Febrile Neutropenia In Patients Research Articles

Interim results of a multicenter retrospective-prospective observational post-marketing study of Extimia® BIOCAD (INN: empegfilgrastim) to evaluate safety and efficacy in patients with lymphoproliferative diseases receiving cytotoxic therapy

Aim. To assess the efficacy and safety of using the drug Extimia BIOCAD (international nonproprietary name INN: empegfilgrastim) in order to reduce the frequency and duration of neutropenia, the frequency of febrile neutropenia (FN) and infections manifested by FN in patients with lymphoproliferative diseases receiving myelosuppressive therapy.
 Materials and methods. This publication presents the interim results of a multicenter retrospective prospective observational post-marketing study of the safety and efficacy of the drug Extimia BIOCAD (INN: empegfilgrastim) in patients with lymphoproliferative diseases receiving cytotoxic therapy (LEGERITY). The interim data analysis included 40 patients with lymphoproliferative diseases (Hodgkins lymphoma, diffuse large B-cell lymphoma, multiple myeloma, primary mediastinal large B-cell lymphoma, follicular lymphoma, chronic lymphocytic leukemia, splenic marginal zone lymphoma), who were treated in ten research centers of the Russian Federation (Moscow, St. Petersburg, regional clinics). The median age of patients was 48 (2172) years, 13/40 (32.5%) patients belonged to the older age group (60 years). Patients had functional status on the ECOG scale of 02 and received at least 2 chemotherapy injections against the background of prophylaxis with empegfilgrastim. Empegfilgrastim was administered at a dose of 7.5 mg subcutaneously once 24 hours after the end of the administration of cytotoxic chemotherapeutic agents. Primary endpoint: frequency of neutropenia 35 degrees of severity; secondary endpoints: frequency of FN; frequency of severe infections (34 stages); frequency of antibiotic prescription; relative dose intensity of therapy of the conducted chemotherapy courses; the incidence of all adverse reactions in patients who received at least one dose of the study drug empegfilgrastim; the incidence of all serious adverse reactions in patients who received at least one dose of the study drug empegfilgrastim; the incidence of CTCAE 5.0 grade 34 HP in patients who received at least one dose of the study drug empegfilgrastim; discontinuation rate of study drug empegfilgrastim due to adverse reactions.
 Results. The results of this study demonstrate that the incidence of neutropenia of 3 degree of severity after the 1st cycle of chemotherapy developed in 2/40 patients (5%) and as a result of high-dose therapy (R-DHAP). Neutropenia of any severity was reported in 5/40 patients (12.5%). Cases of FN development have not been registered. Severe infections (mucositis, enteropathy, pneumonia, etc.), as well as the use of antibacterial and antifungal drugs during 1 cycle of chemotherapy and in the inter-course period after 1 cycle of therapy were not recorded in any patient. The next course of myelosuppressive therapy was not delayed due to the development of neutropenia in any of the patients during the study. Adverse events, according to the researcher, associated with the use of empegfilgrastim, were registered in 2/40 patients (5%): moderate generalized pain syndrome (diffuse pain) of 1 severity and in one case ossalgia of 2 severity. No serious adverse reactions were reported.
 Conclusion. The results of the interim analysis of the study demonstrate the high efficacy of the first Russian original pegylated granulocyte colony-stimulating factor empegfilgrastim after a single administration of a fixed dose in the treatment of patients with aggressive and indolent lymphomas. The drug has a favorable tolerance profile in any age group of patients, especially in elderly patients. Administration of empegfilgrastim as a prophylaxis of neutropenia in patients with lymphoproliferative diseases receiving myelosuppressive therapy of varying intensity can reduce the burden on medical personnel, improve patient adherence to treatment, and contribute to the implementation of the therapeutic plan.

Utility of Panfungal PCR in the diagnosis of invasive fungal infections in febrile neutropenia.

Background:The prevalence of invasive fungal infections (IFIs) is increasing due to the increasing population of immunocompromised patients. Fungal culture is the gold standard for diagnosis but not sensitive and the turnaround time is long. Samples for histopathology are difficult to obtain because of profound cytopenias. We conducted this study with the aim to evaluate panfungal PCR for the diagnosis of IFIs in patients of febrile neutropenia.Methods:This was a single-centre, cross-sectional observational study. Patients of febrile neutropenia suspected of having IFI were included in the study. Panfungal PCR was performed on the blood of included patients along with other investigations for diagnosis of IFI. The sensitivity, specificity, positive predictive value, and negative predictive value of panfungal PCR were calculated using EORTC/MSG 2008 criteria as the gold standard.Results:Fifty patients of febrile neutropenia were included in the study, of which 52% were diagnosed positive by panfungal PCR assay. The sensitivity, specificity, positive predictive value, and negative predictive value of panfungal PCR assay was found to be 82.76%, 90.48%, 92.31% and 79.17% respectively.Conclusion:Panfungal PCR is a promising and highly sensitive diagnostic test for screening at-risk patients suspected to have IFIs. The use of panfungal PCR assay in combination with other diagnostic modalities and clinical judgment can be very helpful in the early diagnosis of IFI.

The Impact of Modifying Empirical Antibiotic Therapy Based on Intestinal Colonization Status on Clinical Outcomes of Febrile Neutropenic Patients.

