Retrospective study on the management of patients admitted for febrile neutropenia and considered to be at low risk at the Centre Hospitalier Universitaire de Québec.

e18762 Background: Febrile neutropenia is a serious complication of chemotherapy leading to hospitalization in cancer patients. According to a practice guidelines published by ASCO (American Society of clinical Oncology) and IDSA (Infectious Diseases Society of American) in 2018, patients meeting the criteria for low-risk neutropenia according to the MASCC score (Multinational Association for Supportive Care in Cancer Score) could be treated as outpatient and thus avoid hospitalization. The objective of the study was to assess the number and proportion of patients who were hospitalized for febrile neutropenia in university hospital that would have met the low risk criteria of febrile neutropenia. We also wanted to know if these patients had experienced a favorable outcome during hospitalization. Methods: We performed a retrospective study including all patients admitted for febrile neutropenia in 3 hospitals in Quebec City during the period from January 1, 2018 to December 31, 2019. We excluded patients with leukemia, as well as stem cell transplant patients. The chart review retrospectively established the MASCC score for each patient. We also established according to predefined criteria whether the clinical course was favorable or unfavorable. Results: A total of 177 hospitalizations met our inclusion criteria. We found that 101/177 (57.1%) of hospitalized patients met the criteria for low-risk neutropenia according to the MASCC score (score of 21 and above). Of this number 74/177 (41.8%) presented all the criteria suggested for receiving outpatient treatment. In these patients 70/177 (39.5%) presented a favorable evolution during hospitalization and thus 4/177 (2.3%) presented an unfavorable evolution. Among these, 2 patients presented with infections considered major (2 bacteremia), 1 patient developed acute renal failure, and 1 other patient developed delirium. There was no death or admission to the intensive care unit in these 4 patients. Conclusions: According to this retrospective study, about 40% of patients admitted for febrile neutropenia filled the criteria of low risk febrile neutropenia and could be treated as outpatient. Given this represents a significant proportion of patients, a protocol for systematic follow-up of outpatient treatment with low-risk febrile neutropenia should be put in place.

A questionnaire survey on evaluation for penetration and compliance of the Japanese Guideline on Febrile Neutropenia among hematology-oncology physicians and surgeons

Purpose The Japanese Society of Medical Oncology published a guideline (GL) on febrile neutropenia (FN) in 2017. The study’s purpose is to reveal how widely GL penetrated among physicians and surgeons providing chemotherapy. Methods A questionnaire survey was conducted with SurveyMonkey™ for members of the Japanese Association of Supportive Care in Cancer and relevant academic organizations. Each question had four options (always do, do in more than half of patients, do in less than half, do not at all) and a free description form. Responses were analyzed with statistical text-analytics. Result A total of 800 responses were retrieved. Major respondents were experts with more than 10-year experience, physicians 54%, and surgeons 46%. Eighty-seven percent of respondents knew and used GL. Forty-eight percent assessed FN with Multinational Association of Supportive Care in Cancer (MASCC) score “always” or “more than half.” Eighty-one percent chose beta-lactam monotherapy as primary treatment in high-risk patients. Seventy-seven percent did oral antibacterial therapy in low-risk patients ambulatorily. Seventy-eight percent administered primary prophylactic G-CSF (ppG-CSF) in FN frequency ≥ 20% regimen. Fifty-nine percent did ppG-CSF for high-risk patients in FN frequency 10–20% regimen. Ninety-seven percent did not use ppG-CSF in FN frequency < 10% regimen. The medians of complete and complete plus partial compliance rates were 46.4% (range 7.0–92.8) and 77.8% (range 35.4–98.7). The complete compliance rates were less than 30% in seven recommendations, including the MASCC score assessment. Conclusion GL is estimated to be widely utilized, but some recommendations were not followed, presumably due to a mismatch with actual clinical practices in Japan.

