Febrile Neutropenia In Patients Research Articles

Early Therapeutic Drug Monitoring Optimizes Teicoplanin Use in Febrile Neutropenic Patients with Hematological Malignancies.

A target trough concentration (Cmin) of teicoplanin ≥ 15-20mg/L between the fourth and sixth day has been suggested for severe infections or management of febrile neutropenia (FN). Owing to no reports discussing the impact of early target attainment on treatment outcomes, this study aimed to evaluate the dose-Cmin relationship and clinical outcome and estimate the optimal early target Cmin for FN in patients with hematological malignancies. This single-center, prospective study enrolled patients with hematological malignancies who were treated with teicoplanin either as an empirical antibiotic for FN or as targeted treatment for Gram-positive bacteria. Blood samples were collected on day three (48h) post-loading doses, day5 (96h), and day8 (when applicable) and determined by ultrahigh-pressure liquid chromatography-triple quadruple mass spectrometry. A total of 117 samples from 47 patients with FN (27 men, 20 women) were consecutively analyzed. A two-tailed αvalue of 0.05 was considered statistically significant. The mean Cmin values at 48h, 96h, and on day8 were 23.4, 21.4, and 27.8mg/L, respectively. The patients achieving Cmin ≥ 20mg/L at 48h had a higher likelihood of treatment success. The areas under the receiver operating characteristic curves were 0.71 for clinical efficacy and the cutoff value of Cmin at 48h was 18.85mg/L (95% confidence interval 0.55-0.87; P = 0.018). The Cmin of teicoplanin after completion of loading doses could predict the treatment response, with a target concentration ≥ 18.85mg/L.

Effectiveness and safety of empegfilgrastim (Extimia®, BIOCAD) in patients with lymphoproliferative diseases receiving cytotoxic therapy: results of LEGERITY, a multicenter retrospective-and-prospective observational post-marketing study

Aim. To evaluate the effectiveness and safety of Extimia® BIOCAD (international non-proprietary name: empegfilgrastim) to reduce the incidence and duration of neutropenia, the incidence of febrile neutropenia (FN) and infections associated with FN in patients with lymphoproliferative diseases receiving myelosuppressive therapy.
 Materials and methods. The paper presents the results of a multicenter retrospective-and-prospective observational post-marketing study of the safety and effectiveness of Extimia® BIOCAD (international non-proprietary name: empegfilgrastim) in patients with lymphoproliferative diseases receiving cytotoxic therapy. Initially, the study was defined as retrospective-and-prospective. However, only 2 of 671 (0.3%) patients were included retrospectively. Thus, the study is based on the evaluation of prospectively collected data. The analysis describes the characteristics and treatment of 671 patients diagnosed with lymphoma who received one or more cycles of chemotherapy in the LEGERITY study. The endpoints of interest included the incidence of grade 3–4 neutropenia, FN, and grade 3–4 infectious complications, the frequency of antibiotic therapy, and the incidence of all adverse reactions in patients who received at least one dose of the study medication.
 Results. A total of 671 patients were enrolled in the study, the majority having B-cell non-Hodgkin lymphoma (428/671, 64%) and Hodgkin lymphoma (211/671, 31%). The mean age was 54 years (18–84); 35% (236/671) of patients were elderly (over 60). The number of injections of empegfilgrastim for the entire observation period was 3093 (n=671). Adverse events were reported in 57/3093 (1.8%) cases. The most common adverse events were mild to moderate ossalgia and myalgia (27/671, 4%), back pain, and arthralgia (12/671, 1.8%), which did not require drug therapy. Two patients developed serious adverse reactions – CTCAE v.5 grade 4 hypotension events. 529 (78.8%) patients received at least 4 courses of chemotherapy. FN was reported in 14 (2.6%) patients and did not require antimicrobial therapy.
 Conclusion. The final analysis results confirm the high clinical efficacy and safety of the Russian original pegylated granulocyte colony-stimulating factor empegfilgrastim (Extimia®) in patients with indolent and aggressive lymphomas. The data obtained from real-world clinical practice demonstrate a favorable safety and tolerability profile of empegfilgrastim in all age groups, including the elderly population.

Point of care thoracic ultrasound versus chest computed tomography in the approach of febrile neutropenia patients: A diagnostic accuracy cohort study.

