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Background Antibiotic overuse leads to the emergence of antibiotic resistance that threatens immunocompromised cancer patients. Infections caused by MDR Gram-negative pathogens are difficult to treat and associated with high mortality. Hence, empirical therapy with standard-of-care (SOC) antibiotics could be suboptimal in these vulnerable patients. New antibiotics covering potential resistant pathogens may be considered. Methods We conducted a randomized non-inferiority study comparing safety and efficacy of imipenem/cilastatin/relebactam (IPM/REL), a β-lactam/β-lactamase inhibitor combination, with SOC antibiotics (cefepime, piperacillin/tazobactam or meropenem) in cancer patients with febrile neutropenia. Patients received at least 48 h of IV antibiotics and were assessed at end-of-IV (EOIV) therapy, test of cure (TOC; Days 21–28), and late follow-up (LFU; Days 35–42). Results A total of 100 patients were enrolled (49 IPM/REL and 50 SOC). Demographics and rates of documented microbiological infections were similar in both groups. In the SOC arm, 86% of antibiotics consisted of cefepime. Patients on IPM/REL had a higher favourable clinical response at EOIV than those on SOC (90% versus 74%; P  = 0.042); however, responses were similar at TOC and LFU. Microbiological eradication was comparable at all three timepoints. Study drug-related adverse events and adverse events leading to drug discontinuation were similar in both groups, with no study drug-related mortality. Conclusions Our results suggest that compared with SOC antibiotics, predominantly cefepime, IPM/REL for empirical coverage of febrile neutropenia in cancer patients is generally safe and could be associated with a better clinical outcome at EOIV. The current SOC consisting mainly of agents that do not cover for ESBL-producing and carbapenem-resistant Enterobacterales bacteria should be reconsidered. [ABSTRACT FROM AUTHOR]

Febrile neutropenia (FN) is a common consequence of intensive chemotherapy in hematological patients. More than 90% of the patients with acute myeloid leukemia (AML) develop FN, and 5%–10% of them die from subsequent sepsis. FN is very common also in autologous stem cell transplant recipients, but the risk of death is lower than in AML patients. In this review, we discuss biomarkers that have been evaluated for diagnostic and prognostic purposes in hematological patients with FN. In general, novel biomarkers have provided little benefit over traditional inflammatory biomarkers, such as C‐reactive protein and procalcitonin. The utility of most biomarkers in hematological patients with FN has been evaluated in only a few small studies. Although some of them appear promising, much more data is needed before they can be implemented in the clinical evaluation of FN patients. Currently, close patient follow‐up is key to detect complicated course of FN and the need for further interventions such as intensive care unit admission. Scoring systems such as q‐SOFA (Quick Sequential Organ Failure Assessment) or NEWS (National Early Warning Sign) combined with traditional and/or novel biomarkers may provide added value in the clinical evaluation of FN patients. [ABSTRACT FROM AUTHOR]

This letter to the editor discusses a phase II study on the use of the drug duvelisib in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The study aimed to determine if intermittent dosing of duvelisib would improve safety while maintaining efficacy. The results showed that intermittent dosing of duvelisib was well-tolerated and resulted in a clinical benefit for the majority of patients. However, adverse events and treatment discontinuations still occurred, and the desired progression-free survival goal was not reached. The article suggests that further dose adjustments or combination therapies may improve outcomes, but interest in duvelisib has decreased due to concerns about mortality and alternative treatments. [Extracted from the article]

Lutetium-177 [177Lu]Lu-prostate-specific membrane antigen (PSMA)-617 improves survival and quality of life in patients with metastatic castration-resistant prostate cancer, but whether it confers a benefit in hormone-sensitive disease is unknown. We aimed to evaluate [177Lu]Lu-PSMA-617 before docetaxel treatment in patients with de-novo high-volume metastatic hormone-sensitive prostate cancer. UpFrontPSMA was an investigator-initiated, multicentre, open-label, randomised, phase 2 trial done at 11 Australian hospitals. Eligible patients had prostate adenocarcinoma without clinically significant neuroendocrine differentiation or small-cell histology, were aged 18 years or older, had less than 4 weeks on androgen deprivation therapy, had an Eastern Cooperative Oncology Group performance status of 0–2, and had high-volume PSMA-avid disease on [68Ga]Ga-PSMA-11 PET-CT with no major discordance on 2-[18F] fluorodeoxyglucose-PET-CT. Patients were randomly assigned (1:1) to the experimental treatment ([177Lu]Lu-PSMA-617 followed 6 weeks later by docetaxel) or standard-of-care treatment (docetaxel alone) using computer-based block randomisation with random block sizes, stratified by disease volume by conventional imaging and duration of androgen deprivation therapy at the time of registration. Neither patients nor investigators were masked to treatment assignment. Patients in the experimental group received two cycles of [177Lu]Lu-PSMA-617 7·5 GBq every 6 weeks intravenously, followed 6 weeks later by six cycles of docetaxel 75 mg/m2 every 3 weeks intravenously, whereas patients in the standard-of-care treatment group received six cycles of docetaxel 75 mg/m2 every 3 weeks intravenously. All patients received continuous androgen deprivation therapy. The primary endpoint was undetectable prostate-specific antigen (≤0·2 ng/mL) at 48 weeks, assessed using a modified intention-to-treat analysis. The trial is registered with ClinicalTrials.gov , NCT04343885. Between May 5, 2020, and April 18, 2023, 130 patients were randomly assigned, 63 (48%) to [177Lu]Lu-PSMA-617 plus docetaxel and 67 (52%) to docetaxel alone. All patients were male and no race or ethnicity data were collected. Median follow-up was 2·5 years (IQR 1·8–3·0). Four patients in the docetaxel alone group withdrew consent after randomisation and no data beyond screening were collected. An additional four patients were not evaluable for the primary endpoint at 48 weeks (two in each group). 25 (41%) of 61 patients (95% CI 30–54) in the [177Lu]Lu-PSMA-617 plus docetaxel group had undetectable PSA at 48 weeks compared with ten (16%) of 61 patients (9–28) in the docetaxel alone group (OR 3·88, 95% CI 1·61–9·38; p=0·0020). The most common grade 3 or 4 treatment-related adverse events were febrile neutropenia (seven [11%] of 63 patients in the [177Lu]Lu-PSMA-617 plus docetaxel group vs six [10%] of 63 patients in the docetaxel alone group) and diarrhoea (four [6%] of 63 patients vs none). Serious adverse events occurred in 16 (25%) patients in the [177Lu]Lu-PSMA-617 plus docetaxel group (none were definitely related to [177Lu]Lu-PSMA-617) and 16 (25%) patients in the docetaxel alone group. No treatment-related deaths occurred. [177Lu]Lu-PSMA-617 followed by docetaxel improved antitumour activity in patients with de-novo high-volume metastatic hormone-sensitive prostate cancer compared with docetaxel alone, without increased toxic effects. Our data potentially support a role for [177Lu]Lu-PSMA-617 in metastatic hormone-sensitive prostate cancer. Prostate Cancer Research Alliance (Movember Foundation and Australian Government Medical Research Future Fund), US Department of Defence Impact Award-Clinical Trials, Endocyte/Advanced Accelerator Applications (a Novartis company), Australian Nuclear Science and Technology Organization, Victorian Cancer Agency, University of Melbourne, and Peter MacCallum Cancer Foundation. [ABSTRACT FROM AUTHOR]

