Risk Factors For Febrile Neutropenia Research Articles

Effectiveness and safety of empegfilgrastim (Extimia®) in patients with solid tumors receiving cytotoxic therapy: final results of the DEFENDOR study

Aim. To evaluate the effectiveness and safety of Extimia® (empegfilgrastim, JSC "BIOCAD") in reducing the frequency, duration of neutropenia, the incidence of febrile neutropenia (FN) and infections caused by FN in patients with solid tumors receiving myelosuppressive therapy. Materials and methods. The paper presents the final results of a multicenter prospective observational post-marketing study of the safety and effectiveness of Extimia® (empegfilgrastim) in patients with solid tumors receiving cytotoxic therapy. For the primary prevention of FN, all patients received empegfilgrastim at 7.5 mg subcutaneously once per course of chemotherapy (CT) 24 hours after the end of CT administration. The primary endpoint included an assessment of the relative dose-intensity (RDI) of the CT courses administered. The endpoints of interest included the assessment of the RDI of CT courses by nosology and CT regimen, the frequency of dose-limiting neutropenia, and the incidence of all adverse events (AEs) in patients who received at least one dose of the study medication, including serious AEs. Results. From February 2021 to December 2022, 3218 patients with various malignancies were included in 41 study centers of the Russian Fede- ration. Of these, 3217 (99.97%) patients received at least one dose of the study drug, and 2663 (82.8%) patients were included in the RDI evaluation population according to the study protocol. The mean age in this group was 56.9 (18–84) years. RDI ≥85% was achieved in 2,415 (90.7%) patients. The mean RDI was 96.2%, with a median of 100%. FN risk factors were present in 1216 (45.7%) patients, with age ≥65 years being the most common risk factor at 761/2663 (28.6%). It should be noted that in patients younger than 65 years, the RDI was 91.5%, and in elderly patients (≥65 years) 88.7%. Dose-limiting neutropenia was reported in 19 (0.7%) patients. There were 74 cases of grade 3–4 AEs (according to CTCAE v.5) in 59 (1.8%) patients. The most common were neutropenia, anemia, and diarrhea in 19 (0.7%), 7 (0.2%), and 6 (0.2%) patients, respectively. Serious AEs were reported in 17 patients (0.5%). Conclusion. Primary prophylaxis of FN with long-acting granulocyte colony-stimulating factor empegfilgrastim effectively maintains RDI in various nosological and therapeutic groups of patients with different CT regimens in real-world clinical practice.

Chemotherapy-induced febrile neutropenia (FN): healthcare resource utilization (HCRU) and costs in commercially insured patients in the US

PurposeFebrile neutropenia (FN) is a known side effect of chemotherapy, often requiring hospitalization. Economic burden increases with an FN episode and estimates of cost per episode should be updated from real-world data.MethodsA retrospective claims analysis of FN episodes in patients with non-myeloid malignancies from 2014 to 2021 was performed in IQVIA PharMetrics® Plus database. FN episodes were defined as having same-day claims for neutropenia and fever or infection, plus antibiotic in outpatient settings, following a claim for chemotherapy; index date was defined as the first claim for neutropenia/fever/infection. Patients receiving bone marrow/stem cell transplant and CAR-T therapy were excluded, as were select hematologic malignancies or COVID-19. Healthcare utilization and costs were evaluated and described overall, by episode type (w/wo hospitalization), index year, malignancy type, NCI comorbidity score, and age group.Results7,033 FN episodes were identified from 6,825 patients. Most episodes had a hospitalization (91.2%) and 86% of patients had ≥1 risk factor for FN. Overall, FN episodes had a mean (SD) FN-related cost of $25,176 ($39,943). Episodes with hospitalization had higher average FN-related costs versus those without hospitalization ($26,868 vs $7,738), and costs increased with comorbidity score (NCI=0: $23,095; NCI >0-2: $26,084; NCI ≥2: $26,851).ConclusionsFN continues to be associated with significant economic burden, and varied by cancer type, comorbidity burden, and age. In this analysis, most FN episodes were not preceded by GCSF prophylaxis. The results of this study highlight the opportunity to utilize GCSF in appropriate oncology scenarios.

Abstract PO1-12-06: Is it appropriate to select patients for primary prophylactic use of pegfilgrastim based on the risk of febrile neutropenia?