Single-center prospective cohort diagnostic accuracy study. Our study aimed to evaluate the accuracy and reproducibility of Thoracic Ultrasound (TUS) in detecting pulmonary pathology in immunosuppressed patients. We conducted a single-center prospective study. Consecutive patients with febrile neutropenia who underwent CT (Computerized Tomography) underwent TUS evaluation within 24h of CT. Both studies were performed by an expert who was blinded to the clinical information and results of the alternative imaging modalities. 34 patients met the inclusion criteria. The median age was 39.9 years (±17 standard deviation). TUS as a diagnostic test had a sensitivity of 92.9% and specificity of 83.3%, negative predictive value of 71.4%, and positive predictive value of 96.3%. Substantial between-method agreement was demonstrated with a kappa of 0.71 (P = .001) between the TUS and chest CT findings. We obtained a kappa of 1 (P = .001) for the final diagnosis of Pleural Effusion (PE). We concluded that TUS is a promising screening test for immunocompromised individuals. The results showed good diagnostic performance of TUS compared to CT for the detection of pulmonary findings highly suggestive of pathology with high accuracy and reproducibility.

Effectiveness and safety of primary prophylaxis with G-CSF for lung cancer: a systematic review and meta-analysis to develop clinical practice guidelines for the use of G-CSF 2022.

Granulocyte colony-stimulating factor (G-CSF) is commonly administered to cancer patients undergoing myelosuppressive chemotherapy, especially when incidence rate of febrile neutropenia (FN) surpasses 20%. While primary prophylaxis with G-CSF has been proven effective in preventing FN in patients with cancer, there is limited evidence regarding its efficacy in specifically, lung cancer. Our systematic review focused on the efficacy of G-CSF primary prophylaxis in lung cancer. We extracted studies on non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) using the PubMed, Ichushi Web, and Cochrane Library databases. Two reviewers assessed the extracted studies for each type of lung cancer and conducted quantitative and meta-analyses of preplanned outcomes, including overall survival, FN incidence, infection-related mortality, quality of life, and musculoskeletal pain. A limited number of studies were extracted: two on NSCLC and six on SCLC. A meta-analysis was not conducted owing to insufficient data on NSCLC. Two case-control studies explored the efficacy of primary prophylaxis with G-CSF in patients with NSCLC (on docetaxel and ramucirumab therapy) and indicated a lower FN frequency with G-CSF. For SCLC, meta-analysis of five studies showed no significant reduction in FN incidence, with an odds ratio of 0.38 (95% confidence interval 0.03-5.56, P = 0.48). Outcomes other than FN incidence could not be evaluated due to low data availability. Limited data are available on G-CSF prophylaxis in lung cancer. Primary prophylaxis with G-CSF may be weakly recommended in Japanese patients with NSCLC undergoing docetaxel and ramucirumab combination therapy.

Approach to febrile neutropenia in patients undergoing treatments for hematologic malignancies.

Febrile neutropenia (FN) is common among hematologic malignancy patients, including recipients of hematopoietic cell transplantation (HCT) and cellular therapies such as chimeric antigen receptor (CAR)-T-cell therapy. Prompt empiric antibiotic use has been the mainstay for decades but a "one-size-fits-all" approach is no longer broadly accepted, as treatment-related infectious risk are more understood. Growing antimicrobial resistance is an increasing clinical challenge. Evolving strategies on de-escalation of broad-spectrum antibiotics in FN without identified infection are areas of particular interest.

Predictive Model for Occurrence of Febrile Neutropenia after Chemotherapy in Patients with Diffuse Large B-Cell Lymphoma: A Multicenter, Retrospective, Observational Study.

Febrile neutropenia (FN) is a major concern in patients undergoing chemotherapy for diffuse large B-cell lymphoma (DLBCL); however, the overall risk of FN is difficult to assess. This study aimed to develop a model for predicting the occurrence of FN in patients with DLBCL. In this multicenter, retrospective, observational analysis, a multivariate logistic regression model was used to analyze the association between FN incidence and pretreatment clinical factors. We included adult inpatients and outpatients (aged ≥ 18 years) diagnosed with DLBCL who were treated with chemotherapy. The study examined 246 patients. Considering FN occurring during the first cycle of chemotherapy as the primary outcome, a predictive model with a total score of 5 points was constructed as follows: 1 point each for a positive hepatitis panel, extranodal involvement, and a high level of soluble interleukin-2 receptor and 2 points for lymphopenia. The area under the receiver operating characteristic curve of this model was 0.844 (95% confidence interval: 0.777-0.911). Our predictive model can assess the risk of FN before patients with DLBCL start chemotherapy, leading to better outcomes.

