low in heavily treated MM patients treated with second‐generation therapy including monoclonal antibodies. Patients do not appear to have traditional risk factors such as prolonged neutropenia. [ABSTRACT FROM AUTHOR]

There are currently around 200 SARS-CoV-2 candidate vaccines in preclinical and clinical trials throughout the world. The various candidates employ a range of vaccine strategies including some novel approaches. Currently, the goal is to prove that they are safe and immunogenic in humans (phase 1/2 studies) with several now advancing into phase 2 and 3 trials to demonstrate efficacy and gather comprehensive data on safety. It is highly likely that many vaccines will be shown to stimulate antibody and T cell responses in healthy individuals and have an acceptable safety profile, but the key will be to confirm that they protect against COVID-19. There is much hope that SARS-CoV-2 vaccines will be rolled out to the entire world to contain the pandemic and avert its most damaging impacts. However, in all likelihood this will initially require a targeted approach toward key vulnerable groups. Collaborative efforts are underway to ensure manufacturing can occur at the unprecedented scale and speed required to immunize billions of people. Ensuring deployment also occurs equitably across the globe will be critical. Careful evaluation and ongoing surveillance for safety will be required to address theoretical concerns regarding immune enhancement seen in previous contexts. Herein, we review the current knowledge about the immune response to this novel virus as it pertains to the design of effective and safe SARS-CoV-2 vaccines and the range of novel and established approaches to vaccine development being taken. We provide details of some of the frontrunner vaccines and discuss potential issues including adverse effects, scale-up and delivery. [ABSTRACT FROM AUTHOR]

In contrast, serological response rates of 46 and 55% were noted in patients who were vaccinated 12 or more months following anti-CD20 therapy and treatment-naïve patients, respectively [[11]]. Adequately protecting hematology patients on anti-CD20 based therapies during the COVID-19 pandemic is a significant ongoing management dilemma and new approaches, such as heterologous prime-boost or additional dosing vaccination schedules should be urgently evaluated. During the current COVID-19 pandemic, higher rates of serious and adverse outcomes have been reported in patients with hematological malignancies [[1]]. [Extracted from the article]

The article in the New England Journal of Medicine discusses a study on influenza vaccination strategies in patients with hematologic cancer. The study compared two doses of adjuvanted quadrivalent inactivated influenza vaccine with two doses of standard-dose vaccine in patients with specific types of hematologic cancer. The results showed limited benefit from augmented vaccination strategies, with adjuvanted vaccine not providing greater immunogenicity than standard-dose vaccine. The study highlights the challenges of vaccination in patients with hematologic cancer and suggests focusing on increasing vaccination uptake. [Extracted from the article]

Objective: The management of low-risk febrile neutropenia (FN) patients through ambulatory programs has demonstrated comparative safety and effectiveness to in-patient strategies. However, there is limited evidence of benefits of changing practice, particularly on a national scale. The aim of this study was to estimate costs and benefits of the program over a 10-year time horizon. Methods: A comparative cost analysis from a health system perspective was performed, comparing costs and length of stay (LOS) of patients enrolled in an ambulatory program to a historical cohort who did not receive the program. Generalised linear models were used for analysis and bootstrapped to account for uncertainty. National data of identified FN admissions were used to inform future projections, with varying proportions of low-risk patients and eligibility for the ambulatory program. Results: The overall LOS for patients in ambulatory cohort was 1.9 days shorter (95% confidence interval (CI) 1.0–2.8 days), a 50% reduction in in-patient bed-days. Although patients in the ambulatory cohort incurred additional costs due to care received outside hospital (mean (± s.d.) A$828.03 ± 124.30), the mean total cost incurred remained substantially lower than that of the historical cohort (A$2979 lower; 95% CI A$772–5391). On a national scale, this could translate into A$62.7 million in costs averted and 41 347 bed-days saved over 10 years if the low-risk prediction rate and eligibility for ambulatory programs remained at currently observed rates. Conclusions: The wider implementation of a safe and effective ambulatory program to manage low-risk FN patients can result in significant return-on-investment for the healthcare system by eliminating avoidable costs due to unnecessary lengthy hospital admissions. What is known about the topic?: There is strong evidence demonstrating out-patient treatment of low-risk FN patients to be an effective and cost-effective strategy compared with continued in-patient hospitalisation. What does this paper add?: This study demonstrates the sustainability of the ambulatory program in ensuring cost benefits and in-patient beds through real-life implementation data. It also provides evidence of the substantial cost and bed-days potentially averted when the cost savings and difference in LOS are estimated on a national scale over a 10-year time horizon. What are the implications for practitioners?: The management of low-risk FN patients through ambulatory or out-patient programs is a safe and effective approach. There is strong evidence demonstrating the likely cost savings and considerable bed-days saved, which can be reallocated to meet other medical demands. [ABSTRACT FROM AUTHOR]