BackgroundThis paper aimed to inspect factors affecting febrile neutropenia patients with hematologic malignancies. The intestinal colonization rate of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) and carbapenem-resistant Enterobacteriaceae (CRE) was assessed. The rate of subsequent ESBL-E and CRE bacteremia correlated with corresponding bacterial colonization was evaluated. Further, the risk factors for ESBL-E and CRE intestinal colonization were examined. Finally, the impact of rectal swab screening combined with adapted empirical antibiotic therapy on the mortality rate of patients with febrile neutropenia was assessed.Materials and MethodsFebrile neutropenia patients underwent rectal swabs and collection of blood culture specimens upon admission. Empirical treatment was subsequently modified according to rectal swab results if necessary. Bacteremia patients were treated according to blood culture results. Explorative forward-stepwise logistic regression analyses were used to identify risk factors for ESBL-E and CRE fecal carriage and mortality.ResultsIn total, 201 rectal swabs and 402 blood samples were collected from 163 patients during 201 febrile neutropenia episodes. Of these episodes, 38 (18.90%) were colonized with ESBL-E and 30 (14.92%) with CRE. Bloodstream infections developed in 29/201 (14.42%) episodes. Only bacteremia episodes caused by Gram-negative bacilli were included in our analysis. The development of Gram-negative-rod bacteremia was observed in eight out of 38 (21.05%) ESBL-E colonized episodes and four out of 30 (13.33%) CRE-colonized episodes. A BSI developed in three out of 38 (7.89%) ESBL-E colonized episodes, and two out of 30 (6.66%) CRE-colonized episodes developed BSI with the respective organism. Multivariate analysis identified previous quinolone use as the only independent risk factor for fecal colonization of multi-drug-resistant (MDR) Enterobacteriaceae (ESBL-E and CRE) (odds ratio, 17.09; 95% confidence interval, 5.29 - 55.18; P <0.0001). No significant association was observed between ESBL-E and CRE carriage and increased risk of developing subsequent bacteremia. No significant differences were detected between groups receiving modified and non-modified treatments in duration of hospitalization or antibiotic therapy (univariate analysis) and 28-day mortality rate (logistic regression).ConclusionQuinolone exposure was a major risk factor for ESBL-E and CRE fecal carriage. Performing rectal swab screening for MDR Enterobacteriaceae and modifying empirical antibiotic therapy accordingly did not improve clinical outcomes of febrile neutropenia patients.

92. Utility of Sinus CT in the Evaluation of Patients with Febrile Neutropenia

BackgroundThe etiology of febrile neutropenia in patients with hematological malignancy is identified in only 20–30% of cases. Sinus computed tomography (CT) is often used, regardless of symptoms, to rule out rhinocerebral source of infection. There are no clear guidelines on when to perform sinus CT in this population. In this study, we evaluated the role of sinus CT in febrile neutropenic patients.MethodsWe retrospectively reviewed medical records of all adults (age ≥18 years) with febrile neutropenia (T≥ 38.3ºC, ANC < 0.5 x 109/L) and hematological malignancies who underwent sinus CT from January 2014 to May 2020. We present the preliminary analysis of the impact of sinus CT findings on the management of febrile neutropenia.Results47 patients with a total of 56 episodes of febrile neutropenia met the inclusion criteria. The median age at presentation was 57 years (IQR: 42 - 68 years). The most common underlying malignancy was acute myeloid leukemia (51%), followed by myelodysplastic syndrome (19%). At presentation, 47% had refractory disease, 21% were newly diagnosed, 15% had relapsed, 15% were in complete remission, and 2% were in partial remission. Of the total 56 episodes, 29 (52%) had symptoms of rhinorrhea (20%), facial pain (14%), and sinus congestion (14%). The remaining 27 of 56 episodes (48%) had no sinus symptoms. Sinus CT was abnormal in 48 of 56 episodes (86%); the most common finding was mucosal thickening (47/48; 98%), followed by air-fluid levels (7/48; 14.5%), partial opacification (6/48; 12.5%), complete opacification (2/48; 4%), and bony invasion (2/48; 4%). The source of febrile neutropenia was attributed to the CT sinus findings in 9 cases (9/48; 29%), leading to a change in therapeutic management. All 9 patients were symptomatic, with evidence of necrosis in 22% (2/9) and purulence in 22% (2/9) on nasal endoscopy.Table 1 ConclusionMucosal thickening is a frequent and non-specific imaging finding, particularly in patients without sinus symptoms. Sinus CT findings in patients with febrile neutropenia without sinus symptoms had no impact on clinical management. Consequently, sinus CT may be reserved for patients presenting with sinus symptoms.Disclosures M. Rizwan Sohail, MD, Aziyo Biologics (Consultant)Medtronic Inc (Consultant, Research Grant or Support)