Code Heat: Integrating a New Rapid Response in a Blood and Marrow Transplant (BMT) Unit for Febrile Neutropenia Patients to Decrease Time to Antibiotic Administration

Code Heat: Integrating a New Rapid Response in a Blood and Marrow Transplant (BMT) Unit for Febrile Neutropenia Patients to Decrease Time to Antibiotic Administration

Assessment of Delay in Door-to-antibiotic Administration Time after Arrival to the Hospital among Post-chemotherapy Febrile Neutropenia Patients: A Cohort Study

ntroduction: Febrile Neutropenia (FN), a common side effect of chemotherapy, is regarded as an oncologic emergency necessitating prompt treatment. A delay in door-to-antibiotic administration time is associated with poor patient outcomes. Aim: To assess the time lag in the administration of antibiotics after arrival at the hospital in patients with solid/haematological malignancy presenting with post-chemotherapy FN. Materials and Methods: This was a cohort study conducted in the Department of Medical Oncology at Bhagwan Mahaveer Cancer Hospital and Research Centre, Jaipur, Rajasthan, India, over a period of one year from December 2019 to November 2020 among 80 patients with solid or haematological malignancy who presented with fever and Absolute Neutrophil Count (ANC) <1000/mm3 to the Outpatient Department (OPD) or the Emergency Department and were diagnosed with FN post-chemotherapy. Upon obtaining consent, these patients were enrolled, and the timing of antibiotic administration was noted for the study participants. The participants were further followed-up for the assessment of morbidity {in terms of Intensive Care Unit (ICU) admission)}, duration of hospital stay, delay in the further chemotherapy schedule, and survival status. Data was entered into MS Excel and analysed using Statistical Packages for Social Sciences (SPSS) version 16.0. Associations were established using Chi-square tests. Results: Out of a total of 80 study participants, the mean±SD age was 45.6±18.3 years, and the number of males was 43 (53.8%). Total 57 (71.25%) patients were on chemotherapy for solid organ malignancies. The median delay in door-to-antibiotic time was 120 minutes (ranging from 30 to 260 minutes). The median day of presentation with FN after chemotherapy was day 7. Delay in antibiotic administration was found to have a significant impact on the further chemotherapy schedule and doses (p=0.004). However, ICU admission rates (p=0.133), length of hospital stay (p=0.662), and mortality (p=0.201) were not significantly associated with the delay in antibiotic administration. Conclusion: The adoption of standardised algorithms and protocols for the management of FN and ensuring timely healthseeking by the patients shall help reduce the delay in Time-toantibiotic Administration (TTA).

Pharmacoeconomic analysis of using empegfilgrastim for the treatment of early and locally advanced HER2+ breast cancer in the Russian Federation

Objective: to assess budget impact of using empegfilgrastim for the prevention of febrile neutropenia in patients with early and locally advanced human epidermal growth factor receptor 2 positive (HER2+) breast cancer who receive neoadjuvant “docetaxel / carboplatin / trastuzumab + pertuzumab” regimen, considering possible subsequent adjuvant therapy with trastuzumab emtansine or trastuzumab within the Russian healthcare system.Material and methods. We searched and analyzed published clinical, epidemiological and pharmacoeconomic studies as well as regulatory and legal documents. A decision tree model was constructed to reflect the probabilities of switching to different adjuvant therapy regimens depending on the achievement of pathomorphological complete response in patients with early and locally advanced HER2+ breast cancer. The budget impact analysis was carried out comparing two primary prophylactic options, empegfilgrastim and filgrastim.Results. Despite the higher costs of prevention with empegfilgrastim compared to filgrastim (249 vs. 134 thousand rubles), due to the higher rate of achieving a pathomorphological complete response and, accordingly, fewer cases requiring adjuvant therapy with the more expensive trastuzumab emtanzine, savings of 916 thousand rubles per 1 patient per 1 year of therapy are possible. In general, prophylaxis in the target population diagnosed with early and locally advanced HER2+ breast cancer using empegfilgrastim will result in a cost reduction of 9.4 billion rubles per 1 year compared to filgrastim.Conclusion. Empegfilgrastim prophylaxis, despite its higher annual cost, is an efficient option within the Russian healthcare system. In addition to reducing the incidence of febrile neutropenia, the frequency and dose of chemotherapy are preserved, resulting in increased efficacy of the primary therapy.

