Chemotherapy-induced Neutropenic Fever Research Articles

Classification of Chemotherapy-Induced Febrile Neutropenic Episodes Into One of the Three Febrile Neutropenic Syndromes.

Introduction Febrile neutropenia is a commonly encountered medical emergency in patients undergoing cancer treatment and can delay and modify the course of treatment and even lead to dire outcomes, including death. The cause of fever in a post-chemotherapy-induced neutropenic patient can be confusing to treating physicians. A review of the literature demonstrated that blood culture results could determine the cause of febrile neutropenia in only approximately 10% to 25% of patients. The objective of our study was to measure the incidence of positive blood cultures, urine cultures, and other body fluid cultures resulting in chemotherapy-induced neutropenia and further classify fever episodes into three neutropenic fever syndromes, such as microbiologically documented, clinically suspected, or unknown causes of fever, respectively. Methods We conducted a prospective observational study on 399 chemotherapy-induced neutropenic fever episodes with the aim of classifying them into one of the three neutropenic syndromes. Wetried to document the cause of the fever in these patients. We also noted the type of cancer treatment regimen they were on and correlated their clinical profile with their body fluid cultures, including blood cultures, urine cultures, and other body fluid cultures. We then categorized each fever episode into one of three neutropenic syndromes. Results We studied 399 febrile neutropenic episodes. We were able to microbiologically document the cause of fever in 39% of the cases, and we obtained growth in 51 out of 399 blood cultures (13%), which was comparable to the available literature, and urine culture showed growth in 62 out of 399 cultures (16%), while other body cultures such as pus culture, bile culture, and bronchioalveolar lavage cultures collectively showed growth in 42 out of 399 episodes (10%). The most common bacteria isolated in both blood and urine cultures were Escherichia coli. Cumulatively, including blood, urine, and body fluid cultures, we were able to classify 39% (155 out of 399 cases) of febrile neutropenic episodes as microbiologically documented. The cause of fever was clinically suspected by means of careful history taking and an extensive physical examination in 31% (125 out of 399) without growth evidence in blood cultures, urine cultures, or any other body fluid culture. The cause of fever remained unknown in 119 cases (30%) of patients and was classified under the unknown cause of fever. Conclusions We conclude by stating that the study of fever in a neutropenic patient should include a thorough history and clinical evaluation of blood, urine, and other body fluid cultures instead of solely relying on blood culture results. We recommend further classifying patients into one of the three neutropenic fever syndromes, such as those that are microbiologically documented, clinically suspected, or unknown. Our blood cultures were able to give us a 13% positivity rate, whereas microbiologically, we were able to isolate an organism likely causing feverin 39% of patients. The cause of fever was suspected clinically in 31% of patients, but we were unsuccessful in microbiologically documenting any culture growth in blood, urine, or any other body fluid culture. The cause of fever remained a mystery and unknown to us without any microbiological or clinical cues in 119 cases (30%) of febrile neutropenic episodes.

Fever and breast cancer: A critical review of the literature and possible underlying mechanisms

Fever is a common feature in various pathological conditions that manifests a series of molecular events in the internal milieu. Much less attention has been paid to the clinical importance and the management of fever in breast cancer patients. However, several studies have reported an association between postoperative fever and poor treatment outcomes in breast cancer patients. The fever is a side effect of chemotherapy and a manifestation of cancer recurrence. The postmenopausal breast cancer patients experience another body temperature disturbance that is known as a hot flashes. Here, we reviewed the literature regarding postoperative fever and the possible underlying molecular and cellular mechanisms. Then the efficacy of non-steroidal anti-inflammatory drugs was discussed as a therapeutic option to control postoperative fever. Finally, we reviewed the chemotherapy-induced neutropenic fever and cancer vaccination-induced fever.