1107. Third Generation Cephalosporins Monotherapy Experience in Pediatric Patients with High-Risk Febrile Neutropenia

BackgroundFever during neutropenia is common in children with cancer. The updated guidelines recommend empirical antibiotic monotherapy using an antipseudomonal ß-lactam, a fourth generation cephalosporin or a carbapenem for high-risk febrile neutropenia. However, local epidemiology and resistance patterns should be evaluated regularly. In our hospital there are not Pseudomonas aeruginosa isolates in oncology pediatric patients, therefore, we use ceftriaxone as monotherapy in high risk febrile neutropenia without other risk factors. The goal of our investigation is to describe the experience of using third generation cephalosporins in these patients.MethodsDescriptive study of high-risk febrile neutropenia episodes in patients admitted to the Pediatric Oncology Unit of Hospital Dr. Sótero del Río, Santiago, Chile. We included patients ≤15 years from June 2016 until December 2019.ResultsWe found 140 episodes in 53 patients, 42 (79%) were leukemia and 11 (21%) solid tumor patients. Of the 140 episodes, 97 (69%) had clinical signs at admission, mostly respiratory in 48 (49%) of the cases. Ninety one (65%) cases started ceftriaxone at admission, 27 (30%) maintained ceftriaxone for 7 days of treatment. Sixty four (70%) cases changed treatment: 38/64 (42%) started second line antibiotics for clinical worsening, 19/64 (20%) required second and third line antibiotics for persistent fever and clinical worsening, and 7/64 (8%) received third line antibiotics from the start for past microbiological history. Eighteen (13%) cases evolved with sepsis requiring intensive care unit management.We had 32 (23%) episodes with positive blood culture, 13 (41%) due to gram positive bacteria, 16 (50%) gram negative bacteria, and 3 (9%) cases of fungal infections. Of the gram negative bacteria, 7 (44%) were ESBL producers, without Pseudomonas aeruginosa isolates.One case died (0.7%) for refractory sepsis due to gram negative bacteria.ConclusionMonotherapy with ceftriaxone is not a good option as initial therapy for high risk febrile neutropenia patients due to the spread of ESBL strains. The empiric therapy has to be evaluated regularly and should always be based in local epidemiology.Disclosures All Authors: No reported disclosures

Change in Body Weight and Serum Albumin Levels in Febrile Neutropenic Lung Cancer Patients.

Although advances have been made in the treatment and prevention of febrile neutropenia (FN) in cancer patients treated with chemotherapy, it is still a complication that requires clinical attention. Impaired nutritional status in patients who develop FN can affect the continuation of cancer treatment, but it has not been investigated. We conducted a retrospective longitudinal study in order to clarify (1) if body weight and serum albumin levels change in lung cancer patients who do and do not develop FN, and (2) if these indicators are more likely to worsen in patients with FN than in patients without FN. Patients undergoing cytotoxic chemotherapy between January 2011 and June 2020 were consecutively included in the study. Changes in body weight and serum albumin levels were investigated in a case–control study of patients with FN, and control patients without FN who were matched by age, gender, histopathology, and stage of lung cancer, at a ratio of 1:2. During the study period, 226 patients received cytotoxic chemotherapy. Among those, 33 (14.6%) patients developed FN during the first course of cytotoxic chemotherapy. We found a more pronounced decrease in both body weight and serum albumin level at four weeks after the initiation of chemotherapy in FN patients. In order to safely administer effective chemotherapy, medical staff need to pay close attention to the nutritional status of patients receiving chemotherapy.

Predictive Factors of Severe Adverse Events in Pediatric Oncologic Patients with Febrile Neutropenia.

Objectives:Febrile neutropenia (FN) is severe and potentially life-threatening in oncologic patients. The objective of this study is to define the factors associated with severe adverse outcomes of pediatric FN. Methods:A retrospective and prospective descriptive study performed in pediatric patients diagnosed with FN at King Chulalongkorn Memorial Hospital from January 2013 to December 2017. Severe adverse events defined as the presence in one of these following oxygen therapies, mechanical ventilator, shock, admission to ICU, renal dysfunction, and liver dysfunction. Results:The study included 267 patients with 563 febrile neutropenia episodes. The median (range) age was 5.1 years (1 month-15 year). Among 563 febrile neutropenia episodes, 115 episodes (20%) developed severe adverse events. The FN patients were classified into low and high-risk groups, 91% of patients with severe adverse events and all 21 patients who died were in high risk group. The overall mortality rate was 3.1%. Factors associated with severe adverse events were fungal infection (aOR 6.51, 95%CI 2.29-18.56), central venous catheter insertion (aOR 4.28, 95% CI 2.51-7.29), CPG defined high risk (aOR 3.35, 95%CI 1.56-7.17), viral infection (aOR 2.72, 95%CI 1.05-7.06), lower respiratory tract infection (aOR 2.52, 95%CI 1.09-5.82) and treatment not according to CPG (aOR 2.47, 95% CI 1.51-4.03). Conclusions:Fungal and viral infection, central venous catheter insertion, lower respiratory tract infection, CPG defined high risk and treatment not according to CPG were associated factors of increased risk for severe adverse events. Our current institutional CPG for FN in children was applicable and improved clinical outcomes for this group of patients.

Reduction of febrile neutropenia by using long-acting granulocyte colony-stimulating factors in patients with solid tumors receiving every-2-week chemotherapy

Neutropenia is a common hematological complication of chemotherapy (СT). The number of studies showed that the underperformance of the treatment program due to the development of this type of hematological toxicity could lead to the decrease in therapy efficacy and to the increase in cancer mortality. Infections that occur as a result of prolonged neutropenia are extremely dangerous. The most severe manifestation of grade 4 neutropenia is febrile neutropenia (FN), which can lead to death from severe infections. Such patients should be immediately hospitalized and should receive empirical therapy with broad-spectrum antibiotics. The costs, associated with the hospitalization, due to FN increase total cost of cancer patients treatment. The application of recombinant forms of the natural protein granulocyte colony-stimulating factor (G-CSF) in clinical practice has solved the number of important problems on that front. The clinical studies and common use show that primary and secondary prevention using recombinant G-CSF reduces the risk of FN development and improves the results of the treatment of malignancies. The review provides actual data concerning pharmacological properties, clinical efficacy and reasonable use of G-CSF with prolonged action to prevent FN in patients with solid tumors during 2-week CT cycles. Special attention is paid to CH regimens with the inclusion of 5-fluorouracil, oxaliplatin, irinotecan in the treatment of colorectal cancer (CRC). The use of neoadjuvant treatment in such patients allows to achieve resectability of the tumor and to perform radical surgery. The maintenance of drugs dose intensity throughout the cycle of CT plays an important role in achieving the treatment success. Therefore, the prevention of CT-induced severe neutropenia and FN is especially important in patients who are the candidates for surgical treatment. The results of some studies confirm the necessity of using G-CSF with prolonged action during 2-week CT cycles in patients with CRC.