Abstract Background: Febrile neutropenia (FN), a major hematologic adverse event in perioperative chemotherapy for breast cancer, is more prevalent among Asians than in Caucasian populations. Four main guidelines, i.e., ASCO, EORTC, NCCN, and ESMO, provide recommendations regarding the appropriate use of hematopoietic growth factors. These guidelines recommend primary prophylaxis with granulocyte colony-stimulating factor (G-CSF) based on the estimated incidence of FN, primarily defined by the chemotherapy regimen. G-CSF administration is recommended when the incidence of FN is ≥20% or 10–20% with risk(s). However, the incidence of FN varies depending on the trial and design, and patient-specific risk factors for FN remain unclear. We previously performed a multicenter prospective cohort study in Japan, the CSPOR-BC FN study, evaluating the incidence of FN during perioperative chemotherapy for breast cancer. Herein, we conducted an additional analysis to explore thresholds of patient-specific risk factors for FN that could be evaluated before chemotherapy. We analyzed the risk factors for FN and verified the appropriateness of patient selection for prophylactic G-CSF administration. Methods: The previously reported CSPOR-BC FN study (PubMed ID=33631458) consecutively enrolled 1005 patients with stage I–III breast cancer between August 2015 and July 2017. In the current additional analysis, we intended to have 477 patients in the visiting group that evaluated true-FN, defined as ≥37.5℃ and grade 4 neutropenia. Multivariate analysis of risk factors for FN was performed, followed by the determination of cutoff values for age and pretreatment absolute neutrophil count (ANC) as risk factors. Results: Chemotherapy regimens administered were FEC (fluorouracil, epirubicin, and cyclophosphamide) in 170 patients (36%), E(A)C (epirubicin (doxorubicin) + cyclophosphamide) in 165 patients (35%), and TC (docetaxel + cyclophosphamide) in 142 patients (30%). The incidence of FN was 28.7% (N = 137). To evaluate the risk factors for FN, we predefined regimens, age, performance status (PS), stage, chemotherapy or radiotherapy history, infectious wounds, open wounds, ANC, and renal and liver dysfunction as potential risk factors. Multivariate analysis of risk factors for FN identified regimen (TC), age (≥65), low pretreatment ANC, treatment setting, and no primary pegfilgrastim prophylaxis as significant risk factors. Two patient-specific risk factors (age and pretreatment ANC) were analyzed. Logistic regression analysis revealed that age≥65 years was a significant risk factor (odds ratio=2.24, 95% confidence interval: 1.34–3.75). Applying a cutoff of 65 years (age) to predict FN, the sensitivity and specificity were 28.4 and 83.8%, respectively, which were inaccurate. Despite applying a cutoff of 67 years optimized from the receiver operating characteristic (ROC) curve, the sensitivity (22.4%), specificity (90.7%), and area under the curve (0.519) indicated low discrimination for predicting FN. The incidence of FN by age group was as follows: < 45 years, 30.8%; 45–55 years, 26.4%; 55–64 years, 20.9%; ≥65 years, 39.6%. Additionally, applying a cutoff of 2436/µL (pretreatment ANC) optimized from the ROC curve, the observed sensitivity (27.6%) and specificity (83.8%), and area under the curve (0.558) also indicated low discrimination for predicting FN. The incidence of FN by stratum of pretreatment ANC was as follows: < 2000, 33.3%; 2000–3000, 30.7%; 3000–4000, 29.9%; and >4000, 24.6. Accordingly, setting a cutoff value to predict FN incidence using age and/or pretreatment ANC was deemed inappropriate. Conclusion: Selecting patients for primary prophylactic G-CSF based on the existing FN risk can be challenging. Primary prophylactic G-CSF would be considered for every patient undergoing perioperative chemotherapy for breast cancer, especially Asians. ROC curve for FN and age. The AUC was 0.519. ROC curve for FN and neutrophil count. The AUC was 0.558. Citation Format: Kazutaka Narui, Takashi Ishikawa, Ikumi Takashima, Kosuke Kashiwabara, Yukari Uemura, Yuichiro Kikawa, Naruto Taira, Hirofumi Mukai. Is it appropriate to select patients for primary prophylactic use of pegfilgrastim based on the risk of febrile neutropenia? [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-12-06.

Analysis of Risk Factors for Febrile Neutropenia in Patients with Small-Cell Lung Cancer Receiving Carboplatin Plus Etoposide Therapy