Performance of the Karius Plasma Next Generation Sequencing Test in Determining the Etiologic Diagnosis of Febrile Neutropenia: Results from a Pilot Study

BackgroundBlood cultures (BC) fail to detect a pathogen in most patients with neutropenic fever (NF). We examined the performance of the Karius next generation sequencing plasma test (plasma NGS) compared with that of BC in chemotherapy-induced NF.MethodsPatients 18 years or older with absolute neutrophil count <500 cells/mm3 anticipated for > 7 days were enrolled at the time of BC collection (T0) due to fever. Plasma samples were collected at T0 and twice weekly until neutrophil recovery or discharge. Samples were shipped to the Karius CLIA/CAP laboratory (Redwood City, CA) where cell-free plasma was prepared, DNA extracted, and NGS performed. After removing human reads, remaining sequences were aligned to a curated pathogen database. Organisms present at a significance- level above a predefined threshold were reported. T0 BC and plasma NGS results were compared, excluding organisms (eg, viruses) not recoverable by BC. Positive agreement was defined as plasma NGS identification of at least one isolate seen on BC. Plasma NGS+/BC- results underwent adjudication by 3 infectious diseases specialists. Diagnosis was Definite if microbiology confirmed NGS result within 7 days of enrollment; Probable if clinical, radiologic, and laboratory data were compatible with plasma NGS test result; and otherwise Indeterminate.ResultsThe first 18 patients were evaluated. At the time of enrollment, 6 patients were on antibiotics and 3 were on antifungals. There were 4 positive BC (each monomicrobial) at T0 and all were concordant with plasma NGS. The plasma NGS test identified additional organisms in 2 of the BC+ patients with surgical abdomen. Compared with BC, plasma NGS positive agreement was 100% (4/4) with lack of agreement in 43% (6/14). All 8 NGS+/BC- cases were deemed Probable by adjudication. These included patients with single or mixed organisms in patients with enterocolitis or severe mucositis. In one sample, Aspergillus fumigatus was detected in a patient with new lung nodules.ConclusionThe etiologic diagnosis of NF is frequently unknown, leading to broad antibiotics and sometimes delay of targeted treatment. Plasma NGS may provide useful data for managing NF given its ability to detect a breadth of pathogens even when patients are pretreated with antibiotics.Disclosures H. Seng, Karius, Inc: Employee, Salary; D. Hollemon, Karius, Inc: Employee, Salary; D. Hong, Karius, Inc.: Collaborator, Research support and Salary T. A. Blawkamp, Karius Inc.: Board Member and Employee, Salary; M. Kertesz, Karius Inc.: Board Member and Employee, Salary

INTERNATIONAL PERSPECTIVE: Management of chemotherapy-induced febrile neutropenia among adult oncology patients: A review

The aim of this literature review is to investigate the safest and most appropriate actions for the management of chemotherapy-induced febrile neutropenia. A literature search was undertaken, including major computerized electronic databases (PUBMED, SPRINGER, and WILEY). All studies that discuss colony stimulating factor plus antibiotics versus antibiotics or colony stimulating factors alone for the treatment of febrile neutropenia in adult oncology patients were sought. A review of the selected studies was performed. Most studies focus on the prompt assessment and management for oncology patients who are experiencing febrile neutropenia by using appropriate antibiotics and highlight the importance of using antibiotics and colony stimulating factor in the management of chemotherapy-induced neutropenic fever. Key words: febrile neutropenia, chemotherapy, management, oncology patients

Granulocyte Colony-Stimulating Factor for Effective Management of Chemotherapy-Induced Neutropenic Fever

Purpose: Chemotherapy-induced febrile neutropenia is a frequent event for cancer patients undergoing of chemotherapy treatment and it is potentially a life threatening situation. The purpose from this search is to investigate the effectiveness of granulocyte colony-stimulating factor on the management of neutropenic fever following chemotherapy in oncology patients.Methods: An exhaustive literature search was undertaken including major computerize electronic databases (PUBMED, SPRINGER, and WILLEY). All studies that discuss granulocyte colony- stimulating factor for the treatment of febrile neutropenia in adult's oncology patients were sought. A review of the selected studies was performed.Findings: 33 references were screened, with 8 studies meeting eligibility criteria for inclusion. Most studies focus on the important of prompt assessment and management of oncology patients whose in febrile neutropenia by using appropriate dose of granulocyte colony-stimulating factor as prophylactic before the nadir period or management of neutropenic fever, and the role of that in the minimize mortality related infection in neutropenic patients, time of hospitalization, treatment side effects, and time to defervescence.Conclusion: Appropriate use of granulocyte colony- stimulating factor during and after chemotherapy cycle treatment in oncology patients and before they became in febrile neutropenia is most effective than use it after developed neutropenia, that prophylactic is first line of management.

