Febrile Neutropenia Research Articles

779. IMMUNE CHECKPOINT INHIBITOR WITH CHEMOTHERAPY (CISPLATIN+5FU) FOR ADVANCED ESOPHAGEAL CANCER

Abstract Background First-line chemotherapy for advanced esophageal carcinoma results in poor outcomes. Compared with placebo plus chemotherapy, pembrolizumab plus chemotherapy improved overall survival in patients with previously untreated, advanced oesophageal squamous cell carcinoma according to the KEYNOTE-590. We studied 17patients for the unresectable esophageal cancer and gastroesophageal junction adenocarcinoma cases treated with pembrolizumab and chemotherapy at our hospital between November 2023 and May 2024. Methods 17 patients with advanced carcinoma of the thoracic esophagus having either T4 tumor or distant lymph node metastasis were enrolled in this study. pembrolizumab 200mg/m2 and CDDP 80 mg/m2 was administered on days 1 and 5-FU 800 mg/m2 was administered on days 1-5 intravenously 3corse in 3-week cycles. Results Back ground: Averaged Age 76 (55-86), male: female =16:1, location (Ce: Ut: mt: Lt: Jz =1:1:6:6:3), strength 71mm (30-120), Stage (IVA: IVB= 7:10), Pathology (SCC: AD= 16:1), Times (3 courses completed: uncompleted: ongoing=9:3:5), Response PR:SD:PD: unknown=6:1:2:8, Toxicity: iRAE: liver dysfunction: Febrile neutropenia=4:2:6, The incidence of Grade 3 or higher adverse events was 3/15. One toxicity-related death occurred. We performed conversive esophagectomy for 2 patients. After chemotherapy: operation: radiation: observation: death:=2:2:10:3 Conclusion and discussion Due to the small number of cases, it is unclear whether the treatment was safe in a single center. I would like to consider increasing the number of cases. We will show one toxicity-related death and two conversive operation.

NEWS, NEWS2, and qSOFA accuracy in predicting sepsis-related mortality in acute myeloid leukemia: a retrospective single-center analysis.

Acute myeloid leukemia (AML) treated with intensive chemotherapy carries a high risk of severe infection. The development of reliable assessment tools to promptly identify patients at risk of developing critical illness is essential to prevent delays in intensive care unit (ICU) admission. This study evaluated the accuracy of quick Sequential Organ Failure Assessment (qSOFA) score, National Early Warning Score (NEWS), and NEWS2 score in predicting ICU admission and sepsis-related mortality in this population. A retrospective analysis was conducted, including 365 episodes of febrile neutropenia in 126 patients. The results showed that all three scores-qSOFA, NEWS, and NEWS2-demonstrated good accuracy for all outcomes, with area under the receiver-operating characteristic curve values for sepsis-related mortality of 0.812, 0.858, and 0.848, respectively. In addition, the scores exhibited excellent accuracy in predicting ICU admission and the composite outcome of ICU admission or sepsis-related mortality. To our knowledge, this is the first study to evaluate the accuracy of NEWS in a population of patients with AML who did not undergo stem cell transplantation. These findings suggest that NEWS and NEWS2 are effective tools for identifying patients with AML at high risk of clinical deterioration during febrile neutropenia, supporting their use in clinical practice.

ALL-008 Compliance With Clinical Protocols for Treating Febrile Neutropenia in Hematopoietic Stem Cell Transplant Recipients: Do Healthcare Practices in Low- and Middle-Income Countries Align With the Guidelines Set Forth by IDSA and NCCN?

ALL-008 Compliance With Clinical Protocols for Treating Febrile Neutropenia in Hematopoietic Stem Cell Transplant Recipients: Do Healthcare Practices in Low- and Middle-Income Countries Align With the Guidelines Set Forth by IDSA and NCCN?

Application of cell-free DNA fungal polymerase chain reaction for invasive fungal disease evaluation in pediatric oncology and stem cell transplant patients.

Molecular diagnostics may enable early, noninvasive detection of invasive fungal disease (IFD) in immunocompromised patients. Cell-free deoxyribonucleic acid (cfDNA) fungal polymerase chain reaction (PCR) assays were recently incorporated into institutional prolonged febrile neutropenia pathways. We aimed to evaluate the performance of plasma cfDNA PCR panels (mold and Candida panels) in pediatric oncology and hematopoietic stem cell transplant (HSCT) patients with clinical concern for IFD. This single-center, observational study assessed plasma cfDNA fungal PCR performance for noninvasive IFD detection in hospitalized pediatric oncology and HSCT patients. The primary outcome was IFD diagnosis per published consensus definitions within 1month. Positive and negative agreement between plasma cfDNA fungal PCR and consensus definitions were calculated. We also described test turnaround time and patient survival. From October 2021 to 2022, 54 patients underwent 60 evaluations with 11 proven/probable IFD cases. Comparing plasma cfDNA fungal PCRs to consensus definitions for proven/probable IFD, there was 73% positive agreement and 96% negative agreement. Two proven/probable cases with negative PCRs were caused by organisms not included on either panel. Median time to cfDNA fungal PCR result was 35hours (interquartile range: 19-69) in eight proven/probable cases detected by cfDNA fungal PCR. There were 17 deaths among 54 patients, and IFD contributed to 45% of deaths in patients with proven/probable IFD. Plasma cfDNA fungal PCRs detected relevant molds or yeast in most cases classified as proven/probable IFD. However, this targeted approach missed some cases. More studies are required to determine optimal utilization of molecular diagnostics in pediatric patients.

