Febrile Neutropenia Research Articles

Plasma Cell-free DNA Metagenomic Next-Generation Sequencing in Immunocompromised Children

Abstract Background Plasma cell-free DNA metagenomic next-generation sequencing (mNGS) is a novel diagnostic tool for infectious diseases [1]. Data suggests that plasma mNGS may be useful in immunocompromised adults, changing management in up to 60% of the patients [2]. A prospective study evaluating utility of plasma mNGS for pneumonia in immunocompromised adults concluded that mNGS provided an additive diagnostic value of 12.1% [3]. A similar study in adults with febrile neutropenia reported a sensitivity and specificity of 85 and 100%, respectively [4]. However, there is limited data evaluating the utility of mNGS in immunocompromised children. Methods We retrospectively reviewed all pediatric immunocompromised patients who had plasma mNGS testing performed from December 2018 to July 2023 at St. Jude Children’s Research Hospital. Electronic medical records were reviewed to extract relevant clinical data and microbiologic data including results of mNGS, contemporaneous cultures, and related antimicrobial treatment. Descriptive statistics are presented as frequencies and medians (interquartile range, IQR). Comparisons were performed using Fisher’s exact test or Wilcoxon rank-sum test, as appropriate, using R version 3.6.3. Results A total of 18 immunocompromised children underwent plasma mNGS testing. Acute lymphoblastic leukemia was the most common malignancy (33.3%), followed by acute myeloid leukemia (22.2%). Two patients (11.1%) had undergone hematopoietic cell transplant, both allogeneic. At the time of testing, 16 patients (88.9%) had fever and 10 (55.6%) had an absolute neutrophil count of <500/mm3. All except one were on antimicrobial therapy at the time of testing, with a median duration of 8 days (IQR=12.25). Only 9 (50%) patients had a positive mNGS result. A positive mNGS resulted in broadening or extending antibiotics course in 4 patients (22.2%); negative mNGS results did not lead to changes in management in any of the cases. There were no significant differences in age, sex, days of fever, neutropenia, gastrointestinal (GI) symptoms, and days of fever before testing between those with positive versus negative results. However, a higher frequency of GI symptoms at the time of testing among those with positive results was observed. Clinical characteristics and impact on management in patients with positive and negative results are summarized in Table 1. Conclusion Plasma mNGS had a limited impact on the management of immunocompromised children at our institution. Negative results did not lead to de-escalation of therapy, and positive results led to additional exposure to antibiotics. Further research is needed to determine the role of mNGS in this population, and the interpretation of positive testing in the setting of gastrointestinal disease.

Clinical insights into Invasive Aspergillosis in Mexican children with cancer

Abstract Background In the last years Invasive Aspergillosis (IA) has become the most frequent invasive fungal infection (IFI) affecting children with hematological malignancies. This complication results in the delay of cancer treatment and/or poor prognosis mainly due to late diagnosis and late start of antifungal treatment. Therefore, antifungal prophylaxis and preemptive approaches have been proposed for these patients based on risk factors and local epidemiological data. For this reason, we performed a unicenter, descriptive and prospective study to determine the frequency and clinical course of IA in hospitalized cancer patients with fever and neutropenia. Methods we included events of fever and neutropenia of hospitalized patients with cancer and either with persistent febrile neutropenia (PFN: fever for >96h with total neutrophil count of <500cells/mm3) or profound prolonged neutropenia (PPN: total neutrophil count of <500cells/mm3 for >7 days). Informed consent was requested prior inclusion and follow up of these events was performed with weekly measurement of serum galactomannan antigen (until the recovery of neutrophil count), lung computed tomography (CT) and/or sinus and/or central nervous system (CNS) imaging, depending on clinical findings, and if feasible bronchoscopy to obtain bronchioalveolar lavage (BAL) samples. Clinical and laboratory data were obtained; with this information diagnosis of IA was classified as possible, probable, and proven, according to the EORTC/MSG guidelines. This protocol was approved by the hospital’s research and ethics committees (INP 041/2021). For data analysis categorical variables were presented as frequencies and numerical variables as median and range. Statistical analysis was made with X2 and U Mann Whitney tests. Results Seventy events were included, 14 (20%) had IA diagnosis; 2 possible, 11 probable and 1 proved. Median of age was 10.2y (5.5 – 17) and 64.3% were male. Acute lymphoblastic leukemia was the main oncologic diagnosis (71.4%), 35.7% during induction phase; followed by acute myeloblastic leukemia (21.4%). 92.9% of events with IA presented as PFN (p=0.001) with a fever duration of 3.5 days (1-8) (p=0.004). Pulmonary disease was evident in all events with IA, two had disseminated infection. In 5/14 events serum galactomannan antigen was positive in the first measurement. Only 8 events underwent bronchoscopy: BAL was positive in 6 and 4 had positive culture with Aspergillus spp. Lung CT scan showed different findings, lobar/segmental consolidation and nodule with halo sign were the most common; 85.7% of cases presented with more than one radiological sign (p=0.003). Voriconazole monotherapy was given to 78.5% of IA cases and 21.4% required combined antifungal therapy (added caspofungine or liposomal amphotericin B) due to disseminated disease or severe clinical course. Intensive care admission resulted with statistical significance for the events with diagnosis of IA (64.3% p= 0.019). Within the IA events survival at 60 days was of 78.6%. Conclusion Frequency of IA was high among our high risk cancer patients. This study demonstrates the importance of a complete work up for invasive fungal infection in high-risk patients with persistent febrile neutropenia. The information obtained is of great use for the implementation of pre-emptive approaches and antifungal prophylaxis in this patient population.