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.

Lower uric acid and adequate hydration are associated with lower risk of febrile neutropenia following autologous bone marrow transplantation in patients with lymphoma

Background. Despite the promising results of autologous bone marrow transplantation (BMT) in patients with lymphoma, infectious complications limit its positive outcomes. This study evaluated the incidence and associated factors of febrile neutropenia (FN) following BMT in patients with lymphoma. Materials and methods. The study consecutively included 147 patients with lymphoma who were candidates for BMT. Clinical and laboratory results were recorded, and after BMT, the occurrence of FN was investigated through the daily evaluation of neutrophil count and body temperature. Results. On average, FN occurred in 91 patients (61.9%) after 12.77 ± 2.45 days after BMT. Lower fluid balance was associated with a higher risk of FN (lowest adjusted odds ratio [OR] at day -2 = 0.602, 95% confidence interval [CI] = 0.299 – 0.870, p-value = 0.007). The higher uric acid level was associated with a higher risk of FN (highest adjusted OR at day -10 = 1.617, 95% CI = 1.328 – 1.963, p-value = 0.035). LDH was also positively correlated with FN (highest adjusted OR at day 0 = 1.501, 95% CI = 1.198 – 2.104, p-value = 0.004). Conclusions. Adequate hydration of the patients is of paramount importance for preventing FN in patients who receive BMT. Furthermore, uric acid and LDH could be considered in future studies for the risk stratification of FN.

Meta-Analysis of Randomized Controlled Trials to Evaluate the Incidence of Pneumonia, Upper Respiratory Tract Infections and Febrile Neutropenia in Patients with Multiple Myeloma Treated with Isatuximab

Introduction Multiple myeloma is a cancer of plasma cell and accounts for approximately 13% of all haematologic malignancies. Isatuximab is an anti CD38 IgG1 monoclonal antibody which binds to and kills myeloma cells through antibody-dependent cellular-mediated cytotoxicity, complement-dependent cytotoxicity, antibody-dependent cellular phagocytosis, and direct induction of apoptosis. The incorporation of isatuximab to standard treatment in patients with relapsed refractory multiple myeloma (RRMM) has shown to significantly improve efficacy, with notable toxicities. We performed a combined analysis of randomized controlled trials (RCT) to determine the risk of pneumonia and upper respiratory tract infections (URTIs) and febrile neutropenia in patients with RRMM treated with isatuximab. Methods We systematically conducted a comprehensive literature search using MEDLINE, EMBASE databases and meeting abstracts from inception through June 30 th, 2023. Phase III RCTs utilizing isatuximab in patients with relapsed or refractory multiple myeloma that mention pneumonia, URTIs and febrile neutropenia as adverse effects were incorporated in the analysis. Mantel-Haenszel (MH) method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). Heterogeneity was assessed with Cochran's Q- statistic. Random effects model was applied. Results A total of 600 patients with RRMM from 2 phase III RCTs (ICARIA-MM and IKEMA) were eligible. ICARIA-MM and IKEMA compared isatuximab (I) + pomalidomide (P) + dexamethasone (d) vs Pd, and isatuximab (I) + Carfilzomib (K) + dexamethasone (d) vs Kd respectively. The randomization ratios were 1:1 in ICARIA-MM, and 3:2 in IKEMA studies. The I 2 statistic for heterogeneity was 0, suggesting homogeneity among RCT. The incidence of any-grade pneumonia was 30.1% in study group vs 25.8% in control group (RR, 1.19; 95% CI: 0.91 - 1.54; P=0.20). High-grade pneumonia rate was nearly 4% higher in isatuximab group compared to control arm but RR was not statistically significant at 1.26 (95% CI: 0.90 - 1.75; P = 0.18). More events of any-grade URTIs were reported in study arm (36.8%) versus 23.2% in control arm with RR of 1.55 (95% CI: 1.20- 2.01; P = 0.0008). The incidence of high-grade URTIs was low in both groups: 3.3% in study group versus 1.47% in control arm (RR, 2.25; 95% CI: 0.72 - 6.98; P = 0.16). Febrile neutropenia was noted in 20 (6%) of patients in study group compared to 5 (1.8%) in control group with RR of 3.52 (95% CI: 1.40- 8.83; P = 0.007). Conclusions Our meta-analysis showed that the addition of isatuximab to standard anti-myeloma regimen contributed to higher incidence of any-grade URTIs and febrile neutropenia in patients with RRMM, with RR of 1.55 for any-grade URTIs and RR of 3.5 for febrile neutropenia. However, risks of high-grade URTIs, any-grade and high-grade pneumonia were found to be statistically not significant between the two groups. Early recognition and proper supportive care are required to improve any-grade URTIs and febrile neutropenia.