Background: Neutropenic fever (NF) is a common complication of cancer chemotherapy. Patients at low risk of medical complications from NF can be identified using a validated risk assessment and managed in an outpatient setting. This is a new model of care for Australia. This study described the implementation of a sustainable ambulatory program for NF at a tertiary cancer centre over a 12-month period.Methods: Peter MacCallum Cancer Centre introduced an ambulatory care program in 2014, which identified low-risk NF patients, promoted early de-escalation to oral antibiotics, and early discharge to a nurse-led ambulatory program. Patients prospectively enrolled in the ambulatory program were compared with a historical-matched cohort of patients from 2011 for analysis. Patient demographics, clinical variables (cancer type, recent chemotherapy, treatment intent, site of presentation) and outcomes were collected and compared. Total cost of inpatient admissions was determined from diagnosis-related group (DRG) codes and applied to both the prospective and historical cohorts to allow comparisons.Results: Twenty-five patients were managed in the first year of this program with a reduction in hospital median length of stay from 4.0 to 1.1 days and admission cost from Australian dollars ($AUD) 8580 to $AUD2360 compared to the historical cohort. Offsetting salary costs, the ambulatory program had a net cost benefit of $AUD 71895. Readmission for fever was infrequent (8.0%), and no deaths were reported.Conclusion: Of relevance to hospitals providing cancer care, feasibility, safety, and cost benefits of an ambulatory program for low-risk NF patients have been demonstrated. [ABSTRACT FROM AUTHOR]

Background: A translational study in patients with myeloma to determine the utility of immune profiling to predict infection risk in patients with hematological malignancy was conducted. Methods: Baseline, end of induction, and maintenance peripheral blood mononuclear cells from 40 patients were evaluated. Immune cell populations and cytokines released from 1 x 106 cells/ml cultured in the presence of a panel of stimuli (cytomegalovirus, influenza, S. pneumoniae, phorbol myristate acetate/ionomycin) and in media alone were quantified. Patient characteristics and infective episodes were captured from clinical records. Immunological variables associated with increased risk for infection in the 3-month period following sample collection were identified using univariate analysis (p < 0.05) and refined with multivariable analysis to define a predictive immune profile. results: 525 stimulant samples with 19,950 stimulant-cytokine combinations across three periods were studied, including 61 episodes of infection. Mitogen-stimulated release of IL3 and IL5 were significantly associated with increased risk for subsequent infection during maintenance therapy. A lower Th1/Th2 ratio and higher cytokine response ratios for IL5 and IL13 during maintenance therapy were also significantly associated with increased risk for infection. On multivariable analysis, only IL5 in response to mitogen stimulation was predictive of infection. The lack of cytokine response and numerical value of immune cells were not predictive of infection. conclusion: Profiling cytokine release in response to mitogen stimulation can assist with predicting subsequent onset of infection in patients with hematological malignancy during maintenance therapy. [ABSTRACT FROM AUTHOR]

Introduction: Clostridium difficile infection (CDI) is a significant cause of healthcare-associated diarrhoea, and the emergence of endemic strains resulting in poorer outcomes is recognised worldwide. Patients with cancer are a specific high-risk group for development of infection. Areas covered: In this review, modifiable and non-modifiable risk factors for CDI in adult patients with haematological malignancy or solid tumours are evaluated. In particular, the contribution of antimicrobial exposure, hospitalisation and gastric acid suppression to risk of CDI are discussed. Recent advances in CDI treatment are outlined, namely faecal microbiota transplantation and fidaxomicin therapy for severe/refractory infection in cancer populations. Outcomes of CDI, including mortality are presented, together with the need for valid severity rating tools customised for cancer populations. Expert commentary: Future areas for research include the prognostic value of C. difficile colonisation in cancer patients and the potential impact of dedicated antimicrobial stewardship programs in reducing the burden of CDI in cancer units. [ABSTRACT FROM AUTHOR]