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Background: Granulocyte transfusions for patients with prolonged neutropenia and severe infections has been a controversial practice. Previous studies suggest a benefit of high-dose granulocyte transfusions (≥0.6 × 10 9 /kg), although, until recently, the consistent production of high-dose units has been challenging. Here, we present our experience and results utilizing high-dose granulocyte transfusions at a large, tertiary academic medical center for the treatment of infections in adult, neutropenic patients., Study Design/methods: A retrospective chart review (2018-2021) was conducted for all patients who received high-dose granulocyte transfusions from donors stimulated with granulocyte colony-stimulating factor (G-CSF) and dexamethasone. Gathered parameters included patient demographics, clinical history, infection status, dose, clinical outcomes, pre- and post-absolute neutrophil count (ANC), and transfusion times including time between granulocyte collection, administration, and posttransfusion ANC count. Gathered parameters were summarized using descriptive statistics, outcomes were assessed utilizing Kaplan-Meier curves/log-rank/regression testing., Results: Totally 28 adult, neutropenic patients refractory to antimicrobial agents and/or G-CSF received a total of 173 granulocyte concentrates. Median ANC increased from 0.7 × 10 9 /L pre-transfusion to 1.6 × 10 9 /L posttransfusion. The mean granulocyte yield was 77.4 × 10 9 resulting in an average dose per kilogram of 0.90 × 10 9  ± 0.30 × 10 9 granulocytes. Composite day 42 survival and microbial response was 42.9% (n = 12/28) without significant adverse reactions., Discussion: Here, we demonstrate the successful and safe implementation of high-dose granulocyte transfusions for neutropenic patients. Given the rapid and consistent production, distribution, and improved granulocyte quality, further investigations to determine the clinical efficacy of G-CSF primed granulocyte transfusions is now possible., (© 2024 AABB.)

Background: ECIL-2021 recommends discontinuing empirical antibiotic therapy (EAT) in febrile-neutropenic children after 72 h of treatment and at least 24-48 h of apyrexia in the case of fever of unknown origin (FUO). These guidelines are rarely applied to high-risk children's neutropenia., Material and Methods: We retrospectively included all consecutive FUO episodes occurring during profound neutropenia ≥ 10 days in children in our institution. We evaluated the safety of EAT discontinuation in patients for whom the ECIL guidelines were followed compared to those for whom they didn't. We used a combined criterion of mortality and intensive care unit admission at 30 days. We identified risk factors for recurrent fever after EAT discontinuation., Results: Fifty-one FUO episodes occurred in 37 patients. EAT discontinuation followed ECIL guidelines in 19 (37 %) episodes. No deaths and-or transfers in ICU occurred in the ECIL group. The duration of EAT was shorter by nine days in the group following ECIL guidelines (p < 0.001). We observed 14 (27 %) episodes of recurrent fever. Mucositis was significantly associated with recurrent fever (p < 0.01)., Conclusion: EAT discontinuation seems feasible and safe in FUO during prolonged febrile neutropenia in children. However, mucosal lesions should prompt thorough surveillance due to the risk of recurrent fever., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: It is important to predict adverse outcomes in febrile children with hematology/oncology diseases. Procalcitonin (PCT) is a promising biomarker for the prediction of infection severity, but further studies have revealed its performance in excluding adverse outcomes of infection. IL-6 and IL-10 were reported to have a close association with those infection outcomes. The aim of the study was to investigate the performance of IL-6 and IL-10 in febrile pediatric hematology/oncology patients with normal PCT., Methods: This was a retrospective study conducted in a tertiary children's hospital in China over the past ten years. Inflammatory biomarkers, including IL-6, IL-10, PCT and C-reactive protein (CRP), were detected at the onset of infection. Separate analyses were conducted in patients with neutropenia and without neutropenia., Results: In total, 5987 febrile cases were enrolled. For patients with neutropenia, IL-6, IL-10 and PCT were significantly increased in patients with bloodstream infection (BSI), gram-negative bacteremia (GNB) and severe sepsis (SS), but only IL-6 and IL-10 were predictive of GNB and SS. For patients without neutropenia, IL-6, IL-10 and PCT were significantly increased in patients with BSI, GNB and SS, but no biomarkers were predictive of adverse outcomes. All biomarkers failed to exclude patients with fever of unknown origin or upper respiratory infection/bronchitis in patients with neutropenia., Conclusions: IL-6 and IL-10 could be predictors for GNB and SS in febrile patients with neutropenia and had some association with unfavorable outcomes in febrile patients without neutropenia. All biomarkers failed to exclude patients with fever of unknown origin or upper respiratory infection/bronchitis., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Filgrastim is approved for several indications, including reduction of the incidence and duration of chemotherapy-induced neutropenia and for stem cell mobilization. The filgrastim biosimilar, EP2006, has been available in Europe since 2009, and in the United States since 2015. In this time, preclinical and clinical data used to support the approval of EP2006 have been published. These data established the biosimilarity of EP2006 to reference filgrastim in terms of structure, pharmacokinetics, pharmacodynamics, efficacy, safety, and immunogenicity. Additional real-world evidence studies have also demonstrated equivalent efficacy and safety of EP2006 compared with reference filgrastim, both in the reduction of neutropenia and in stem cell mobilization in clinical practice. This review summarizes these preclinical, clinical, and real-world data, as well as the available cost-effectiveness data, for EP2006 since its approval 15 years ago., Competing Interests: Declaration of Competing Interest PG has received honoraria for lectures and/or consulting from Amgen, Pfizer, and Sandoz. NH has received honoraria for lectures and/or consulting from AstraZeneca, Daiichi-Sankyo, Gilead, Lilly, MSD, Novartis, Pierre-Fabre, Pfizer, Roche, Sandoz, Sanofi, and Seagen. IB and SH are employees of Sandoz Group AG. BLR has received research grants and support from Gilead Sciences and Roche South Africa, and consulting/advisory fees from AstraZeneca, Gilead Sciences, Lilly, MSD, Novartis, OBI Pharma, and Roche South Africa . RA has no conflicts of interest to declare. MA has received honoraria for lectures and/or consulting from Amgen, Bayer Schering, BMS, Celgene, Cephalon, Chugai, Clinigen, Eisai, Genomic Health, GSK, G1 Therapeutics, Helsinn, Hospira, Ipsen, Johnson & Johnson, Kyowa Hakko Kirin, Lilly, Novartis, Merck, Merck Serono, Mundipharma, Novartis, OrthoBiotech, Pfizer, Pierre Fabre, Roche, Sandoz, Sanofi, Taiho, Tesaro, Teva, and Vifor., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Neutropenic sepsis is a common complication of systemic anticancer treatment. There is variation in practice in timing of switch to oral antibiotics after commencement of empirical intravenous antibiotic therapy., Objectives: To establish the clinical and cost effectiveness of early switch to oral antibiotics in patients with neutropenic sepsis at low risk of infective complications., Design: A randomised, multicentre, open-label, allocation concealed, non-inferiority trial to establish the clinical and cost effectiveness of early oral switch in comparison to standard care., Setting: Nineteen UK oncology centres., Participants: Patients aged 16 years and over receiving systemic anticancer therapy with fever (≥ 38°C), or symptoms and signs of sepsis, and neutropenia (≤ 1.0 × 10 9 /l) within 24 hours of randomisation, with a Multinational Association for Supportive Care in Cancer score of ≥ 21 and receiving intravenous piperacillin/tazobactam or meropenem for < 24 hours were eligible. Patients with acute leukaemia or stem cell transplant were excluded., Intervention: Early switch to oral ciprofloxacin (750 mg twice daily) and co-amoxiclav (625 mg three times daily) within 12-24 hours of starting intravenous antibiotics to complete 5 days treatment in total. Control was standard care, that is, continuation of intravenous antibiotics for at least 48 hours with ongoing treatment at physician discretion., Main Outcome Measures: Treatment failure, a composite measure assessed at day 14 based on the following criteria: fever persistence or recurrence within 72 hours of starting intravenous antibiotics; escalation from protocolised antibiotics; critical care support or death., Results: The study was closed early due to under-recruitment with 129 patients recruited; hence, a definitive conclusion regarding non-inferiority cannot be made. Sixty-five patients were randomised to the early switch arm and 64 to the standard care arm with subsequent intention-to-treat and per-protocol analyses including 125 (intervention n = 61 and control n = 64) and 113 (intervention n = 53 and control n = 60) patients, respectively. In the intention-to-treat population the treatment failure rates were 14.1% in the control group and 24.6% in the intervention group, difference = 10.5% (95% confidence interval 0.11 to 0.22). In the per-protocol population the treatment failure rates were 13.3% and 17.7% in control and intervention groups, respectively; difference = 3.7% (95% confidence interval 0.04 to 0.148). Treatment failure predominantly consisted of persistence or recurrence of fever and/or physician-directed escalation from protocolised antibiotics with no critical care admissions or deaths. The median length of stay was shorter in the intervention group and adverse events reported were similar in both groups. Patients, particularly those with care-giving responsibilities, expressed a preference for early switch. However, differences in health-related quality of life and health resource use were small and not statistically significant., Conclusions: Non-inferiority for early oral switch could not be proven due to trial under-recruitment. The findings suggest this may be an acceptable treatment strategy for some patients who can adhere to such a treatment regimen and would prefer a potentially reduced duration of hospitalisation while accepting increased risk of treatment failure resulting in re-admission. Further research should explore tools for patient stratification for low-risk de-escalation or ambulatory pathways including use of biomarkers and/or point-of-care rapid microbiological testing as an adjunct to clinical decision-making tools. This could include application to shorter-duration antimicrobial therapy in line with other antimicrobial stewardship studies., Trial Registration: This trial is registered as ISRCTN84288963., Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 13/140/05) and is published in full in Health Technology Assessment ; Vol. 28, No. 14. See the NIHR Funding and Awards website for further award information.