Surveillance of fever and neutropenia episodes at Yeolyan Hematology and Oncology Center in Armenia

Abstract Background Fever and neutropenia frequently occur as complications in pediatric patients with malignancies, significantly escalating morbidity and mortality if not appropriately addressed. We implemented a fever registry to identify patient factors and outcomes associated with fever in patients undergoing treatment at our facility. Methods We conducted a single-center prospective observational study at the Pediatric Cancer and Blood Disorders Center of Armenia. All patients aged 0-21 years with a malignancy diagnosis and developing fever and neutropenia between June 25 and November 20, 2023, were included. Variables collected included age, gender, date and time of fever onset, patient symptoms, time to antibiotic administration, identified microbiologic and clinical infections, and subsequent outcomes, including mortality and requirement for critical care level interventions. Data were entered in Microsoft Excel 2016 and analyzed using descriptive statistical methods. Results Sixty-one patient episodes in 36 patients met the inclusion criteria. Of these, 22% of episodes had fever at home. The most common malignancy was acute leukemia, specifically B-ALL (21/61), followed by T-ALL (9/61), AML (7/61), and mixed T- and B-type (1/61). Eight out of 61 fever episodes occurred in patients with relapsed disease. The median time-to-antibiotics was 100 minutes (max: 24 hours 40 minutes) in patients developing fever outside the hospital; for inpatient cases, the median time-to-antibiotics was 30 minutes (max: 6 hours 45 minutes). The time-to-antibiotics was longer for patients experiencing fever at home compared to those in inpatient settings (p=0.043). 21% of patient episodes were pretreated, however 11 out of 61 patient episodes (18%) had a positive blood culture. Of 13 total positive cultures, ten were obtained at the time of the patient’s presentation. The most common pathogens identified were Staphylococcus spp. (8/13) including coagulase-negative (3/8), and Klebsiella spp. (3/13). Polymicrobial-positive cultures were observed during two fever and neutropenia episodes. During 35 episodes, patients presented with no complaints except for general weakness. Among the identified sources of infection (20/61), central-line-related bloodstream infections (n=6), bacteremia (n=5), and Clostridiodes difficile colitis (n=5) were the most common. One febrile neutropenia episode resulted in death (1.6%). Conclusion In summary, over 75% of episodes were observed among patients with hematologic malignancies, and localizing symptoms were absent in half of episodes at presentation. We have identified opportunities for quality improvement in time to administration of antibiotics in outpatient fever episodes. The adaptation of an electronic-based medical record system will simplify the tracking process for a febrile episode.

Use of Data from a Fever Registry (FEVEREG) to Identify Quality Improvement Opportunities in a Third-Level Hospital in Panama