Improving Service Provision to Manage Chemotherapy-induced Neutropenic Fever in an Oncology Unit

Objectives: Neutropenic fever is a serious complication of cytotoxic chemotherapy with significant morbidity and mortality, for which prompt initiation of antibiotics improves clinical outcomes. International guidelines recommend a ‘door-to-needle’ time (DTN) for antibiotic administration within 2 hours as a performance standard in the management of neutropenic fever. This study set out to evaluate whether this target of DTN within 2 hours was being met in our institution. By identifying hurdles in the existing system, we anticipated deriving strategies to set up new workflow arrangements to improve our practice. Methods: Two-stage retrospective audits were carried out. Oncology patients who were admitted for neutropenic fever after recent chemotherapy were identified from the hospital computer database. All paper and electronic medical records were reviewed and analysed to determine the DTN of antibiotic administration. System factors and attributes leading to major delays were identified along the patient care pathway. The result of the first audit was summarised, shared, and discussed among teams; strategies to overcome impediments were derived and implemented. A second audit using the same criteria was then carried out to evaluate the effectiveness of the changes. Results: In the first phase of audit from 1 April 2011 to 30 November 2011, there were 32 patients. Overall, the median DTN was 261 minutes (range, 62-531 minutes); two patients (6%) achieved the 2-hour target. Patients admitted through the emergency department had a shorter median DTN than those admitted through the oncology clinic (222 vs 315 minutes). One patient (3%) died due to uncontrolled chest infection and cancer progression. Major attributes to prolonged DTNs were identified. They included (but were not limited to): a long waiting time for clinician assessment prior to hospital admission, and after being hospitalised, a long time interval between antibiotic prescription and administration. A list of actions to overcome these delays was proposed and worked out in departmental multidisciplinary meetings. At the same time, in the emergency department a clinical management protocol was set up and implemented to deal with patients having suspected neutropenic fever. After implementation of new workflows (both in the oncology and emergency departments), the second phase of audit was carried out from 1 April to 31 July 2012. This entailed 30 patients. Overall, there was a 64% reduction in the median DTN to 95 minutes (range, 25-231 minutes). The reduction in median DTN was noted in patients admitted via the emergency and oncology departments, being 79% (from 222 to 46 minutes) and 69% (from 315 to 98 minutes), respectively. Moreover, 63% (19/30) of the patients achieved the 2-hour target, which translated into a 11-fold improvement. Conclusion: By modifying the existing system and workflows, clinical audits and collaborative multidisciplinary efforts significantly improved the service provided for the clinical management of patients with neutropenic fever.

Management of Chemotherapy-Induced Neutropenic Fever

Fever occurs at high rates in patients with chemotherapy-induced neutropenia and is considered an oncologic emergency. Numerous algorithms have been developed to guide treatment decisions. Prompt care and the initiation of empiric antibiotic therapy are critically important universal aspects of these treatment-decision schemata. Fever may be the only sign of infection, as in patients with cancer who are undergoing chemotherapy, the immune response is attenuated. In the majority of cases, no etiology for neutropenic fever is uncovered; nonetheless, a thorough workup is essential. The workup allows practitioners to risk stratify patients as being at low or high risk for infectious complications so that appropriate care can be administered. Although it is important to note that there are management algorithms to follow, every patient may present and respond differently. We generally start with broad-spectrum monotherapy for Gram-negative bacteria and then consider whether Gram-positive or antifungal coverage is necessary based on the clinical picture, including factors such as duration and degree of neutropenia. It is important for all practitioners to understand how to care for patients with neutropenic fever because it is a common and treatable condition.

Utilidad de la escala de MASCC en el tratamiento de la neutropenia febril inducida por quimioterapia en pacientes con neoplasia sólida

Background and objectives We aimed to describe chemotherapy-induced neutropenic fever (NF) in patients with solid neoplasms (SN), to validate the Multinational Association of Support Treatment in Cancer (MASCC) scale, and to evaluate whether the use of the MASCC scale was useful for reducing hospital costs for this oncologic emergency and improving the quality of life. Patients and method We performed a prospective study on the incidence of chemotherapy-induced NF from December 2005 to November 2006 and calculated the sensitivity and specificity of the MASCC scale. We compared different parameters before and after (periods 1 and 2) the inclusion of the MASCC scale. Results We included 80 episodes of NF, 48.8% being of low risk. The sensitivity and the specificity of the MASCC scale were 86.3% (19/22) and 62% (26/58), respectively. 16 patients were discharged early (<3 days). Hospital costs were significantly lower during period 2. Conclusions The MASCC scale is a safe tool for stratifying the risk of cancer patients and chemotherapy–induced NF. However, greater specificity would allow a greater reduction in hospital costs and improve the quality of life of these patients.