Bacteriological Spectrum and Antimicrobial Sensitivity of Pathogens in Children with Hematologic Malignancies and Febrile Neutropenia Research

Objectives: This study aimed to investigate the spectrum of bacterial pathogens and their antimicrobial sensitivity in pediatric patients admitted with febrile neutropenia (FN) and hematologic malignancies. Methods: This prospective, cross-sectional study was carried out on 65 children (60% boys, mean age 7.3 5.3 years) with hematologic malignancies and FN hospitalized at the Amir Hematology and Oncology Hospital, Shiraz, Iran, between December 2018 and May 2019. Samples were taken from blood, nose, axilla, and inguinal area (NAI). NAI cultures were repeated after 72 hours of admission, and blood culture was repeated if needed. A demographic questionnaire on age, sex, and admission time was filled out for each patient. Results: The most common grown bacteria in the NAI samples were coagulase-negative staphylococci (CoNS). Second cultures from these sites revealed nosocomial contamination. Eighteen patients (27.7%) had positive blood cultures, with 61.1 % of the isolated pathogens being Gram-negative (mostly Escherichia coli and Pseudomonas aeroginosa) and 38.9% Gram-positive. The blood cultures results did not match those of the NAI cultures in 61.1% of the patients. About one-fourth of the Gram-negative pathogens isolated from blood were resistant to cefepime, the main empirical antibiotic for FN management at our center. Conclusions: Gram-negative bacteria are predominant organisms in pediatric FN patients at our center, most resistant to cefepime. If a similar antimicrobial sensitivity pattern is observed in future studies, a change in local guidelines might be considered for FN management.

Surveillance Stool Culture and its Association with Microbiologically Documented Infection During Febrile Neutropenia in Patients with Acute Leukemia (AL) Undergoing Induction Chemotherapy.

The study aimed at identifying the profile of gut colonization of patients with acute leukemia who underwent induction chemotherapy and its association with induction events and outcome. Baseline bacterial stool culture with resistance pattern of isolates were recorded. Multi-drug resistance was defined as resistance to at least two antibiotic classes including beta lactam and fluoroquinolones. During induction chemotherapy, blood and clinically indicated cultures were taken during febrile neutropenic episodes. Association studies were done between gut colonization and induction events/outcome. Among 109 patients enrolled, 71 (65.13%) patients undergoing induction chemotherapy were colonized with bacteria, with nearly 50% of colonizers harboring multi-drug resistant bacteria. Organisms isolated from stool pre-induction were mostly gram negative (98%), with Escherichia coli and Klebsiella pneumoniae being the commonest. 65.13% patients developed febrile neutropenia. Overall multi-drug resistant positivity during febrile neutropenia was 70.14%. Concordance of 8.45% was observed between isolates from stool and organisms isolated from cultures during febrile neutropenia. There were significant proportion of gut colonized gram-negative multi-drug resistance bacteria among patients with acute leukemia. There was a low concordance rate between baseline stool isolates and subsequent cultures during the induction. There was no significant association between gut colonization and induction events/outcomes studied.

Detailed Assessment of Blood Culture and Clinical Factors in Febrile Neutropenia Patients with High-Risk Hematological Malignancy in Japan: A Subgroup Analysis of the Cedmic Trial