Abstract Background Infectious diseases in childhood cancer patients are frequent and increase the morbimortality of these patients. Hospital del Niño doctor José Renán Esquivel initiated data collection in a registry of fever and neutropenia (FEVEREG) to evaluate outcomes and management of these diseases and identify opportunities for quality improvement. The objective of this study is to describe data collected to date. Methods Data was collected through a data collection instrument (CRF) using Trial Master platform. It was analyzed with R Data Analytics (version 4.3.2) and descriptive statistics summarized. Only patients who were admitted due to the febrile episode or were hospitalized when fever started were included. Results From Sept 2021 to October 2023, we captured 138 episodes in 70 patients, with a mean age of 8 years (range 0-15) and a similar percentage of female and male patients. The most common diagnosis was acute lymphoblastic leukemia (57.14%) and the episodes occurred more during the induction phase (24%) and in patients with a relapse protocol (31.5%). The time of administration of the antibiotic varied depending on the patient location at fever onset. 44% of outpatients (46/105) received the first dose of antibiotic more than 4 hours after the onset of fever, while hospitalized patients received this dose in the first hour in 64% of cases (21/33). Time from registration of outpatients until the first dose of antibiotic was an average of 71 minutes, with 60% of the patients receiving the antibiotic during the first 60 minutes. In 45.8% of the episodes, a blood culture was taken before starting the antibiotic. The febrile neutropenia algorithm was followed on 64.5% of the days evaluated, with the main cause of deviation being treatment to the focus of infection (55%) followed by clinical decision (41%). Bacteremia occurred in 26% of episodes (20/78) and 14% of episodes had documented viral infection (11/78). The most frequently isolated bacteria in blood was Pseudomonas aeruginosa (13/33, 39.3%). Approximately 4% of the episodes (6/138) were admitted to the intensive care unit and died, half from septic shock and half from progressive disease. The average length of hospital stay was 12 days. Conclusion Data from FEVEREG has suggested opportunities for quality improvement in time to antibiotics and use of guideline compliant antibiotics (antimicrobial stewardship).

Survival Dynamics of Invasive Fungal Diseases in Pediatric Hemato-Oncology Patients at a Tertiary Medical Facility in Mexico from July 2020 to July 2023

Abstract Background Invasive fungal diseases (IFD) have been increasing in prevalence over the past two decades, with filamentous fungi being the most common cause. However, candidiasis remains the predominant etiology of infection, especially in cases of neutropenic fever accompanied by neutropenic colitis. The prevalence of infections caused by Aspergillus species, Mucor species, Fusarium, and other species is higher among individuals with severe and extended neutropenia and those who have undergone hematopoietic progenitor cell transplantation. Methods A retrospective, descriptive, observational study was conducted to identify cases of patients diagnosed with invasive fungal diseases, categorizing them as possible, probable, or confirmed. In our comprehensive analysis of cases, we prioritize the examination of diseases induced by filamentous fungi, while considering the specific chemotherapy regimen administered and the particular oncological condition. Results The predominant etiology observed was invasive aspergillosis, followed by mucormycosis. A total of 18 cases suggestive of invasive Aspergillosis were identified, but clinical or histopathological investigations were not conducted due to limitations. The majority of cases were pulmonary, accounting for 92% of cases, while rhinosinusal involvement was identified in 8%. Factors such as clinical characteristics, imaging studies, serum galactomannan determination, and microbiological culture were considered. The patient survival rate was found to be 86.7%, with an average treatment duration of six weeks. A mortality rate of 3.7% was observed due to the underlying disease during the consolidation phase of invasive fungal diseases. Conclusion In our study, invasive aspergillosis emerged as the predominant invasive fungal disease in pediatric hemato-oncology patients. Despite challenges in conducting comprehensive investigations, our findings underscore the importance of timely diagnosis and management. The 86.7% survival rate reflects the efficacy of the treatment approach employed, while the observed mortality emphasizes the impact of underlying diseases on outcomes. This study contributes valuable insights to the understanding and improvement of survival dynamics in pediatric patients facing invasive fungal diseases.

Gas gangrene with Clostridium septicum in a neutropenic patient.

Gas gangrene is a rare presentation of a necrotizing fasciitis, caused by Clostridium perfringens, C. septicum and other clostridial species. With its rapid progression it is a potentially life-threatening infection, that poses as a challenge in the clinical management requiring an interdisciplinary approach.Here we present a 62-year-old woman, who developed neutropenic fever while undergoing chemotherapy for triple negative breast cancer. She presented with a high fever, reporting little pain in her left thigh accompanied by redness and induration locally. Subsequently the patient developed pain and redness of the back of the left hand. The initial findings suggested cellulitis and immediate empiric treatment with intravenous meropenem was started. Despite the antibiotic treatment the patient rapidly developed septic shock along with progression of the local infection. Emergency surgical debridement revealed extensive necrosis of the soft tissues including extensive myonecrosis of the thigh. On the left hand an extensive debridement was performed, the left lower limb could not be preserved and exarticulation of the left hip was required. Microbiologically C. septicum was isolated in different samples, confirming gas gangrene. As there was no local entry portal on the skin, hematogenous seeding from intestinal translocation in this neutropenic patient was suspected. The empiric antibiotic treatment was tailored to intravenous penicillin and complemented with clindamycin for toxin inhibition. Following radical debridement and antibiotic treatment, the patient could be stabilized. After repetitive debridement wound closure was achieved and the patient was discharged for rehabilitation. Antibiotic treatment was continued for four weeks.This rare case of gas gangrene in a neutropenic patient shows the complexity in the diagnostic and therapeutic management of necrotizing soft tissue infections in immunocompromised patients. It particularly highlights the importance of an interdisciplinary management with fast recognition of the disease and rapid, if needed radical, surgical debridement as well as tailored antibiotic treatment for a successful outcome.

