Febrile Neutropenia In Cancer Patients Research Articles

Early hospital discharge versus continued hospitalization in febrile pediatric cancer patients with prolonged neutropenia: A randomized, prospective study

Hospitalization with single or multi-agent antibiotic therapy has been the standard of care for treatment of febrile neutropenia in cancer patients. We hypothesized that an empiric antibiotic regimen that is effective and that can be administered once-daily will allow for improved hospital utilization by early transition to outpatient care. Febrile pediatric cancer patients with anticipated prolonged neutropenia were randomized between a regimen of once-daily ceftriaxone plus amikacin (C + A) and imipenem monotherapy (control). Afebrile patients on C + A satisfying "Early Discharge Criteria" at 72 hr continued treatment as outpatients. We compared the outcome, adverse events, duration of hospitalization, and cost between both groups. A prospective randomized controlled clinical trial was conducted on 129 febrile episodes in pediatric cancer patients with prolonged neutropenia. No adverse events were seen in 32 children (84% of study arm) treated on an outpatient basis. We found a statistically significant difference between the duration of hospitalization of the C + A group [median 5 days] and control [median 9 days](P < 0.001), per episode antibiotic cost (P < 0.001) and total episode cost (P < 0.001). There was no statistically significant difference in the response to treatment at 72 hr or after necessary antimicrobial modifications. We conclude that pediatric febrile cancer patients initially considered at risk for sepsis due to prolonged neutropenia can be re-evaluated at 72 hr for outpatient therapy. The convenience, low incidence of adverse effects, and cost benefit of the once-daily regimen of C + A may be particularly useful to reduce the overall treatment costs and duration of hospitalization.

Risk-adapted strategy for the management of febrile neutropenia in cancer patients

Among patients who develop fever and neutropenia after having received cancer chemotherapy, we have to distinguish at least three categories of risk levels for complications and death: patients at low risk and eligible for oral treatment and possibly outpatient management, patients at low risk who require intravenous therapy, and patients at higher risk. The Multinational Association for Supportive Care in Cancer scoring system identifies patients at low risk (<5%) of severe complications with very low mortality (<1%) during an episode of febrile neutropenia; this group represents roughly 70% of an unselected population of patients with febrile neutropenia. A significant percentage (approximately 50%) of these patients are eligible for treatment with orally administered antibiotics and can be discharged early and safely from the hospital after a short (24-48 h) observation period.

Neutropenia febril en niños con cáncer en un centro asistencial en Santiago, Chile

Febrile neutropenia in cancer patients is a common complication associated to chemotherapy and can be the first manifestation of a potentially lethal infection. In order to adapt our clinical practice to national clinical guidelines, we performed a retrospective review of clinical charts of all children admitted to the Pediatric Unit of Clinica Davila, from May 1, 2003 to December 31, 2004, with cancer, fever and neutropenia. A total of 57 febrile neutropenic episodes occurred in 25 children and in 44% (25/57) of them an infectious focus could be identified; respiratory infections were the most common (11/25). A microorganism could be identified in 16/57 (x%) of episodes, e.g. 12 recovered from blood cultures (42% coagulase negative Staphylococcus, 17% group viridans Streptococci, 17% Escherichia coli and Enterococcus sp, Candida albicans y Pseudomonas aeruginosa in 8% each one), 3 from a catheter (coagulase negative Staphylococci) and 1 from a bronchoalveolar lavage (Pneumocystis jiroveci). At admission, 63% of children received treatment with 2 antibiotics, mostly ceftazidime and amikacin (39%) and 21% received vancomycin. In 37% of patients therapy required adjustment due to a poor response. Fifty six episodes had a favorable resolution with one patient diying of septic shock. Frequency of microorganism detection, the distribution of species recovered and the favorable resolution are comparable to that reported from industrialized countries.

Prevention of febrile neutropenia in cancer patients by probiotic strain Enterococcus faecium M-74. Phase II study

Febrile neutropenia (FN) remains a potentially life-threatening complication of anticancer chemotherapy. Bacterial translocation via intestinal mucosa is a significant mechanism of FN development. Competitive inhibition of bowel colonization by pathogenic microorganisms by lactic acid bacteria could be a useful prevention of FN. The aim of the study was the prevention of FN by probiotic strain Enterococcus faecium M-74 enriched with selenium in leukemic patients. Fourteen (six males/eight females) patients with myelogenous leukemia treated by induction or consolidation chemotherapy were included in the study. Patients received prophylaxis with E. faecium M-74 during one cycle of chemotherapy. The daily dose was 36 x 10(9) CFU tid. Prophylaxis started between day -2 and day +2 of chemotherapy and continued until the absolute neutrophile count (ANC) was >1,000/microl. All patients experienced febrile neutropenia. During 231 days of severe neutropenia, 30 febrile episodes occurred. No any febrile episode or infection provoked by the strain tested was noticed. Tolerance of therapy was excellent without significant adverse effects. Our results demonstrate the safety of the probiotic strain E. faecium M-74 enriched with selenium in leukemic patients with severe neutropenia. However, its administration was not effective in the prevention of febrile neutropenia, but this does not preclude the protective effect of other probiotic strains.