A Pilot Study to Determine the Safety and Efficacy of Repeated Hyperbaric Oxygen Therapy in Multiple Myeloma Patients Undergoing High-Dose Therapy and Autologous Stem/Progenitor Cell Transplantation

Background Serum erythropoietin (EPO) negatively impacts hematopoietic stem cell homing and engraftment. Hyperbaric oxygen (HBO) therapy can reduce serum EPO in healthy volunteers and when given prior to stem cell infusion may improve engraftment after hematopoietic stem cell transplant (HSCT). We previously performed a phase II trial randomizing patients with multiple myeloma undergoing high dose melphalan and autologous HSCT 1:1 between a single HBO treatment and no HBO. HBO was given as 100% oxygen, 2.5 ATA for a total of 90 min, in a single treatment on Day 0 prior to the transplant. A total of 99 patients were enrolled with 52 randomized to HBO. HBO significantly reduced EPO levels for the first 24 hours after auto transplant, but EPO levels quickly rebounded by 48 hours after transplant. We hypothesized multiple HBO treatments will keep EPO levels low during the duration of stem cell homing (i.e: the first 72 hours after HSCT) and may improve neutrophil and NK cell recovery. Methods We performed a pilot study to evaluate the safety and tolerability of multiple HBO treatments during autologous HSCT. Patients with multiple myeloma undergoing autologous HSCT were eligible. Patients received HBO therapy, consisting of hyperbaric oxygen at 2.5 ATA for a total of 90 minutes breathing 100% oxygen on days 0 (prior to HSCT), 1, and 2 of transplant. The primary objective of this pilot study was to determine the safety of repeated HBO therapy in the setting, as defined by treatment limiting toxicity (TLT) including occurrence of seizure disorder, pneumothorax, death, or any irreversible grade Ill or any grade IV toxicity within 24 hours of HBO therapy. Secondary objectives were to determine the effects of multiple HBO therapy on neutrophil count recovery and the effect of multiple HBO on serum EPO. Results 10 patients have been enrolled that are evaluable for the primary objective. All patients had multiple myeloma and 4 were female. 9/10 patients successfully completed all 3 HBO treatments and 1/10 completed HBO on days 1 and 2 only because of ear pain on day 0. No patients experienced treatment limiting toxicity. The median times to neutrophil and platelet engraftment was 12 days (range 11-14) and 16 days (range 14-28), respectively. The median length of hospitalization was 13 days (range 12-16). Febrile neutropenia occurred in 3/10 patients with just one incidence of documented infection. This was significantly less than the rate of febrile neutropenia in patients receiving a single treatment of HBO or no HBO (81% and 47%, respectively, p<0.05). 3 patients required red blood cell transfusion and 5 platelet transfusion. Conclusions Multiple HBO treatment were well tolerated without treatment limiting toxicity during autologous HSCT for multiple myeloma.

1653. Cost effectiveness of Levofloxacin Vs Amoxicillin/Clavulanate And Ciprofloxacin In The Outpatient Management Of Low-Risk Febrile Neutropaenia In Children With Cancer: A Randomised Control Study.