Association of Granulocyte Colony-Stimulating Factor Treatment with Risk of Brain Metastasis in Advanced Stage Breast Cancer.

The routine use of granulocyte colony-stimulating factor (GCSF) is not recommended for the prevention or treatment of chemotherapy-induced neutropenia or febrile neutropenia because risks associated with certain types of cancers, distant organ metastases, and primary tumor growth cannot be excluded. We examined the association between GCSF use and the incidence of brain metastasis (BM), as well as BM-free survival (BMFS). This retrospective cohort study included 121 stage IV breast cancer patients without confirmed BM at the time of diagnosis and who received at least one course of systematic chemotherapy or target therapy at a tertiary teaching hospital between 1 January 2014 and 31 December 2022. The effect of GCSF use on BM was assessed with other confounding factors in Cox regression analyses. In this retrospective cohort, patients who received GCSF treatment had a significantly higher incidence of BM than those who did not (34.9% vs. 13.8%, p = 0.011). Univariate Cox regression analysis showed that GCSF use, menopause status, hormone treatment, HER2 treatment, cumulative dosage, dosage density, and neutropenia were independent risk factors for BMFS (p < 0.05). GCSF users had a higher risk of BM (adjusted HR: 2.538; 95% CI: 1.127-5.716, p = 0.025) than nonusers. BM risk was significantly associated with those with neutropenia (RR: 1.84, 95% CI: 1.21, 2.80) but not with those without neutropenia (RR: 0.59, 95% CI: 0.41-0.84, Interaction p-value < 0.05). The higher the dose density of GCSF, the higher the risk compared with those who do not use GCSF (p for trend < 0.01). These preliminary results suggest that GCSF is associated with BM in patients with stage IV breast cancer who did not have BM at initial diagnosis. Further comprehensively designed large-scale observational studies are needed to confirm our preliminary results.

7245 A case of refractory methimazole-induced agranulocytosis treated with high-dose G-CSF

Abstract Disclosure: S. Shah: None. D. Mathur: None. G. Bao: None. S. Shah: None. D.M. Antoniucci: None. Case Presentation: Despite their efficacy in treating hyperthyroidism, antithyroid drugs (ATDs) carry a rare risk of life-threatening agranulocytosis (ANC &amp;lt;500/μL), with incidence varying from 0.1 to 0.4%. Patients with agranulocytosis may benefit from granulocyte-colony stimulating factor (G-CSF) to shorten recovery and reduce hospitalization costs. We present the case of a 37-year-old woman with Graves disease, who developed methimazole (MMZ)-induced agranulocytosis and was treated with high-dose G-CSF. At diagnosis, MMZ 10 mg BID was started and later reduced to 5 mg BID. After 2 months, she presented to the ED with a dental infection, an arm abscess after a cat scratch, and fevers. Blood-work showed WBC of 1500/μL, ANC of 0/μL, and rare granulocytes on manual differential. Flow cytometry did not show clonal lymphoid or blast populations. MMZ was stopped and antibiotics were started. Her hyperthyroidism was managed with propranolol and iodine solution in anticipation of definitive thyroidectomy. On day 4 of admission, tbo-filgrastim 450 mcg daily injections were started for persistent neutropenia. Despite 3 doses of G-CSF, ANC remained at 0/μL, prompting a bone marrow biopsy that showed no dysplastic or aplastic phenotype. After 9 doses of G-CSF up to 600 mcg daily, ANC fully recovered on day 14. She underwent thyroidectomy, and 2 months later her ANC and thyroid hormone levels were within normal. Discussion: This report illustrates a case of severe, refractory ATD-induced agranulocytosis and highlights the utility of G-CSF in treating high risk patients. Classically, ATD-induced agranulocytosis occurs in those aged &amp;gt;65 years, follows high dose therapy, and occurs within 60 days of treatment initiation. G-CSF is often used in clinical practice, although its efficacy is not well established. A recent meta-analysis demonstrated that G-CSF can hasten recovery by 3 days. Other studies report no difference or prolonged agranulocytosis up to 14 days despite G-CSF, especially in patients with ANC &amp;lt;100/μL. Whether this is a lack of true benefit or inadequate dosing is unclear. This case reviews the use of high dose G-CSF in a patient with profound neutropenia. Prompt ANC recovery was crucial given neutropenic fevers and need for thyroidectomy. Even with escalating doses of G-CSF, her ANC required 14 days to recover - twice the typical length of recovery. Whether G-CSF impacted the time course of her recovery is difficult to discern. Identifying the mechanisms underlying ATD induced agranulocytosis may explain delayed responses to G-CSF. Notably, the 2016 ATA guidelines do not incorporate G-CSF into ATD-induced agranulocytosis management. This conservative approach reflects a paucity of evidence supporting G-CSF use. Further research must investigate underlying mechanisms and clarify indications for G-CSF use to improve outcomes and reduce costs of care. Presentation: 6/1/2024