Background: 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., Methods: 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., Results: 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 7 days 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., Conclusion: 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., (© 2023. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Objectives: To determine whether early switch to oral antibiotic treatment in adults with neutropenic sepsis at low risk of complications is non-inferior to switching later., Methods: This non-inferiority, parallel-group, randomized, open-label clinical trial enrolled UK adults hospitalized with neutropenic sepsis. Participants were randomly assigned to either switch to oral ciprofloxacin plus co-amoxiclav within 12-24 hours or to continue intravenous treatment for at least 48 hours. The primary outcome was a composite measure of treatment failure, 14 days after randomization. The non-inferiority margin was 15%., Results: There were 129 participants from 16 centres and 125 were assessed for the primary outcome. Of these, 113 patients completed protocolized treatment and comprised the per-protocol population. In total, 9 (14.1%) of 64 patients in the standard care arm met the primary end point, compared with 15 (24.6%) of 61 in the early switch arm, giving a risk difference of 10.5% (1-sided 95% CI, -∞% to 22%; p 0.14). In the per-protocol population, 8 (13.3%) of the 60 patients in the standard care arm met the primary end point, compared with 9 (17%) of 53 in the intervention arm giving a risk difference of 3.7% (one-sided 95% CI, -∞% to 14.8%; p 0.59). Duration of hospital stay was shorter in the intervention arm (median 2 [inter-quartile range (IQR) 2-3] vs. 3 days [IQR 2-4]; p 0.002)., Discussion: Although non-inferiority of early oral switch was found in the per-protocol population, the intervention was not non-inferior in the intent-to-treat population., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The use of fluoroquinolones to prevent infections in neutropenic patients with cancer or undergoing hematopoietic stem cell transplantation (HSCT) is a controversial issue, with international guidelines providing conflicting recommendations. Although potential benefits are clear, concerns revolve around efficacy, potential harms, and antimicrobial resistance (AMR) implications., Discussion: Fluoroquinolone prophylaxis reduces neutropenic fever (NF) bloodstream infections and other serious bacterial infections, based on evidence from systematic reviews, randomized controlled trials, and observational studies in adults and children. Fluoroquinolone prophylaxis may also reduce infection-related morbidity and healthcare costs; however, evidence is conflicting. Adverse effects of fluoroquinolones are well recognized in the general population; however, studies in the cancer cohort where it is used for a defined period of neutropenia have not reflected this. The largest concern for routine use of fluoroquinolone prophylaxis remains AMR, as many, but not all, observational studies have found that fluoroquinolone prophylaxis might increase the risk of AMR, and some studies have suggested negative impacts on patient outcomes as a result., Conclusions: The debate surrounding fluoroquinolone prophylaxis calls for individualized risk assessment based on patient characteristics and local AMR patterns, and prophylaxis should be restricted to patients at the highest risk of serious infection during the highest risk periods to ensure that the risk-benefit analysis is in favor of individual and community benefit. More research is needed to address important unanswered questions about fluoroquinolone prophylaxis in neutropenic patients with cancer or receiving HSCT., (© 2023 Wiley Periodicals LLC.)

Introduction: Pegfilgrastim is indicated to decrease the incidence of chemotherapy-induced febrile neutropenia. It is the first granulocyte-colony stimulating factor approved for prophylactic use regardless of carcinoma type and is marketed in Japan as G-LASTA (Kyowa Kirin Co., Ltd., Tokyo, Japan). MD-110 is a biosimilar of pegfilgrastim. This phase III, multicenter, open-label, single-arm study investigated the efficacy and safety of MD-110 in early-stage breast cancer patients receiving neoadjuvant or adjuvant myelosuppressive chemotherapy., Methods: A total of 101 patients received the study drug. Each patient received docetaxel 75 mg/m 2 and cyclophosphamide 600 mg/m 2 (TC) for four cycles on day 1 of each cycle. MD-110 (3.6 mg) was administered subcutaneously on day 2 of each cycle. The primary efficacy endpoint was the duration of severe neutropenia during cycle 1 (days with absolute neutrophil count < 500/mm 3 ). The safety endpoints were adverse events and the presence of antidrug antibodies., Results: The mean (SD) duration of severe neutropenia for MD-110 was 0.2 (0.4) days. The upper limit of the two-sided 95% confidence interval for the mean duration of severe neutropenia was 0.2 days, below the predefined threshold of 3.0 days. The incidence of febrile neutropenia, the secondary efficacy endpoint, was 6.9% (7/101). Adverse events, occurring in more than 50% of patients, were alopecia, constipation, and malaise, which are common side effects of TC chemotherapy. Antidrug antibodies were negative in all patients., Conclusion: MD-110 was effective against chemotherapy-induced neutropenia. No additional safety concern, compared with the originator, was observed in patients with breast cancer receiving TC chemotherapy.(JapicCTI-205230)., (© 2023 Mochida Pharmaceutical Co., Ltd. Cancer Medicine published by John Wiley & Sons Ltd.)

Fusarium, a common fungus, emerges as a pathogen in severely immunocompromised patients. We present a series of patients who developed invasive fusariosis (IF) during admission to an acute leukaemia ward: an outbreak of 12 cases in June and July 2018, followed by four sporadic cases until 2021. No case was reported earlier. All patients were clustered in the same location with indoor air and water installations found to be contaminated with Fusarium spp. thus a nosocomial outbreak was assumed. Following the water installation replacement, the number of Fusarium cases dramatically dropped to one or two isolated instances per year in the same location. All 16 patients had acute leukaemia and developed IF during severe neutropenia following induction therapy. IF diagnosis was based on positive blood cultures (14 patients) and/or on tissue biopsies (3 patients). The median time from admission to the IF onset was 20 days, and from the first day of severe neutropenia (≤500/mm3) was 11.5 days. All patients were febrile, eight had moderate-to-severe myalgias, eight had respiratory involvements: lung lesions and/or sinusitis and seven had characteristic skin lesions. Follow-up: 12 out of 16 (75%) were alive on Day 90; nine out of 15 (60%) were alive on Month 6. All with intractable neutropenia died. In severely neutropenic febrile patients, the triad of respiratory involvement/skin lesions/severe myalgia may suggest Fusarium aetiology. The ability to recover from neutropenia is critical to surmount IF. The indoor environment in immunocompromised dedicated settings must be constantly controlled., (© 2023 Wiley-VCH GmbH.)

Background: To compare the clinical value of recombinant human granulocyte colony-stimulating factor (rhG-CSF) and pegylated rhG-CSF(PEG-rhG-CSF) in early-stage breast cancer (EBC) patients receiving adjuvant chemotherapy, compare the efficacy of PEG-rhG-CSF with different dose and explore the timing of rhG-CSF rescue treatment., Methods: Patients in two PEG-rhG-CSF subgroups were given 3 mg or 6 mg PEG-rhG-CSF within 24 ~ 48 h after chemotherapy for preventing myelosuppression, while patients in the rhG-CSF group were given rhG-CSF. Observation indicators include the incidence of febrile neutropenia (FN) and grade 3/4 chemotherapy-induced-neutropenia (CIN), the overall levels and nadir values of white blood cells (WBC) and absolute neutrophil count (ANC), comparison of WBC and ANC curves over time, the incidence of CIN-related complications, the incidence of adverse events in each group and the timing of rescue treatment for rhG-CSF., Results: There was no significant difference in the incidence of FN in the first cycle among the groups (P = 0.203). But the incidence of ≥ 3 grade CIN in two PEG-rhG-CSF subgroups was significantly lower than that in the rhG-CSF group (P < 0.001). The overall WBC and ANC levels in the PEG-rhG-CSF group were significantly higher than those in the rhG-CSF group (P < 0.001). In terms of CIN-related complications, less chemotherapy delay rate (1.1 vs. 7.5%, P = 0.092), less dose reduction rate (6.9 vs. 7.5%, P = 1.000), less antibiotic use rate (3.4 vs. 17.5%, P = 0.011) and less proportion of rhG-CSF rescue therapy (24.1 vs. 85.0%, P < 0.001) in the PEG-rhG-CSF group, and there were no significant differences between PEG-rhG-CSF subgroups. In the incidence of adverse events among the groups, there were no statistical differences. All patients undergoing rhG-CSF rescue treatment were mainly 4 grade (63.6%) and 3 grade (25.5%) CIN, and 10.9% of patients with 1 ~ 2 grade CIN who had high infection risk or had been infected., Conclusion: PEG-rhG-CSF has better efficacy and equal tolerance compared with rhG-CSF in preventing CIN in EBC patients receiving EC regimen. Moreover, a half-dose 3 mg PEG-rhG-CSF also had good efficacy. Last, patients with ≥ 3 grade CIN and others who have been assessed to be at high risk of infection or have co-infection should consider rhG-CSF or even antibiotic rescue treatment., (© 2023. The Author(s).)

Chemotherapy-induced neutropenia (CIN) is a common hematological adverse events and dose-limiting toxicities of chemotherapy. CIN may lead to dose reduction and delay of chemotherapeutic agents, febrile neutropenia and severe infection, which results in increased treatment cost, reduced efficacy of chemotherapy, and even life-threatening morbidities. Assessment of risk of CIN, early detection of FN and infection, and proper prevention and treatment play a crucial role in reducing the occurrence of CIN-related morbidities, improving patient treatment safety and anticancer efficacy. Based on evidence and expert opinion, the expert committee of Chinese Anti-Cancer Association issued "the consensus on diagnosis and treatment of chemotherapy-induced neutropenia in China (2023 edition)", which is an update version of the 2019 edition, aiming to provide reference for the diagnosis and treatment of CIN for Chinese oncologists.

