A Risk-Prediction Nomogram for Neutropenia or Febrile Neutropenia after Etoposide-Based Chemotherapy in Cancer Patients: A Retrospective Cohort Study.

INTRODUCTION: This study was conducted to develop and validate a nomogram for predicting the risk of neutropenia or febrile neutropenia (FN) in tumor patients in the first cycle of etoposide-based chemotherapy. METHODS: This retrospective cohort study used an information system to monitor patients with non-Hodgkin's lymphoma or solid tumors receiving an etoposide regimen in the first chemotherapy cycle in our hospital from 2009 to 2020. Binary logistic regression analysis was used to identify the influencing factors of patients with neutropenia or FN. Those factors were then used to develop a nomogram. RESULTS: A total of 1,554 patients were divided into the development group (n = 1,072) and validation group (n = 482). Variables used to predict neutropenia or FN were Karnofsky performance status (odds ratio [OR] = 0.85, 95% confidence interval [CI] = 0.81-0.89, p < 0.01), metastatic sites ≥3 (OR = 6.33, 95% CI = 2.66-15.11, p < 0.01), comorbidity of heart disease (OR = 4.88, 95% CI = 1.74-13.67, p < 0.01), recent surgery (OR = 7.96, 95% CI = 1.96-32.36, p < 0.01), administration of alkylating agents (OR = 4.50, 95% CI = 1.10-18.48, p < 0.01), total bilirubin ≥25 µmol/L (OR = 11.42, 95% CI = 4.00-32.61, p < 0.01), and lymphocyte count <0.7 × 109/L (OR = 4.22, 95% CI = 2.00-9.75, p < 0.01). CONCLUSION: This model can aid the early identification and screening of the potential risk of neutropenia or FN in the first cycle of treatment for patients using etoposide-based chemotherapy.

Recent advances in the management of chemotherapy-induced neutropenia: biosimilar granulocyte colony-stimulating factor use in Italy.

During the National Congress of the Italian Association of Medical Oncology, which was held in Rome, Italy, October 2019, experts met to discuss advantages of febrile neutropenia prevention based on biosimilar G-CSF. This issue is of paramount importance in oncology as recent biological products may be of great benefit, provided that costs are sustainable.

Association of time to antibiotics and clinical outcomes in patients with fever and neutropenia during chemotherapy for cancer: a systematic review.

PURPOSE: Prompt antibiotic therapy is standard of care for patients with fever and neutropenia (FN) during chemotherapy for cancer. We systematically reviewed the association between time to antibiotics (TTA) and clinical outcomes. METHODS: The search covered seven databases; confounding biases and study quality were assessed with the ROBINS-I tool. Safety (death, intensive care unit (ICU) admission, sepsis) and treatment adequacy (relapse of infection, persistence or recurrence of fever) were assessed as primary outcomes. RESULTS: Of 6296 articles identified, 13 observational studies were included. Findings regarding safety were inconsistent. Three studies controlling for triage bias showed a possible association between longer TTA and impaired safety. Meta-analysis for TTA ≤ 60 min versus > 60 min was feasible on four studies, with three studies each reporting on death (OR 0.78, 95%CI 0.16-3.69) and on ICU admission (OR 1.43, 95%CI 0.57-3.60). No study reported data on treatment adequacy. Triage bias, i.e. faster treatment of patients with worse clinical condition, was identified as a relevant confounding factor. CONCLUSION: There seems to be an association between longer TTA and impaired safety. More knowledge about TTA effects on safety are important to optimise treatment guidelines for FN. Controlling for triage and other biases is necessary to gain further evidence. TRIAL REGISTRATION: Registration: PROSPERO [http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42018092948].

Predictive value of monocytes and lymphocytes for short-term neutrophil changes in chemotherapy-induced severe neutropenia in solid tumors.