A risk model for first cycle febrile neutropenia in cancer patients receiving systemic chemotherapy

8122 Introduction: Myelosuppression remains the major dose-limiting toxicity of cancer chemotherapy. A prospective, nationwide study was undertaken to develop and validate a risk model for febrile neutropenia (FN) in cancer patients receiving chemotherapy. Methods: More than 2,300 patients with cancers of the breast, lung, colon and ovary or lymphoma initiating a new regimen have been prospectively registered at 137 randomly selected sites. Data on at least 1 cycle of chemotherapy are available on 2,106. A standard regimen has been defined in 1,464 patients permitting an estimation of planned dose intensity (PDI). A logistic regression model for cycle 1 FN in those with known PDI was developed and test performance characteristics estimated. Results: Of 222 patients experiencing FN events, 125 (56%) did so in cycle 1 with prophylactic growth factors reported in only 3.5%. Major independent clinical factors in the risk model include: anthracycline chemotherapy (OR=7.80;P=.001); immune disorders (OR=5.14;P=.014); pretreatment neutropenia (OR=4.00;P<.001); elevated bilirubin (OR=3.73;P=.009); ECOG PS ≥2 (OR=2.84;P=.010); stage 1–2 disease (OR=2.66;P=.009); pretreatment lymphopenia (OR=2.51;P=.001); elevated alkaline phosphatase (OR=2.15; P=.012); pretreatment thrombocytopenia (OR=1.5;P=.024), and anemia (OR=1.43;P=.069). The risk model was adjusted for practice, planned dose intensity, BSA and patient demographics. The risk model accounted for over 80% of the variability (R2=0.829) with a c-statistic of 0.874 [0.847,0.902](P<.0001). Model discrimination was optimized for an estimated risk ≥5% distinguishing high and low risk groups with average cycle 1 FN risks of 20% and 1%, respectively. The model was associated with a sensitivity[±95%CL] of 93%[86–96], specificity of 66%[63–68], predictive value + and - of 20%[17–24] and 99%[98–100], respectively and diagnostic odds ratio of 22[12–43]. Discussion: Based on excellent test performance characteristics, the risk model identified patients at increased risk for first cycle FN for possible targeted prophylaxis with filgrastim or pegfilgrastim. Validation of the model in phase 2 of this ongoing registry study is currently underway. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen Amgen

First Cycle Risk of Severe and Febrile Neutropenia in Cancer Patients Receiving Systemic Chemotherapy: Results from a Prospective Nationwide Study.

Introduction: Myelosuppression represents the major dose-limiting toxicity of cancer chemotherapy. This prospective, nationwide study was undertaken to better define risk of neutropenia and its complications and to develop risk models for selecting patients for appropriate supportive care.Methods: More than 3,500 patients initiating a new chemotherapy regimen have been prospectively registered at 137 randomly selected practice sites. Major disease sites include breast, lung, colorectal, ovary and lymphoma. Primary outcomes include severe neutropenia (SN; absolute neutrophil count nadir <500) and febrile neutropenia (FN) (fever/infection and nadir <1000) by cycle of treatment and overall.Results: This analysis is based on the first 2,361 patients treated to date including 924 (39%) age ≥65. Severe neutropenia was documented in 28% and FN in 16% across all cancer categories. The proportion of patients with ANC <500 over the first four cycles of treatment include: colorectal (8%); lung (18%); ovary (23%); lymphoma (27%) and breast (37%). Likewise, the proportion of patients with FN during the first four cycles include: colorectal (7%); lung (11%); ovary (13%); lymphoma (18%) and breast (20%). As shown in the table, approximately half of the initial episodes of ANC <500 and FN over four cycles of treatment occurred in cycle 1.Neutropenic Events By Cycle (% Patients)Primary OutcomeCycle 1 (N=2361)Cycle 2 (N=2032)Cycle 3 (N=1724)Cycle 4 (N=1246)Total (N=2361)Any SN16111011481st Cycle SN1664228Any FN8651201st Cycle FN843116The proportion of initial episodes of severe neutropenia that occur in cycle 1 include: colorectal (67%); lung (59%); ovary (44%); lymphoma (62%) and breast (70%). Likewise, the proportion of initial episodes of FN occurring in cycle 1 include: colorectal (53%); lung (60%); ovary (57%); lymphoma (56%) and breast (58%).Conclusions: Rates of severe and febrile neutropenia vary with tumor type. The initial episode of severe or febrile neutropenia is most likely to occur during the first cycle of chemotherapy across all major cancer types.