Background: Pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) can be used in pediatric patients. This study assessed the safety and efficacy of PEG-rhG-CSF as a primary prophylactic drug against neutropenia after chemotherapy in pediatric patients with solid tumors or non-Hodgkin lymphoma (NHL)., Patients and Methods: This phase II study (between October 2020 and March 2022) enrolled pediatric patients with solid tumors or NHL treated with high-intensity chemotherapy and with grade ≥3 myelosuppression for at least 14 days during chemotherapy. Prophylactic PEG-rhG-CSF was given at 100 μg/kg body weight (maximum total dosage of 6 mg) once 24-48 h following chemotherapy for two cycles. The primary endpoint was the incidence of PEG-rhG-CSF-related adverse events (AEs). The key secondary endpoints were the rates of grade 3/4 neutropenia and febrile neutropenia (FN)., Results: This study included 160 pediatric patients with a median age of 6.22 (0.29, 18.00) years. Fifty-eight patients (36.25%) were diagnosed with sarcoma. AEs potentially related to PEG-rhG-CSF included bone pain (n = 32), fatigue (n = 21), pain at the injection site (n = 21), and myalgia (n = 20). The rates of grade 3/4 neutropenia and FN during treatment were 57.28% and 29.45%, respectively., Conclusion: PEG-rhG-CSF is well tolerated and effective in pediatric patients with solid tumors or NHL. These findings should be substantiated with further trials., Clinical Trial Registration: ClinicalTrials.gov identifier: NCT04547829., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

BRCA1 and BRCA2 play a central role in DNA repair and their germline pathogenic variants (gBRCA) confer a high risk for developing breast and ovarian cancer. Standard chemotherapy regimens for these cancers include DNA-damaging agents. We hypothesized that gBRCA carriers might be at higher risk of developing chemotherapy-related hematologic toxicity and therapy-related myeloid neoplasms (t-MN). We conducted a retrospective study of women newly diagnosed with invasive breast or ovarian cancer who were screened for gBRCA1/gBRCA2 at Geneva University Hospitals. All patients were treated with (neo-)adjuvant chemotherapy. We evaluated acute hematologic toxicities by analyzing the occurrence of febrile neutropenia and severe neutropenia (grade 4) at day 7-14 of the first cycle of chemotherapy and G-CSF use during the entire chemotherapy regimen. Characteristics of t-MN were collected. We reviewed medical records from 447 patients: 58 gBRCA1 and 40 gBRCA2 carriers and 349 non-carriers. gBRCA1 carriers were at higher risk of developing severe neutropenia (32% vs. 14.5%, p = 0.007; OR = 3.3, 95% CI [1.6-7], p = 0.001) and of requiring G-CSF for secondary prophylaxis (58.3% vs. 38.2%, p = 0.011; OR = 2.5, 95% CI [1.4-4.8], p = 0.004). gBRCA2 carriers did not show increased acute hematologic toxicities. t-MN were observed in 2 patients (1 gBRCA1 and one non-carrier). Our results suggested an increased acute hematologic toxicity upon exposure to chemotherapy for breast and ovarian cancer among gBRCA1 but not gBRCA2 carriers. A deeper characterization of t-MN is warranted with the recent development of PARP inhibitors in frontline therapy in gBRCA breast and ovarian cancer., (© 2023. The Author(s).)

Currently there are no guidelines on a safe neutrophil count(ANC) for intravenous antibiotic(IVAB) cessation and hospital discharge in patients recovering after febrile neutropenia(FN). We assessed the safety in selected patients after recent FN of prompt IVAB cessation and hospital discharge. Safety was defined as no fever recurrence after IVAB cessation and readmission in the 10-days post-discharge for infections.A retrospective, single center audit conducted on 92 adult hematology patients admitted with de novo acute myeloid leukemia (AML) for intensive chemotherapy or for an autograft. Most admissions ( n  = 128/141;91%) were complicated by FN. Half of FN episodes ceased IVAB promptly with a median(range) ANC of 0.6(0.1-4.9x10 9 /L); none of these episodes had recurrent fever requiring IVAB resumption. Prompt discharge occurred in 45% overall. Subsequent unplanned readmission rates were low.In afebrile, stable AML and autograft patients without medico-social barriers to discharge, IVAB can be ceased and hospital discharges safely done ≤24h of ANC ≥ 0.2x10 9 /L.

Background: Epidemiology of infectious diseases causing febrile illness varies geographically with human attributes. Periodic institutional surveillance of clinical and microbiological profiles in adding data to updating trends, modulating pharmatherapeutics, signifying possible excessive treatments and risk of drug resistance in post-chemotherapy neutropenic fever (NF) in hematological malignancy (HM) is limited. We aimed to review institutional clinical and microbiological data and explore clinical phenotype pattern groups among data., Methods: Available data from 372 NF episodes were included. Demographics, types of malignancies, laboratory data, antimicrobial treatments and febrile-related outcome data such as predominant pathogens and microbiological diagnosed infections (MDIs) were collected. Descriptive statistics, two-step cluster analysis and non-parametric tests were employed., Results: The occurrences of microbiological diagnosed bacterial infections (MDBIs; 20.2%) and microbiological diagnosed fungal infections (MDFIs; 19.9%) were almost equal. Gram-negative pathogens (11.8%) were comparable with gram-positive pathogens (9.9%), with gram-negative being slightly predominant. Death rate was 7.5%. Two-step cluster analysis yielded four distinct clinical phenotype pattern (cluster) groups: cluster 1 'lymphomas without MDIs', cluster 2 'acute leukemias MDBIs', cluster 3 'acute leukemias MDFIs' and cluster 4 'acute leukemias without MDIs'. Considerable NF events with antibiotic prophylaxis being not identified as MDI might have cases in low-risk with non-infectious reasons causing febrile reactions that might possibly not require prophylaxis., Conclusions: Regular institutional surveillance with active parameter assessments to signify risk levels in the post-chemotherapy stage, even prior to the onset of fever, might be an evidence-based strategy in the management of NF in HM., (© 2023. The Author(s).)

Neutropenia is the major toxicity of myelosuppressive cancer chemotherapy. Grade 4 neutropenia (Gr4N) is a measure of chemotherapy-induced neutropenia (CIN) severity. We conducted a meta-analysis of CIN data. Gr4N incidence was significantly correlated with febrile neutropenia (FN), days of severe neutropenia (DSN), and nadir absolute neutrophil count (ANC), which are all important predictors of morbidity. With a Gr4N threshold of 65%, both FN and DSN were below levels for low risk of adverse CIN outcomes. Gr4N was highly predictive for adverse CIN outcomes, and a 65% threshold demarcated low vs. high risk for FN and other adverse CIN outcomes.

Study Objective: To identify the risk factors that may predispose breast cancer patients to Chemotherapy-induced neutropenia (CIN) and its associated complications for the years 2018 and 2020. CIN is an established complication of breast cancer treatment. Clinical Pharmacists can play an important role in the treatment of CIN through involvement in risk assessment to identify patients for oral antimicrobial therapy, drug therapy monitoring, and development of suitable guidelines or policies., Methodology: A retrospective study was performed by collecting data of 72 breast cancer patients for the last two years from department of Medical Oncology in a tertiary care hospital., Results: The overall occurrence of CIN was 59.7% in our study population. Out of 72 patients studied, 43 patients were found to be neutropenic. Using Pearson Chi square test, chemotherapy-induced neutropenia was associated with older age (over 60 y) ( p  < 0.038), diabetes mellitus ( p  < 0.050), tumour stage IIIa ( p  < 0.024), AC ( p  < 0.051) and taxane chemotherapy regimens ( p  < 0.041). Febrile neutropenia occurred in 37.28% of patients and the incidence of infection-related mortality [severe septicaemia] was 3.38%., Conclusion: The incorporation of clinical pharmacist must be brought into practice in our country for providing proper guidance to the patient on CIN and its complications. By identifying risk factors for neutropenia, the safe management of CIN may be possible in patients with breast cancer.

Objective: Real-world evidence on the application of the granulocyte colony-stimulating factor lipegfilgrastim for the reduction of chemotherapy-induced neutropenia and febrile neutropenia (FN) is limited. The NADIR study aimed to evaluate effectiveness and safety of lipegfilgrastim as primary or secondary prophylaxis in patients with lung cancer undergoing chemotherapy in routine clinical practice., Methods: The non-interventional study NADIR (German Clinical Trials Register (DRKS) Number DRKS00005711) enrolled 156 patients with small-cell lung cancer (SCLC) and 145 patients with non-small-cell lung cancer (NSCLC), who received lipegfilgrastim during chemotherapy. Primary endpoint was the incidence of severe neutropenia (CTCAE grade 3/4) and FN. The analysis was stratified for age groups (≤65 years vs. >65 years)., Results: Approximately half of the patients were aged >65 years (SCLC 54.5%; NSCLC 46.9%). Intention of antineoplastic treatment was mostly palliative (SCLC 89.1%; NSCLC 73.1%). Patients with high FN risk (SCLC 44.9%; NSCLC 28.3%) mostly received lipegfilgrastim for primary prophylaxis (SCLC 81.4%; NSCLC 70.7%). FN was reported in 1.9% SCLC and 1.4% NSCLC patients. At least one severe neutropenia was documented in 30.1% SCLC and 17.9% NSCLC patients. For NSCLC patients aged >65 years, less severe neutropenia was reported as compared to younger patients (14.7% vs. 20.8%). Lipegfilgrastim-related adverse events were reported in 10.3% SCLC and 7.7% NSCLC patients., Conclusion: Lipegfilgrastim in routine clinical practice of patients with lung cancer showed similar effectiveness and safety as compared to the pivotal trial. Interestingly, in older patients severe neutropenia was reported less frequently. While most patients with high FN risk received lipegfilgrastim for primary prophylaxis as recommended, there are still 20-30% of patients at high FN risk without primary prophylaxis who could benefit from better adherence to guidelines.