"Voriconazole-Associated Motor Neuropathy In Acute Myeloid Leukemia: A Case Report And Literature Review"

Introduction: Voriconazole, a commonly used antifungal in immunocompromised patients is effective against various fungal pathogens. Despite its efficacy, it is associated with numerous adverse effects, including the less frequently documented motor neuropathy. Case Presentation: We report a case of a 60-year-old male with acute myeloid leukemia (AML) who developed motor neuropathy following voriconazole administration. Initially treated with standard chemotherapy and prophylactic antifungals, he developed febrile neutropenia and was subsequently administered voriconazole. Within a week, he presented with bilateral foot drop. The neurological assessment revealed severe motor weakness without sensory loss. MRI indicated lumbar disc protrusion and nerve conduction studies confirmed severe demyelinating polyneuropathy. Upon cessation of voriconazole, the patient's symptoms completely resolved, as confirmed by follow-up electromyography. Discussion: Voriconazole-associated neuropathy, though rare, can present as motor neuropathy, contrary to the more commonly reported sensory neuropathy. The exact mechanism remains unclear, and while symptoms often resolve after discontinuation, some cases may result in permanent damage. Conclusion: This case highlights the importance of recognizing voriconazole-induced motor neuropathy in AML patients. Early identification and discontinuation of the drug are crucial for symptom resolution. Further research is needed to understand the underlying mechanisms and to develop preventive and management strategies.

1863P Circulating biomarkers for risk stratification of cancer patients with chemotherapy associated febrile neutropenia

1863P Circulating biomarkers for risk stratification of cancer patients with chemotherapy associated febrile neutropenia

A retrospective single institutional analysis of outpatient chemotherapy in patients with cancer during the COVID-19 pandemic.

Providing treatment to patients with cancer, even during the coronavirus disease (COVID-19) pandemic, is essential. In collaboration with infectious disease specialists, we established guidelines for the management of patients with cancer receiving ambulatory treatment during the pandemic on April 8, 2020. This study examined the practice and management of ambulatory chemotherapy under emergency conditions. Following the guidelines, our Breast and Medical oncology department developed a chemotherapy strategy for the phases. Additionally, to distinguish fever during chemotherapy, we developed a flow chart for fever. As part of a fact-finding survey, the status of outpatient chemotherapy was investigated: (1) whether there was any change in the number of chemotherapies before and after the declaration of a state of emergency by the Tokyo Metropolitan Government and (2) the frequency and severity of febrile neutropenia (FN) cases. Compared to before the first declaration of the state of emergency, the number of chemotherapies decreased except after the declaration, but no decrease was observed during the rest of the period; no difference was observed in the frequency or severity of FN outbreaks or in the use of pegfilgrastim for primary prevention before and after the epidemic. With appropriate treatment guidelines, routine chemotherapy can be performed in an outpatient setting during an outbreak.

Variation in Antibiotic Prescription in High-Risk Febrile Neutropenia in Portuguese Hospitals.

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. 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. 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.

Real-world outcomes of FOLFOXIRI plus bevacizumab in patients with metastatic colorectal cancer: the JSCCR-TRIPON study.

FOLFOXIRI plus bevacizumab is a standard first-line chemotherapy for patients with metastatic colorectal cancer (mCRC). However, due to the severe toxicities, this regimen is not widely used. There is limited data on the real-world efficacy and safety. We conducted a retrospective analysis of clinical data from mCRC patients who received FOLFOXIRI plus bevacizumab as first-line chemotherapy at 31 institutions. The initial dose was standardized according to the TRIBE regimen. Induction therapy was defined as a combination of oxaliplatin, irinotecan, and fluorouracil. Out of 104 patients who met the criteria, the median age was 58years (range, 16-72). 81% of patients had an eastern cooperative oncology group performance status (PS) of 0. An initial dose reduction was observed in 63% of patients. The median number of preplanned induction therapy cycles was 12 (range, 4-12). The completion of scheduled induction therapy cycles was observed in 45% of patients, with treatment-related toxicities being the main reason for discontinuation (63%). The median progression-free survival and overall survival were 12.8months (95% CI, 10.6-15.0) and 27.9months (95% CI 21.6-34.2), respectively. The objective response rate and disease control rate were 63.7% and 98.9%, respectively. The R0 resection rate was 21.2%. The main grade 3 or higher toxicities were neutropenia (51%), febrile neutropenia (10%), and nausea/vomiting (5%). No treatment-related deaths were observed. In a real-world clinical setting, FOLFOXIRI plus bevacizumab demonstrated efficacy and safety comparable to previous clinical trials.