Gram-positive bacteria are frequently resistant to empirical beta‐lactams in febrile neutropenic patients with cancer. As microbiology and antibiotic susceptibility changes, we reevaluated the risk factors for resistant Gram-positive bacteremia in febrile neutropenic patients with cancer. Episodes of bacteremic febrile neutropenia in Seoul National University Hospital from July 2019 to June 2022 were reviewed. Resistant Gram-positive bacteria were defined as a pathogen susceptible only to glycopeptide or linezolid in vitro (e.g., methicillin-resistant staphylococci, penicillin-resistant viridans streptococci, and ampicillin-resistant enterococci). Episodes were compared to identify independent risk factors for resistant Gram-positive bacteremia. Of 225 episodes, 78 (34.7%) involved resistant Gram-positive bacteremia. Multivariate analysis revealed that breakthrough bacteremia while being administered antibiotics (adjusted odds ratio [aOR], 6.794; 95% confidence interval [95% CI], 3.130–14.749; P < 0.001) and catheter-related infection (aOR 4.039, 95% CI 1.366–11.946; P = 0.012) were associated with resistant Gram-positive bacteremia. Chronic liver disease (aOR 0.231, 95% CI 0.059–0.905; P = 0.035) and hypotension at bacteremia (aOR 0.454, 95% CI 0.218–0.945; P = 0.035) were inversely associated with resistant Gram-positive bacteremia. Resistant Gram-positive bacteria should be considered in breakthrough bacteremia and catheter-related infection in febrile neutropenic patients with cancer. [ABSTRACT FROM AUTHOR]

Background: Recent data support 18F-FDG PET-CT for the management of infections in immunocompromised patients, including invasive fungal infection (IFI). However, its role is not well established in clinical practice. We performed an international survey to evaluate the knowledge of physicians about the usefulness of 18F-FDG PET-CT in IFI, in order to define areas of uncertainty. Methods: An online survey was distributed to infectious diseases working groups in December 2023-January 2024. It included questions regarding access to 18F-FDG PET-CT, knowledge on its usefulness for IFI and experience of the respondents. A descriptive analysis was performed. Results: 180 respondents answered; 60.5% were Infectious Diseases specialists mainly from Spain (52.8%) and Italy (23.3%). 84.4% had access to 18F-FDG PET-CT at their own center. 85.6% considered that 18F-FDG PET-CT could be better than conventional tests for IFI. In the context of IFI risk, 81.1% would consider performing 18F-FDG PET-CT to study fever without a source and around 50% to evaluate silent lesions and 50% to assess response, including distinguishing residual from active lesions. Based on the results of the follow-up 18F-FDG PET-CT, 56.7% would adjust antifungal therapy duration. 60% would consider a change in the diagnostic or therapeutic strategy in case of increased uptake or new lesions. Uncovering occult lesions (52%) and diagnosing/excluding endocarditis (52.7%) were the situations in which 18F-FDG PET-CT was considered to have the most added value. There was a great variability in responses about timing, duration of uptake, the threshold for discontinuing treatment or the influence of immune status. Conclusion: Although the majority considered that 18F-FDG PET-CT may be useful for IFI, many areas of uncertainty remain. There is a need for protocolized research to improve IFI management. [ABSTRACT FROM AUTHOR]