Purpose: We assessed the occurrence of neutropenia and febrile neutropenia (FN) and the associated healthcare resource in cancer patients receiving myelosuppressive chemotherapy in combination with pegfilgrastim versus lipegfilgrastim., Methods: This is a retrospective analysis using a German health insurance claims database. Adults receiving chemotherapy with a prescription code for pegfilgrastim (n = 734) or lipegfilgrastim (n = 346) were observed over a 1-year follow-up period. Patient subgroups were analyzed according to cancer type and FN risk. FN risk was based on the chemotherapy regimen and any additional neutropenia risk factors. Outcomes were adjusted via regression analysis., Results: Most patients were classified as high FN risk (70.0% pegfilgrastim; 65.6% lipegfilgrastim cohort). The mean age was 58.2 years in the pegfilgrastim cohort and 58.0 years in the lipegfilgrastim cohort, with more female patients than male patients (77.3% vs 79.8%, respectively), and the majority had breast cancer (64.9% and 68.8%, respectively). Overall, 10.0% and 10.4% of patients receiving pegfilgrastim or lipegfilgrastim experienced a neutropenia event (p = 0.82), with 4.4% and 3.5% of patients experiencing a FN event (p = 0.49). The mean neutropenia event-related healthcare costs were €604 and €441 for the pegfilgrastim and lipegfilgrastim cohorts; among patients with lymphoma, these costs were significantly greater (p = 0.03) with pegfilgrastim (€1,612) versus lipegfilgrastim (€382). The mean all-cause hospitalizations were significantly (p < 0.01) higher for lymphoma patients receiving pegfilgrastim (2.76) versus lipegfilgrastim (1.60)., Conclusion: Overall, patients treated with pegfilgrastim and lipegfilgrastim were comparable in terms of neutropenia occurrences in the 1-year follow-up. In patients with lymphoma, neutropenia event-related healthcare costs and all-cause hospitalizations were significantly higher with pegfilgrastim compared with lipegfilgrastim in this study; however, this should be interpreted with caution in light of the limited sample size and the absence of clinical information., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Febrile neutropenia (FN) is one of the complications of chemotherapy that can increase the risk of infection and mortality. Granulocyte colony-stimulating factors (G-CSFs) are used in practice to prevent and treat episodes of neutropenia. The use of G-CSFs in children with cancer has not been studied much for primary prophylaxis of FN., Areas Covered: Current data suggest that G-CSFs have a similar pharmacokinetic profile in children and adults. Clinical trials published from 2002 to 2021 using G-CSFs in pediatric cancer patients were reviewed. All evaluated clinical trials used a dosage of 5 mcg/kg of filgrastim daily until neutrophil recovery or a single dose of 100 mcg/kg pegfilgrastim. Filgrastim demonstrated the benefit in decreasing the duration of fever, hospital stay, and antibiotic use in high-risk neuroblastoma patients. Pegfilgrastim showed similar efficacy in reducing the occurrence of FN and infections, with bone pain as an adverse effect., Expert Opinion: Filgrastim 5 mcg/kg/day or pegfilgrastim 100 mcg/kg single dose is appropriate when given at least 24 hours or after the chemotherapy in pediatric patients who weigh 45 kg or more. More prospective randomized trials are necessary to further investigate the efficacy and safety of G-CSFs in children with different types of cancer.

Background: Myelosuppressive effects of chemotherapy for breast cancer treatment may trigger chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN). Filgrastim has been widely used as prophylaxis against CIN and FN. However despite filgrastim administration, some study showed FN still occur and cause patient vulnerability to infection. This study aims to evaluate factors associated with Absolute Neutrophil Count (ANC) dynamics and Docetaxel-Adryamicin-Cyclophosphamide (TAC) CIN during extended filgrastim administration in breast cancer patients., Methods: Patients were selected among breast cancer in-patients who fulfilled the eligibility criteria. Patient characteristics data and ANC were collected. The entire patients received 5μg/kg/day filgrastim by subcutaneous injection 24 hours post-chemotherapy. ANC was monitored daily and filgrastim administration was stopped when ANC reached >10000/mm3 or 14 days of administration. Kruskall-Wallis test and Spearman Correlation test was performed to analyze ANC dynamics and CIN-related factors., Results: This study included 42 breast cancer patients. Patient age median was 52 (31-70) years old. ANC nadir could be observed around 5-7 days after chemotherapy and FN occurred in two out of 38 grade 4 neutropenia patients (4.8%). Critical ANC lasted for 1 day, 2 days, and 3 days respectively in 9 (23.7%), 25 (65.8%) and 4 (10.5%) patients. There was no correlation between neutropenia and age. ANC slope and recovery duration did not show a significant difference. However, depth of nadir is inversely correlated with the duration of ANC recovery (>10000/mm3) and the duration during the peak on the 2nd day until reaching nadir both with fair strength, r = -0.489 and r = -0.438 (p <0.05), respectively. No sepsis incidence had manifested., Conclusion: CIN still occured in breast cancer patient receiving filgrastim primary prophylaxis regardless of age and neutropenia severity. Nadir as the lowest point of ANC should be noted as a pivotal milestone for ANC slope and recovery evaluation.

Introduction: Chagas disease is an endemic parasitic infection in Latin America transmitted by triatomines. It is associated with risk factors such as poverty and rurality. After acute infection, a third of patients will present target organ involvement (heart, digestive tract, central nervous system). The remaining two thirds remain asymptomatic throughout their life. Pharmacological immunosuppression breaks the balance between the immune system and the parasite, favoring its reactivation. Clinical case: We present the case of a 58-year-old man from a Colombian rural area with a diagnosis of multiple myeloma refractory to the first line of treatment who required a new chemotherapy scheme and consolidation with autologous stem cell transplant. During the post-transplant period, he suffered from febrile neutropenia. Initial microbiological studies were negative but the peripheral blood smear evidenced trypomastigotes in blood. With a diagnosis of acute Chagas disease in a post-transplant patient, benznidazole was started. The evolution of the patient was satisfactory. Conclusions: Positive serology prior to transplantation makes it necessary to rule out reactivation of the pathology in the setting of febrile neutropenia. More studies are required to determine tools for estimating the probability of reactivation of the disease and defining the best cost-risk-benefit relation for the prophylactic therapy.

Febrile neutropenia, a serious complication that can occur during the treatment of hematological malignancies, can sometimes be fatal owing to fungal infection. Prospective randomized trials indicated the utility of liposomal amphotericin B or caspofungin as an empirical antifungal therapy. Itraconazole, a broad-spectrum tri azole antifungal agent, is poorly absorbed in the intestines after oral absorption and makes it difficult to achieve a stable serum drug concentration. Therefore, an intravenous formulation might offer a potentially safer and more effective alternative. To compare the efficacy and safety of empirical antifungal therapy, patients will be randomly assigned to either the liposomal amphotericin B 3.0 mg/kg once daily group or the intravenous itraconazole 200 mg dose group with five stratification factors (disease risk, previous antifungal prophylaxis, age, sex, and institute). The primary endpoint will be overall favorable response, comprising five secondary endpoints: successful treatment of baseline infection by the end of the treatment; absence of breakthrough infection; no discontinuation of the antifungal treatment due to drug-related toxicity; fever resolution during neutropenia; and 7-day survival after termination of the antifungal treatment. The target sample size of 850 subjects is sufficient to prove the non inferiority of itraconazole compared with liposomal amphotericin B, with a non-inferiority margin of 10%, one sided significance level of 5%, and power of 90%.

Background: Fever in neutropenia (FN) remains a frequent complication in pediatric patients undergoing chemotherapy for cancer. Preventive strategies, like primary antibiotic prophylaxis, need to be evidence-based., Procedure: Data on pediatric patients with any malignancy from the prospective multicenter SPOG 2015 FN Definition Study (NCT02324231) were analyzed. A score predicting the risk to develop FN with safety-relevant events (SRE; bacteremia, severe sepsis, intensive care unit admission, death) was developed using multivariate mixed Poisson regression. Its predictive performance was assessed by internal cross-validation and compared with the performance of published rules., Results: In 238 patients, 318 FN episodes were recorded, including 53 (17%) with bacteremia and 68 (21%) with SRE. The risk-prediction score used three variables: chemotherapy intensity, defined according to the expected duration of severe neutropenia, time since diagnosis, and type of malignancy. Its cross-validated performance, assessed by the time needed to cover (TNC) one event, exceeded the performance of published rules. A clinically useful score threshold of ≥11 resulted in 2.3% time at risk and 4.1 months TNC. Using external information on efficacy and timing of intermittent antibiotic prophylaxis, 4.3 months of prophylaxis were needed to prevent one FN with bacteremia, and 5.2 months to prevent one FN with SRE, using a threshold of ≥11., Conclusions: This score, based on three routinely accessible characteristics, accurately identifies pediatric patients at risk to develop FN with SRE during chemotherapy. The score can help to design clinical decision rules on targeted primary antibiotic prophylaxis and corresponding efficacy studies., (© 2021 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Introduction Fever during chemotherapy induced neutropenia is a common and potentially life-threatening complication of the treatment of childhood cancer. Predictions of poor outcome could be enhanced by incorporating serum biomarkers of inflammation at presentation and reassessment. Methods A prospective cohort study was conducted of children under 18 years old, being treated for cancer or a cancer-like condition, who presented with fever (≥ 38.0°C) and neutropenia (neutrophil count < 0.5*10 9 /L). Clinical features were recorded, along with three experimental inflammatory biomarkers: procalcitonin (PCT), interleukin-6 (IL-6) and interleukin-8 (IL-8). Outcomes included serious medical complications (SMC): any infection related mortality, critical care and organ support, severe sepsis, septic shock, significant microbiologically defined infection, or radiologically confirmed pneumonia. Results Biomarker assessments were undertaken in 43 episodes of fever and neutropenia, from 31 patients aged between four months and 17 years old (median six years): 20 were female and 22 had acute leukaemia. Five episodes of SMC were noted. PCT, IL-6 and IL-8 had poor individual discriminatory ability (C-statistic 0.48 to 0.60) and did not add to the value of clinical risk stratification tools. Insufficient data were collected to formally assess the value of repeated assessments. Conclusions Incorporating serum biomarkers of inflammation at presentation of episodes of fever with neutropenia in childhood does not clearly improve risk stratification. Repeated assessments over time may be of value., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 Phillips B.)