Introduction: Febrile neutropenia (FN) is an oncologic emergency requiring immediate empiric antibiotic therapy. Although carboplatin plus etoposide combination chemotherapy is associated with a relatively high frequency of FN, the risk factors are unclear. Hence, this retrospective study aimed to identify predictive markers of carboplatin/etoposide-induced FN. Methods: We conducted a retrospective cohort analysis of patients with previously untreated small-cell lung cancer (SCLC) who received combination chemotherapy with carboplatin (area under the concentration curve: 5 mg/mL·min, day 1) and etoposide (80 or 100 mg/m2, days 1–3) between July 2007 and June 2022. FN was assessed during the 21 days after initiation of carboplatin and etoposide therapy according to the Japanese Society of Medical Oncology’s definition. Fisher’s exact test for categorical variables and Mann-Whitney U test for continuous variables were used to compare the two groups. Statistical significance was set at p values p values Results: Among the 176 eligible patients, the incidence of FN during the first cycle of chemotherapy was 25.0% (44/176). Multivariate analysis revealed that co-administration of proton pump inhibitors (PPIs) or potassium-competitive acid blockers (PCABs) and body mass index (BMI) were significantly associated with FN (p = 0.0035 and 0.0011, respectively). Patients with both co-administration of PPIs or PCABs and a BMI ≤22.509 kg/m2 presented with significantly higher frequencies of FN compared with the other patients (13/24 [54.2%] vs. 31/152 [20.4%] patients; odds ratio: 4.56, 95% confidence interval: 1.70–12.48; p = 0.00147). Conclusion: Patients who received carboplatin plus etoposide for SCLC with co-administration of PPIs or PCABs and a BMI ≤22.509 kg/m2 more frequently present with FN than those without the two factors.

Malnutrition as a predictor of adverse outcomes of febrile neutropenia in children with acute lymphoblastic leukemia during induction phase chemotherapy

Background: Adequate nutrition is an important concern in children with leukemia. Malnutrition impairs immune function, leading to increased incidence of infection, poor quality of life, as well as death. Febrile neutropenia (FN) has a high prevalence in children with acute lymphoblastic leukemia (ALL) and a poor outcome as well. Methods: This prospective observational study was done in the department of pediatrics hematology and oncology (PHO), BSMMU, from January 2021 to October 2021. A total of 60 patients of ALL were selected purposively. Patients were evaluated by taking anthropometric parameters before getting chemotherapy and were prospectively followed up for the development and outcome of FN until recovery. Statistical analysis was performed by using SPSS (Statistical package for the social sciences) for Windows version 26.0. Result: Analysis of nutritional status as a risk factor for FN based on anthropometric indices, was found statistically significant for, weight for height (≤5 years) p=0.036, OR=0.24 (95% CI= 0.06-0.958), weight for age p=0.006, OR=0.23 (95% CI=0.07-0.67), but for BMI for age (>5 years) p=0.28, OD=0.28 (95% CI=0.02-3.19), and height for age p=0.513, OD=0.66 (95% CI=0.18-2.33) no statistically significant value was found. In this study, we found mortality rate was 15%. The mortality rate was significantly worse (27.3%) for patients who were malnourished at diagnosis as compared to those who were well nourished (7.9%) at diagnosis. Conclusions: FN and its complications are more common in malnourished children with ALL. Malnutrition is associated with adverse outcomes of FN in children with ALL.

Incidence and risk factors for febrile neutropenia of patients with diffuse large B-cell lymphoma receiving R-CHOP-21 in China

ObjectiveFebrile neutropenia (FN) is a serious complication of patients with diffuse large B-cell lymphoma (DLBCL) receiving R-CHOP-21. The prophylactic use of granulocyte colony–stimulating factors (G-CSFs) can significantly reduce the risk of FN. International guidelines recommend G-CSFs for patients receiving chemotherapy with FN risk of 20% or 10 to 20% with defined risk factors. However, there are few studies on the incidence and risk factors of FN in patients with DLBCL receiving R-CHOP-21, especially in patients without primary G-CSF prophylaxis.MethodsWe conducted a retrospective analysis for the clinical data of 103 patients with DLBCL who underwent first R-CHOP-21 without primary G-CSF prophylaxis. The objective of the assessment was the incidence and risk factors of FN after the first chemotherapy cycle.ResultsAfter the first chemotherapy cycle, the incidence of FN was 20.4%. Multivariate analysis showed that age ≥ 65 years, bone marrow involvement, albumin < 35 g/L, and average relative dose intensity ≥ 80% were independent risk factors for FN. According to risk factors, we created a risk score system. The incidence of FN in the low-, intermediate- and high-risk groups was 5.6%, 17.2%, and 61.9%, respectively.ConclusionOur data indicated that R-CHOP-21 itself is associated with a high-risk regiment for FN. We recommend that intermediate/high-risk patients should actively consider primary G-CSF prophylaxis to reduce the incidence of FN after chemotherapy.

Pegfilgrastim for the management of neutropenia during neoadjuvant chemotherapy with docetaxel, cisplatin, and 5-fluorouracil in esophageal cancer patients.