Background: During chemotherapy for hematological malignancies, febrile neutropenia (FN) is a frequent and serious complication. The causative organisms of FN vary from era to era and depending on bacterial resistance in each country. Therefore, epidemiological data are required for each era and country from prospective large clinical trials. We previously reported a prospective clinical trial indicating the importance of the D-index, a measure of neutropenia severity (CEDMIC trial, J Clin Oncol. 2020 10; 38: 815). We hypothesized that analyzing these data would provide accurate contemporary epidemiological data for hematological malignancies. Furthermore, as encountered in practice, we suspected that gram-negative (GN) bloodstream infections (BSIs) are more common at high body temperatures (BTs) than at low BTs and examined the relationship between causative bacteria and BT. Patients and Methods: Between June 2013 and April 2017, we enrolled patients with hematological malignancies aged 16-79 years post-chemotherapy or -stem cell transplantation (SCT) with expected neutropenia durations &amp;gt;7 days. Neutrophil counts &amp;lt;500/mL reflected neutropenia, and all fevers had axillary temperatures ≥37.5°C. Prophylactic antibiotics (Abx) were drugs administered post-chemotherapy and pre-FN onset. The FN incidence and blood culture (BC) positivity rate were examined in 4 treatment groups: allogeneic SCT (Allo-SCT), autologous SCT (Auto-SCT), induction chemotherapy for acute leukemia, and other treatments. Results: In total, 423 patients were enrolled, and 413 (median age: 56 years) were included in the intention-to-treat analyses (Table 1). The treatments included induction chemotherapy (n=67), Allo-SCT (n=106), Auto-SCT (n=158), and others (n=82). Prophylactic Abx were administered in 281 (68.5%) patients (only quinolone, n=222; with β-lactam, n=59). Prophylaxis rates were significantly higher in the Allo-SCT (n=94, 88.7%, p&amp;lt;0.001) and induction chemotherapy (n=49, 73.1%, p&amp;lt;0.017) groups. FN occurred in 356/413 patients (86.4%, Table 1). The Allo-SCT group had a higher FN incidence than that in the other treatments group (93.4% vs. 72%, p&amp;lt;0.001). D-indices ≥5500 and &amp;lt;5500 were associated with FN incidences of 100% and 81.8%, respectively (p&amp;lt;0.001). Prophylaxis did not reduce the FN incidence. In total, 1272 BC sets were collected from 356 patients with FN. At FN onset, BCs were collected from 346 patients; 72 (20.8%) were positive (Table 2). Among initial BCs, 46 (63.9%) harbored gram-positive (GP) and 28 (38.9%) harbored GN bacteria. Three patients had multiple bacterial infections. The 2 most frequent GP bacteria were coagulase-negative Staphylococcus (n=21, 44.7%) and viridans streptococci (n=14, 29.8%). The 3 most frequent GN bacteria were Escherichia coli (n=13, 44.9%), Klebsiella pneumoniae (n=4, 13.8%), and Pseudomonas aeruginosa (n=4, 13.8%). Among initial BCs, prophylactic Abx use did not reduce BC positivity. However, the GN BSI incidence was significantly lower in the prevention group vs. non-prevention group (23.8% vs. 56.7%, p=0.007). Among patients who received prophylactic β-lactam, GN BSIs did not occur. Maximum BTs (maxBTs) were significantly higher in patients with positive BCs than negative BCs (38.4°C vs. 38.0°C, p&amp;lt;0.001). The BTs associated with GN BSIs were significantly higher than those associated with negative BCs and GP BSIs (38.7°C vs. 38.0°C vs. 38.2°C, p&amp;lt;0.001, Figure 1). The maxBTs and BC positivity rates were strongly related (Table 3). The BC positivity rates were significantly higher in patients with BTs ≥38°C vs. &amp;lt;38°C (26.5% vs. 14.5%, p=0.008), 38.5°C vs. &amp;gt;38.5°C/&amp;lt;38.5°C (39.7% vs. 15.3%, p&amp;lt;0.001), and ≥39°C vs. &amp;lt;39°C (52.6% vs. 16.9%, p&amp;lt;0.001). Among patients who did not receive prophylactic Abx (n=106), the GN BSI positivity rate was significantly lower in patients with maxBTs &amp;lt;38°C vs. ≥38°C (14.3% vs. 76.2%, p=0.007). Conclusion: In FN patients with high-risk hematological malignancies in Japan, the frequency of GP BSIs is high. Prophylactic Abx use reduces the GN BSI risk but not the FN or BSI risk. Fever severity and BC positivity at FN onset are strongly associated. The BTs of patients with GN BSIs are high. Disclosures Kanda: Astellas Pharma: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; Meiji Seika Kaisha: Honoraria; Merck Sharp &amp; Dohme: Honoraria; Pfizer: Honoraria, Research Funding; Shionogi: Research Funding; Celgene: Honoraria; Sumitomo Dainippon Pharma: Honoraria; Eisai: Honoraria, Research Funding; Novartis: Honoraria; Kyowa Kirin: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria; Takeda Pharmaceuticals: Honoraria; Alexion Pharmaceuticals: Honoraria; Shire: Honoraria; Daiichi Sankyo: Honoraria; Ono Pharmaceutical: Honoraria; Nippon Shinyaku: Honoraria, Research Funding; Mochida Pharmaceutical: Honoraria; Otsuka: Honoraria, Research Funding; Chugai Pharma: Honoraria, Research Funding; Janssen: Honoraria; Mundipharma: Honoraria. Kimura:Takeda Pharmaceuticals: Honoraria; Astellas Pharma: Honoraria; Pfizer: Honoraria; Sumitomo Dainippon Pharma: Honoraria; Merck Sharp &amp; Dohme: Honoraria; Nippon Kayaku: Honoraria; Kyowa Hakko Kirin: Honoraria; Ono Pharmaceutical: Honoraria; Celgene: Honoraria; Asahi Kasei: Honoraria. Oyake:Astellas Pharma: Honoraria; Bayer: Research Funding; Chugai Pharma: Honoraria, Research Funding; Celgene: Honoraria; Kyowa Hakko Kirin: Honoraria, Research Funding; Sumitomo Dainippon Pharma: Honoraria; Bristol-Myers Squibb Japan: Honoraria; Pfizer: Honoraria; Sionogi: Research Funding. Tamura:Asahi Kasei: Honoraria; Ono Pharmaceutical: Honoraria; Eisai: Honoraria; Kyowa Hakko Kirin: Honoraria.

Protein Energy Malnutrition Significantly Increases Mortality and Adverse Outcomes in Acute Myelogenous Leukemia (AML) Patients with Neutropenic Fever: Findings of a Nationwide Inpatient Sample Analysis