Background: Death during paediatric cancer treatment is common in sub-Saharan Africa. Using the infrastructure of Supportive Care for Children with Cancer in Africa (SUCCOUR), our objective was to describe fever and neutropenia (FN) characteristics and outcomes in order to identify potential areas for future intervention., Methods: A multicentre prospective, observational cohort study was conducted in sub-Saharan Africa. Data were collected from September 2019 to March 2020. Children below 16 years with newly diagnosed cancer treated with curative intent were included. Data were abstracted in real time using standardised case report forms by trained personnel. Characteristics and outcomes of FN during the first 3 months of treatment were documented., Results: A total of 252 patients were included (median age 6.0, range 0.2-15.0 years, 54% male). The most common cancer was Burkitt lymphoma (63/252, 25%). Among 104 FN episodes, 21 (21%) were associated with prolonged neutropenia (>1 week) and 32 (31%) were associated with profound neutropenia (absolute neutrophil count <0.1 × 10 9 /L). In 10/104 (10%) episodes, empiric antibiotics were started within 1 hour following fever onset and in 16/104 (15%) episodes, a blood culture was obtained before starting antibiotics. Malaria parasitaemia was detected in four of 104 (4%). A total of 11/104 (11%) patients died in the FN episodes., Conclusions: Although in most, FN was not associated with prolonged or profound neutropenia, 11% resulted in death. Areas to target include blood cultures prior to antibiotics and earlier initiation of empiric antibiotics. Future efforts should modify FN practices to reduce treatment-related mortality., (© 2021 Wiley Periodicals LLC.)

Introduction: Severe neutropenia is a dose-limiting factor that occurs in up to 82% of patients with metastatic castration-resistant prostate cancer (mCRPC) treated with cabazitaxel. This study evaluated the effectiveness of granulocyte colony-stimulating factor (G-CSF) plus ciprofloxacin as prophylaxis in post-docetaxel patients with mCRPC treated with cabazitaxel and at high risk for neutropenia., Patients and Methods: This was a phase IV, multicenter, open-label, single-arm interventional study with men aged ≥ 65 years (or < 65 years and ≥ 25% irradiated bone marrow), presenting with mCRPC after docetaxel failure, performance status ≤ 1, and life expectancy > 12 weeks. Cabazitaxel 25 mg/m 2 and prednisone were given on day 1, every 21 days. G-CSF was administered on days 2 to 8 of each cycle or until an absolute neutrophil count > 2000/mm 3 , and ciprofloxacin 1000 mg was given orally on days 5 to 12. The rate of neutropenia grade ≥ 3 during the first cycle (primary endpoint), and frequency of neutropenia grade ≥ 3, febrile neutropenia, diarrhea grade ≥ 3, prostate-specific antigen response, and quality of life during treatment (secondary end points) were estimated., Results: We included 46 patients. The mean number of cabazitaxel cycles was 9.5. During the first cycle, 40.0% of patients had neutropenia grade ≥ 3, and 42.2% had at least 1 episode of neutropenia during treatment. Febrile neutropenia and diarrhea grade ≥ 3 occurred in 1 patient each. Twenty-nine (64.4%) patients achieved prostate-specific antigen response, and 77.2% improved quality of life scores in at least 1 visit., Conclusions: Prophylactic G-CSF was effective in preventing neutropenia grade ≥ 3 and other hematologic complications during treatment with cabazitaxel 25 mg/m 2 in post-docetaxel patients with mCRPC at high risk for neutropenia. The role of prophyclatic ciprofloxacin to prevent febrile neutropenia in this setting is still unclear and needs to be further evaluated., (Copyright © 2021. Published by Elsevier Inc.)

The aim of this study is to clarify the characteristics of gram-negative bacteremia (GNB), including extended-spectrum β-lactamase (ESBL)-producing pathogens, among allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients on levofloxacin (LVFX) prophylaxis. A retrospective analysis on GNB at the first episode of febrile neutropenia (FN) was conducted among allo-HSCT recipients (age ≥ 20 years) on 500 mg/day of oral LVFX prophylaxis. Epidemiological and microbiological features of GNB were investigated and compared between the inappropriate and appropriate empiric therapy groups. In total, FN occurred in 414 allo-HSCT cases, and bacteremia at the first episode of FN occurred in 169 cases. Overall, 29 GNB cases were documented, and the causative organisms identified were Escherichia coli in 21 cases (including 10 ESBLs), Klebsiella pneumoniae in 2, Pseudomonas aeruginosa in 2, and other in 4. The crude 30-day mortality rate was not significantly different among cases of GNB (6.9%), gram-positive bacteremia (GPB) (7.1%), or non-bacteremia (5.4%; P = 0.78). Cefepime (CFPM) was administered in all cases in the inappropriate empiric therapy group, and all causative organisms were ESBL-producing E. coli (ESBL-EC). All patients in the inappropriate empiric therapy group had a low Pitt bacteremia score (≤ 2). Thirty-day mortality did not differ significantly between the inappropriate and appropriate empiric therapy groups (1/10 vs. 1/15, P = 0.61). In conclusion, GNB was not a significant cause of death. In LVFX breakthrough ESBL-EC bacteremia among allo-HSCT recipients, the administration of CFPM as empiric therapy did not lead to significantly poor prognosis. Empiric CFPM administration might be an acceptable strategy.

Background: Lipegfilgrastim has been shown to be non-inferior to pegfilgrastim for reduction of the duration of severe neutropenia (DSN) in breast cancer patients. This open-label, non-inferiority study assessed the efficacy and safety of lipegfilgrastim versus pegfilgrastim in elderly patients with aggressive B cell non-Hodgkin lymphoma (NHL) at high risk for chemotherapy-induced neutropenia., Patient and Methods: One hundred and one patients (median age, 75 years) were randomized to lipegfilgrastim or pegfilgrastim (6 mg/cycle) during six cycles of R-CHOP21., Results: Lipegfilgrastim was non-inferior to pegfilgrastim for the primary efficacy endpoint, reduction of DSN in cycle 1. In the per-protocol population, mean (standard deviation) DSN was 0.8 (0.92) and 0.9 (1.11) days in the two groups, respectively; the adjusted mean difference between groups was - 0.3 days (95% confidence interval, - 0.70 to 0.19). Non-inferiority was also demonstrated in the intent-to-treat population. The incidence of severe neutropenia in cycle 1 was 51% (21/41) in the lipegfilgrastim group and 52% (23/44) in the pegfilgrastim group. Very severe neutropenia (ANC < 0.1 × 10 9 /L) in cycle 1 was reported by 5 (12%) patients in the lipegfilgrastim group and 8 (18%) patients in the pegfilgrastim group. However, over all cycles, febrile neutropenia (strict definition) was reported by only 1 (2%) patient in each treatment group (during cycle 1 in the lipegfilgrastim group and cycle 6 in the pegfilgrastim group). The mean time to absolute neutrophil count recovery (defined as ≥ 2.0 × 10 9 /L) was 8.3 and 9.4 days in the two groups, respectively. Serious adverse events occurred in 46% of patients in each group; none were considered treatment-related. Eight patients died during the study (2 in the lipegfilgrastim group, 5 in the pegfilgrastim group, and 1 who died before starting study treatment). No deaths occurred during the treatment period, and all were considered to be related to the underlying disease., Conclusions: This study shows lipegfilgrastim to be non-inferior to pegfilgrastim for the reduction of DSN in elderly patients with aggressive B cell NHL receiving myelosuppressive chemotherapy, with a comparable safety profile., Trial Registration Number: ClinicalTrials.gov identifier NCT02044276; EudraCT number 2013-001284-23.

Objective: To investigate whether the use of a steroid-sparing antiemetic protocol (substituting dexamethasone with olanzapine) affects the incidence of neutropenia and associated hospital admissions in patients receiving bleomycin, etoposide and cisplatin (BEP) chemotherapy., Patients and Methods: Records from 108 patients who received BEP at St Bartholomew's Hospital, London were divided into two groups according to antiemetic regimen. Group 1 (treated 2008-2013) were treated with a steroid-containing antiemetic protocol and group 2 (treated 2014-2017) were treated according to a steroid-sparing protocol, i.e. using olanzapine. Outcomes included incidence of neutropenia at nadir blood count, severity of neutropenia, hospital admissions attributable to febrile neutropenia (FN) and baseline risk factors associated with FN. Statistical analyses were performed using two-sided chi-squared tests., Results: The baseline characteristics of the two groups were balanced with regard to age, gender, histology, and proportion of patients with International Germ Cell Cancer Collaborative Group poor-risk disease. The incidence of neutropenia of any grade (group 1, 96.2%; group 2, 98.1%) was similar, although group 2 had more patients with severe neutropenia than group 2 (77.7% vs 88.8%). There was a significant difference in FN incidence (group 1, 22%; group 2 7.5%; P = 0.030). Most cases of FN occurred in cycle 1. Two baseline characteristics were over-represented in patients who developed FN: female sex and age ≥50 years., Conclusion: By comparing two cohorts who received prophylactic antibiotics, our audit suggests that rates of FN-related admissions were lower in the cohort of patients in whom we employed a steroid-sparing antiemetic protocol., (© 2020 The Authors BJU International © 2020 BJU International Published by John Wiley & Sons Ltd.)