Neoadjuvant docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy is a new standard for locally advanced esophageal squamous cell carcinoma. The optimal timing of pegfilgrastim with the DCF regimen to prevent febrile neutropenia (FN) remains controversial. The effectiveness of concomitant pegfilgrastim administration with continuous 5-fluorouracil (5-FU) infusion in the DCF regimen was therefore assessed. All patients who received neoadjuvant DCF for esophageal cancer were retrospectively assessed. Patients who had been scheduled to receive pegfilgrastim on days 3-5 (early group) or days 7-9 (regular group) of the DCF regimen were included. Uni- and multivariate analyses were used to assess risk factors for FN. Eighty-eight patients were included in the analysis. The 26 patients in the early group received pegfilgrastim as scheduled. In the 62 patients of the regular group, 51 received pegfilgrastim at a median of 7days after starting DCF chemotherapy. However, 11 patients in the regular group could not receive pegfilgrastim. Twenty-two patients of the regular group and 2 patients of the early group developed FN after the first session of DCF. Early administration of pegfilgrastim and grade 4 neutropenia were significantly associated with onset of FN, with multivariate analysis identifying early administration of pegfilgrastim as an independent preventive factor and grade 4 neutropenia as a risk factor, after adjusting for sex and age. Early pegfilgrastim administration is a safe approach that reduces the incidence of FN in DCF therapy. Using pegfilgrastim with continuous 5-FU infusion in the DCF regimen represents a reasonable option to prevent FN.

A study indicates an essential link between a mild deterioration in excretory kidney function and the risk of neutropenia during cancer chemotherapy

PurposeNeutropenia, defined as a number of neutrophils in patients’ blood specimen lower than 1500 cells/μm3, is a common adverse event during myelosuppressive oncological chemotherapy, predisposing to febrile neutropenia (FN). Patients with coexisting moderate-to-severe chronic kidney disease (CKD) have an increased risk of FN, included in the guidelines for the primary prophylaxis of FN. However, this does not include mild kidney function impairment with estimated glomerular filtration rate (eGFR) 60–89 ml/min/1.73 m2. This prospective study analyzed the risk of neutropenia in patients on chemotherapy without indication for the primary prophylaxis of FN.MethodsThe study enrolled 38 patients starting chemotherapy, including 26 (68.4%) patients aged 65 years or more. The median duration of follow-up was 76 days. The methodology of creatinine assessment enabled the use of the recommended CKD-EPI formula for identifying patients with a mild reduction of glomerular filtration.ResultsSixteen (42.1%) patients developed at least G2 neutropenia without episodes of FN. Only five (13.1%) patients had eGFR < 60 ml/min/1.73 m2, while 15 (62.5%) eGFR < 90 ml/min/1.73 m2. The relative risk of neutropenia in patients with impaired eGFR was over six times higher than in patients with eGFR > 90 ml/min/1.73 m2 (RR = 6.08; 95%CI:1.45–27.29; p < 0.01).ConclusionsOur observation indicates that even a mild reduction in eGFR is a risk factor for the development of neutropenia and a potential risk factor for FN.

Prevention and treatment of neutropenia in routine clinical practice. How to improve the quality of cancer care and reduce treatment costs?

Neutropenia is a common complication during anti-cancer therapy. Risk factors for febrile neutropenia, its diagnostic criteria, and methods of its prevention and treatment have been well described. In this article, we demonstrated the need to assess cost effectiveness of primary prevention of complications associated with polychemotherapy and treatment of neutropenia, as well as the need to analyze their incidence. Individual risk assessment of febrile neutropenia, implementation of the antimicrobial drug registry, and administration of pegylated granulocyte colony-stimulating factor reduced the incidence of neutropenia, its duration, and the number of antimicrobial drugs used. This, in turn, improved the quality of healthcare and optimized the use of hospital resources.

How Asian Breast Cancer Patients Experience Unequal Incidence of Chemotherapy Side Effects: A Look at Ethnic Disparities in Febrile Neutropenia Rates.

The majority of published findings on chemotherapy-induced febrile neutropenia (FN) are restricted to three ethnic groups: Asians, Caucasians, and African Americans. In this two-part study, we examined FN incidence and risk factors in Chinese, Malay, and Indian chemotherapy-treated breast cancer (BC) patients. Hospital records or ICD codes were used to identify patients with FN. In both the Singapore Breast Cancer Cohort (SGBCC) and the Joint Breast Cancer Registry (JBCR), the time of the first FN from the start of chemotherapy was estimated using Cox regression. Multinomial regression was used to evaluate differences in various characteristics across ethnicities. FN was observed in 170 of 1014 patients in SGBCC. The Cox model showed that non-Chinese were at higher risk of developing FN (HRMalay [95% CI]:2.04 [1.44-2.88], p < 0.001; HRIndian:1.88 [1.11-3.18], p = 0.018). In JBCR, FN was observed in 965 of 7449 patients. Univariable Cox models identified ethnicity, a lower baseline absolute neutrophil count, non-luminal A proxy subtypes, and anthracycline-containing regimens as risk factors. Disparities across ethnicities' risk (HRMalay:1.29 [1.07-1.54], p = 0.006; HRIndian:1.50 [1.19-1.88], p < 0.001) remained significant even after further adjustments. Finally, an age-adjusted multinomial model showed that Malays (p = 0.006) and Indians (p = 0.009) were significantly more likely to develop multiple episodes of FN during treatment. Ethnic differences in chemotherapy-induced FN among BC patients exist. Further studies can focus on investigating pharmacogenetic differences across ethnicities.