Objective To investigate the real-world factors influencing the clinical outcome of Febrile neutropenia (FN) in oncology patients. Methods We conducted a retrospective analysis of clinical data from 130 FN patients admitted to our hospital between January 2020 and December 2022. The patients were categorized into three groups based on their clinical efficacy: cured group, effective group, and ineffective group. A comparison was made among the three groups regarding general data and laboratory examination results. Univariate and ordered multicategorical logistic regression analyses were performed to identify factors affecting the clinical efficacy of FN. Results The overall effective rate of FN in our hospital was 86.15%. Univariate analysis revealed statistically significant differences among the three patient groups regarding the duration of granulomatous defects, Physical Status Score (PS Score), procalcitonin (PCT) levels, and timing of administration (P < 0.05). Ordinal multicategorical logistic regression analysis demonstrated that patients with PS scores < 2, granulomatous defects lasting less than 7 days, and PCT levels below 0.5 ng/mL exhibited better clinical treatment outcomes. Conclusion In the management of FN, it is crucial to prioritize patients with high PS scores and elevated PCT levels while optimizing drug utilization to enhance clinical efficacy. Timely intervention should be implemented to address granulopathy and improve overall clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Febrile neutropenia (FN) poses a significant challenge in cancer treatment, with a high incidence among patients undergoing standard therapies. Predicting FN complications and outcomes remains crucial for improving patient management strategies. Biomarkers, including procalcitonin and albumin, have garnered attention for their potential prognostic value in FN. Methods: We conducted a prospective observational study at a tertiary hospital, enrolling 185 adult cancer patients experiencing FN episodes. We assessed serum albumin levels and incorporated them into the Multinational Association for Supportive Care in Cancer (MASCC) risk index to enhance risk stratification. Results: Serum albumin levels displayed promising prognostic utility in febrile neutropenia (FN). They exhibited moderate specificity and sensitivity in predicting mortality during FN and 28-day mortality. Serum albumin levels were significantly associated with gastrointestinal infections, serving as an independent predictor. Integrating serum albumin into the MASCC risk index improved predictive accuracy for FN mortality by 50%, 28-day mortality by 66.67%, and respiratory tract infections by 62.50%, enhancing in this way risk stratification for FN-related complications. Conclusion: Serum albumin emerges as a promising biomarker for prognostication in FN, complementing existing risk assessment frameworks. Its incorporation into the MASCC risk index enhances predictive capabilities, aiding clinicians in identifying high-risk patients promptly. While albumin shows potential in predicting mortality and complications, further research is warranted to optimize sensitivity and specificity, ensuring its clinical utility. [ABSTRACT FROM AUTHOR]

Background: Reversible splenial lesion syndrome (RESLES) is known as a neuro-imaging syndrome with recurrent but reversible lesion of the corpus callosum, characterized by nonspecific but usually mild encephalopathies and specific imaging manifestations.There are few published reports in the field of oncology. Case presentation: A 33-year-old female with right breast cancer and with no particular family history was admitted to hospital with high fever and severe headache, after receiving adjuvant radiotherapy. Blood routine test upon admission suggested neutropenia, considering myelosuppression associated with radiotherapy. There were no definite findings of common pathogenic microorganism, and no imaging indication of certain infectious sites other than a likely reversible corpus callosum syndrome suggested by brain MRI, which was relieved after systemic antibiotic therapy and granulocyte colony-stimulating factor injection. Conclusions: Reversible splenial lesion syndrome is a kind of clinical-imaging syndrome with multiple clinical manifestations and etiologies. This breast cancer patient after postoperative adjuvant radiotherapy develops a complication of RESLES that rings an alarm bell to the oncologists not to easily recognize the corpus callosum lesion as infarction or metastasis. Meanwhile, the potential pathogenic mechanisms need to be explored further. [ABSTRACT FROM AUTHOR]

This article explores the impact of the COVID-19 pandemic on the treatment of acute myeloid leukemia (AML) patients in India. The study analyzed data from the Indian Acute Leukemia Research Database and compared outcomes before and during the pandemic. The study found a decrease in AML treatment registrations at large referral centers, but an increase at smaller centers. Despite changes in treatment protocols, survival outcomes remained similar. The study suggests that standard AML care is still possible during crises like the COVID-19 pandemic. [Extracted from the article]

ABSTRACT Introduction Patients and Methods Results Conclusions The prognosis of patients with refractory or relapsed AML (R/R‐AML) is very limited. To (re)achieve complete remission, there has recently been increasing evidence that the combination of venetoclax (VEN) with chemotherapy is associated with improved outcomes.Our retrospective, single‐center study of 53 R/R‐AML patients with a median follow‐up time of 11.0 months compared standard salvage chemotherapy (FLAG‐Ida or HAM in n = 35 patients) with a combination of venetoclax (VEN) and FLAG‐Ida (FLAVIDA in n = 18 patients) concerning safety and efficacy.Regarding the primary endpoints, there was a statistically significant increased event free survival (EFS) in the FLAVIDA group compared to patients with standard chemotherapy based on the univariate log‐rank‐test and in the multivariate Cox regression analysis (HR 0.22 [95% CI 0.05, 0.97]). There were no differences between the two groups in terms of patients developing febrile neutropenia CTCAE III° and IV° or a delay in hematological recovery. In addition, a clear trend towards an improved overall response rate (78% vs. 51%) was demonstrated in the FLAVIDA group.The FLAVIDA regimen represents a promising treatment alternative for R/R AML patients with a high response rate and significantly improved EFS compared to standard chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Pembrolizumab plus cisplatin and 5-fluorouracil administered as first-line therapy for advanced esophageal cancer patients has shown a better objective response and survival than conventional chemotherapy with less severe hematological adverse events. The safety and efficacy of this regimen were evaluated in patients with T4b esophageal squamous cell carcinoma (ESCC). Methods: Eight consecutive patients with T4b ESCC received this regimen according to KEYNOTE-590 as induction, and they were evaluated after 1–3 courses. The programmed death-ligand 1 (PD-L1) combined positive score (CPS) was also evaluated before chemotherapy. Efficacy for the primary lesion was evaluated by our original formula for the tumor reduction rate. Results: The numbers of patients with partial response (PR), stable disease, and progressive disease (PD) were 5, 1, and 2, respectively. The tumor reduction rate ranged from 69 to 87% in PR patients, and all PR patients had relief from T4b. Two patients underwent conversion surgery with R0 resection. PD-L1 CPS was over 90 in 2 PR patients, but under 10 in 2 other PR patients. PD-L1 CPS was under 10 in PD patients. One patient had hyperprogression, resulting in an esophago-pulmonary fistula. Greater than grade 3 adverse events were bleeding gastric ulcer in one patient (12.5%), neutropenia without G-CSF in 3 patients (37.5%), and hypopotassemia in 1 patient (12.5%). No patient had febrile neutropenia. Conclusions: Marked tumor reduction was confirmed in 62.5% of patients with pembrolizumab plus cisplatin and 5-fluorouracil with less adverse events. This regimen could be administered as induction chemotherapy for patients with T4b ESCC. [ABSTRACT FROM AUTHOR]