Abstract Background outpatient management of low-risk fever and neutropenia should be implemented if close monitoring is accessible and patient compliance is feasible.In this study, we aimed to assess the efficacy and safety of single-agent Levofloxacin versus the Augmentin /ciprofloxacin regimen used in our institute. Methods This is a randomized prospective interventional 2 arm study of low-risk febrile neutropenia patients presenting to the emergency department at the National Cancer Institute, Cairo University starting from December 2021 to July 2022. Eligible patients were children< 18 years with Low-risk febrile neutropenia without an aetiological diagnosis.Patients were randomized to double-agent ciprofloxacin and amoxicillin-clavulanic acid in comparison to single-agent levofloxacin. Follow up of the outpatient cases on; Day 1, Day 3, and Day 7 for Resolution of infection and stopping of antibiotics regardless of neutropenia. Drug-related side effects encountered in both arms of the study were reported. A decision analytic model was created to compare the two different treatment strategies Outcome measures were quality-adjusted FN episodes, costs, and incremental cost-effectiveness ratios (ICER). The clinical parameters of the model were derived mainly from data collected at National Cancer Institute. Health effects were expressed in terms of QALY gain.One-way sensitivity analysis (DSA) was conducted. Results 200 patients (100 in each group) were enrolled. 100% of patients achieved marrow recovery in both arms by D7. Fever subsided in 100% on the Levofloxacin arm compared to 60% in the other group. only 1 patient on the double agent arm was upgraded to HR.Levofloxacin was tolerable in all patients with no significant side effects, while patients in the double agent arm; 4 had diarrhea, 2 nausea, and 2 complained of a bad drug taste. Levofloxacin is the dominant strategy versus Augmentin/ciprofloxacin with incremental QALY 0.0001and lower cost 62.4996 L.E in the treatment of home-based care of febrile neutropenia with a willingness to pay threshold of 77,520 LE per QALY (1 GDP/CAPITA) Figure 1 Conclusion Levofloxacin is cost effective and can be administered safely in children with low-risk FN, however close follow-up for long-term side effects and emerging bacterial resistance is warranted. Disclosures All Authors: No reported disclosures

Utilization of cefepime therapeutic drug monitoring in febrile neutropenia patients with hematologic malignancies

Introduction Cefepime is a fourth-generation cephalosporin and is a workhorse for the empiric treatment of febrile neutropenia (FN). Beta-lactam therapeutic drug monitoring (TDM) has emerged as a dose optimization strategy in patient populations with altered kinetics. Prior literature has demonstrated that patients with FN exhibit augmented renal clearance which may lead to subtherapeutic drug concentrations with standard dosing regimens. The aim of this study was to evaluate pharmacokinetic/pharmacodynamic (PK/PD) target attainment and clinical outcomes in patients with hematologic malignancies and FN who were treated empirically with cefepime. Methods This was a prospective, single-center study of adults with hematologic malignancies and FN admitted to the inpatient unit. The primary outcome was PK/PD target attainment (defined as 100% free time greater than minimum inhibitory concentration (100% fT > MIC)). Secondary clinical outcomes were time to defervescence, time to ANC recovery, in-hospital mortality, and cefepime failure. Results There were 55 patients in our study. Forty-three (78%) patients achieved the primary outcome of PK/PD target attainment. The mean time to defervescence was similar between those that achieved PK/PD target attainment and those that did not (95% CI −0.75 to 1.25, p = 0.62). Conclusions This study showed that standard cefepime dosing in patients with hematologic malignancies and FN does not result in achievement of 100% fT > MIC in all patients. Patients in the group that did not achieve PK/PD target attainment were younger with increased creatinine clearance, indicating that cefepime TDM may be especially beneficial in these patients.

Predictors of the development of febrile neutropenia in chemotherapy for advanced germ cell tumors.