The predictive value of interleukin-8 (IL-8) in hospitalised patients with fever and chemotherapy-induced neutropenia

Aim To demonstrate whether serum Interleukin-8 (IL-8) is a relevant parameter to select hospitalised patients with chemotherapy-induced neutropenic fever with low or high probability of infection. Results 90 assessable febrile episodes in 73 patients were evaluated; 46% of the febrile episodes were microbiologically documented infection (MDI), 8% clinical documented infection (CDI), and 47% fever of unknown origin (FUO). Median IL-8 level was lower in the FUO group compared to CDI and MDI ( p < 0.0005). In 45 of 48 episodes (94%) with CDI/MDI, IL-8 level at the start was ⩾60 ng/l while in 18 of 21 episodes (86%) with IL-8 level <60 ng/l, no infectious cause was demonstrated. FUO and CDI/MDI patients with IL-8 ⩾60 ng/l and responsive on antibiotic treatment showed a decline of IL-8 levels within days in contrast to non-responding patients. Conclusions Serum IL-8 level can be a useful marker to identify hospitalised FUO patients with low probability of infection.

Nijmegen breakage syndrome 1 (NBS1) gene polymorphism and chemotherapy-induced neutropenic fever in breast cancer patients

574 Background: Neutropenic fever (NF) is a serious complication of the chemotherapies given to breast cancer patients and often limits their use. Hence, identifying which patients are at increased risk to develop NF is very important. The NBS1 gene product is important for the repair of double-strand DNA breaks and is activated by chemotherapy. The objective of this study was to determine if genetic variations of NBS1 polymorphisms predict the risk of chemotherapy-induced NF in breast cancer patients. Methods: Blood from 306 newly diagnosed breast cancer patients treated with chemotherapy were prospectively collected on a study approved by the institutional review board. The relationship of chemotherapy administration (e.g. dose, timing) and growth factor use were correlated with the absolute neutrophil count (ANC) and NF development. For each patient, we assessed three polymorphisms (924T&gt;C, 8360G&gt;C, and 30537G&gt;C) of NBS1 gene using polymerase chain reaction-restriction fragment length polymorphism method. Two-sided Chi-square test was used for univariate analysis and a multivariable logistical regression analysis was used to calculate odds ratios. Results: In total, 167 (55%) patients experienced ANC less than 1,000 cells/microliter (CIN1000) and 30 (10%) patients developed NF. For 8360G&gt;C polymorphism, 9.7% of patients had a 8360CC variant genotype and these patients had increased risk of NF than the other genotypes (NF in CC 20.7% vs. in others 8.1%; Odds Ratio [OR] = 3.0; 95% confidence interval [CI] = 1.1 - 8.0, p = 0.034). In multivariable logistic regression model, 8360CC genotype (OR = 5.0, 95% CI = 1.6 - 16.1, p = 0.007) and growth factor support (OR = 19.6, 95% CI = 4.4 - 87.6, p &lt; 0.001) were significantly associated with NF development. No genotypes of 924T&gt;C and 30537G&gt;C polymorphisms increased the risk of NF and there was no statistical association between the three NBS1 gene polymorphisms and CIN1000. Conclusions: Breast cancer patients with 8360CC variant polymorphism in NBS1 gene have increased risk in developing NF with systemic chemotherapy. Analysis of polymorphisms of NBS1 and other DNA repair genes could potentially help identify who will develop chemotherapy-induced bone marrow toxicities. No significant financial relationships to disclose.