Poor Renal Function and a High Modified Glasgow Prognostic Score Are Predictive Factors for Nedaplatin/5-Fluorouracil Combination Therapy-induced Febrile Neutropenia.

Nedaplatin (NDP)/5-fluorouracil (5-FU) combination therapy frequently causes severe neutropenia and febrile neutropenia (FN). However, there is no consensus on the risk factors for FN caused by NDP/5-FU combination therapy. Mouse models of cancer cachexia are known to be susceptible to infections. Conversely, the modified Glasgow prognostic score (mGPS) is believed to reflect cancer cachexia. We hypothesized that mGPS is a predictive factor for FN caused by NDP/5-FU combination therapy. We analyzed the relationship between mGPS and FN in patients who received NDP/5-FU combination therapy at Nagasaki University Hospital using multivariate logistic analysis. In total, 157 patients were studied, 20 of whom developed FN (12.7%). Multivariate analysis revealed that mGPS 1-2 [odds ratio (OR)=4.13, 95% confidence interval (CI)=1.42-12.02, p=0.009] and creatinine clearance <54.4 ml/min (OR=5.81, 95% CI=1.81-18.59, p=0.003) were significantly associated with the development of FN. Several guidelines suggest that patients receiving chemotherapy with an FN rate 10-20% should be considered for prophylactic granulocyte colony-stimulating factor (G-CSF), depending on the individual patient's risk of developing FN. When NDP/5-FU combination therapy is administered to patients with risk factors identified in this study, prophylactic administration of G-CSF should be considered. In addition, the neutrophil count and axillary temperature should be monitored more frequently.

Risk factors and predictors of adverse outcomes of in paediatric febrile neutropenia

Background: Febrile neutropenia (FN) is the commonest acute complication of cancer treatment in children. The identification of patients at risk for FN as well as adverse outcomes has been described.Aim: To evaluate the prevalence and potential risk factors for FN and describe adverse outcomes in a cohort of children treated for cancer.Setting: The study was carried out in a paediatric oncology unit in a children’s hospital, Cape Town, South Africa.Methods: A retrospective study from 01 January 2017 to 31 December 2019 on children with cancer at Red Cross War Memorial Children’s Hospital, Cape Town, South Africa.Results: Two hundred and sixty-seven episodes of FN occurred in 179 patients. Independent predictors of FN were acute myeloid leukaemia (AML) (p = 0.039), acute lymphocytic leukaemia (ALL) (p = 0.020) and intensive chemotherapy (p ≤ 0.001). Mucositis (p = 0.001), central venous access device (CVAD) placement (p = 0.004), haematologic malignancies (p = 0.040), blood transfusion during FN episode (p 0.001) and severe neutropenia (white cell counts 0.3 × 109 cells/L) (p ≤ 0.001) were risk factors for adverse outcomes. The mortality rate from FN was 3.57%. Independent predictors of adverse outcomes in those with FN were AML (p = 0.001), CVAD placement (p = 0.019) and severe neutropenia (p = 0.005).Conclusion: Treatment related adverse outcomes following chemotherapy-induced FN are likely in children with AML, severe neutropenia and with CVAD placement.Contribution: Adverse outcomes from paediatric febrile neutropenia is high. There is need for clinical decision making aimed at prevention and early identification of individuals at risk.

MANAGEMENT OF FEBRILE NEUTROPENIA IN LUNG CANCER

Febrile neutropenia (FN) is defined as an oral temperature of &gt;38.3° C or two consecutive measures &gt; 38° C within 2 hours accompanied by an absolute neutrophil count (ANC) of 500/L or a predicted decrease below 500/L in individuals undergoing systemic chemotherapy for cancer. FN is one of the oncological emergencies that can influence cancer patients' outcomes since it can increase morbidity, treatment delays, decreased survival, and expanded costs. The incidence of FN is 3.7-28% in lung cancer patients. Mortality associated with FN episodes is 15%. FN risk factors include chemotherapy regimen, age, comorbidities, mucositis, performance status, and previous FN history. Validated predicted instruments such as The Multinational Association for Supportive Care in Cancer (MASCC) or The Clinical Index of Stable Febrile Neutropenia (CISNE) score could assist in risk assessment of FN and determine advanced management. Effective therapy of FN requires investigation of diagnosis as soon as possible and acknowledging the potential source of infection. The prophylactic granulocyte colony-stimulating factors (G-CSF) and anti-microbials successfully reduced mortality due to FN.