Substantiation of Multinational Association for Supportive Care in Cancer (MASCC) Score in Risk Assessment of Febrile Neutropenic Patients in Hematological Disorders: A Regional Study from Pakistan

Background: The incidence of neutropenia in hematological malignancies comprises of huge burden of febrile neutropenia. Multinational Association of Supportive Care in Cancer (MASCC) risk index score is the most widely used model for forecast of complications. Objective: The aim of this study was to determine diagnostic accuracy of MASCC scoring system in febrile neutropenia patients suffering from hematological disorders. Materials & Methods: Patients suffering from hematological disorders and presenting with febrile neutropenia were stratified into low and high risk groups according to MASSC score. The standard score range from 0 to 26 points; score of more than or equals to 21 were considered to be low risk and score of less than 21 was high-risk category. As an in-patient at National Institute of Blood Disease & Bone Marrow Transplantation, they were followed over the course of illness for development of any serious medical condition until resolution of febrile neutropenia. Results: Of 217 patients, serious medical conditions were documented in (63%) of individuals among the high-risk group cohort and (13%) developed serious medical conditions in low-risk cohort. Major disease encountered was acute leukemia (69%). Hypotension 14 (22.2%) and hepatic failure 14 (22.2%) were among the two most common variables of established serious medical condition. The overall sensitivity and specificity of MASCC score was 69.8% and 81.8%, with the positive and negative predictive value of 61.1% and 86.8% respectively. Conclusion: The score has been re-validated in this study and determined its significance in ascertainment of high-risk cohort among febrile neutropenic patients in the current era, thereby helping the physicians to tailor the management approach accordingly. Keywords: MASCC, Febrile neutropenia, Leukemia, Hematological disorders, Cytotoxic chemotherapy.

Comparison of CISNE and MASCC Score in Predicting Complications on Post Chemotherapy Febrile Neutropenia

Objective Despite the routine use of MASCC score in febrile neutropenia patients, researches showed that serious complications still occur in 15-42% of low-risk patients; therefore, a new scoring system Clinical Index of Stable Febrile Neutropenia (CISNE) is developed to predict the complication better. This retrospective cohort study aimed to assess the role of CISNE score compared to MASCC score as a risk stratification in post-chemotherapy FN in solid and hematologic malignancy. Patients who underwent inpatient treatment with FN between July 2015 and December 2019 were grouped based on both scores, while complications during inpatient was recorded. Both score's areas under the receiver operating characteristics curve were compared using DeLong method. Results CISNE score showed a better performance both in solid malignancy with AUC of CISNE score (0.893; 95% CI 0.829 - 0.95, p = 0.03) compared to AUC of MASCC score (0.77; 95% CI 0.68 – 0,86, p = 0.04) and in hematologic malignancy with AUC of CISNE score (0.91; 95% CI 0.84 - 0.97, p = 0.03) and AUC MASCC score (0.735 ; 95% CI 0.68 - 0.86, p = 0.04). CISNE score showed a better diagnostic performance with cut-off point value of 2.

Retrospective study of the evaluation and management of febrile neutropenia in cancer patients in a tertiary center.

e19100 Background: Febrile neutropenia is a medical emergency often managed by internists, but adherence to guidelines has not been well-described. We aimed to describe care and outcomes of a retrospective cohort of patients hospitalized with febrile neutropenia at a single tertiary care hospital. Methods: We included adults ≥18 years old who had a cancer diagnosis and required hospital admission for a principal diagnosis of fever and neutropenia (ANC < 500) from October 2015 - April 2019. We reviewed records to identify demographics, cancer diagnosis and stage, and outcomes, including death. Results: We included 193 patients; all were cared for by hospitalists. About half (52%) were classified as high risk [ < 21 Multinational Association of Supportive Care in Cancer (MASCC)score], but only 1 patient had a documented MASCC score in hospital progress notes. The majority of patients were female (55%) and white (84%). Twenty-three percent had a stage IV diagnosis. Most (89.1%) patients were within their first chemotherapy cycle, and 23% received GCSF. Approximately half (47%) had solid tumors; the remainder had hematologic malignancies. About one quarter (27%) had positive blood cultures (of these, 43.4 % were gram positive cocci (GPC); 49.1% were gram negative rods (GNR)). Most patients received empiric coverage for GPC and GNR: 82% received cefepime and 42% received empiric MRSA coverage. Few patients had cultures positive for resistant organisms such as MRSA (n = 3) or pseudomonas (n = 4). Hematology/Oncology was consulted for most (82%) cases. Inpatient mortality occurred in 12% of patients. Compared to those who survived, patients who died had lower MASCC score 13.9 (vs. 19.1) and were more likely to receive critical care therapies during hospitalization (70% vs. 14%). Few patients (n = 24, 12%) had documented goals of care (GOC) discussions. Conclusions: Although MASCC is predictive of outcomes, internists caring for patients with fever and neutropenia do not document this score. Hospitalist-focused education efforts about MASCC score could improve care. Few patients had documented GOC discussions. Oncologists should maintain good communication with internal medicine colleagues, who may be hesitant to address GOC in patients receiving chemotherapy.