PURPOSE: To explore whether monocytes, lymphocytes, and platelets have a predictive value for short-term neutrophil changes in patients with severe neutropenia (SN) induced by chemotherapy. METHODS: Complete blood counts (CBC) were collected from a total of 62 patients with chemotherapy-induced SN from December 2013 to March 2018. CBCs at intervals of 1 day, 2 days, 3 days, 4 days, and 5 days were recorded, and logistic regression analyses were performed to determine whether the monocyte percentage (MP), absolute monocyte count (AMC), lymphocyte percentage (LP), absolute lymphocyte count (ALC), or platelet count (PC) were correlated with short-term neutrophil changes. The areas under the receiver operating characteristic (ROC) curves (AUCs) were calculated for parameters with a P value < 0.05. RESULTS: The MP was significantly correlated with changes in neutrophils for intervals of 1 to 5 days, while the LP was significantly correlated with changes in neutrophils for intervals of 2 to 5 days. A cutoff value of 6.5% for the MP yielded a sensitivity of 80%, a specificity of 88.6%, and an AUC of 0.908 for predicting an increase in neutrophils on the third day. A cutoff value of 14.75% for the LP yielded a sensitivity of 93.3%, a specificity of 70.3%, and an AUC of 0.812 for predicting an increase in neutrophils on the sixth day. CONCLUSIONS: In chemotherapy-induced neutropenia patients, the MP is the best predictor of short-term neutrophil changes. Close monitoring and proper interpretation of the MP and LP are informative in managing chemotherapy-induced neutropenia.

Prophylaxis of chemotherapy-induced neutropenia and febrile neutropenia with lipegfilgrastim in patients with non-Hodgkin lymphoma (NADIR study).

OBJECTIVE: The prospective non-interventional study (NIS) NADIR was designed to evaluate both effectiveness and safety of prophylactic use of lipegfilgrastim (Lonquex® ), a glycopegylated granulocyte colony-stimulating factor, in cancer patients with different tumor entities undergoing chemotherapy in routine clinical practice. The primary objective was incidence of severe neutropenia, febrile neutropenia (FN), and neutropenia-associated complications. METHOD: NADIR was a national, multicenter, prospective NIS. RESULTS: Here, we present the data on patients with non-Hodgkin lymphoma (NHL). Final analysis comprised 337 NHL patients having received ≥1 administration of lipegfilgrastim. Primary prophylaxis with lipegfilgrastim was documented in 78.7% of patients with high risk to develop FN. In total, ≥1 severe neutropenia (grade 3/4) was reported in 115 (34.1%) patients and ≥1 event of FN documented in 15 (4.5%) patients. Grade 3/4 infections were reported in 22 (6.5%) patients overall. Most frequently reported adverse events (AEs) related to lipegfilgrastim in total were bone pain (5.4%), leukocytosis (2.1%), back pain (1.8%), platelet count decreased (1.2%), and myalgia (1.2%). Fatal serious AEs were documented in 9 (2.7%) patients; none were attributable to lipegfilgrastim. CONCLUSION: Prophylaxis or therapeutic intention with lipegfilgrastim in NHL patients in routine clinical practice showed similar effectiveness and safety as demonstrated in the pivotal trials.

Meta-analysis comparing incidence of grade 3-4 neutropenia with ALK inhibitors and chemotherapy in patients with non-small-cell lung cancer.

Aim: This meta-analysis compared incidence of grade 3-4 neutropenia with ALK inhibitors versus chemotherapy in patients with non-small-cell lung cancer. Materials & methods: PubMed/MEDLINE was searched to identify Phase II and III randomized clinical trials published up to 25 October 2018. Summary incidence, relative risk and corresponding 95% CIs were calculated for grade 3-4 neutropenia. Results: Five randomized clinical trials were included. Relative risk (95% CI) of developing grade 3-4 neutropenia with ALK inhibitor versus chemotherapy was 0.27 (0.07-1.06). Probabilities of developing grade 3-4 neutropenia were 6.56 and 14.19%, respectively; no significant difference was found. Conclusion: In patients with non-small-cell lung cancer, incidence of grade 3-4 neutropenia with ALK-targeted therapy is not significantly different compared with chemotherapy.

Pelvic cellulitis caused by Raoultella planticola in a neutropenic patient.

Raoultella planticola is a gram-negative, encapsulated, aerobic bacterium within the Enterobacteriaceae family. It has been primarily described as pathogen in cases with pneumonia and gastrointestinal infections. Here we describe a case of severe pelvic cellulitis in a patient with neutropenia following induction therapy for myeloid sarcoma. The patient experienced a septic shock and was treated successfully with antibiotic therapy. A literature review is provided to put this case in context with previous reports on R. planticola. This report highlights that awareness for uncommon pathogens is crucial in the clinical management of infections in neutropenic patients.

Randomised phase III trial of vinflunine plus capecitabine versus capecitabine alone in patients with advanced breast cancer previously treated with an anthracycline and resistant to taxane.