Problems and their solutions in accompanying therapy of oncological patients: regulatory and financial strategic approaches to solutions

Accompanying therapy (AT) is vital for oncological patients as it allows to alleviate complications associated with both cancer and antitumor therapy. These complications include anemia, febrile neutropenia, nausea, and chronic pain syndrome. The problem is that many patients do not receive sufficient AT because of the lack of clinical guidelines and regulations. Currently, clinical guidelines only for anemia are approved and none for the other complications. The main barriers are the absence of legislative funding of AT and impossibility to obtain medications on the outpatient basis. The system of clinical-statistical disease groups also causes difficulties with payment for medical treatment. Low cost ratios and impossibility to combine AT payment with payment for the main therapy also limit its availability.To solve these problems, separate clinical guidelines for AT should be developed, tariffs for the clinical-statistical disease groups should be revised, and coefficients of treatment complexity should be increased for wider medication coverage.

Febrile neutropenia in patients with Duffy-null–associated neutrophil counts and multiple myeloma or AL amyloidosis

Febrile neutropenia in patients with Duffy-null–associated neutrophil counts and multiple myeloma or AL amyloidosis

Use of empegfilgrastim for primary prevention of febrile neutropenia in patients receiving myelosuppressive therapy. Experience of the Arkhangelsk Clinical Oncological Dispensary

Background. Granulocyte colony-stimulating factors (G-CSFs) are used in oncology practice for prevention of febrile neutropenia caused by cytotoxic chemotherapy. Despite the proven safety of G-CSFs use in randomized clinical trials and in real clinical practice, clinicians have questions about the tolerability of this group of drugs.Aim. To demonstrate the safety profile of a long-acting G-CSF produced in Russia which was used to prevent febrile neutropenia and maintain dose intensity of drug therapy in patients with various solid tumors undergoing chemotherapy at the Arkhangelsk Clinical Oncological Dispensary.Materials and methods. The retrospective analysis included patients with a confirmed diagnosis of malignant neoplasm who received various chemotherapy regimens that required the inclusion of G-CSF. For primary prevention of febrile neutropenia, patients were prescribed empegfilgrastim (Extimia®) at a dose of 7.5 mg subcutaneously once per course of chemotherapy.Results. Data of 151 patients were analyzed for the period from July 2021 to April 2023. The average age was 57 years (28–75). The group of elderly patients (over 65 years) consisted of 38 (25 %) patients. The majority of patients were diagnosed with breast cancer (56 (37 %) patients) and gastric cancer (37 (25 %) patients). The number of empegfilgrastim injections over the entire observation period was 773. Adverse reactions associated with the use of empegfilgrastim were registered in 13 (8.6 %) patients, the most common of which was grade 1–2 leukocytosis according to the CTCAE v.5 classification. One patient developed a serious adverse reaction: grade 4 neutropenia according to the CTCAE v.5 classification. A subgroup of patients with metastatic pancreatic cancer treated with FOLFIRINOX was analyzed separately to assess the relative dose intensity of the chemotherapy courses. Nine patients with metastatic pancreatic cancer received FOLFIRINOX therapy with a median of 8 (5–12) courses. A total of 69 chemotherapy cycles were administered to 9 patients with a median of 7.5 (2–13) cycles. The relative dose intensity of the chemotherapy courses was 83.71 ± 19.33.Conclusion. Empegfilgrastim has shown a favorable safety and tolerability profile in patients with various solid tumors in real-world clinical practice including the highly toxic FOLFIRINOX regimen.

DNA methylation inhibitors adverse reaction characteristic analysis: a descriptive analysis from WHO-VigiAccess.