Clinical impact of neutropenia and febrile neutropenia in mCRC pts treated with FOLFOXIRI/bevacizumab (bev): A pooled analysis of TRIBE and TRIBE2 studies.

11591 Background: FOLFOXIRI/bev is a valid option as first-line therapy for unresectable mCRC. TRIBE and TRIBE2 trials reported better activity and efficacy of the triplet/bev when compared with doublets/bev at the price of a higher incidence of chemo-related toxicities, including neutropenia (N). Here we aim at providing a detailed description of this adverse event, including the occurrence of febrile neutropenia (FN) and the use of granulocyte-colony stimulating factors (G-CSFs), in order to estimate the clinical relevance of N during FOLFOXIRI/bev. Methods: Safety data of 1175 pts enrolled in the TRIBE and TRIBE2 studies were reviewed. The incidence of N, the incidence and severity of FN, and the use of G-CSF in the triplet/bev and in the doublets/bev arms were compared using the Chi-square or the Fisher exact test as appropriate. Results: Out of 1175 pts included in the final analysis, 586 (49.8%) were treated with FOLFOXIRI/bev. Five pts (0.8%) in the doublets/bev arms and 29 (4.9%) in the triplet/bev arms received a primary prophylaxis with G-CSF. Among other pts, 118 (20.2%) in the doublets/bev arms and 276 (49.9%) in the triplet/bev arms experienced ≥ G3 N (p < 0.001). FN occurred in 25 (4.3%) and 41 (7.4%) cases respectively (p=0.041). Out of 78 FN episodes, 4 (13.3%) out of 30 in the doublets/bev arms and 13 out of 48 (27.1%) in the triplet/bev arms were associated with a poor MASCC score (<21) (p=0.17). G-CSF was used in 1069 (10.8%) cycles, 270 (5.3%) in doublets/bev and 799 (16.6%) in triplet/bev arms. In both arms, the majority of N and FN episodes were observed in the first two months (318 ≥ G3 N episodes out of 675 (47.1%), and 54 FN episodes out of 78 (69.2%)). Conclusions: FOLFOXIRI/bev was associated with a higher risk of N and FN than doublets/bev. However, the risk of FN was lower than 10%, thus not requiring a systematic use of primary G-CSF prophylaxis. The majority of FN episodes was associated with a good MASCC score, thus having a limited clinical impact. The vast majority of FN episodes occurred in the first two months of treatment, suggesting a closer monitoring of this adverse event during the first courses of therapy.

Prognostic value of procalcitonin and lipopolysaccharide binding protein in cancer patients with chemotherapy-associated febrile neutropenia presenting to an emergency department

Introduction: Cancer patients with chemotherapy-induced febrile neutropenia are a heterogeneous group with a significant risk of serious medical complications. In these patients, the Multinational Association for Supportive Care in Cancer (MASCC) score is the most widely used tool for risk-stratification. The aim of this prospective study was to analyse the value of procalcitonin (PCT) and lipopolysaccharide binding protein (LBP) to predict serious complications and bacteraemia in cancer patients with febrile neutropenia, compared with MASCC score. Materials and methods: Data were collected from 111 episodes of febrile neutropenia admitted consecutively to the emergency department. In all of them, MASCC score was calculated and serum samples were collected for measurement of PCT and LBP by well-established methods. The main and secondary outcomes were the development of serious complications and bacteraemia, respectively. Results: A serious complication occurred in 20 (18%) episodes and in 16 (14%) bacteraemia was detected. Areas under the receiver operating characteristic curve (ROC AUC) of MASCC score, PCT and LBP to select low-risk patients were 0.83 (95% confidence interval (CI): 0.74 - 0.89), 0.85 (95% CI: 0.77 - 0.91) and 0.70 (95% CI: 0.61 - 0.78), respectively. For bacteraemia, MASCC score, PCT and LBP showed ROC AUCs of 0.74 (95% CI: 0.64 - 0.82), 0.86 (95% CI: 0.78 - 0.92) and 0.76 (95% CI: 0.67 - 0.83), respectively. Conclusion: A single measurement of PCT performs similarly as MASCC score to predict serious medical complications in cancer patients with febrile neutropenia and can be a useful tool for risk stratification. Besides, low PCT concentrations can be used to rule-out the presence of bacteraemia.