Introduction Exposure to high doses of ionizing radiation can result in hematopoietic acute radiation syndrome. Currently, there is no radiation medical countermeasure approved by the U.S. FDA which can be used before radiation exposure to protect exposed individuals. Here we aimed to evaluate the therapeutic potential of an aqueous suspension of synthetic genistein nanoparticles (BIO 300) as a radioprotectant in a pilot efficacy study using a nonhuman primate model of total body irradiation. Materials and Methods Eight rhesus macaques were divided into two groups; four received vehicle and four received BIO 300 Injectable Suspension 24 h before 5.8 Gy total-body irradiation. Survival, blood cell counts, blood chemistry, and clinical parameters were monitored over the 60 days of the study. Tissues were collected at necropsy 60 days post-irradiation or from animals that met unscheduled euthanasia criteria and subjected to histopathological analysis. Tissues analyzed included the duodenum, jejunum, ileum, sternum, lung, heart, liver, kidney, spleen, gut-associated lymphoid tissue, and urinary bladder. Results In this pilot study, all BIO 300 Injectable Suspension treated animals survived to day 60, while only 50% of the vehicle-treated animals survived. We found that BIO 300 Injectable Suspension did not mediate an improvement in blood cell counts (e.g. neutrophils, platelets, white blood cells). However, BIO 300 Injectable Suspension treated animals had a lower incidence of fever and febrile neutropenia, were able to better maintain their body weight post radiation exposure, and exhibited less anemia and faster recovery from anemia. Histopathological analysis revealed that BIO 300-treated animals had less irradiation-induced damage to the sternum and other tissues compared to vehicle controls. Conclusions BIO 300's mechanism of action is complex and protection against irradiation is attainable without much improvement in the complete blood count (CBC) profile. BIO 300's mechanism for radioprotection involves multiple biological pathways and systems. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to compare hematological parameters preand early post-chemotherapy, and evaluate their values for predicting febrile neutropenia (FN). Methods: Patients diagnosed with malignant solid tumors receiving chemotherapy were included. Blood cell counts peri-chemotherapy and clinical information were retrieved from the hospital information system. We used the least absolute shrinkage and selection operator (LASSO) method for variable selection and fitted selected variables to a logistic model. We assessed the performance of the prediction model by the area under the ROC curve. Results: The study population consisted of 4,130 patients with common solid tumors receiving a three-week chemotherapy regimen in Sichuan Cancer Hospital from February 2019 to March 2022. In the FN group, change percentage of neutrophil count decreased less (-0.02, CI: -0.88 to 3.48 vs. -0.04, CI: -0.83 to 2.24). Among hematological parameters, lower postchemotherapy lymphocyte count (OR 0.942, CI: 0.934-0.949), change percentage of platelet (OR 0.965, CI: 0.955-0.975) and higher change percentage of post-chemotherapy neutrophil count (OR 1.015, CI: 1.011- 1.018), and pre-chemotherapy NLR (OR 1.002, CI: 1.002-1.002) predicted an increased risk of FN. These factors improved the predicting model based on clinical factors alone. The AUC of the combination model was 0.8275. Conclusion: Peri-chemotherapy hematological markers improve the prediction of FN. [ABSTRACT FROM AUTHOR]

Introduction: High-risk febrile neutropenia (FN) is one of the main causes of morbidity and mortality in onco-hematology. The initiation of empirical antibiotic therapy is an emergency that can change the prognosis of some patients. Given the emergence of increasingly resistant Gram-positive bacteremia, glycopeptides, as an empirical treatment, have an important place in the management of high-risk FN. The aim of this study is to evaluate the appropriateness of glycopeptide prescription in high-risk FN patients. Methods: This study was conducted in the Hematology Department of Fattouma Bourguiba University Hospital of Monastir, Tunisia. Patients with high-risk FN were enrolled during the period between January 1 and December 31, 2020. Results: Of the 29 patients included in this study, 88 FN episodes were noted of which 39 episodes treated with glycopeptides were evaluated. Twenty-four febrile episodes were empirically treated with glycopeptides (27.3%) of which 17 prescriptions (70.8%) were appropriate according to the European Conference on Infection in Leukemia and the Infectious Diseases Society of America recommendations. A therapeutic escalation using glycopeptides was noted in 17% of cases and appropriately opted in 6 FN episodes (40%). Conclusion: Prescriptions of glycopeptides were appropriate according to the international recommendations in 71% of the empirical prescriptions and in 40% of the therapeutic escalation using glycopeptides. In high-risk FN episodes, glycopeptides prescriptions should be rationalized and limited to the indications detailed in the international guidelines to control the emergence of multidrug-resistant bacteria. [ABSTRACT FROM AUTHOR]

Simple Summary: Squamous cell carcinoma of the anus or anal cancer is increasing in prevalence, and the standard treatment of mitomycin and 5-fluorouracil is too toxic for many patients. Unfortunately, there is currently no standard of care for what to do for this disease when someone is not a candidate for this aggressive treatment. Here, we demonstrate the promising preliminary toxicity profile and efficacy of the combination of weekly carboplatin and paclitaxel chemotherapy for patients with localized anal cancer. This regimen was able to complete 80% of the intended treatments with anticipated toxicities, and 89% achieved a complete clinical response. This combination is a promising regimen and is already being investigated further in a clinical trial. Background: Although squamous cell carcinoma of the anus (SCCA) is a relatively uncommon malignancy in the United States, it continues to increase in incidence. Treatment for locoregional disease includes mitomycin and 5-fluorouracil with radiation. This combination is associated with significant toxicity, limiting its use in patients who are older or have certain comorbidities. Carboplatin and paclitaxel (C/P) is an accepted treatment regimen for metastatic SCCA. We aim to evaluate the efficacy and toxicity of weekly C/P given with radiation for patients unable to receive standard chemoradiation for SCCA. Methods: From our cancer registry, adult patients who received weekly intravenous C/P concurrent with standard-dose radiation for localized SCCA were included in this study. Clinical response was determined based on the evidence of disease on imaging and/or anoscopy. Toxicities were graded according to the CTCAE v5. Results: Ten patients were included; eight were female, and the median age was 75.5 years (54–87). Six had T2 disease, and four had T3 tumors. Four had node-positive disease. The majority (70%) of patients were dosed at standard C (AUC 2) and P (50 mg/m2), with a limited subset requiring dose reduction for baseline performance status. Patients completed a mean of 78.3% (40–100%) of the intended treatments. A total of 89% of the patients achieved a complete clinical response. With a median follow-up of 25.8 months (3.4–50.4 months), 67% of the patients are alive and without recurrence. Two patients have had local recurrence, and one patient had metastatic progression. The most common toxicities of any grade included leukopenia (100%), anemia (100%), radiation dermatitis (100%), diarrhea (100%), and fatigue (100%). Grade 3 or higher toxicities included neutropenic fever (20%), neutropenia (30%), and anemia (30%). Conclusions: This study demonstrates promising tolerability and efficacy for weekly C/P chemoradiation for patients with anal cancer unable to receive mitomycin and 5-fluorouracil. This regimen merits further investigation in prospective clinical trials. [ABSTRACT FROM AUTHOR]