Background: Capecitabine is an approved standard therapy for anthracycline- and taxane-pretreated locally advanced or metastatic breast cancer (BC). Vinflunine has demonstrated single-agent activity in phase II studies in this setting and activity and tolerability when combined with capecitabine. We compared the combination of vinflunine plus capecitabine (VC) with single-agent capecitabine. Patients and methods: Patients with locally recurrent/metastatic BC previously treated or resistant to an anthracycline and resistant to taxane therapy were randomly assigned to either vinflunine (280 mg/m2, day 1) plus oral capecitabine [825 mg/m2 twice daily (b.i.d.), days 1-14] every 3 weeks (q3w) or single-agent oral capecitabine (1250 mg/m2 b.i.d., days 1-14) q3w. The primary end point was progression-free survival (PFS) assessed by an independent review committee. The study had 90% power to detect a 30% improvement in PFS. Results: Overall, 770 patients were randomised. PFS was significantly longer with VC than with capecitabine alone [hazard ratio, 0.84, 95% confidence interval (CI), 0.71-0.99; log-rank P = 0.043; median 5.6 versus 4.3 months, respectively]. Median overall survival was 13.9 versus 11.7 months with VC versus capecitabine alone, respectively (hazard ratio, 0.98; 95% CI, 0.83-1.15; log-rank P = 0.77). No difference in quality of life was observed between the two treatment arms. The most common adverse events (NCI CTCAE version 3.0) in the combination arm were haematological and gastrointestinal. Grade 4 neutropenia was more frequent with VC (12% versus 1% with capecitabine alone); febrile neutropenia occurred in 2% versus 0.5%, respectively. Hand-foot syndrome was less frequent with VC (grade 3: 4% versus 19% for capecitabine alone). Peripheral neuropathy was uncommon in both arms (grade 3: 1% versus 0.3%). Conclusions: Vinflunine combined with capecitabine demonstrated a modest improvement in PFS and an acceptable safety profile compared with capecitabine alone in patients with anthracycline- and taxane-pretreated locally recurrent/metastatic BC. ClinicalTrials.gov: NCT01095003.

Febrile neutropenia (FN) occurrence outside of clinical trials: occurrence and predictive factors in adult patients treated with chemotherapy and an expected moderate FN risk. Rationale and design of a real-world prospective, observational, multinational study.

BACKGROUND: Febrile neutropenia (FN) is a common occurrence during chemotherapy. Granulocyte colony-stimulating factors (G-CSFs) can significantly reduce the risk of FN. International guidelines recommend G-CSF for patients receiving chemotherapy with FN risk of ≥20% or 10% to 20% with defined risk factors. Prophylaxis is not typically recommended for FN risk of < 10%; however, few studies have investigated FN incidence in lower-risk patients in real-world settings and tried to identify higher-risk subgroups. METHODS: This real-world prospective, observational, multinational study aims to estimate the rate of development of FN with a chemotherapy line expected to be associated with a 10% to 20% risk of FN. Eligible patients (> 18 years of age) will have a solid tumour or Hodgkin/non-Hodgkin lymphoma and a planned chemotherapy regimen with expected risk of FN of 10% to 20% (according to published guidelines). Patients will be observed for the duration of the chemotherapy line (first cycle administered without FN prophylaxis). Primary endpoint is incidence of FN after the first chemotherapy cycle. Secondary outcomes include: FN-associated morbidity and mortality; time to first FN occurrence; other FN risk factors and impact of FN on quality of life. A risk model using occurrence of FN as a binary outcome will be developed. Data will be stratified by age, comorbidities and other risk factors. DISCUSSION: This study will provide insight into the real FN risk for common chemotherapy regimens and predictive factors for FN, including patients generally excluded from randomised clinical trials, from which reported FN rates have been variable. This study builds on knowledge of predictive factors from other research and will provide information on patients with 10% to 20% FN risk.

Real-World Impact of a Decision Support Tool on Colony-Stimulating Factor Use and Chemotherapy-Induced Febrile Neutropenia Among Patients With Breast Cancer.