To identify the predictive factors for the development of febrile neutropenia (FN) in the course of chemotherapy for patients with germ cell tumors. From January 2005 to December 2018, 80 patients were treated with induction chemotherapy for advanced germ cell tumors at Kanagawa Cancer Center Hospital, Japan. Of these, we retrospectively analyzed 267 cycles of chemotherapy. The incidence of FN was used as the objective variable. As predictive factors, we analyzed age, international germ cell consensus classification (IGCCC), laboratory data at the start of chemotherapy in each cycle, length of the largest metastatic lesion, number of cycles, and prophylactic use of granulocyte colony stimulating factor (G-CSF). We finally analyzed 267 cycles in 78 patients. The median age was 36 years (15-64). There was a total of 267 cycles. FN occurred in 40 cycles (15%) in 31 patients (40%). The first cycle was accompanied by a significantly higher FN than the subsequent cycles (p < 0.001). The univariate analysis identified age ≧36 years (p = 0.001), creatinine clearance (CCr) <70 (p < 0.001), serum albumin <3.3 (p = 0.002), maximum tumor diameter ≧60 mm (p = 0.036), and first cycle as significant risk factors. The multivariate analysis identified age, CCr, and first cycle as independent predictive factors of FN development. We identified older age, renal dysfunction, and first cycle of chemotherapy as predictive factors for FN. No statistically significant difference was shown in the usage of prophylactic G-CSF. Special attention should be given to FN in patients with high-risk factors.

Assessment of Antimicrobial Utilization among Cancer Patients with Febrile Neutropenia at the Lebanese Hospitals.

Febrile neutropenia is a prevalent oncologic complication. Initiating rapid treatment with empirical antimicrobials in febrile neutropenia patients reduces mortality due to infections. The study aims to evaluate antimicrobial utilization among FN patients in Lebanon in terms of drug choice, dose, and duration of the treatment. This is a retrospective, multicenter, observational study conducted at three different Lebanese university hospitals (in which the Infectious Diseases Society of America (IDSA) guidelines are adopted), between February 2014 and May 2017. Adult cancer patients aged 18 years and older with febrile neutropenia were included in the study. Using the IDSA guidelines as a reference, patients were assessed whether they received the antimicrobial regimen inconsistent with the IDSA reference or not. Statistical analysis was performed using the Statistical Package for the Social Science software (SPSS version 22.0). The adherence to guidelines for the indication and doses of antibiotics and anti-fungal in patients with febrile neutropenia. A total of 124 patients with a mean age of 54.43 ± 17.86 years were enrolled in the study. Leukemia (29.7%) was the most prevalent cancer and the most common infection was sepsis (20.2%). Combination antibiotic lactams are the most prescribed antibiotics (86.8%). Only 94 (86.23%) patients were given the antibiotic therapy appropriate for choice, dose, and duration. Empirical antifungal therapy was initiated in 63.7% of the patients and fluconazole was the most used antifungal (36.3%). In contrast to antibiotics, the majority of antifungal choices were not selected according to the recommendations and they were considered inappropriate for doses and the required treatment duration as proposed by (IDSA). Fifty-eight percent of patients received antivirals, even though it is not recommended as empirical treatment. In conclusion, this study reveals a non-consistent antimicrobial utilization practice at the involved sites concerning FN treatment. Inappropriateness was encountered in drug selection, dose, and duration of treatment with antifungals and antivirals.

Respiratory viral infections in pediatric hematology/oncology patients

Respiratory viral infections (RVIs) are the most frequent type of infection in the pediatric population, and are identified in up to 57 % of episodes of febrile neutropenia (FN). Nevertheless, they are frequently overlooked and have been historically considered inconsequential in infection treatment strategies for FN patients. Over the past two decades, a rekindled interest has provided insights into the epidemiology and clinical impact of RVIs in FN settings. This, along with the SARS-CoV-2 pandemic and its impact on molecular testing, as well as breakthroughs in immunology host-pathogen interactions, has set up the stage for re-instating the debate on RVIs role in FN. Capitalizing on these milestones, we propose a path to optimize diagnosis and treatment in RVIs afflicted FN patients, which could minimize hospitalizations and antimicrobial use. We also delve into the innate immunity's distinguishing features in response to RVIs, highlighting the importance of grounding therapeutic strategies in this understanding, while exploring the most recent research breakthroughs proposing immune-guided approaches that examine the impact of RVIs on host outcomes and susceptibility to co-infections. In conclusion, we call for future research to be geared toward enhancing RVIs diagnosis, understanding host-microorganism interactions more deeply, incorporating RVIs considerations into antimicrobial stewardship, and evaluating the cost-effectiveness of routine RVIs testing. This multifaceted approach could reduce antimicrobial resistance, as well as direct and indirect mortality rates in pediatric oncology.