Risk of chemotherapy-induced febrile neutropenia in intermediate-risk regimens: Clinical and economic outcomes of granulocyte colony-stimulating factor prophylaxis.

BACKGROUND: Chemotherapy-induced neutropenia increases the risk of febrile neutropenia (FN) and infection with resultant hospitalizations, with substantial health care resource utilization (HCRU) and costs. Granulocyte-colony stimulating factor (GCSF) is recommended as primary prophylaxis for chemotherapy regimens having more than a 20% risk of FN. Yet, for intermediate-risk (10%-20%) regimens, it should be considered only for patients with 1 or more clinical risk factors (RFs) for FN. It is unclear whether FN prophylaxis for intermediate-risk patients is being optimally implemented. OBJECTIVE: To examine RFs, prophylaxis use, HCRU, and costs associated with incident FN during chemotherapy. METHODS: This retrospective study used administrative claims data for commercial and Medicare Advantage enrollees with nonmyeloid cancer treated with intermediate-risk chemotherapy regimens during January 1, 2009, to March 31, 2020. Clinical RFs, GCSF prophylaxis, incident FN, HCRU, and costs were analyzed descriptively by receipt of primary GCSF, secondary GCSF, or no GCSF prophylaxis. Multivariable Cox regression analysis was used to examine the association between number of RFs and cumulative FN risk. RESULTS: The sample comprised 13,937 patients (mean age 67 years, 55% female). Patients had a mean of 2.3 RFs, the most common being recent surgery, were aged 65 years or greater, and had baseline liver or renal dysfunction; 98% had 1 or more RFs. However, only 35% of patients received primary prophylaxis; 12% received secondary prophylaxis. The hazard ratio of incident FN was higher with increasing number of RFs during the first line of therapy, yet more than 54% of patients received no prophylaxis, regardless of RFs. Use of GCSF prophylaxis varied more by chemotherapeutic regimen than by number of RFs. Among patients treated with rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride (doxorubicin hydrochloride), vincristine, and prednisone, 76% received primary prophylaxis, whereas only 22% of patients treated with carboplatin/paclitaxel received primary prophylaxis. Among patients with a first line of therapy FN event, 78% had an inpatient stay and 42% had an emergency visit. During cycle 1, mean FN-related coordination of benefits-adjusted medical costs per patient per month ($13,886 for patients with primary prophylaxis and $18,233 for those with none) were driven by inpatient hospitalizations, at 91% and 97%, respectively. CONCLUSIONS: Incident FN occurred more often with increasing numbers of RFs, but GCSF prophylaxis use did not rise correspondingly. Variation in prophylaxis use was greater based on regimen than RF number. Lower health care costs were observed among patients with primary prophylaxis use. Improved individual risk identification for intermediate-risk regimens and appropriate prophylaxis may decrease FN events toward the goal of better clinical and health care cost outcomes. DISCLOSURES: This work was funded by Sandoz Inc., which participated in the design of the study, interpretation of the data, writing and revision of the manuscript, and the decision to submit the manuscript for publication. The study was performed by Optum under contract with Sandoz Inc. The author(s) meet criteria for authorship as recommended by the International Committee of Medical Journal Editors. The authors received no direct compensation related to the development of the manuscript. Dr Li is an employee of Sandoz Inc. Drs Bell and Lal and Mr Peterson-Brandt were employees of Optum at the time of the study. Ms Anderson and Dr Aslam are employees of Optum. Dr Lyman has been primary investigator on a research grant from Amgen to their institution and has consulted for Sandoz, G1 Therapeutics, Partners Healthcare, BeyondSpring, ER Squibb, Merck, Jazz Pharm, Kallyope, Teva; Fresenius Kabi, Seattle Genetics, and Samsung.

Low pretherapy skeletal muscle mass index is associated with an increased risk of febrile neutropenia in patients with esophageal cancer receiving docetaxel + cisplatin + 5-fluorouracil (DCF) therapy