DNA methylation inhibitors (azacitidine, decitabine) have revolutionized the treatment dilemma of myelodysplastic syndromes (MDS), a group of malignant hematopoietic disorders. This study evaluates the adverse drug reactions (ADRs) following the use of DNA methylation inhibitors in the World Health Organization (WHO) VigiAccess database and compares the characteristics of ADRs between the two drugs to select the drug with the minimum individualized risk for patients. This study employed a retrospective descriptive analysis method. We compiled ADR reports for two marketed DNA methylation inhibitors for the treatment of MDS from WHO-VigiAccess. Data collected included demographic data such as age groups, gender, and regions of global patients covered by ADR reports, as well as data on the disease systems and symptoms caused by ADRs recorded in the annual reports and reports received by WHO. By calculating the proportion of ADRs reported for each drug, we compared the similarities and differences in ADRs between the two drugs. Overall, 23,763 adverse events (AEs) related to the two DNA methylation inhibitors were reported in VigiAccess. The results showed that the top 10 most common AEs were febrile neutropenia, bone marrow suppression, neutropenia, anemia, pancytopenia, leukopenia, thrombocytopenia, bone marrow failure, agranulocytosis, and hematotoxicity. The top five common types of DNA methylation inhibitor AEs were blood and lymphatic system disorders (11,178 cases, 47.0%), cardiac organ diseases (1,488 cases, 6.3%), various congenital familial genetic diseases (49 cases, 0.2%), ear and labyrinth diseases (100, 4.2%), and endocrine system diseases (57, 2.4%). There is no Strong correlation between DNA methylation inhibitors and ADRs. Current comparative observational studies of these inhibitors show that there are common and specific adverse reactions in the ADR reports received by WHO for these drugs. Clinicians should improve the rational use of these drugs based on the characteristics of ADRs.

Efficacy of extended infusion of β-lactam antibiotics for the treatment of febrile neutropenia in haematologic patients (BEATLE): a randomised, multicentre, open-label, superiority clinical trial

ObjectivesThe efficacy of extended infusions (EI) of β-lactam antibiotics for optimising outcomes in febrile neutropenia is unclear. We assessed whether the administration of β-lactams was more effective in EI than in intermittent infusion (II) for the treatment of febrile neutropenia. MethodsWe performed a randomised, open-label, superiority clinical trial of patients with febrile neutropenia at four Spanish university hospitals. Patients undergoing haematopoietic stem cell transplantation or with acute leukaemia receiving chemotherapy who required empirical antibiotic treatment for febrile neutropenia were randomly assigned (1:1) to receive EI of β-lactam or II after a first dose in bolus. The choice of antipseudomonal β-lactam was left to the discretion of the attending physician. The primary endpoint was treatment success at day 5, defined as defervescence without modifying the antibiotic treatment. Secondary endpoints included adverse events, attainment of the pharmacokinetic/pharmacodynamic target of 50, 75 and 100%ƒuT>MIC, and 30-day mortality. ResultsBetween November 19, 2019 and June 22, 2022, 295 patients we screened for eligibility, of whom 150 were randomly assigned to receive EI (n=77) or II (n=73) of the antipseudomonal β-lactam of choice. In the intention-to-treat analysis, treatment success at day 5 was achieved in 39/77 patients (50.6%) receiving EI versus 46/73 patients (63.0%) receiving II (risk difference -12.4%; 95% confidence interval, -29.4 to 4.7, p=0.17). The pharmacokinetic/pharmacodynamic targets of 75 and 100% ƒuT>MIC for empirical treatment were achieved more frequently in the EI group. No statistically-significant differences were found between groups in terms of adverse events or 30-day mortality. ConclusionsOur findings do not support the routine use of empirical EI of β-lactams in febrile neutropenia. Further studies should consider the clinical heterogeneity of febrile neutropenia and focus on patients with sepsis/septic shock and microbiologically documented infections, particularly those with infections caused by microorganisms less susceptible to β-lactams.

Association between inappropriate empirical antimicrobial therapy and mortality in gram-negative bloodstream infections in patients with febrile neutropenia and hematological malignancy

Background and objectiveInappropriate initial antimicrobial therapy has been associated with high mortality in patients with gram-negative bacilli bloodstream infections during febrile neutropenia following chemotherapy for hematological malignancies. The aim of this study is to determine this association in our hospital. MethodsA single center, retrospective, cohort study of bloodstream infection due to gram-negative bacilli and febrile neutropenia was conducted. Clinical characteristics, microbiological etiology, antimicrobial resistance profile, empirical and targeted antibiotic therapy, intensive care unit admission, persistent bacteremia and mortality were analyzed. ResultsOf the 171 episodes of bloodstream infection due to gram-negative bacilli, empirical antimicrobial therapy was inappropriate in 43 episodes (25.1 %). There was a significant difference in mortality at 7 and 30 days between patients who received appropriate versus inappropriate empirical treatment (4.6 % versus 13.9 %, p = 0.04; 15.6 % versus 32.5 %, p = 0.016). Inappropriate empirical treatment (RR, 2.97 [95 % CI, 1.01–8.74]), shock at the time of febrile neutropenia diagnosis (RR, 6.5 [95 % CI, 1.83–23.05]) carbapenem-resistant microorganism (RR, 3.73 [95 % CI, 1.14–12.24]) and persistent bacteremia (RR, 84.6 [95 % CI, 11.3–629.4]) were associated with an increased mortality at 7 and 30 days. In the multivariate analysis, shock (RR, 4.85 [95 % CI, 2.10–11.65]) and persistent bacteremia was independently associated with increased 30-day mortality, but inappropriate empirical antimicrobial therapy was not an independent prognostic determinant (RR, 1.66 [0.53–4.82]). ConclusionShock at the time of febrile neutropenia diagnosis contributes to mortality in patients with gram-negative bacilli bloodstream infection, in this scenario, appropriate empirical antimicrobial therapy should be encouraged.