1016. Bloodstream Infection Survey in High-Risk Oncology Patients (BISHOP) With Fever and Neutropenia (FN): Predictors for Morbidity and Mortality

Background Blood stream infection (BSI) during neutropenia is associated with high risk for morbidity and mortality in patients with hematologic malignancies receiving chemotherapy or undergoing hematopoietic cell transplant (HCT). We sought to identify factors associated with increased risk for critical illness (CI) morbidities within 7 days of BSI with index FN following chemotherapy. Methods A prospective ongoing survey among 14 high-volume US cancer centers submitting clinical and microbiologic data from consecutive HM patients with blood stream infection (BSI) during first FN after cytotoxic chemotherapy or HCT. We evaluated factors influencing poor outcomes defined as critical illness (need for pressor support, mechanical ventilation, new pneumonia or new BSI) within 7 days of BSI with index FN. Concordance between antibiotic and BSI isolate was determined by investigator (AZ, AF) interpretation of susceptibility reports provided by each center compared with the initial antimicrobial regimen (IAR) used, for single organism bacteremias only. Results Among 294 FN bacteremic episodes (93 HCT) were 336 bacterial pathogens (48.5% Gram-negative [GN], 46.5% Gram-positive [GP], and 6% anaerobes). Death occurred in 11/294 (4%) and 41/294 (14%) had CI by day 8. At FN presentation, mean MASCC score of those with CI vs. those without was 16.9 vs. 18.6 (P = 0.03) and there was a trend toward higher mean PITT scores for patients with CI by day 8 vs. those without (1.54 vs. 0.82 (P = 0.08)). Among GN bacteremias, 15% developed CI vs. 14.5% in nonviridans group Streptococci (VGS) GP bacteremias, and 10.9% in VGS bacteremias (NS). Among patients with single organism bacteremias (88% of all BSI), mismatch of IAR coverage with isolate susceptibilities occurred in 16.7% (38/227). Among patients whom IAR was active vs. inactive against BSI isolate, 16% vs 14.3%, respectively, developed CI (P = 0.81). Conclusion These data indicate that the MASCC score applied to high-risk inpatients may be a predictor for CI in the first week after bacteremia FN. The PITT shows less correlation with poor outcomes. There was no association between isolate type (GN, GP, or VGS) and CI. Notably there was no association between mismatched BSI susceptibility and antimicrobial spectrum of the IAR and early CI. Disclosures A. G. Freifeld, Merck: Investigator, Research grant. A. Zimmer, Merck: Investigator, Research grant. S. Pergam, Merck: Consultant, Consulting fee. Chimerix: Consultant, Consulting fee. K. V. Rolston, Merck: Investigator, Research grant. JMI Laboratories: Investigator, Research grant. Shionogi (Japan): Investigator, Research grant. S. Shoham, Merck: Investigator and Scientific Advisor, Consulting fee and Grant recipient. Astellas: Investigator, Grant recipient. Shionogi (Japan): Investigator, Grant recipient. Gilead: Investigator, Grant recipient. Shire: Investigator, Grant recipient. T. J. Walsh, Merck: Grant Investigator, Research grant. Atellas: Consultant, Grant Investigator and Scientific Advisor, Consulting fee and Research grant. Gilead: Scientific Advisor, Consulting fee. Allergan: Grant Investigator and Scientific Advisor, Consulting fee and Research grant. Scynexis: Grant Investigator, Research grant. Amplyx: Grant Investigator, Research grant. Shionogi: Scientific Advisor, Consulting fee. J. A. Young, GSK: Investigator, The University of Minnesota is reimbursed for contract costs associated with conducting clinical trials of vaccine. I receive no personal financial benefit. Y. Zhang, Merck: Investigator, Research grant. J. Meza, Merck: Investigator, Research grant.