Introduction: Invasive fungal diseases are crucial causes of morbidity and mortality among patients with febrile neutropenia (FN). Though liposomal amphotericin B (L-AMB) is one of the agents recommended for first-line empirical antifungal therapy in patients with FN, large-scale clinical studies have not been performed in Japan., Methods: An open-label prospective multi-center study was carried out to evaluate the safety and efficacy of L-AMB in Japanese patients with FN suspected of having fungal infection., Results: Of the 426 patients registered, safety and efficacy evaluations were conducted for 424 and 399, respectively. By clinical response criteria using 5 composite endpoints, the response rate was 46.6% (186/399). The response rate by age were 54.5% (child: 30/55), 47.5% (adult: 97/204), 42.1% (elderly: 59/140) respectively. Regarding the composite endpoints, resolution of fever was observed in 61.2% (244/399), no breakthrough fungal infection in 99.0% (395/399), survival for 7 days or longer after the completion of treatment in 83.7% (334/399), no discontinuation of treatment due to toxicity or lack of efficacy in 60.9% (243/399), and successful treatment of any baseline fungal infection in 10/18. Adverse drug reactions (ADRs) developed in 61.1% (259/424), and frequent ADRs were hypokalemia, kidney dysfunction, and liver dysfunction, as previously reported., Conclusions: The safety and efficacy profile of L-AMB in Japanese patients with FN suspected of having fungal infection were elucidated for the first time, through the analysis of a large number of cases including pediatric patients under real-world clinical settings collected in this nationwide study., Competing Interests: Declaration of competing interest MY, KT and TM received advisory fees from Sumitomo Dainippon Pharma Co., Ltd. EN is an employee of Sumitomo Dainippon Pharma Co., Ltd., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Evidence-based US guidelines provide recommendations for the use of granulocyte colony-stimulating factor (G-CSF) as supportive therapy in patients with cancer receiving chemotherapy. Pegfilgrastim is recommended for FN prophylaxis in patients with non-myeloid malignancies receiving a high-risk chemotherapy regimen, or an intermediate-risk regimen if one or more risk factors are present. The guidelines highlight the patient characteristics and chemotherapy regimens for solid tumors and hematologic malignancies that may influence a patient's overall risk of FN and may benefit from pegfilgrastim support. This review aimed to evaluate how pegfilgrastim use in patients with cancer receiving myelosuppressive chemotherapy in routine clinical practice aligns with evidence-based US guidelines. Examination of the literature revealed widespread deviation in relation to under- and over-prescribing, and timing of administration in US clinical practice. Pegfilgrastim is often over-prescribed in patients receiving palliative chemotherapy and those at low risk of FN. Potential under-prescribing of pegfilgrastim was also observed. In this literature search, data that appear to support same-day administration of pegfilgrastim were from uncontrolled studies that were limited in size. Analyses of healthcare claims data clearly favored next-day use, with statistically significant increases in FN incidence among patients receiving same-day pegfilgrastim versus those treated 1-4 days post-chemotherapy. Earlier-than-recommended administration typically occurs at the physician's discretion where next-day administration might present barriers to the patient receiving supportive therapy.There is a need to ensure appropriate prescribing to optimize patient outcomes, as deviation from the guideline recommendations was associated with increased incidence of FN and hospitalization., (Copyright © 2021. Published by Elsevier Ltd.)

Purpose: Describe temporal changes in use of myelosuppressive chemotherapy, primary prophylactic colony-stimulating factor, and neutropenia-related hospitalization, in commercially insured patients., Methods: Using a large commercial administrative database, we identified annual cohorts of adult patients diagnosed with breast or lung cancer, or non-Hodgkin lymphoma and initiating myelosuppressive chemotherapy during 2005-2017. We described yearly changes in proportions of myelosuppressive chemotherapy by febrile neutropenia risk category (high, intermediate, unclassified) and proportion of prophylactic colony-stimulating factor use and unadjusted incidence of neutropenia-related hospitalization in the first cycle of myelosuppressive chemotherapy., Results: Annual cohorts included 4383-5888 eligible patients during 2005-2017. The proportion of eligible patients aged ≥ 65 years increased from 26.0% in 2005 to 58.2% in 2017. Myelosuppressive chemotherapy use with regimens with high risk for febrile neutropenia increased from 15.1% in 2005 to 31.0% in 2017; and regimens with intermediate risk for febrile neutropenia decreased from 63.7% to 48.1% in 2017. Prophylactic colony-stimulating factor use increased from 41.6% in 2005 to 54.3% in 2017. Crude incidence of neutropenia-related hospitalization for all cancers increased from 2.0% to 3.1%, with a substantial increase in neutropenia-related hospitalization observed among non-Hodgkin lymphoma patients (2.8% to 8.5%) during 2005-2017., Conclusion: Among adult patients with breast and lung cancer, and non-Hodgkin lymphoma receiving myelosuppressive chemotherapy, use of regimens with high risk for febrile neutropenia increased, as did the use of prophylactic colony-stimulating factors after 2005. Incidence of neutropenia-related hospitalization increased slightly, particularly among non-Hodgkin lymphoma patients. Further studies are required to understand this increasing trend of neutropenia-related hospitalization, changing patient-level risk factors, and febrile neutropenia management.

Aims: In this pharmacoeconomic simulation, we: (1) modeled the cost-efficiency of converting patients from reference pegfilgrastim to biosimilar pegfilgrastim-cbqv for prophylaxis of chemotherapy-induced (febrile) neutropenia (CIN/FN) from the US payer perspective, (2) simulated how savings enable, on a budget-neutral basis, expanded access to pegfilgrastim-cbqv, and (3) estimated the number-needed-to-convert (NNC) to purchase one additional dose of pegfilgrastim-cbqv., Methods: In a hypothetical panel of 20,000 patients, we modeled cost-savings utilizing: two reference formulations (pre-filled syringe [PFS] and on-body injector [OBI]), three medication cost inputs (average sales price [ASP], wholesale acquisition cost [WAC], and an age-proportionate blended ASP/WAC rate), administration cost for injection (PFS) and device application (OBI), conversion rates of 10-100%, and 1-6 cycles of prophylaxis. Cost-savings were used to estimate additional doses of pegfilgrastim-cbqv that could be purchased and the NNC to purchase one additional dose., Results: Using ASP and 10% conversion from reference OBI to pegfilgrastim-cbqv, savings range from $326,744 (1 cycle) to $2.0M (6 cycles) which could provide 93-556 additional doses of pegfilgrastim-cbqv, respectively; the NNC to purchase one additional dose of pegfilgrastim-cbqv ranges from 21.6 (1 cycle) down to 3.6 patients (6 cycles). The WAC model saves $41.1M per cycle and $246.7M over 6 cycles at 100% conversion from reference PFS which could provide 9,709-58,253 additional pegfilgrastim-cbqv doses; the NNC ranges from 2.1 (1 cycle) to 0.3 (6 cycles). Using the blended ASP/WAC rate, converting 50% from reference OBI to pegfilgrastim-cbqv would save $10.2M per cycle and $60.9M over 6 cycles providing 2,638-15,829 additional doses of pegfilgrastim-cbqv; NNCs are 3.8 (1 cycle) and 0.6 patients (6 cycles)., Conclusions: Converting 20,000 patients from reference to pegfilgrastim-cbqv over 6 cycles can generate savings up to $246.7M, enough to purchase up to 58,253 additional doses of pegfilgrastim-cbqv. This simulation provides economic justification for prophylaxis with biosimilar pegfilgrastim-cbqv.

Background: Since decades, fever and infections have been the most important complications of intensive chemotherapy and hematopoietic stem cell transplantation (HSCT) in the treatment of hematologic malignancies. Neutropenia has long been considered to be the most important risk factor for these complications. However, recent studies have shown that not neutropenia, but the development of mucositis is the most important cause of these complications. Currently, limited options for the prevention and treatment of mucositis are available, of which most are only supportive. The pro-inflammatory cytokine interleukin-1 (IL-1) plays a crucial role in the pathogenesis of mucositis. Pre-clinical studies of chemotherapy-induced mucositis have shown that recombinant human IL-1 receptor antagonist anakinra significantly ameliorated intestinal mucositis. In our pilot study AFFECT-1, we examined the safety and maximal tolerated dose of anakinra in patients with multiple myeloma, treated with high-dose melphalan (HDM) and autologous HSCT, selecting a dose of 300 mg daily for the phase IIb trial. The aim of the AFFECT-2 study is to determine the efficacy of anakinra in preventing fever during neutropenia (FN) and mucositis in this study population., Methods/design: A multicenter, randomized, placebo-controlled, double-blind phase IIb trial will be conducted. Ninety patients with multiple myeloma scheduled for treatment with HDM and autologous HSCT will be included. Patients will be randomized between intravenous treatment with anakinra (300 mg) or placebo. Each group will be treated from day - 2 (day of HDM; day 0 is HSCT) up until day + 12. Outcome measures will be assessed at baseline, during admission, at discharge or day + 30, at day + 90, and + 1 year. The primary outcome will be reduction of FN. Secondary outcome measures include mucositis scores, bloodstream infections, citrulline levels, quality of life, and fatigue severity., Discussion: The AFFECT-2 trial will examine the efficacy of anakinra in the management of fever during neutropenia and mucositis in patients with multiple myeloma treated with HDM and autologous HSCT. The results of this study may provide a new treatment option for these important complications. Also, this study will give us more insight in the pathophysiology of mucositis, including the role of IL-1 and the role of the microbiota in mucositis., Trial Registration: Clinicaltrials.gov NCT04099901 . Registered on September 23, 2019. EudraCT: 2018-005046-10.