Background: Despite common global usage, fluoropyrimidine (FP; 5‐flurouracil and capecitabine)‐related chemotherapy toxicity is poorly reported in the literature, with serious toxicity ranging from 10% to 40% and early toxicity (within 60 days of exposure) quoted at 14%. Data reflecting the incidence of Grades 3–5 FP‐related toxicity in Australian cancer patients is scant, despite the significant impact of toxicity on patients (hospitalisations, intensive care unit (ICU) admissions and even death). Aims: This retrospective audit evaluated Grades 3–5 toxicities in a contemporaneous cohort of 500 patients receiving FP chemotherapies within the Hunter‐New England Local Health District from June 2020 to June 2022. Data were extracted from public hospital records and oncology‐specific e‐records to determine rates of toxicity and associated hospitalisations, intensive care admissions and deaths that occurred within 60 days of first exposure to FP chemotherapy‐containing regimens. Results: One hundred and fifty incidents of Grades 3–4 toxicity in the first 60 days led to 87 patients presenting to hospital (87/500, 17.4%). The most common serious toxicities were diarrhoea (39.3%), nausea and vomiting (22.7%) and febrile neutropaenia (10%). Four patients were admitted to the ICU, and four patients died of toxicity. Within the first 60 days, 22.2% of patients required treatment delays, 21.4% required dose reductions, and 7.8% of patients ceased treatment because of toxicities. Discussion and Conclusion: Our experience reflects international reports and is likely generalisable to the Australian population. These data are a basis to understand the potential benefits of precision medicine strategies such as pharmacogenomic screening to improve patient tolerability and the cost‐effectiveness of FP chemotherapy prescribing. [ABSTRACT FROM AUTHOR]

We investigated the influence of a local guideline on the quality of febrile neutropenia (FN) management and the applicability of a computerized decision support system (CDSS) using real-life data. The study included 227 FN patients between April 2016 and January 2019. The primary outcome measure was the achievement of a 20% increase in the rate of appropriate empirical treatment of FN in bacteremic patients. The compatibility of the CDSS (the development of which was completed in November 2021) with local protocols was tested using standard patient scenarios and empirical antibiotic recommendations for bacteremic FN patients. In total, 91 patients were evaluated before (P1: between April 2016 and May 2017) and 136 after (P2: between May 2017 and January 2019) the guideline's release (May 2017). The demographic characteristics were similar. Appropriate empirical antibacterial treatment was achieved in 58.3% of P1 and 88.1% of P2 patients (p = 0.006). The need for escalation of antibacterial treatment was significantly lower in P2 (49.5% vs. 35.3%; p = 0.03). In P2, the performance of the CDSS and consulting physicians was similar (CDSS 88.8% vs. physician 88.83%; p = 1) regarding appropriate empirical antibacterial treatment. The introduction of the local guideline improved the appropriateness of initial empirical treatment and reduced escalation rates in FN patients. The high rate of compliance of the CDSS with the local guideline-based decisions in P2 highlights the usefulness of the CDSS for these patients. [ABSTRACT FROM AUTHOR]

Introduction: Febrile neutropenia (FN) is a potentially severe entity, particularly in hemato-oncologic patients who have higher incidence of colonization with multidrug-resistant bacteria. Discrepancies among guidelines contribute to divergence in antimicrobial practices. Our objective was to assess the variation of practices in antimicrobial therapy in high-risk FN among Portuguese hematologists. Methods: We conducted a cross-sectional study through the implementation of an online survey, open to all clinical hematologists in the country. To characterize practice patterns regarding critical elements in FN management, three clinical vignettes were designed to describe typical situations where narrow-spectrum empiric antibiotics (vignette 1), short-course therapy (vignette 2) and de-escalation (vignette 3) could be performed. The remaining questions characterized clinical experience, department size, and differentiation and decision-making process regarding FN antibiotic therapy. Results: The survey yielded 31 responses from 11 hospitals across four regions. All respondents opted for empiric narrow-spectrum antibiotics, 22.6% opted for short-course therapy (mostly senior specialists from larger settings) and 35.5% for de-escalation (mostly young specialists). Availability of an FN protocol seemed to favor both approaches. These findings should be complemented by qualitative assessments of barriers to best practices and should support the need for interventions to improve antibiotic use in febrile neutropenia. [ABSTRACT FROM AUTHOR]