Background: White blood cell colony-stimulating factors (CSFs) decrease the incidence of chemotherapy-induced febrile neutropenia (FN). Widespread use of CSFs that is not guideline-concordant has been reported. Among patients with breast cancer receiving chemotherapy, the ability of evidence-based decision support tools to promote risk-appropriate reductions in CSF use without increased incidence of FN has not been examined. Methods: A retrospective cohort design and US commercial claims data were used. The impact of CSF decision support was analyzed among women with breast cancer receiving first-cycle chemotherapy from April 1, 2013, to March 30, 2015. The tool was implemented as part of a prior authorization process in 9 states starting July 1, 2014. Patients were assigned to intervention (ie, states where the decision support tool had been implemented) or nonintervention states (ie, 39 states where the tool had not been implemented). CSF use and subsequent incidence of FN were compared using difference-in-difference (DID) regressions adjusting for baseline differences in FN risk factors such as comorbidities and various infections. Results: The study sample of 7,224 patients (intervention states: pre-implementation, 1,991 and post-implementation, 2,010; nonintervention states: pre-implementation, 1,569 and post-implementation, 1,654) showed no significant difference in risk factors. Before and after implementation, a significant decrease in the proportion of patients with CSF use was observed in the intervention states (75% to 69%) compared with no significant change in the nonintervention (72% to 71%) states (DID, -5.4%; 95% CI, -6.0% to -4.7%; P=.006). No significance increase in FN incidence occurred in intervention (5.0% to 5.5%) and nonintervention (5.4% to 4.8%) states (DID, 0.2%; 95% CI, -0.20 to 0.30; P=.78). Similar results were obtained in subgroups by comorbidities and in sensitivity analyses by claims-based FN definitions. Conclusions: CSF use decreased modestly after implementation of the decision support tool, with no observed changes in FN rates. Such tools can reduce practice variation to improve care standards.

Comparison of the MASCC and CISNE scores for identifying low-risk neutropenic fever patients: analysis of data from three emergency departments of cancer centers in three continents.

PURPOSE: Patients with febrile neutropenia are a heterogeneous group with a minority developing serious medical complications. Outpatient management of low-risk febrile neutropenia has been shown to be safe and cost-effective. Scoring systems, such as the Multinational Association for Supportive Care in Cancer (MASCC) score and Clinical Index of Stable Febrile Neutropenia (CISNE), have been developed and validated to identify low-risk patients. We aimed to compare the performance of these two scores in identifying low-risk febrile neutropenic patients. METHODS: We performed a pooled analysis of patients presenting with febrile neutropenia to three tertiary cancer emergency centers in the USA, UK, and South Korea in 2015. The primary outcome measures were the occurrence of serious complications. Admission to an intensive care unit (ICU) and 30-day mortality were secondary outcomes. The predictive performance of each score was analyzed. RESULTS: Five hundred seventy-one patients presented with febrile neutropenia. With MASCC risk index, 508 (89.1%) were classified as low-risk febrile neutropenia, compared to 60 (10.5%) with CISNE classification. Overall, the MASCC score had a greater discriminatory power in the detection of low-risk patients than the CISNE score (AUC 0.772, 95% CI 0.726-0.819 vs. 0.681, 95% CI 0.626-0.737, p = 0.0024). CONCLUSION: Both MASCC and CISNE scores have reasonable discriminatory value in predicting patients with low-risk febrile neutropenia. Risk scores should be used in conjunction with clinical judgment for the identification of patients suitable for outpatient management of neutropenic fever. Developing more accurate scores, validated in prospective settings, will be useful in facilitating more patients being managed in an outpatient setting.

Development of a simplified multivariable model to predict neutropenic complications in cancer patients undergoing chemotherapy.

PURPOSE: Neutropenic complications remain the major dose-limiting toxicities of cancer chemotherapy. The aim of this study was to develop and internally validate a comprehensive and easily measurable scoring system for prediction of severe or febrile neutropenia in the first chemotherapy cycle of patients with solid tumors or lymphoma. METHODS: This prospective cohort study included consecutive patients at a tertiary referral hospital. Many clinical and laboratory-independent variables were measured at baseline. A multivariable logistic regression analysis was applied after unadjusted analysis, and the multivariable model was transformed into a simplified risk score based on 6 bootstrapped regression coefficients. The simplified scoring system was internally validated using cross-validation. All statistical tests were two-sided. RESULTS: A total of 305 patients were enrolled and followed during 1732 chemotherapy cycles. Of these, 259 were eligible for analysis. The multivariable model revealed 6 predictive factors for severe or febrile neutropenia (scores in parentheses): high-risk regimen without colony-stimulating factor (4 points), intermediate-risk regimen without colony-stimulating factor (3 points), age > 65 years and elevated ferritin (3 points), body mass index < 23 kg/m2 and body surface area < 2 m2 (2 points), estimated glomerular filtration rate < 60 mL/min/1.73m2 (2 points), and elevated C-reactive protein (1 point). The receiver operating characteristic curve was 0.832 (95% confidence interval [Cl], 0.767-0.897) for the simplified model and 0.816 (95% Cl, 0.771-0.860) for the cross-validation. CONCLUSIONS: We developed and internally validated a user-friendly prediction model to guide personalized decision-making using available clinical data and few cost-effective laboratory tests. External validation in other centers with different patients is required.