Preneutropenic Fever in Patients With Hematological Malignancies: A Novel Target for Antimicrobial Stewardship.

Many patients with hematological malignancy develop fever after chemotherapy/conditioning but before chemotherapy-induced neutropenia (preneutropenic fever [PNF]). The proportion of PNF with an infectious etiology is not well established. We conducted a single-center, prospective observational substudy of PNF (neutrophils >0.5 cells/μL, ≥38.0°C) in adults receiving acute myeloid leukemia (AML) chemotherapy, or allogeneic hematopoietic cell transplant (allo-HCT) conditioning enrolled in a neutropenic fever randomized controlled trial between 1 January and 31 October 2018. Eligible patients had anticipated neutropenia ≥10 days and exclusions included concurrent infection and/or neutropenia prior to chemotherapy or conditioning. PNF rates and infections encountered were described. Associations between noninfectious etiologies and fever were explored. Antimicrobial therapy prescription across preneutropenic and neutropenic periods was examined. Of 62 consecutive patients included (43 allo-HCT, 19 AML), 27 had PNF (44%) and 5 (19%) had an infective cause. Among allo-HCT, PNF occurred in 14 of 17 (82%) who received thymoglobulin; only 1 of 14 (7%) had infection. During AML chemotherapy, 18 of 19 received cytarabine, of which 8 of 18 (44%) had PNF and 3 of 8 (38%) had infection. Most patients with PNF had antimicrobial therapy continued into the neutropenic period (19/27 [70%]). Those with PNF were more likely to be escalated to broader antimicrobial therapy at onset/during neutropenic fever (5/24 [21%] vs 2/30 [7%]). Rates of PNF were high, and documented infection low, leading to prolonged and escalating antimicrobial therapy. In the absence of infection, early cessation of empiric therapy after PNF is recommended as an important stewardship intervention.

Infections in Children with Acute Lymphoblastic Leukemia.

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.

Electrochemical DNA Biosensor for Detection of Microbial Infections and Antibiotic Resistance in Patients with Febrile Neutropenia in Hematological Malignancies

Electrochemical DNA Biosensor for Detection of Microbial Infections and Antibiotic Resistance in Patients with Febrile Neutropenia in Hematological Malignancies

AML-054 Efficacy Profile of Daily Injection Filgrastim in Chemotherapy-Induced (CT) Febrile Neutropenia (FN) in Patients With Acute Leukemia (AL): Ukrainian Retrospective Study in a Real-Life Cohort

AML-054 Efficacy Profile of Daily Injection Filgrastim in Chemotherapy-Induced (CT) Febrile Neutropenia (FN) in Patients With Acute Leukemia (AL): Ukrainian Retrospective Study in a Real-Life Cohort

Efficacy Profile of Daily Injection Filgrastim in Chemotherapy-Induced (CT) Febrile Neutropenia (FN) in Patients With Acute Leukemia (AL): Ukrainian Retrospective Study in a Real-Life Cohort

Efficacy Profile of Daily Injection Filgrastim in Chemotherapy-Induced (CT) Febrile Neutropenia (FN) in Patients With Acute Leukemia (AL): Ukrainian Retrospective Study in a Real-Life Cohort

AML-684 Electrochemical DNA Biosensor for Detection of Microbial Infections and Antibiotic Resistance in Patients with Febrile Neutropenia in Hematological Malignancies

AML-684 Electrochemical DNA Biosensor for Detection of Microbial Infections and Antibiotic Resistance in Patients with Febrile Neutropenia in Hematological Malignancies

Microbiological Profile in the Management of Febrile Neutropenia in the Pediatric Hematology and Oncology Department

Microbiological Profile in the Management of Febrile Neutropenia in the Pediatric Hematology and Oncology Department

Compliance With Clinical Protocols for Treating Febrile Neutropenia in Hematopoietic Stem Cell Transplant Recipients: Do Healthcare Practices in Low- and Middle-Income Countries Align With the Guidelines Set Forth by IDSA and NCCN?

Compliance With Clinical Protocols for Treating Febrile Neutropenia in Hematopoietic Stem Cell Transplant Recipients: Do Healthcare Practices in Low- and Middle-Income Countries Align With the Guidelines Set Forth by IDSA and NCCN?

Economic implications of step-down outpatient management for fever and neutropenia episodes in pediatric cancer patients: a cost minimization analysis

BackgroundThe 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.MethodsA 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.ResultsA 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.ConclusionThis 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.

Clinical Profile of Febrile Neutropenia in Children with Hematological Malignancies

Clinical Profile of Febrile Neutropenia in Children with Hematological Malignancies

BIO 300: A Prophylactic Radiation Countermeasure for Acute Radiation Syndrome.

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. 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. 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. 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.