Background and Objectives: Infections are the most common and potentially life-threatening complications of the treatment of children with acute lymphoblastic leukemia (ALL). The aim of this study was to determine epidemiological, clinical, and microbiological characteristics of infections in pediatric patients with ALL. Materials and Methods: Twenty-three children (16 males and 7 females, with a mean age of 5.9 years (range of 1.3 to 12.2 years)) with ALL, treated at the Division of Hematology, Oncology, and Clinical Genetics, Department of Pediatrics, Clinical Hospital Center Rijeka, Croatia, from 1 January 2015 to 31 December 2020, were included in the study. Results: One hundred and four infectious episodes (IEs) were reported (an average of 4.5 IE per patient). IEs were more frequent in the intensive phases of antileukemic treatment. Neutropenia was present in 48 IEs (46.2%) with a duration greater than 7 days in 28 IEs (58.3%). The respiratory tract was the most common infection site (48.1%). We documented 49 bacterial (47.1%), 4 viral (3.9%), 4 fungal (3.9%), and 10 mixed isolates (9.6%), while in 37 IEs (35.6%), a pathogen was not isolated. The most common causes of bacteremia were coagulase-positive staphylococci. The most frequent empirical therapy was third- and fourth-generation cephalosporins, followed by piperacillin/tazobactam. The modification of first-line antimicrobial therapy was performed in 56.9% of IEs. Granulocyte-colony stimulating factor was administered in 53.8% of IEs, and intravenous immunoglobulins were administered in 62.5% of IEs. One patient required admission to the intensive care unit. No infection-related mortality was reported. Conclusions: ALL patients have frequent IEs. Close monitoring, the identification of risk factors, the rapid empirical use of antibiotics in febrile neutropenia, and the timely modification of antimicrobial therapy play key roles in reducing infection-related morbidity and mortality in children with ALL. [ABSTRACT FROM AUTHOR]

Background: The management of febrile neutropenia (FN) in pediatric cancer patients has traditionally been conducted in a hospital setting. However, recent evidence has indicated that outpatient management of FN can be equally effective compared to inpatient care. Based on this evidence, we conducted a cost-minimization analysis (CMA) specifically focused on pediatric cancer patients in Mexico. Methods: A piggy-back study was conducted during the execution of a non-inferiority clinical trial that compared outpatient treatment to inpatient treatment for FN in children with cancer. A CMA was performed from a societal perspective using patient-level data. In the previous study, we observed that step-down oral outpatient management of low-risk FN was as safe and effective as inpatient intravenous management. Direct and indirect costs were collected prospectively. The costs were adjusted for inflation and converted to US dollars, with values standardized to July 2022 costs. Statistical analysis using bootstrap methods was employed to obtain robust estimations for decision-making within the Mexican public health care system. Results: A total of 117 FN episodes were analyzed, with 60 in the outpatient group and 57 in the inpatient group; however, complete cost data were available for only 115 FN episodes. The analysis revealed an average savings of $1,087 per FN episode managed on an outpatient basis, representing a significant 92% reduction in total cost per FN episode compared to inpatient treatment. Length of hospital stay and inpatient consultations emerged as the primary cost drivers within the inpatient care group. Conclusion: This CMA demonstrates that the step-down outpatient management approach is cost-saving when compared to inpatient management of FN in pediatric cancer patients. The mean difference observed between the treatment groups provides support for decision-making within the public health care system, as outpatient management of FN allows for substantial cost savings without compromising patient health. [ABSTRACT FROM AUTHOR]

The article focuses on comparing the efficacy of venetoclax plus hypomethylating agents (VEN + HMA) versus intensive chemotherapy in treating acute myeloid leukemia with myelodysplasia-related gene mutations (AML-MR). Topics include the impact of genetic mutations on treatment decisions, the outcomes of VEN + HMA compared to standard chemotherapy, and the effects of different treatment regimens on overall and event-free survival rates in AML-MR patients.

Background: The chemotherapy regimens recommended for both rhabdomyosarcoma (RMS) and Ewing sarcoma (ES) patients are myelosuppressive and can reduce the absolute neutrophil count (ANC) and subsequently increase the risk of febrile neutropenia (FN). However, only a few studies have focused on the efficacy and safety of granulocyte-colony stimulating factor (G-CSF) drugs in pediatric and adolescent patients with RMS and ES. Our objective was to investigate the efficacy and safety of mecapegfilgrastim, a biosimilar of pegfilgrastim, in prophylaxis of FN for pediatric and adolescent patients with RMS or ES. Methods: In this single-arm, single-center, prospective study, pediatric and adolescent patients with RMS or ES were enrolled to receive either VAC (vincristine, cyclophosphamide, dactinomycin) regimen or VDC (vincristine, cyclophosphamide, doxorubicin) regimen in a 3-week cycle, followed by treatment with mecapegfilgrastim (100 μg/kg, maximum 6 mg) given at 24 h after completing chemotherapy. The primary endpoint was the incidence rate of FN. Secondary endpoints included the incidence rate of grade 4 neutropenia, duration of ANC ≤ 0.5 × 109/L, incidence rate of chemotherapy delay or reduction, use of antibiotics, and safety profile. Results: In total, 2 of the 30 (6.7%, 95% CI: 0.82–22.07) patients experienced FN after the first cycle of chemotherapy. Eight (26.7%, 95% CI: 12.28–45.89) patients experienced grade 4 neutropenia after receiving prophylactic mecapegfilgrastim. Eight patients experienced ANC ≤ 0.5 × 109/L with a median duration of 4.5 days; among them, 6 patients reached the lowest point of their ANC level on day 7, and 5 of them recovered by day 10. No dose reductions, delays, or discontinuation of chemotherapy was reported. Twenty-one (70.0%) patients received antibiotics during the treatment period. No patient experienced FN in the 0–5 years and the 13–18 years groups, and 2 patients experienced FN in the 6–12 years group. Two patients, 6 patients, and no patient experienced grade 4 neutropenia in the 0–5 years, 6–12 years, and 13–18 years groups, respectively. Conclusion: Mecapegfilgrastim showed acceptable efficacy and safety profile in pediatric and adolescent patients with RMS or ES. Further randomized studies with large sample size are warranted. Trial registration: This clinical trial was registered at Chictr.org.cn (No.ChiCTR1900022249). Registered on March 31, 2019. [ABSTRACT FROM AUTHOR]