Perioperative chemotherapy and nivolumab in non-small-cell lung cancer (NADIM): 5-year clinical outcomes from a multicentre, single-arm, phase 2 trial

Perioperative immunotherapy improves short-term outcomes in resectable non-small-cell lung cancer (NSCLC). We now report 5-year survival from the NADIM trial to assess its long-term benefit. NADIM was a multicentre, single-arm, phase 2 trial conducted across 18 hospitals in Spain. Patients were aged 18 years or older, had an Eastern Cooperative Oncology Group performance status of 0 or 1, and had histologically or cytologically confirmed, treatment-naive, resectable stage IIIA NSCLC (American Joint Committee on Cancer, 7th edition criteria). The neoadjuvant treatment consisted of three cycles of intravenous paclitaxel (200 mg/m2) and carboplatin (area under the curve 6 mg/mL per min) with nivolumab (360 mg). After surgery, 1 year of adjuvant treatment with intravenous nivolumab monotherapy was administered (240 mg every 2 weeks for 4 months, followed by 480 mg every 4 weeks for 8 months). The primary endpoint was 24-month progression-free survival, with 5-year progression-free survival and overall survival as secondary endpoints, assessed in the intention-to-treat population (ie, all patients who received neoadjuvant treatment). Toxicity profile was also assessed as a secondary endpoint. This trial is registered at ClinicalTrials.gov (NCT03081689) and is complete; this is the final report of the trial. Between April 26, 2017, and Aug 25, 2018, 51 patients were assessed for eligibility, of whom 46 comprised the intention-to-treat population (34 [74%] male and 12 [26%] female, median age 63 years [IQR 58-70]). Follow-up was concluded at 60 months (data cutoff July 11, 2023; median follow-up 60·0 months [IQR 60·0-60·0]). 5-year progression-free survival in the intention-to-treat population was 65·0% (95% CI 49·4-76·9), and overall survival was 69·3% (53·7-80·6). Disease progression occurred in 11 (24%) patients; 14 (30%) patients died, including nine (20%) from disease relapse and five (11%) from non-tumour-related causes. Treatment-related adverse events (TRAEs) of grade 3 or worse occurred in 14 (30%) of 46 patients during neoadjuvant treatment and in seven (19%) of 37 during adjuvant treatment. The most common grade 3 or worse TRAEs were increased lipase and febrile neutropenia (three [7%] each) during neoadjuvant treatment, and elevated serum lipase (four [7%]) and elevated serum amylase (three [8%]) during adjuvant treatment. Serious TRAEs included elevated serum lipase and neutropenia (one [2%] each) during neoadjuvant treatment, and elevated serum lipase (one [3%]) during adjuvant treatment. No treatment-related surgery delays, deaths, or unexpected long-term toxicities were reported. Perioperative chemoimmunotherapy showed a promising long-term benefit with no concerning safety data, reinforcing its use in resectable stage IIIA NSCLC. Bristol-Myers Squibb, Spanish Ministry of Science, Instituto de Salud Carlos III, European Union.

CP1-2 Questionnaire on compliance with Febrile Neutropenia (FN) Guidelines 2nd ed. and risk-based patient selection for outpatient treatment in the 3rd ed.

CP1-2 Questionnaire on compliance with Febrile Neutropenia (FN) Guidelines 2nd ed. and risk-based patient selection for outpatient treatment in the 3rd ed.

The impact of admitting ward on resource utilization and outcomes among hospitalized cancer survivors.