Introduction: Neutropenic fever is a major cause of morbidity and mortality in all malignancies, especially acute leukemia. Protein energy malnutrition (PEM) is also a well-established risk factor for overall cancer related mortality. Acute myelogenous leukemia (AML) patients are frequently afflicted with neutropenic fever due to protracted neutropenia and community acquired, nosocomial, and opportunistic infections. They are also commonly malnourished due to poor oral intake, cachexia from underlying disease, and the toxicity of chemotherapy. To date, few studies have attempted to link neutropenic fever and PEM outcomes in AML. We thus aim to explore the prevalence and outcome of PEM in patients with AML and neutropenic fever. Methods: The Nationwide Inpatient Sample (NIS) database for 2016 and 2017 was searched for patients with primary discharge diagnosis of AML who had NF. This group was divided based on the presence or absence of PEM. The primary outcome was a comparison of inpatient mortality between the groups. Secondary outcomes included diagnosis of sepsis, mean total hospital charges (THC) and mean length of hospital stay (LOS). Outcomes were compared using multivariate regression analysis adjusting for sociodemographic and hospital characteristics and Charlson comorbidity index as a marker of severity. Results: A total of 10145 admissions met the inclusion criteria with AML and NF. Among the included patients, 1700 (16.7%) had PEM. Patient with PEM were significantly older (58.1 vs 55.2 years of age, p&amp;lt;0.001) but had no significant difference in sex (52.0 vs 55.0% females, p=0.308) and racial distribution, compared with patients without PEM. Overall, 825 (8.1%) hospitalizations had inpatient mortality. Patients with PEM had significantly higher adjusted odds ratio (aOR) of mortality (aOR: 2.00, 95% CI 1.335 - 2.998), developing sepsis (aOR: 2.06, 95% CI 1.514 - 2.812), as well as increase mean difference in LOS(8.6 days, 95% CI 5.77 - 11.37) and THC (105,600 USD 95% CI 57,000 - 154,000), compared to patients without PEM. Conclusion: PEM is associated with a significantly adverse outcome in patients with febrile neutropenia-- an almost double mortality rate and increased risk of complications like sepsis, increased LOS, and hospital costs. Neutropenic patients are markedly susceptible to fulminant systemic infections from various sources. PEM furthers this risk via weakening of host defenses including natural barriers and both innate and acquired immunity. Furthermore, in neutropenic patients with systemic infections, malnutrition may delay and impede wound healing along with immune responses which often contributes to a protracted course and adverse outcome. Nutrition in neutropenia has garnered limited attention, with some randomized trials showing limited to no benefit of the "neutropenic diet" in patients while depriving them of essential macro- and micronutrients. Nonetheless, current management guidelines for malnutrition in malignancies, particularly acute leukemias, are sparse. The profound impact of malnutrition in febrile neutropenia patients warrants further study, and we thus recommend further attention to screening practices and management strategies alongside primary treatment for malignancy and infection. Disclosures No relevant conflicts of interest to declare.

Protecting high-risk oncology patients during the pandemic of COVID-19 by creating an outpatient cancer clinic for febrile neutropenia (California clinic).

191 Background: Delivering care for vulnerable cancer patients during a pandemic is challenging given the competing risks of death from cancer versus the high case fatality rates from SARS-COV-2 (CV-19). Data currently available suggests a total fatality rate close to 30%-50% with CV-19 in active malignancy patients. In addition to adapting guidelines from national organizations to reduce the social footprint of patients in order to minimize risk of exposure of CV-19, our cancer center implemented an isolated clinic with personal protective equipment (PPE) and direct access to a CV-19 rule out floor (if admission warranted) in order to manage those with febrile neutropenia (FN) who otherwise would have been triaged to the emergency room (ED). Methods: We implemented an outpatient isolated extended hour clinic with access to PPE, blood work, intravenous antibiotics and fluids for FN patients as a pilot project from mid-April with expected duration during the pandemic with the aim to decrease the ED admissions for FN by 50%. We used the Multinational Association of Support Care in Cancer (MASCC) validated tool to assist with outpatient versus inpatient management of these patients. All patients were screened via polymerase chain reaction nasal swab for CV-19 to identify CV-19 in a high-risk population. Our PDSA (Plan Do Study Act) cycles have been in 2-week sessions with constant re-education to multiple providers. Results: Prior to CV-19, our databases show an approximate 15 to 20 FN hematology and oncology patients per month who are triaged to ED during the business hours. Since the implementation of our clinic in the last 45 days, we have screened 8 patients, of which 2 were discharged home with oral antibiotics on isolation until CV-19 testing returned, 6 were directly admitted to CV-19 rule out floor avoiding ED. Our overall patient numbers were low during the peak of the pandemic and we expect to see increasing number of patients utilizing the clinic over the next few months. Conclusions: Implementing the California clinic has thus far successfully decreased the social footprint of our highest-risk cancer patients, those with FN, in hopes of decreasing their possible exposure to CV-19 as well as the unnecessary exposure of the clinical personnel. [Table: see text]

Febrile neutropenia in patients with acute myeloid leukemia: Outcome in relation to qSOFA score, C-reactive protein, and blood culture findings.

To evaluate quick Sequential Organ Failure Assessment (qSOFA) score during febrile neutropenia (FN) in adult patients receiving intensive chemotherapy for acute myeloid leukemia (AML). qSOFA score, as well as the association of qSOFA score with ICU admission, infectious mortality, blood culture findings, and C-reactive protein (CRP) measurements during FN were assessed among 125 adult AML patients with 355 FN periods receiving intensive chemotherapy in a tertiary care hospital from November 2006 to December 2018. The multivariate model for qSOFA score≥2 included CRP≥150mg/L on d0-2 [OR 2.9 (95% CI 1.1-7.3), P=.026], Gram-negative bacteremia [OR 2.7 (95% CI 1.1-6.9), P=.034], and treatment according to AML-2003 vs more recent protocols [OR 2.7 (95% CI 1.0-7.4), P=.047]. Age or gender did not gain significance in the model. qSOFA score≥2 was associated with ICU treatment and infectious mortality during FN with sensitivity and specificity of 0.700 and 0.979, and 1.000 and 0.971, respectively. qSOFA offers a useful tool to evaluate the risk of serious complications in AML patients during FN.