Introduction: Enfortumab vedotin (EV) is an antibody-drug conjugate combining a monoclonal antibody targeting nectin-4 with a highly potent microtubule disrupting agent. EV is expected to be a candidate for the third-line treatment for urothelial carcinoma previously treated with platinum-based chemotherapy and PD-1/PD-L1 inhibitors. Very few cases of patients experienced hyperglycemia of unknown cause. Case Presentation: We describe a 72-year-old Asian man with mild obesity, type 2 diabetes, hyperlipidemia, hypertension, and chemo-resistant metastatic urothelial carcinoma. He developed hyperglycemia and febrile neutropenia after 3 doses of EV. He had hyperglycemia of 489 mg/dL and was started on continuous intravenous insulin infusion (CVII). The patient’s intravenous insulin requirements peaked at 316 units per day. He also developed febrile neutropenia and consequent sepsis caused acute kidney injury. Continuous hemodialysis filtration (CHDF) together with antibiotics were started to treat the septic condition. The blood glucose level gradually decreased after CHDF treatment and CHDF was continued for 14 days. The timing of liberation from CHDF correlated with the elimination half-life of EV of 3.4 days. CVII was treated for 26 days and the patient was finally released from the intensive care unit. Conclusion: This case indicates that the uncontrollable hyperglycemia induced by EV during metastatic urothelial carcinoma treatment is effectively managed with CVII and CHDF until the elimination of the adverse effect of EV. [ABSTRACT FROM AUTHOR]

AbstractThis study reports characteristics and outcomes of adults who received Azacitidine-Venetoclax (AZA-VEN) compared to other salvage therapies (NO-AZA-VEN) as first salvage therapy for acute myeloid leukemia (AML). The clinical data of 81 patients with a diagnosis of relapsed or refractory AML were analyzed. The ORR was comparable for both groups (55% vs 57%, p = 0.852). Median OS (6.8 vs 11.2 months, p = 0.053) and median RFS (6.9 vs 11.2 months, p = 0.488) showed a trend in favor of the NO-AZA-VEN group. OS was significantly longer with NO-AZA-VEN for ELN 2022 risk category sub-group, patients under 60 years old, primary AML and for patients who underwent allo-hematopoietic stem cell transplant after salvage therapy. There was no statistical difference in complications of treatment such as febrile neutropenia, intensive care unit stay, septic shock and total parenteral nutrition. Those results do not support the preferential use of AZA-VEN over other regimens in R/R acute myeloid leukemia. [ABSTRACT FROM AUTHOR]

Invasive fungal disease (IFD) presents a life-threatening condition in immunocompromised patients, thus often prompting empirical administration of antifungal treatment, without adequate mycological evidence. Over the past years, wide use of antifungal prophylaxis resulted in decreased occurrence of IFD but has contributed to changes in the spectrum of fungal pathogens, revealing the occurrence of previously rare fungal genera causing breakthrough infections. The expanding spectrum of clinically relevant fungal pathogens required the implementation of screening approaches permitting broad rather than targeted fungus detection to support timely onset of pre-emptive antifungal treatment. To address this diagnostically important aspect in a prospective setting, we analyzed 935 serial peripheral blood (PB) samples from 195 pediatric and adult patients at high risk for IFD, involving individuals displaying febrile neutropenia during treatment of hematological malignancies or following allogeneic hematopoietic stem cell transplantation. Two different panfungal-PCR-screening methods combined with ensuing fungal genus identification by Sanger sequencing were employed. In the great majority of PB-specimens displaying fungal DNAemia, the findings were transient and revealed fungi commonly regarded as non-pathogenic or rarely pathogenic even in the highly immunocompromised patient setting. Hence, to adequately exploit the diagnostic potential of panfungal-PCR approaches for detecting IFD, particularly if caused by hitherto rarely observed fungal pathogens, it is necessary to confirm the findings by repeated testing and to identify the fungal genus present by ensuing analysis. If applied appropriately, panfungal-PCR-screening can help prevent unnecessary empirical therapy, and conversely, contribute to timely employment of effective pre-emptive antifungal treatment strategies. [ABSTRACT FROM AUTHOR]

Primary central nervous system lymphoma (PCNSL) is an aggressive lymphoma that primarily affects the central nervous system. Current treatments, such as surgery, chemotherapy, and whole-brain radiotherapy, often fail to achieve satisfactory results. The prognosis for patients with refractory or relapsed (R/R) PCNSL is bleak. The optimal treatment for refractory or relapsed PCNSL is poorly defined due to a limited number of studies in this setting. Bruton's tyrosine kinase (BTK) inhibitors, as part of targeted therapy regimens, have undergone testing in several clinical trials against PCNSL and have shown promising results in the treatment of R/R PCNSL. In this meta-analysis, we aim to explore and critically appraise the evidence regarding the efficacy of BTK inhibitors in the treatment of refractory or relapsed PCNSL. A systematic search was conducted on multiple databases including PubMed, Embase, Cochrane library, Wanfang Data Knowledge Service Platform, and CNKI, covering the period up to November 2023. The inclusion criteria for studies were patients with R/R PCNSL who received BTK inhibitors, and reported data on overall response rate (ORR) and complete remission (CR). The pooled rates were calculated using a random-effects or fixed-effects model with a double arcsine transformation, and 95% CIs were determined for all outcomes. In total, 1 studies involving 185 patients were identified and included in the meta-analysis. The pooled complete remission (CR) rate of BTK inhibitors-based treatment for R/R PCNSL was found to be 50%. Subgroup analysis revealed that the CR rates for BTK inhibitor monotherapy, BTK inhibitor combined with chemotherapy, and BTK inhibitor combined with radiotherapy for R/R PCNSL were 7%, 68%, and 80%, respectively. The ORR for BTK inhibitors-based treatment for R/R PCNSL was 70%. Subgroup analysis showed that the ORR rates for BTK inhibitor monotherapy and BTK inhibitor combined with chemotherapy for R/R PCNSL were 55% and 83%, respectively. The most common adverse events (AEs) reported were hematologic AEs, including neutropenia, anemia, and thrombocytopenia. Severe nonhematologic AEs included rash, febrile neutropenia, increased levels of aspartate aminotransferase, and increased blood bilirubin. BTK inhibitors can be regarded as a safe and effective treatment option for R/R PCNSL, thereby providing a potential new avenue for R/R PCNSL treatment. However, it is important to note that further large-sample prospective randomized controlled trials are needed to validate these findings and establish their wider applicability. [ABSTRACT FROM AUTHOR]