Prior treatment with oxaliplatin-containing regimens and higher total bilirubin levels are risk factors for neutropenia and febrile neutropenia in patients with gastric or esophagogastric junction cancer receiving weekly paclitaxel and ramucirumab therapy: a single center retrospective study

BackgroundWeekly paclitaxel + ramucirumab (wPTX + RAM) therapy is recommended as the standard second-line chemotherapy regimen for unresectable advanced/recurrent gastric cancer (GC) or esophagogastric junction cancer. Recent subgroup analysis of the RAINBOW trial revealed a higher frequency of severe neutropenia due to wPTX + RAM in Japanese compared to Western patients. However, no risk factors for severe neutropenia have been identified.MethodsThis retrospective observational study included patients with advanced/unresectable gastric or esophagogastric junction cancer who received wPTX + RAM after failure to respond to platinum and fluoropyrimidine doublet chemotherapy between June 2015 and April 2020. We conducted multivariable logistic regression analyses to identify the risk factors associated with grade 4 neutropenia and febrile neutropenia (FN). In addition, we investigated the relationship between the number of risk factors and overall survival (OS) and progression-free survival (PFS).ResultsAmong 66 patients who met the inclusion criteria, grade 4 neutropenia and FN occurred in 21 (31.8%) and 12 (18.2%) patients, respectively. Prior treatment with oxaliplatin-containing regimens was identified as an independent risk factor for developing grade 4 neutropenia (odds ratio (OR) 20.034, 95% confidence interval (95% CI) 3.216–124.807, P = 0.001). Total bilirubin of > 1.5 mg/dL (OR 31.316, 95% CI 2.052–477.843, P = 0.013) and prior treatment with oxaliplatin-containing regimen (OR 12.502, 95% CI 1.141–137.022, P = 0.039) were identified as independent risk factors for developing FN. Next, we classified patients with 0, 1, 2 risk factor(s) as RF-0, RF-1, and RF-2 subgroups, respectively, and compared the PFS and OS among the three subgroups. PFS was not significantly different among the three subgroups, whereas OS was significantly shorter in the RF-2 subgroup (median 1.4 month, 95% CI 0.0–5.3 month) than in the RF-0 subgroup (median 10.2 month, 95% CI 6.8–13.5 month, P < 0.01 vs RF-2) and RF-1 subgroup (median 13.3 month, 95% CI 10.9–15.7 month, P < 0.01 vs RF-2).ConclusionsCareful monitoring for grade 4 neutropenia and FN is needed for patients receiving wPTX + RAM therapy who have a history of treatment with oxaliplatin-containing regimens and higher total bilirubin levels.

An observational, prospective, open label, multicenter study to evaluate the safety and effectiveness of pegfilgrastim as secondary prophylaxis to decrease the incidence of febrile neutropenia in Korean female patients with breast cancer

PurposePegfilgrastim is a widely used long-acting granulocyte colony-stimulating factor (G-CSF) that prevents febrile neutropenia (FN) in patients with breast cancer receiving chemotherapy. This study aimed to evaluate the incidence of chemotherapy-related FN events and other adverse events (AEs) during chemotherapy in Korean patients with breast cancer treated with pegfilgrastim as secondary prophylactic support. Materials and methodsThis was a multicenter, open-label, prospective, observational study. A total of 1255 patients were enrolled from 43 institutions. The incidence of FN was evaluated as the primary endpoint. The secondary endpoints included (1) incidence of bone pain, (2) proportion of patients with a relative dose intensity (RDI) of ≥85%, and (3) proportion of patients with AE. ResultsPegfilgrastim administration reduced FN by 11.8–1.6%. The highest incidence of bone pain was observed at the time point of the 1st day after the administration and mild bone pain was the most common of all bone pain severity. The mean RDI was 98.5 ± 7.3%, and the proportion of the patients with and RDI≥85% was 96.9% (1169/1233). AEs were reported in 52.6% of the patients, and serious drug reactions occurred in only 0.7%. ConclusionThe use of pegfilgrastim as secondary prophylaxis was effective and safe for preventing FN in patients with breast cancer who were treated with chemotherapy.