Background: Polymerase chain reaction (PCR) respiratory viral panel (RVP) testing is often used in evaluation of pediatric cancer patients with febrile neutropenia (FN), but correlation with adverse outcomes has not been well characterized., Procedure: A retrospective cohort of all children ages 0-21 years with cancer admitted to Children's Healthcare of Atlanta for FN from January 2013 to June 2016 was identified. Patient demographic and clinical variables such as age, RVP results, length of stay (LOS), and deaths were abstracted. Relationship between RVP testing and positivity and LOS, highest temperature (Tmax), hypotension and intensive care unit (ICU) admission were compared using Wilcoxon rank sums, chi-square, or Fisher's exact tests adjusting for age, sex, bacteremia, and diagnosis., Results: The 404 patients identified had 787 total FN admissions. RVPs were sent in 38% of admissions and were positive in 59%. Patients with RVPs sent were younger (median 5.5 vs 8.0 years, P < .0001) with higher Tmax (39.2° vs 39.1°, P = .016). The most common virus identified was rhinovirus/Enterovirus (61%). There were no significant differences in highest temperature or lowest blood pressure based on RVP positivity. Patients admitted to the ICU were more likely to have RVPs sent (odds ratio [OR] = 3.19, P < .002); however, neither having RVP testing nor RVP positivity were significantly associated with increased LOS or death. Coinfection with bacteremia and a respiratory virus was identified in 9.1% of patients., Conclusions: These data raise the question of the utility of sending potentially costly RVP testing as RVP positivity during febrile neutropenia does not impact LOS, degree of hypotension, or ICU admission., (© 2020 Wiley Periodicals LLC.)

Purpose: Evaluate the relationship between duration of primary prophylactic short-acting granulocyte colony-stimulating factor (PP-sG-CSF) and risk of neutropenia-related hospitalization (NRH) in older patients receiving myelosuppressive chemotherapy., Methods: Using the Medicare claims database, we conducted a nested case-control study in a cohort of patients aged ≥66 years with breast, colorectal, lung, ovarian, or prostate cancer, or non-Hodgkin lymphoma who initiated a first cycle of any myelosuppressive chemotherapy January 1, 2008-September 30, 2016, and received PP-sG-CSF. We matched up to four controls to each NRH case by age, cancer type, regimen febrile neutropenia (FN) risk category, and year using incidence density sampling. We used conditional logistic regression adjusted for race, sex, and modified Charlson comorbidity index (CCI) to estimate relative risk of NRH related to duration of PP-sG-CSF categorized as <5 and ≥ 5 days., Results: Of 2148 patients receiving PP-sG-CSF, 108 (5%) experienced NRH in the first cycle. We matched 333 controls to 96 cases. Cases were similar to controls in mean age, tumor type, and intermediate/high-risk regimen, but were more likely to have CCI ≥5 and less likely to use PP-sG-CSF ≥5 days (31% vs. 39%). Adjusted ORs (95% CI) for NRH were 0.69 (0.40-1.19) for ≥5 vs. <5 days of PP-sG-CSF among patients receiving any myelosuppressive chemotherapy, 0.43 (0.21-0.89) for intermediate/high-risk regimen, and 0.42 (0.19-0.89) for any myelosuppressive chemotherapy with all agents given on cycle day one only., Conclusions: Among older patients with cancer who are receiving PP-sG-CSF, ≥5 days of use was associated with substantial reduction in NRH risk., Competing Interests: Declaration of Competing Interest Shuling Li, Jiannong Liu, Tingting Gong, and Haifeng Guo are employees of Chronic Disease Research Group, Hennepin Healthcare Research Institute, which has received project funding from Amgen, Inc. Prasad L. Gawade, Michael A. Kelsh, Brian D. Bradbury, and Rajesh Belani are employees of and own stock in Amgen Inc. Gary Lyman has worked as a consultant for Amgen, Inc., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The clinical impact of pegfilgrastim in day-to-day practice remains unclear. This study evaluated the effectiveness of pegfilgrastim compared with daily filgrastim in patients with DLBCL who received the first-cycle of R-CHOP treatment by using a Japanese national inpatient database. Patient characteristics were adjusted by using propensity-score matching and stabilized inverse probability of treatment weighting (IPTW). In 1295 propensity-score-matched pairs, the incidence of febrile neutropenia was significantly lower in the pegfilgrastim group (risk difference 6.1%, 95% CI 4.1%-8.1%) than in the filgrastim group. In the pegfilgrastim group, the length of hospital stay and the total costs were also significantly reduced (percent reduction 34% [95% CI: 31%-37%], percent reduction 12% [95% CI: 9%-15%], respectively). The stabilized IPTW showed comparable results. In day-to-day practice, the simple mode of pegfilgrastim administration may be advantageous.

The safety and feasibility of oral fluoroquinolone monotherapy in patients with low-risk febrile neutropenia (FN) were demonstrated in recent studies. Levofloxacin (LVFX) is a commonly prescribed antibiotic; however, evidence for its efficacy against FN is limited. Therefore, in this study, we retrospectively investigated the efficacy of LVFX against low-risk FN in patients with malignant lymphoma at our institution. Treatment success was defined as recovery from fever and neutropenia without alteration of the initial regimen. We recruited 29 patients between January 2013 and December 2018. The median age of the cohort was 64 (range: 21-87) years; 13 (44.8%) were aged over 65 years. In total, 22 patients had diffuse large B-cell lymphoma (DLBCL). Therapy was successful in 24 (82.8%) patients, whereas 5 had treatment failure requiring a change from LVFX to intravenous broad-spectrum antibacterial agents. No deaths related to FN were observed. Two patients required FN-related chemotherapy dose reduction in subsequent cycles. Although this cohort comprised many elderly patients, our study confirmed the efficacy of LVFX in patients with low-risk FN. This may improve the treatment of low-risk FN and malignant lymphoma.

Background: Cytomegalovirus (CMV) is a rare cause of prolonged febrile neutropenia (PFN) among pediatric oncology patients, especially in non-stem cell transplant setting (Non-SCTS). Infectious Diseases Society of America (IDSA) guidelines stated briefly that neutropenia is not considered as an indication of CMV re-activation, and thus preventive strategies are not needed; however, multiple studies pressed on the need to treat CMV viremia among patients with PFN even when there is no evidence of end-organ involvement. Therefore, this study aimed to prospectively investigate the significance of CMV as a cause of PFN among pediatric oncology patients in a Non-SCTS., Patients and Methods: This was a prospective cohort study that was done at Princess Norah Oncology Center, King Abdulaziz Medical City in Jeddah, Saudi Arabia. CMV viral load was monitored weekly once the subject was identified as a case of PFN until resolution. Subjects and treating physicians were blinded to CMV viral load results., Results: The data of 27 PFN episodes (48% males) were analyzed. The incidence of CMV viremia was reported as 29.6%. Both CMV positive and negative episodes of PFN had similar rate of spontaneous resolution (p=0.669), with overall mortality as 105 and 125 per 1000 PFN episodes, respectively. No subject received anti-CMV in the positive CMV group; however, one subject did in the negative group for reasons other than CMV infection., Conclusion: This study demonstrated that CMV was not a significant cause of PFN in Non-SCTS. CMV also had no significant role in terms of survival and severity of the PFN episode., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Neutropenia is the most frequent side effect of commercially available myelosuppressive drugs and its most significant complication is febrile neutropenia. It is associated with increased hospital admissions and higher probability of death. Prophylaxis with the administration of granulocyte colony-stimulating factor can prevent neutropenia caused by anticancer drugs. The correct administration of these drugs and the management of febrile neutropenia are extremely important in the treatment of patients with cancer.

Purpose: Investigation of the current practice of diagnostics and treatment in pediatric cancer patients with febrile neutropenia., Methods: On behalf of the German Society for Pediatric Oncology and Hematology and the German Society for Pediatric Infectious Diseases, an Internet-based survey was conducted in 2016 concerning the management of febrile neutropenia in pediatric oncology centers (POC). This survey accompanied the release of the corresponding German guideline to document current practice before its implementation in clinical practice., Results: In total, 51 POCs participated (response rate 73%; 43 from Germany, and 4 each from Austria and Switzerland). Identified targets for antimicrobial stewardship concerned blood culture diagnostics, documentation of the time to antibiotics, the use of empirical combination therapy, drug monitoring of aminoglycosides, the time to escalation in patients with persisting fever, minimal duration of IV treatment, sequential oral treatment in patients with persisting neutropenia, indication for and choice of empirical antifungal treatment, and the local availability of a pediatric infectious diseases consultation service., Conclusion: This survey provides useful information for local antibiotic stewardship teams to improve the current practice referring to the corresponding national and international guidelines.