Safe and effective outpatient treatment of adults with chemotherapy-induced neutropenic fever

The safe and effective outpatient treatment of adults with chemotherapy- induced neutropenic fever is reviewed. Chemotherapy-induced neutropenic fever is a potentially life-threatening circumstance in high-risk patients. The standard of care for neutropenic fever is inpatient treatment with i.v. broad-spectrum antibiotics. Within the past 5-10 years, there has been growing interest in oral therapy and outpatient treatment for carefully selected low-risk patients. Outpatient treatment has the potential to avoid patient exposure to multidrug-resistant organisms found in the hospital, provide a more comfortable environment for the patient and his or her family, and achieve significant cost savings. Two risk-assessment tools have been developed to identify patients with a low risk of developing complications from neutropenic fever. A limited number of clinical trials have been conducted to evaluate outpatient treatment of low-risk patients. The evidence from well-designed randomized controlled trials comparing the safety and efficacy of outpatient therapy with standard therapy is not extensive. However, some centers have reported successful outpatient therapy in low-risk patients with febrile neutropenia. The greatest amount of evidence for outpatient treatment of neutropenic fever is available for the combination regimen of ciprofloxacin plus amoxicillin-clavulanate. Clinical practice guidelines are available to guide patient evaluation, antibiotic selection, monitoring, and follow-up. The accepted standard for treatment of neutropenic fever remains inpatient therapy with i.v. broad-spectrum antibiotics. However, some centers have had success treating selected low-risk patients with neutropenic fever as outpatients.

The Role of Oral Mucositis on the Systemic Inflammation Parameter IL-8 in Febrile Neutropenic Cancer Patients

Purpose: Cancer patients treated with cytostatic drugs often develop oral mucositis, considered to be a mucosal injury in which various cytokines, such as interleukin 8 (IL-8), may play a role. Plasma IL-8 is a systemic inflammatory response parameter. This study investigated whether oral mucositis affects plasma IL-8 levels in febrile neutropenic cancer patients. Patients and Methods: Patients (n = 57) who were hospitalized with chemotherapy-induced neutropenic fever were scored for oral mucositis on the second day of hospitalization according to a validated oral mucositis assessment scale (OMAS) and WHO toxicity grading. Patients (n = 20) with a clinical sepsis or local bacterial infection were excluded from this evaluation. The remaining 37 patients were divided in groups with and without oral mucositis. Results: The difference in plasma IL-8 level between patients with and without mucositis was not significant (P = 0.7). Similarly no difference was observed in the degree and duration of granulocytopenia. Conclusion: These results indicate that low-grade oral mucositis is not related to the systemic plasma IL-8 level in febrile neutropenic cancer patients without a clinical sepsis or local bacterial infection.

Randomized placebo-controlled trial of granulocyte-macrophage colony-stimulating factor in patients with chemotherapy-related febrile neutropenia.

To determine whether granulocyte-macrophage colony-stimulating factor (GM-CSF) used in addition to standard inpatient antibiotic therapy shortens the period of hospitalization due to chemotherapy-induced neutropenic fever. One hundred thirty-four patients with a hematologic (n = 47) or solid tumor (n = 87) who had severe neutropenia (< 0.5 x 10(9)/L) and fever (> 38.5 degrees C once or > 38 degrees C twice over a 12-hour observation period) were randomly assigned to receive GM-CSF 5 micrograms/kg/d (n = 65) or placebo (n = 69) in conjunction with broad-spectrum antibiotics for a minimum of 4 days and a maximum of 14 days. GM-CSF/placebo and antibiotics were stopped if the neutrophil count was greater than 1.0 x 10(9)/L and temperature less than 37.5 degrees C during 2 consecutive days, or for a leukocyte count > or = 10 x 10(9)/L, both followed by a 24-hour observation period (hospitalization period). Compared with placebo, GM-CSF enhanced neutrophil recovery. Median neutrophil counts at day 4 were 2.5 x 10(9)/L (range, 0 to 25) in the GM-CSF arm and 1.3 x 10(9)/L (range, 0 to 9) in the placebo arm (P < .001). No significant difference was observed with regard to median number of days with less than 1.0 x 10(9)/L neutrophils (4 v 4) or days of fever (3 v 3). The median number of days patients were hospitalized while on study was comparable in the GM-CSF and placebo groups at 6 (range, 3 to 14) versus 7 (range, 4 to 14), respectively, according to an intention-to-treat analysis (P = .27). Quality-of-life scores in 90 patients demonstrated significant differences in favor of the placebo group. Hospital costs were significantly higher for GM-CSF-treated patients if GM-CSF was included in the price (median costs, $4,140 [US] for GM-CSF v $590 for placebo; P < .05). These results indicate that GM-CSF does not affect the number of days for resolution of fever or the hospitalization period for this patient group, although a significant effect of GM-CSF was observed on neutrophil recovery.