PurposeDocetaxel + cisplatin + 5-fluorouracil (DCF) therapy, a frequently prescribed regimen for esophageal cancer, is associated with a high risk of febrile neutropenia (FN). This study investigated whether a low skeletal muscle mass index (SMI) is an independent risk factor for FN.MethodsThis retrospective, observational study investigated the SMI of patients with esophageal cancer who received DCF therapy between March 2018 and July 2020. Based on the Asian sarcopenia criteria, patients were divided into two groups: high and low SMI (SMI of < 7.0 and 5.7 kg/m2 for males and females, respectively). The incidence of FN was then compared between the two groups.ResultsThirty-nine patients (20 and 19 in the high- and low-SMI groups, respectively) were included in this study. The incidence of FN was significantly higher in the low-SMI group (63.2% vs. 20.0%, P = 0.006). Univariable and multivariable logistic regression analyses revealed that a low SMI was an independent risk factor for FN (odds ratio, 7.178; 95% confidence interval, 1.272–40.507; P = 0.026). In addition, the frequency of dose reduction in DCF therapy was significantly higher in the low-SMI group (68.4% vs. 35.0%, P = 0.037).ConclusionLow SMI is an independent risk factor for FN in patients with esophageal cancer receiving DCF therapy.

Decreased febrile neutropenia during inpatient chemotherapy for urologic cancer during coronavirus disease 2019 pandemic.

Since 2020, the COVID‐19 pandemic has led to the widespread practice of hand hygiene and wearing face masks, not only among healthcare workers, but also among the general public. Thus, there is a need to verify the impact of the COVID‐19 pandemic on the incidence of febrile neutropenia (FN). This study aimed to examine the incidence of FN in hospitalized chemotherapy patients at Kanazawa University Hospital. Among inpatients at the Department of Urology receiving chemotherapy, we compared the incidence of FN between 317 cases in 2018–2019 and 276 cases in 2020. We retrospectively analyzed the factors of FN via binominal logistic regression analysis based on patient characteristics and the characteristics of primary diseases, with statistical significance set at p < 0.05. FN occurred in 20/317 cases in 2018–2019, but only in 1/276 cases in 2020, with a significant decrease in the latter (p = 0.005). On multivariate analysis, we identified the following independent risk factors for FN: non‐COVID‐19 era (p = 0.005), first course of therapy (p = 0.005), malnutrition (p = 0.032), and past history of FN (p = 0.018). Due to the COVID‐19 pandemic, hygiene policies for healthcare workers and quarantine measures for patients were thoroughly implemented. As a result, the incidence of FN in 2020 decreased to 1/15 of the previous incidence. Thus, hygiene measures for healthcare workers and patients during the expected period of chemotherapy‐induced neutropenia are important for FN prevention.

Impact of oral hygiene on febrile neutropenia during breast cancer chemotherapy.

Oral hygiene is crucial in the management of oral and febrile complications during chemotherapy for cancer. This study aimed to investigate the impact of oral hygiene on the incidence of febrile neutropenia (FN) throughout the course of chemotherapy for breast cancer. A total of 137 patients with breast cancer who underwent four cycles of adjuvant chemotherapy with docetaxel and cyclophosphamide (TC) combination therapy or docetaxel alone were assessed for oral hygiene by quantifying the number of oral bacteria they harbored. These patients received professional oral health care (POHC). Eighteen patients underwent primary prophylaxis with granulocyte colony-stimulating factors. The relationship between oral bacteria count and FN incidence was retrospectively assessed. The FN incidence rate was 47.4% throughout all treatment cycles (32.8%, 13.5%, 14.3%, and 14.4% in cycles 1, 2, 3, and 4, respectively). The oral bacteria count decreased with each treatment cycle (cycle 1: 9.10 × 106 colony-forming units (CFU)/mL, cycle 2: 5.89 × 106CFU/mL, cycle 3: 4.61 × 106CFU/mL, cycle 4: 5.85 × 106CFU/mL, P = 0.004). Among 281 treatment cycles, FN occurred in 63 (22.4%). In the treatment cycle-based analysis, high oral bacteria count was an independent risk factor for FN. FN incidence decreased with each treatment cycle and was associated with changes in oral bacteria counts. The oral bacterial count was one of risk factors for FN development in breast cancer.

Maximum daily dose of G-CSF is critical for preventing recurrence of febrile neutropenia in patients with gynecologic cancer: A case-control study.