Introduction: Current guidelines advocate empirical antibiotic treatment (EAT) in haematological patients with febrile neutropenia. However, the optimal duration of EAT is unknown. In 2011, we have introduced a protocol, promoting discontinuation of carbapenems as EAT after 3 days in most patients and discouraging the standard use of vancomycin. This study assesses the effect of introducing this protocol on carbapenem and vancomycin use in high-risk haematological patients and its safety., Methods: A retrospective before-after study was performed comparing a cohort from 2007 to 2011 (period I, before restrictive EAT use) with a cohort from 2011 to 2014 (period II, restrictive EAT use). Neutropenic episodes related to chemotherapy or stem cell transplantation (SCT) in patients with acute myeloid leukaemia (AML) or high-risk myelodysplastic syndrome (MDS) were analysed. The primary outcome was the use of carbapenems and vancomycin as EAT during neutropenia, expressed as days of therapy (DOT)/100 neutropenic days and analysed with interrupted time series (ITS). Also the use of other antibiotics was analysed. Safety measurements included 30-day mortality, ICU admittance within 30 days after start of EAT and positive blood cultures with carbapenem-susceptible microorganisms., Results: Three hundred sixty-two neutropenic episodes with a median duration of 18 days were analysed, involving 201 patients. ITS analysis showed decreased carbapenem use with a step change of - 16.1 DOT/100 neutropenic days (95% CI - 26.77 to - 1.39) and an overall reduction of 21.6% (8.7 DOT/100 neutropenic days). Vancomycin use decreased with a step change of - 13.7 DOT/100 neutropenic days (95% CI - 23.75 to - 3.0) and an overall reduction of 54.7% (14.6 DOT/100 neutropenic days). The use of all antibiotics combined decreased from 155.6 to 138 DOT/100 neutropenic days, a reduction of 11.3%. No deaths directly related to early discontinuation of EAT were identified, also no notable difference in ICU-admission (9/116 in period I, 9/152 in period II) and positive blood cultures (4/116 in period I, 2/152 in period II) was detected., Conclusion: The introduction of a protocol promoting restrictive use of EAT resulted in reduction of carbapenem and vancomycin use and appears to be safe in AML or high-risk MDS patients with febrile neutropenia during chemotherapy or SCT.

Background: Patients with haematological malignancies have higher risk of acquiring bloodstream infection (BSI). Neutropenia resulting from cytotoxic chemotherapy is the most common risk factor. Infections can progress rapidly with poor outcomes. Understanding the epidemiology may enable prevention and effective management. We investigated and compared the incidence of BSI amongst patients with haematological malignancies and neutropenia and examined the changing spectrum of organisms, and their antimicrobial profiles., Methods: BSI data between July 1st 2009 and June 30th 2015 was reviewed., Results: Three hundred and fifty five BSI were identified in 255 neutropenic patients. Acute myeloid leukaemia (AML) accounted for 40%, Non-Hodgkin's lymphoma for 22% and Acute lymphocytic leukaemia (ALL) for 11.8%. A neutrophil count of <500 cells/μL was present in 93.2%. The overall incidence was 5.40 BSI per 1000 Haematology Occupied Bed days (OBD). Viridans streptococci and Enterococcus species were the most predominant Gram-positives. Vancomycin resistant Enterococcus faecium (VRE) emerged as the predominant Enterococcus species during the study period. Escherichia coli was the most predominant Gram-negative and Extended-spectrum beta-lactamases (ESBL) were detected in 7.1% of isolates. Amongst the Enterobacteriaceae and Pseudomonas aeruginosa dual resistance to Piperacillin-tazobactam and Gentamicin was detected in 5.4%., Conclusion: Our incidence of BSI was 5.40 per 1000 OBD, however variability in reporting of rates in neutropenic patients with haematological malignancies makes comparison between studies difficult, highlighting the need for rate reporting standardization. The epidemiology of organisms causing BSI has changed over time. There is a trend towards an increasing incidence of VRE and multidrug resistant Gram-negatives., (Copyright © 2019 Australasian College for Infection Prevention and Control. Published by Elsevier B.V. All rights reserved.)

Background: Prophylactic antibiotics decrease mortality and morbidity in patients with hematological malignancies following intensive chemotherapy. However, the efficacy of prophylactic antibiotics for pediatric patients with solid tumors remains unclear., Methods: We retrospectively assessed 103 neutropenic periods from 26 patients with neuroblastoma or brain tumors following three different intensity chemotherapy regimens (05A3, A, and B). While piperacillin was intravenously administered as prophylaxis (PIPC prophylaxis group), the historical control group received no prophylaxis. As patients exhibited a variable degree of myelosuppression based on the intensity of the chemotherapy regimen, we separately evaluated the frequency and severity of febrile neutropenia (FN) in each regimen., Results: Following intensive chemotherapy, we observed a significantly lower frequency of FN in the PIPC prophylaxis group compared with the historical control group in both regimen 05A3 (20% vs 65%; P = 0.01) and regimen A (56% vs 93%; P = 0.02). We also observed a shorter duration of fever, lower maximum fever, and lower C-reactive protein levels in the PIPC prophylaxis group compared with the historical control group after regimens 05A3 and A. Conversely, the frequency and severity of FN were not different between the two groups after moderate-intensity chemotherapy (regimen B). However, a longitudinal routine surveillance study of Pseudomonas aeruginosa also indicated a reduction in the susceptibility to PIPC throughout the study period., Conclusions: Although PIPC prophylaxis might provide an advantage for severe neutropenia in pediatric patients with solid tumors, there is concern regarding bacterial resistance to antibiotics. Therefore, further careful examination is necessary for adaptation., (© 2019 Japan Pediatric Society.)

Objective: Patients in anticancer treatment with a known side effect of neutropenia are monitored closely with laboratory measurements of white blood cell count (WBC) and differentiation. This study sought to evaluate measurement properties and feasibility of patients' self-testing using a point-of-care testing (POCT) device., Methods: A prospective feasibility and measurement study comparing the standard measurement of cancer patients' WBC and neutrophil count with POCT measurements. The study included 60 outpatients and 22 inpatients from a department of oncology at a university hospital., Results: Patients successfully conducted 106 measurements using the POCT device. 46% of the patients were >70 years. Weighted Deming regression analysis showed minimal yet significant proportional bias between methods, with POCT increasingly underestimating both total WBC and neutrophils compared with the standard method the higher the count. Over 90% of patients reported they were willing and considered themselves able to use the POCT device at home., Conclusions: The instrument can be used for self-testing of post-anticancer leukopenia and has sufficient measurement precision for patient risk stratification. Patients are able and willing to conduct measurements including when in a situation of acute illness. Further studies are needed to confirm safety and value within patients' own home., (© 2019 John Wiley & Sons Ltd.)

What Is Known and Objective: Patients who receive hematopoietic stem cell transplantation (HSCT) are usually administered a calcineurin inhibitor. Because vancomycin is associated with an increased incidence of nephrotoxicity, neutropenic patients receiving HSCT are considered a high-risk population for nephrotoxicity with vancomycin. We retrospectively compared the efficacy and safety of vancomycin and teicoplanin in febrile neutropenic patients receiving HSCT., Methods: A single-centre, retrospective cohort study was conducted at the 614-bed Gifu University Hospital in Japan. Patients who received HSCT and were administered vancomycin or teicoplanin by injection for febrile neutropenia from 1 January 2012 to 31 August 2017 were enrolled. Time to attain an effective trough concentration, clinical efficacy and adverse events were compared between the two groups., Results: Time to attain an effective trough concentration of over 10 μg/mL tended to be shorter in the teicoplanin group than in the vancomycin group (median 3, 95% confidence interval [CI] 2.4-3.6 days vs median 6, 95% CI 1.5-10.5 days; hazard ratio [HR] 0.4, 95% CI 0.15-1.06; P = .066). The rate of clinical failure was lower in the teicoplanin group than in the vancomycin group (18.8% vs 53.8%, P = .113). In addition, the overall incidence of nephrotoxicity was significantly lower in the teicoplanin group (0% vs 46.2%, P = .004)., What Is New and Conclusion: Our findings suggest that administration of teicoplanin may lead to early attainment of the effective concentration with a lower rate of clinical failure and incidence of nephrotoxicity compared to vancomycin in febrile neutropenic patients receiving HSCT., (© 2019 John Wiley & Sons Ltd.)

A major consequence of the intensive multi-modal chemotherapy commonly used to treat malignancies in childhood is life-threatening infection, frequently during periods of profound neutropenia. Recent advances have been made in all areas of management, from trying to prevent infection to getting patients off antimicrobials and home again in the shortest, safest way. Potential avenues of further research are outlined for readers to be aware of in the next few years., Competing Interests: No competing interests were disclosed.No competing interests were disclosed.No competing interests were disclosed., (Copyright: © 2019 Phillips B.)

Background: Cancer is associated with a variety of complications, including neutropenic fever, which can result in severe morbidity and mortality. This oncologic emergency requires ED management., Objective: This narrative review provides focused updates for emergency clinicians regarding neutropenic fever., Discussion: Neutropenic fever is defined by fever with oral temperature >38.3°C or temperature >38.0°C for 1 hour with an absolute neutrophil count (ANC) < 1000 cells/microL. Patients who have received chemotherapy within 6 weeks of presentation are at high risk for neutropenia. While most patients with neutropenic fever do not have an identifiable bacterial source of fever, clinicians should treat patients for bacterial infection. Rapid assessment and management are vital to improving outcomes in patients with suspected or confirmed neutropenic fever. History and examination should focus on the most common sites of infection: the gastrointestinal tract, blood, skin, lung, and urinary tract. However, physical examination and laboratory or imaging assessment may not display classic signs of infection. Blood cultures should be obtained, and broad-spectrum antibiotics are recommended. Oncology consultation is an integral component in the care of these patients. Several risk scores can assist in stratifying patients who may be appropriate for discharge home and follow-up., Conclusions: Neutropenic fever is an oncologic emergency. Rapid diagnosis and care of patients with neutropenic fever can improve outcomes, along with oncology consultation., (Published by Elsevier Inc.)