Patient Outcomes With Febrile Neutropenia Based on Time to Antibiotics in the Emergency Department.

Although bacteremia in pediatric oncology patients with febrile neutropenia (FN) is not uncommon, sepsis and mortality are rare. Because of the lack of clinically meaningful decision tools to identify high-risk patients with bacteremia, time to antibiotic administration (TTA) is increasingly considered an important quality and safety measure in the emergency department. Because little evidence exists suggesting that this benchmark is beneficial, we sought to determine whether TTA of 60 minutes or less is associated with improved outcomes. We retrospectively reviewed patients presenting to a pediatric emergency department with FN from November 2013 to June 2016. Clinical outcomes including mortality, pediatric intensive care unit admission, imaging, fluid resuscitation of 40 mL/kg or greater in the first 24 hours, and length of stay were compared between TTA of 60 minutes or less and more than 60 minutes. One hundred seventy-nine episodes of FN were analyzed. The median TTA was 76 minutes (interquartile range, 58-105). The incidence of bacteremia was higher in patients with TTA of more than 60 minutes (12% vs 2%, P = 0.04), but without impact on mortality, pediatric intensive care unit admission, fluid resuscitation, or median length of stay. The median TTA was not different for those who were and were not bacteremic (91 vs 73 minutes, P = 0.11). Time to antibiotic administration of more than 60 minutes did not increase mortality in pediatric oncology patients with FN. Our study adds to the existing literature that TTA of 60 minutes or less does not seem to improve outcomes in pediatric FN. Further larger studies are required to confirm these findings and determine which features predispose pediatric FN patients to morbidity and mortality.

Machine learning improves the prediction of febrile neutropenia in Korean inpatients undergoing chemotherapy for breast cancer

Febrile neutropenia (FN) is one of the most concerning complications of chemotherapy, and its prediction remains difficult. This study aimed to reveal the risk factors for and build the prediction models of FN using machine learning algorithms. Medical records of hospitalized patients who underwent chemotherapy after surgery for breast cancer between May 2002 and September 2018 were selectively reviewed for development of models. Demographic, clinical, pathological, and therapeutic data were analyzed to identify risk factors for FN. Using machine learning algorithms, prediction models were developed and evaluated for performance. Of 933 selected inpatients with a mean age of 51.8 ± 10.7 years, FN developed in 409 (43.8%) patients. There was a significant difference in FN incidence according to age, staging, taxane-based regimen, and blood count 5 days after chemotherapy. The area under the curve (AUC) built based on these findings was 0.870 on the basis of logistic regression. The AUC improved by machine learning was 0.908. Machine learning improves the prediction of FN in patients undergoing chemotherapy for breast cancer compared to the conventional statistical model. In these high-risk patients, primary prophylaxis with granulocyte colony-stimulating factor could be considered.

The Diagnostic Utility and Clinical Implications of Bronchoalveolar Lavage in Cancer Patients With Febrile Neutropenia and Lung Infiltrates.

IntroductionFebrile neutropenia (FN) is a dreaded complication of cancer chemotherapy and frequently associated with respiratory infections. Flexible bronchoscopy (FB) serves as a useful diagnostic tool in this regard.ObjectiveTo determine the diagnostic yield, safety and clinical implications of bronchoalveolar lavage (BAL) in cancer patients with FN, having lung infiltrates on radiographic chest imaging.MethodsWe reviewed medical records of FN patients who underwent FB at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, from July 2015 till July 2018. The culture yield of BAL, resultant change of management and outcome over the subsequent 30 days were retrospectively analysed. Statistical Package for Social Sciences (SPSS) version 20 (IBM Corp., Armonk, NY) was used for data analysis.ResultsNinety FN patients, with mean age 26 ± 18 years and predominantly males (65.6%, n = 59) were included in the study. Seventy-seven (85.6%) had hematological and 13 (14.4%) solid organ malignancy. The mean absolute neutrophil count was 0.20 +/- 0.36/ µL. BAL cultures were diagnostic in 40 (44%) patients; the etiology was bacterial, fungal and mixed in 25 (62.5%), 14 (35%) and one (2.5%) patient, respectively. All patients were on empirical antibiotics prior to bronchoscopy: 32 (35.6%) on antibacterial alone and 58 (64.4%) on antibacterial plus antifungal therapy. Change of management occurred in 51 (56.7%) patients after BAL results, including de-escalation from dual antibiotics in 28 (55%) and initiation of new culture sensitive antibiotic in 23 (45%). FB-associated complications developed in three (5.6%) non-intensive care patients (ICU), including transient hypoxia in two and minor hemoptysis in one patient, while five (14.8%) mechanically ventilated patients in ICU experienced worsening of oxygenation parameters within 48 hours. Overall, 24 (26.7%) patients died. Mortality was 3.7% in non-ICU and 69% in ICU setting and significantly higher in patients with fungal pneumonias (p-value 0.01) and with prolonged neutropenia (p-value 0.001).ConclusionsBAL is a safe diagnostic tool for FN patients with lung infiltrates, with minimal complications and sufficient diagnostic yield to improve diagnosis and management of such patients.