Predictive value of PCT and IL-6 for bacterial infection in children with cancer and febrile neutropenia.

PURPOSE: Only a third of children with cancer and febrile neutropenia (FN) have a proven bacterial infection; nevertheless, most children are hospitalized and treated with intravenous antibiotics. Several biomarkers have been proposed as predictive markers for bacterial infection in this population. We aimed to evaluate the role of interleukin-6 (IL-6) and procalcitonin (PCT) in diagnosing bacterial infection in children with cancer and FN. METHODS: The study population was derived from a prospective database (2006-2013, IL-8 study) comprising children with cancer who presented with FN. From stored plasma samples (taken at admission and/or at 12-24 h), we determined the PCT and IL-6 levels. Consequently, we explored their relation with the presence of bacterial infection (positive blood culture, radiologically documented infection or clinical bacterial focus). We predefined cutoff values at 60 ng/L for IL-6 and 0.25 ng/mL for PCT. RESULTS: Seventy-seven FN episodes in 55 children with cancer were included. In 18 episodes (23.4%), a bacterial infection was documented. Both at presentation and after 12-24 h, median values of IL-6 and PCT were significantly higher in patients with a bacterial infection compared to patients without a bacterial infection. With both biomarkers above cutoff values, sensitivity was 93% (with either one, this was even 100%). The identified group at low risk for bacterial infection comprised 41% of the population. CONCLUSION: PCT and IL-6 are promising markers in identifying bacterial infection in children with cancer and FN. In a subsequent project, we will incorporate these biomarkers in a risk assessment model that we will test prospectively in a clinical trial.

Avoidant conversations about death by clinicians cause delays in reporting of neutropenic sepsis: Grounded theory study.

BACKGROUND: Evidence suggests that patients delay reporting symptoms of neutropenic sepsis (NS) despite the risk to their life. This study aimed to elicit factors that contribute to delayed patient reporting of NS symptoms. METHODS: A constructivist grounded theory study used observations of chemotherapy consultations (13 h) and 31 in-depth interviews to explore beliefs, experiences, and behaviors related to NS. Participants included women with breast cancer, their carers (partners, family, or friends), and clinicians. An explanation for patient delays was developed through theoretical sampling of participants to explore emerging areas of interest and through constant comparison of data and their coding. This entailed iterative and concurrent data collection and analysis. Data were collected until saturation. RESULTS: All patients who developed NS-type symptoms delayed presenting to hospital (2.5 h-8 days), sometimes repeatedly. Moderators of delay included metastatic disease, bereavement, fatalism, religious beliefs, and quality of relationships with clinicians. There was an interplay of behaviors between clinicians, patients, and carers where they subconsciously conspired to underplay the seriousness and possibility of NS occurring. CONCLUSIONS: Findings have implications for health risk communication and development of holistic service models.

Diagnostic performance of procalcitonin, presepsin, and C-reactive protein in patients with hematological malignancies.

INTRODUCTION: Infections represent a major complication of hematological malignancies. C-reactive protein (CRP) and procalcitonin (PCT) have been used as diagnostic biomarkers of infections, but do not produce definitive findings. Recently, a new biomarker, presepsin, has been used as a diagnostic tool for detecting infections in the fields of emergency and neonatal medicine. However, the usefulness of presepsin for identifying infections in patients with hematological malignancies, including those who develop febrile neutropenia, remains unclear. METHODS: In this study, we retrospectively analyzed the utility of PCT, presepsin, and CRP as biomarkers of infections during 49 febrile episodes that occurred in 28 patients with hematological malignancies. RESULTS: The levels of PCT, but not those of CRP or presepsin, were significantly higher in the infection group than in the uninfected group (P<.03), indicating that PCT might be a more sensitive biomarker of infections. No differences in presepsin levels were detected between the patients with and without neutropenia, or between the infected and uninfected patients with neutropenia, indicating that presepsin might have less diagnostic value in patients with neutropenia. CONCLUSIONS: We conclude that PCT might provide additional information and could be used in combination with other biomarkers to detect infections in patients with hematological malignancies.