Background: Invasive fungal diseases (IFD) are high morbidity and mortality infections in children with cancer suffering episodes of high‐risk febrile neutropenia (HRFN). IFD epidemiology has changed in the last two decades, with an increasing incidence in recent years due to the growing number of immunocompromised children at risk for IFD. The aim of this study was to evaluate the incidence of IFD in children with cancer in the period 2016–2020 compared to 2004–2006 in six hospitals in Chile. Methods: Prospective, multicentre study, carried out between 2016 and 2020 in six hospitals in Chile. The defined cohort corresponds to a dynamic group of HRFN episodes in patients <18 years old with cancer, who at the fourth day of evolution still presented fever and neutropenia (persistent HRFN). Each episode was followed until resolution of FN. The incidence of IFD was calculated between 2016 and 2020 and compared with data obtained in the period 2004–2006. The incidence rate was estimated. Results: A total of 777 episodes of HRFN were analysed; 257 (33.1%) were considered as persistent‐HRFN occurring in 174 patients. The median age was 7 years (IQR: 3–12 years) and 52.3% (N = 91) were male. Fifty‐three episodes of IFD were detected: 21 proven, 14 probable and 18 possible. Possible IFD were excluded, leaving 239 episodes of persistent‐HRFN with an IFD incidence of 14.6% (95% CI 10.5–19.9) and an incidence rate of 13.6 IFD cases per 1000 days of neutropenia (95% CI 9.5–20.0). Compared to 2004–2006 cohort (incidence: 8.5% (95% CI 5.2–13.5)), a significant increase in incidence of 6.1% (95% CI 0.2–12.1, p =.047) was detected in cohorts between 2016 and 2020. Conclusion: We observed a significant increase in IFD in 2016–2020, compared to 2004–2006 period. [ABSTRACT FROM AUTHOR]

Introduction: The efficacy of cancer treatments has links to the intestinal microbiome. Mucositis is a dose-limiting intestinal pro-inflammatory side effect of cancer treatments, that increases the risk of diarrhoea, mucositis, and in severe cases, febrile neutropenia. Methods: The effect of cancer treatments on Quality of Life (QoL) was assessed using the FACT C questionnaire that included patient wellbeing and gut adverse symptoms (e.g. diarrhoea). Participants rated faecal samples via the Bristol Stool Chart. In addition, bacterial DNA was extracted from faecal samples, sequenced, and taxonomically examined. The incidence / severity of neutropenia was assessed with white blood cell and neutrophil counts. Circulating SCFAs and plasma lipopolysaccharide (LPS) endotoxin levels were recorded and correlated to intestinal mucositis. Results: Improvement in bowel function, with reduction in constipation and or diarrhoea or absence of significant disturbance to bowel function was recorded in 85% of the participants. One participant developed febrile neutropenia and two developed bowel toxicity during the study, that was unrelated to the test formulation. No significant changes in microbiota alpha- and beta-diversity at the phylum and species levels respectively from baseline to end of study treatment was observed. None of the participants had raised plasma-endotoxin levels from baseline to the first and subsequent treatment cycles for their cancers. Probiotics in this cohort were deemed safe and tolerable. Significant improvement in emotional QoL scores (p = 0.015) was reported with increased number of chemotherapy cycles. In a related observational study of exceptional responders to chemotherapy, participants were found to have had a high intake of fruits, vegetables, and fibre possibly indicative of a more balanced intestinal microbiota. Conclusion: A multi-strain probiotic formulation was safe and tolerated in this chronically ill cohort that were undergoing oncological treatment. The probiotic formulation alleviated diarrhoea, constipation and maintained stool consistency/frequency during the multiple treatments with chemotherapy and radiotherapy. Intestinal dysbiosis that is characterised by decreased microbial diversity and increased pro-inflammatory species was not observed. Probiotic supplementation may have helped reduce dysbiosis during cancer treatments. These improvements may have been critical with the observation that emotional wellbeing was significantly improved from baseline. Hence albeit that the study had limitations, the probiotic intervention provided adjunctive treatment support to the patients. What is of scientifically plausible interest is that probiotics have a long association historically with human hosts and as such ratify their inclusion offering a significant adjunctive therapeutic potential. Future studies warrant larger sample sizes, control groups and should limit recruitment to a largely homogenous group of patients. [ABSTRACT FROM AUTHOR]

Introduction: This study explored the efficacy of repeat blood cultures in bacteremic acute myeloid leukemia (AML) patients following allogeneic hematopoietic stem cell transplantation (HSCT). Methods: This was a retrospective study of AML patients who experienced febrile neutropenia (FN) and bacteremia following HSCT at the Taussig Cancer Center from January 1, 2019, to December 31, 2022. The primary endpoint was the rate of positive repeat blood cultures following initial positive blood culture. Results: Fifty patients were included in the study. There were 50 occurrences of FN with positive initial blood cultures that were diagnosed following HSCT. Fifty initial sets of blood cultures and 96 sets of repeat blood cultures were drawn between the 50 occurrences of FN. Twelve of 96 (12.5%) repeat blood culture sets were positive for a pathogen, which occurred over nine of 50 (18.0%) episodes of FN. Three of 96 (3.2%) repeat blood culture sets grew a pathogen that differed from the pathogen that grew in the preceding positive blood culture. Conclusion: Among bacteremic AML patients in the post‐HSCT period, the yield of repeat blood cultures for detecting previously detected and new pathogens was low. [ABSTRACT FROM AUTHOR]