36 Background: With improvements in both early detection and cancer treatment, there is a growing population of cancer survivors; with a corresponding increase in acute care use. However, models of inpatient care delivery for cancer survivors differ between hospitals and regions, which may impact resource use and outcomes. Understanding how different models influence outcomes may help define optimal models for cancer inpatient care delivery. Methods: We created a multicenter cohort of all cancer patients admitted to medical wards across 26 hospitals in Ontario, Canada from 2015 to 2022, and deterministically linked population level administrative data including ambulatory oncology data, with each hospital’s patient-level electronic information (pharmacy, orders, notes, labs/imaging and results). Multivariable regression models compared characteristics and outcomes between patients admitted on oncology wards vs non-oncology wards adjusting for age, sex, income quintile, rurality, immigrant status, receiving IV systemic therapy within 120 days and comorbidity scores. Results: In total, there were 370,118 hospitalizations from 191,990 unique patients. Among these hospitalizations, 38,075 episodes (10%) were on an oncology ward. Median time from cancer diagnosis to hospitalization was 4 years; 10% received IV systemic therapy within 120 days and 16% within 1 year. The most common disease sites were GU (21%), GI (20%), breast (12%) and lung (10%). The most common discharge diagnoses from oncology wards were inpatient chemotherapy (9%), febrile neutropenia (7%), NHL (4%), AML (4%), myeloma (3%); while for non-oncology wards were heart failure (5%), palliative care (4%), UTI (2%), pneumonia (2%), acute renal failure (2%). In general, cancer patients admitted on oncology wards were younger (64 vs 76), had shorter length of stay (LOS; 9.6 vs 10.1 days), less in-hospital mortality (8% vs 11%), greater 30-day re-admission rates (30% vs 15%) and were more likely to undergo CTs (28% vs 21%), MRIs (11% vs 9%) and interventional procedures (8% vs 6%) (p&lt;0.001, all). Subgroup analysis focusing on the top 5 discharge diagnoses from non-oncology wards, showed that despite no difference in in-hospital mortality rates (aOR 0.92 95% CI [0.58-1.46] p=0.73), admission to a non-oncology ward for those diagnoses was associated with shorter LOS (aOR 0.84 [0.78-0.90] p&lt;0.001), reduced 30-day re-admission rates (aOR 0.60 [0.48-0.75] p&lt;0.001), and reduced use of CTs (aOR 0.60 [0.49-0.74] p&lt;0.001), MRIs (aOR 0.36 [0.25-0.52] p&lt;0.001), and interventional procedures (aOR 0.43 [0.29-0.64] p&lt;0.001). Conclusions: There are differences in resource use and outcomes for cancer survivors hospitalized on oncology versus non-oncology wards, including for patients with the same discharge diagnosis. To optimize inpatient cancer care delivery for hospitalized cancer survivors, further exploration of care models is needed.

The impact of delayed versus early administration of granulocyte colony-stimulating factor following autologous hematopoietic stem cell transplantation on transplantation outcome.

Granulocyte colony-stimulating factor (G-CSF) is routinely administered after autologous hematopoietic stem cell transplantation (auto-HSCT) to decrease the duration of neutropenia and diminish the incidence of febrile neutropenia. Nevertheless, the most advantageous timeframe for administering G-CSF in the transplantation setting remains elusive. We conducted a cross-sectional study of 200 patients diagnosed with hematological malignancies who underwent auto-HSCT between July 2017 and January 2022. Patients were divided into two groups of 100 individuals based on the timing of G-CSF administration after auto-HSCT. In the first group, G-CSF was administered on post-transplantation day +1, while in the second group, G-CSF was administered on post-transplantation day +5. Patient demographics and clinical outcomes, including time to neutrophil engraftment, time to platelet engraftment, length of hospital stay, duration of fever, and incidence of bacterial and fungal bloodstream infections, were compared between the two groups. We identified a significantly shorter platelet engraftment time in the day +5 group than in the day +1 group (P<0.001), though the groups were similar regarding neutrophil engraftment time. The total number of G-CSF injections differed significantly according to the administration schedule. The number of red blood cells and length of hospital stay was greater in the day +1 group (all P<0.001). The incidence of bacterial and fungal bloodstream infections and duration of fever did not differ between the groups. Delayed administration of G-CSF on day +5 is as effective as early administration and can positively influence platelet engraftment, transfusion support, and hospitalization time.

1-Minute Pearls/Pitfalls for the Clinician

This article describes a few pearls/pitfalls pertinent to the management of neutropenic fever in immunocompromised patients and patients with subclinical hyperthyroidism

Chemotherapy-Induced Febrile Neutropenia Managed on an Outpatient Basis at the Pediatric Hematology and Oncology Department of the Ibn Sina Children’s Hospital in Rabat

Introduction: Febrile neutropenia (FN) is an important cause of morbidity and mortality in patients with cancer. The general objective of this study was to collect data and analyze the factors influencing management of the febrile neutropenia at the day hospital at the pediatric department of Hematology and Oncology (SHOP) of Rabat.