Zarzio®, biosimilar of filgrastim, in prophylaxis of chemotherapy-induced neutropenia in routine practice: a French prospective multicentric study.

PURPOSE: Chemotherapy-induced neutropenia is a serious and potentially life-threatening consequence of cancer treatment. Prophylactic treatment with granulocyte-colony stimulating factor (G-CSF) decreases the incidence of febrile neutropenia, the rate of hospitalization, and the use of antibiotics in patients at risk. The aim of this study was to assess efficacy, safety, and use of Zarzio(®)-biosimilar of Neupogen(®) (G-CSF; filgrastim)-in prophylaxis of chemotherapy-induced neutropenia in current practice in cancer patients. METHODS: We conducted an observational, prospective, longitudinal, and multicentric study in France. The incidence of neutropenia was evaluated at each cycle of chemotherapy. RESULTS: One hundred eighty-four patients (women, 64.7 %; mean age, 61.7 years) with solid tumor (89.7 %; breast cancer, 50.5 %) or non-Hodgkin lymphoma (10.3 %) were included. The risk of febrile neutropenia based on chemotherapy regimen was >20 % for 32.1 % of patients. No case of febrile neutropenia was reported. Neutropenia was the cause of hospitalization and/or antibiotic therapy in 10 patients. The most frequent adverse events related to Zarzio(®) were pain, in particular bone pain. No serious adverse event related to Zarzio(®) was reported. CONCLUSION: The results obtained in real-life conditions confirm that Zarzio(®) is efficient and well tolerated in cancer patients.

Can mortality of cancer patients with fever and neutropenia be improved?

PURPOSE OF REVIEW: Neutropenic fever is the most common infective complication in patients receiving cytotoxic chemotherapy, and may result in severe sepsis, septic shock and mortality. Advancements in approaches to empiric antimicrobial therapy and prophylaxis have resulted in improved outcomes. Mortality may, however, still be as high as 50% in high-risk cancer populations. The objective of this review is to summarize factors associated with reduced mortality in patients with neutropenic fever, highlighting components of clinical care with potential for inclusion in quality improvement programs. RECENT FINDINGS: Risks for mortality are multifactorial, and include patient, disease and treatment-related factors. Historically, guidelines for management of neutropenic fever have focused upon antimicrobial therapy. There is, however, a recognized need for early identification of sepsis to enable timely administration of antibiotic therapy and for this to be integrated with a whole of systems approach within healthcare facilities. Use of Systemic Inflammatory Response Syndrome criteria is beneficial, but validation is required in neutropenic fever populations. SUMMARY: In the context of emerging and increasing infections because of antimicrobial-resistant bacteria in patients with neutropenic fever, quality improvement initiatives to reduce mortality must encompass antimicrobial stewardship, early detection of sepsis, and use of valid tools for clinical assessment. C-reactive protein and procalcitonin hold potential for inclusion into clinical pathways for management of neutropenic fever.

Leucopenia and treatment efficacy in advanced nasopharyngeal carcinoma.