No study has evaluated the effect of therapeutic granulocyte colony-stimulating factor (G-CSF) in preventing recurrence of febrile neutropenia (FN) and survival outcomes in gynecologic cancer patients. Objective of this study is to optimize and to identify the use of G-CSF and identify the critical factors for preventing the recurrence of FN in women undergoing chemotherapy for the treatment of gynecologic cancer.The medical records of consecutive patients who underwent chemotherapy for the treatment of gynecologic cancer and experienced FN at least once were retrospectively reviewed. Clinico-laboratory variables were compared between those with and without recurrence of FN to identify risk factors for the recurrence and the most optimal usage of G-CSF that can prevent FN. Student t test, χ2 test, and multivariate Cox regression analysis were used.A total of 157 patients who met the inclusion criteria were included. Of 157, 49 (31.2%) experienced recurrence of FN. Age ≥55 years (P = .043), previous lines of chemotherapy ≤1 (P = .002), thrombocytopenia (P = .025), total dose (P = .003), and maximum daily dose (P = .009) of G-CSF were significantly associated with recurrence of FN. Multiple regression analysis showed that age ≥55 years (HR, 2.42; 95% CI, 1.14–5.14; P = .022), previous chemotherapy ≤1 (HR, 4.01; 95% CI, 1.40–11.55; P = .010), and maximum daily dose of G-CSF ≤600 μg (HR, 5.18; 95% CI, 1.12–24.02; P = .036) were independent risk factors for recurrent FN. Multivariate Cox regression analysis showed that a maximum daily dose of G-CSF ≤600 μg was the only independent risk factor for short recurrence-free survival of FN (HR, 4.75; 95% CI, 1.15–19.56; P = .031).Dose-dense administration of G-CSF >600 μg/day could prevent recurrence of FN in women who undergo chemotherapy for the treatment of gynecologic cancer and FN. Old age and FN at early lines of chemotherapy seem to be associated with FN recurrence.

Incidence of severe and febrile neutropenia in cancer patients treated with myelosuppressive chemotherapy in real clinical oncology practice: Preliminary results from the FLAME study.

e18740 Background: Febrile neutropenia (FN) is a life-threatening complication of myelosuppressive chemotherapy (CT). It can lead to infections, subsequent hospitalizations, treatment delays, dose reductions, and additional health care costs. According to guidelines, use of granulocyte colony-stimulating factors (G-CSF) prevents FN. However, in clinical practice, the need for G-CSF use has not been defined due to the lack of national reports on neutropenic complications (NC). Methods: FLAME is the first Russian retrospective non-randomized non-interventional study designed to include 515 patients (pts) with solid tumors receiving myelosuppressive CT with or without targeting and immuno-oncology drugs. The primary objective of this study is to define the actual incidence of NC in clinical practice and to identify patients at high risk of FN. In addition, this study is intended to demonstrate the unmet need for G-CSF prophylaxis of FN. Patients who completed at least the first 2 cycles of treatment in frame of the course between the 1st’Aug 2020 till 30th’October 2021 were eligible to be included in the study. Results: Data were obtained from 492 pts recruited from cancer hospitals throughout Russia. Their characteristics were as follows: median age 56.5; male/female: 36.5%/63.5%. Among 492 pts with various malignancies, 65% had stage III or IV. Breast (68%), colorectal (10%), urogynecological cancer (10%) were the most common. The remaining were gastrointestinal cancer, lung cancer, sarcoma, and CUP. Clinically significant comorbidities were reported in 53.6% of pts. Thirty percent of patients had ≥1 risk factor for FN based on individual and CT analysis. From 29 different CT regimens, 14% had a high risk of FN. Primary prophylaxis was given only to 44.1% pts with a high risk of FN [empegfilgrastim (Extimia®) 19,1%, filgrastim 25%]. The duration of filgrastim administration was 1 to 3 days in 81% of cases. Treatment of NC with corticosteroids and others was prescribed in 12.8% of cases. Three percent (3%) and 3.8% of pts had FN and dose-limiting neutropenia, respectively. Delayed CT at the second cycle was performed in 27%. The dose of CT was reduced by 20-25% in 8.3% of patients. Conclusions: Preliminary results from this study suggest that the risk of FN is higher from the start of CT. Delaying and reducing the dose of CT is still typical for oncologists. This practice is associated with low adherence to guidelines. Further efforts are needed to decrease the risk of NC in clinical practice.

Malnutrition as Risk Factor for Febrile Neutropenia in Children with Acute Lymphoblastic Leukemia

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Febrile neutropenia is one of medical emergencies in ALL patients. One of the risk factors that associate with febrile neutropenia is malnutrition. Malnutrition reduce the body’s immunity that increase incidence of infection.&#x0D; AIM: aimed to prove malnutrition as risk factor in children with ALL who had febrile neutropenia&#x0D; METHOD: This is case-control study with samples a hundred children aged 1 month to 18 years old with ALL at Sanglah Hospital Denpasar between 2015 - 2021. Subjects were grouped into two, those with febrile neutropenia and without febrile neutropenia. The relationship between malnutrition and febrile neutropenia was analyzed by using chi-square bivariate analysis test.&#x0D; &#x0D; RESULTS: A hundred subjects were devided into two groups with 50 subjects each group. Bivariate analysis showed significant association between malnutrition and febrile neutropenia (OR 4.53; 95%CI 1.95 - 10.51; p-value &lt;0.001).&#x0D; CONCLUSION: Malnutrition as risk factor for febrile neutropenia in children with ALL.&#x0D;