Risk of chemotherapy-induced febrile neutropenia in patients with metastatic cancer not receiving granulocyte colony-stimulating factor prophylaxis in US clinical practice

ObjectivesTo evaluate the use of granulocyte colony-stimulating factor (G-CSF) prophylaxis in US patients with selected metastatic cancers and chemotherapy-induced febrile neutropenia (FN) incidence and associated outcomes among the subgroup who did not receive prophylaxis.MethodsThis retrospective cohort study was conducted at four US health systems and included adults with metastatic cancer (breast, colorectal, lung, non-Hodgkin lymphoma [NHL]) who received myelosuppressive chemotherapy (2009–2017). Patients were stratified by FN risk level based on risk factors and chemotherapy (low/unclassified risk, intermediate risk without any risk factors, intermediate risk with ≥ 1 risk factor [IR + 1], high risk [HR]). G-CSF use was evaluated among all patients stratified by FN risk, and FN/FN-related outcomes were evaluated among patients who did not receive first-cycle G-CSF prophylaxis.ResultsAmong 1457 metastatic cancer patients, 20.5% and 28.1% were classified as HR and IR + 1, respectively. First-cycle G-CSF prophylaxis use was 48.5% among HR patients and 13.9% among IR + 1 patients. In the subgroup not receiving first-cycle G-CSF prophylaxis, FN incidence in cycle 1 was 7.8% for HR patients and 4.8% for IR + 1 patients; during the course, corresponding values were 16.9% and 15.9%. Most (> 90%) FN episodes required hospitalization, and mortality risk ranged from 7.1 to 26.9% across subgroups.ConclusionIn this retrospective study, the majority of metastatic cancer chemotherapy patients for whom G-CSF prophylaxis is recommended did not receive it; FN incidence in this subgroup was notably high. Patients with elevated FN risk should be carefully identified and managed to ensure appropriate use of supportive care.

1715P Plinabulin (Plin) is a more favorable option for the prevention of chemotherapy induced neutropenia (CIN) than pegfilgrastim (Peg) during the COVID-19 pandemic

Due to COVID-19, the NCCN Myeloid Growth Factor Panel expanded prophylactic G-CSF use to chemotherapy with Intermediate Risk (10%-20% risk) of Febrile Neutropenia (FN), and to Low Risk FN patients (pts) who previously developed FN. Preservation of resources for COVID-19 pts by reducing hospitalizations and emergency room visits by cancer chemotherapy pts is the intent of these changed recommendations. Other recommendations include use of self-injecting or on-body injector Peg, to minimize COVID-19 exposure at outpatient center by cancer pts and limiting prophylactic platelet transfusion to preserve blood product supply. Plin is an attractive alternative: it is a novel, non-G-CSF small molecule with CIN protection comparable to Peg, is given once 30 minutes after Chemo, and avoids the need for healthcare system touches on Day 1-3 for G-CSF administration. In contrast to Peg, Plin does not cause bone pain and thrombocytopenia and maintains quality of life. We compared the combined CIN data with single agent (SA) Plin 20 mg/m2 (n=29) vs. SA Peg 6mg (n=35) from 2 different phase II CIN studies over 4 cycles: 1. Study 105 in NSCLC pts given Intermediate FN Risk Docetaxel 75 mg/m2 (Doc) pts with risk factors), and 2. Study 106 in Breast cancer pts given High FN Risk Doc +Doxorubicin 50 mg/m2 + Cyclophosphamide 50mg/m2 (TAC). Plin was given as a single IV infusion on Day (D)1, 30 min after the last Chemo, and Peg 6mg given on D2 by SC injection. Grade 4 Neutropenia (Gr 4 N), Hospitalizations (Hosp), Infection rate (Inf), Sepsis (Sep), all Grade Thrombocytopenia (T) or Gr 2/3 T and Bone Pain (BoP) is summarized for SA Plin and SA Peg. (NS= non-significant). Table: 1715PGr 4 NHospInfSepAll Gr TGr 2/3 TGr 3 TBoPPegfilgrastim42.9%11.4%5.71%0%68.6%20%8.57%YesPlinabulin44.8%13.8%6.90%3.44%24.1%3.4%0%Nop-valueNSNSNSNS0.00020.0250.06- Open table in a new tab . Plin requires at least 50% fewer touches to the health care system and is equally effective as Peg for prevention of CIN and its clinical sequelae. Plin causes less thrombopenia and bone pain. Plin (given as a 40 mg fixed dose) is currently in two phase III trials for CIN.

Febrile Neutropenia in Patients with Solid Tumors Undergoing Intravenous Chemotherapy

Introduction: Febrile neutropenia (FN) is a potentially life-threatening complication of systemic chemotherapy (CT) that often requires hospital admission. Delay in diagnosis and treatment are associated with higher morbidity and mortality. Objective: We aimed to determine the factors that influence FN episodes outcomes in the emergency room (ER). Methods: This was a retrospective study of all FN episodes (with a collected blood culture [BC]) that occurred between 2012 and 2016 at our institution. FN was defined as a temperature ≥38°C and an absolute neutrophil count (ANC) <1,000/μL, expected to decrease to <500/μL in the following week. Results: Between 2012 and 2016, there were 173 FN episodes in 153/1,947 patients treated with intravenous CT. Most of these episodes (n = 121, 70%) were diagnosed in the ER, 29 in the outpatient clinic, and 23 as inpatients. In the ER, the median time was 36 min from hospital nurse triage to medical observation, and 52 min from medical observation to complete blood count specimen collection. There was a positive BC in 33 FN episodes, 72% with Gram-negative bacteria. A total of 160 FN episodes led to hospital admission and 13 were treated as outpatients. Mortality associated with the FN episode was 15% and an ANC <100/μL was predictive of increased mortality. Conclusion: This study confirms that FN is a serious and common complication of IV CT which must be diagnosed and treated promptly. Profound neutropenia was the only predictive factor of mortality.