BACKGROUND: Leucopenia or neutropenia during chemotherapy predicts better survival in several cancers. We aimed to assess whether leucopenia could be a biological measure of treatment and a marker of efficacy in advanced nasopharyngeal carcinoma (ANPC). METHODS: We retrospectively analyzed 3826 patients with ANPC who received chemoradiotherapy. Leucopenia was categorised on the basis of worst grade during treatment according to the National Cancer Institute Common Toxicity Criteria version 4.0: no leucopenia (grade 0), mild leucopenia (grade 1-2), and severe leucopenia (grade 3-4). Associations between leucopenia and survival were estimated by Cox proportional hazards model. RESULTS: Of the 3826 patients, 2511 (65.6 %) developed mild leucopenia (grade 1-2) and 807 (21.1 %) developed severe leucopenia (grade 3-4) during treatment; 508 (13.3 %) did not. A multivariate Cox model that included leucopenia determined that the hazard ratios (HR) of death for patients with mild and severe leucopenia were 0.69 [95 % confidence interval (95 %CI) 0.56-0.85, p < 0.001] and 0.75 (95 %CI 0.59-0.95, p = 0.019), respectively; the HR of distant metastasis for patients with mild and severe leucopenia were 0.77 (95 %CI 0.61-0.96, p = 0.023) and 0.99 (95 %CI 0.77-1.29, p = 0.995), respectively. Leucopenia had no effect on locoregional relapse. CONCLUSIONS: Our results indicate that mild leucopenia during chemoradiotherapy is associated with improved overall survival and distant metastasis-free survival in ANPC. Mild leucopenia may indicate appropriate dosage of chemotherapy. We can identify the patients who may benefit from chemotherapy if they experienced leucopenia during the treatment. Prospective trials are required to assess whether dosing adjustments based on leucopenia may improve chemotherapy efficacy.

Management of fever and neutropenia in children with cancer.

PURPOSE: Febrile neutropenia remains a common, life-threatening complication of chemotherapy in paediatric oncology. Delays in institution of empiric antibiotics have been identified at tertiary and regional centres caring for these patients and associated with decreased survival. Our objective was to reduce the time to administration of empiric antibiotics to less than 60 min from the time of presentation to hospital. METHODS: A retrospective study of the records of oncology patients presenting to the emergency department of a tertiary hospital over a 3-month period was performed and time to first antibiotic administration recorded. Potential causes of delay in commencement of antibiotics were identified and an algorithm-based approach to the management of fever in immunocompromised children developed and implemented. Follow-up evaluation data were collected at 12 and 60 months post-intervention. Causes of delay in commencement of antibiotics at regional hospitals that share care with the tertiary hospital were identified through questionnaires, interviews and focus groups, involving patients and medical and nursing staff. The impact of the introduction of the algorithm at one peripheral hospital was evaluated. RESULTS: The mean time to empiric antibiotics was reduced from 148 min (95% confidence interval (CI) 81-216) at baseline to 76 min (95% CI 50-101) at 12 months post-intervention and sustained at 65 min (95% CI 52-77) 5 years after the intervention. At the peripheral hospital, mean time to antibiotic delivery was reduced from 221 min (95% CI 114-328) to 65 min (95% CI 42-87) at 12 months after the intervention. CONCLUSION: The introduction of the guideline, with teaching and support for staff and parents, resulted in an improvement in practice, meeting international guidelines and achieving sustained results at 5 years after introduction at a tertiary hospital. The guideline has been shown to be feasible and effective at a regional hospital.

The signs, symptoms and help-seeking experiences of neutropenic sepsis patients before they reach hospital: a qualitative study.

PURPOSE: Neutropenic sepsis (NS) is a medical emergency in which urgent treatment with antibiotics is known to improve outcomes, yet there are minimal data about what happens to patients with NS before they reach hospital. We aimed to examine the pre-hospital experiences of patients with NS, identifying its early presenting features and exploring the factors potentially delaying patients' arrival at hospital. METHODS: We conducted in-depth, qualitative interviews with 22 cancer patients admitted to hospital for treatment of NS and 10 patient carers. The setting was a tertiary referral centre in Southern England. RESULTS: Thirty seven percent of patients took over 12 h to present to hospital after symptom onset. The mean delay in presentation was 11 h (range 0-68 h). Thematic analysis of the interviews, using grounded theory, revealed wide-ranging, potentially modifiable factors delaying patients' presentation to hospital. For example, information provided to patients about NS from different sources was inconsistent, with 'mixed messages' about urgency triggering delays. All patients self-monitored their temperature and understood the implication of a fever but few appreciated the potential significance of feeling unwell in the absence of fever. Attempts to obtain treatment were sometimes thwarted by nonspecialists' failure to recognise possible neutropenia in a patient with apparently mild signs, and several patients with NS were discharged without treatment. Some patients denied their symptoms to themselves and others to avoid hospital admission; palliative patients seemed particularly prone to these attitudes, while their carers were keen to seek medical attention. CONCLUSIONS: This investigation of patients' and carers' experiences of NS identifies numerous strategies for improving patient education, support and pre-hospital management, all of which may reduce pre-hospital delays and consequently decrease morbidity and mortality from NS.