Detección de virus respiratorios mediante técnica de inmunofluorescencia directa en niños con leucemia linfoblástica aguda y neutropenia febril

Introduction. Respiratory viruses are one of the most important cause of febrile infection in healthy children; however their role as an aetiological agent in febrile neutropenia in cancer patients has not been stablished in Chile. Objective. To determine the importance of viral respiratory infections in febrile neutropenic children with ALL. Patients and Methods: A retrospective study using a viral direct immunofluorescent test in febrile neutropenic patients between May 2000 and October 2002 attending the Regional Hospital Clinic in Valdivia. Results: 23 samples from 17 patients were analysed, 30.4% were positive for respiratory viruses, being 13.1% influenza A, 8.7% RSV, 4.3% parainfluenza type 3 and 4.3% adenovirus. 57.1% were nosocomial and 85.7% of the episodes were symptomatic. Conclusions: Respiratory viral infections are frequent in neutropenic patients, causing fever in most of the cases, with or without respiratory symptoms. Virology tests should be included in the febrile screen, especially during periods of epidemia.

Variation in antimicrobial utilization for febrile neutropenia in cancer patients. The CEMIC Study Group. Club d'Etudes des Maladies Infectieuses en Cancer.

No previous study has compared hospitals with respect to the variation of antimicrobial utilization (AU) for cancer patients with febrile neutropenia (FNE). We conducted an observational cohort study, carried out in 18 tertiary care centers across nine countries, in order to describe AU patterns for cancer patients with FNE and to evaluate whether prescription was appropriate. A total of 148 patients was exposed to 483 antimicrobial agents and 318 therapeutic courses, corresponding to 1,766 antimicrobial exposure-days. The most frequently used initial treatment consisted of a combination of a broad-spectrum beta-lactam agent and an aminoglycoside (50%). The extent of initial monotherapy varied between 5% in German and 30% in French centers. Glycopeptides, fluconazole and acyclovir were incorporated into initial empiric therapy in 21,13, and nine instances, respectively. The French centers prescribed the largest number of antimicrobial courses per FNE (mean 2.5 +/-1.5), whereas the center with the highest antimicrobial exposure density was observed in the USA (2.8 exposure-days per 1 FNE-day). AU was judged to be inappropriate by at least one criterion in 59 patients (40%). This pilot study revealed important variation in AU intensity and prescription preferences in FNE patients and may help to develop appropriate strategies to improve antimicrobial therapy for this patient population.

Fever associated with chemotherapy-induced neutropenia

The numbers of cancer patients subjected to chemotherapy-induced neutropenia steadily grows as the new indications for systemic treatment expand. When these patients develop fever, or other signs of infection, they must receive immediate medical attention. This paper discusses the current therapeutic strategy for febrile neutropenia in cancer patients and reviews some of the newer approaches, which include empirical monotherapy, outpatient protocols, antibiotic prophylaxis and the use of haematopoietic growth factors.

33 P - A model to assess cost-effectiveness of prophylaxis of febrile neutropenia

Reported incidences of febrile neutropenia in cancer patients undergoing chemotherapy vary widely according to cancer site, chemotherapy regimen, patient characteristics and definition of febrile neutropenia. Human Colony Stimulating Factors are effective in reducing the rate or duration of febrile neutropenia allowing more intensive chemotherapy, but they are expensive. The economic consequences of prophylaxis with HCSFs reported in the literature vary from cost savings to high added costs. Guidelines for the use of primary prophylaxis with HCSF have recommended that this should be restricted for patients with an expected incidence of febrile neutropenia of > 40%. We developed a simple decision analytical model to assess the cost-effectiveness of prophylaxis of febrile neutropenia under various assumptions about the expected incidence of febrile neutropenia, effectiveness and cost of prophylaxis, cost of febrile neutropenia, and potential impact of prophylaxis on quality of life and life expectancy. The model was applied to lung cancer using data from the literature and from EORTC clinical trials. The model illustrates some main principles of economic evaluation and can be used to assess the cost-effectiveness of prophylaxis of febrile neutropenia taking into account the best availaible information on expected toxicity and associated costs with various chemotherapy regimens.

Pharmacoeconomic analysis of empirical therapy with ceftazidime alone or combination antibiotics for febrile neutropenia in cancer patients.

There is evidence to suggest that single-agent broad spectrum antibacterials may be cost-effective alternatives to combination antibiotics for the empirical management of febrile neutropenia in cancer patients. The objectives of the present study were 2-fold. The first objective was to compare the clinical effectiveness of ceftazidime monotherapy with that of 2 combination antibiotic regimens in cancer patients with febrile neutropenia. The 2 comparator regimens consisted of tobramycin plus piperacillin, either with (regimen 'CAP') or without (regimen 'AP') cefazolin. The second objective was to perform a cost-effectiveness analysis of the 3 regimens. Meta-analysis of randomised comparative trials between the 3 therapy groups was performed to determine the average overall response rate after 3 to 5 days of treatment. Seven clinical studies were selected for analysis. The overall incidence of adverse drug reactions (ADRs) was determined using the results of comparative and noncomparative studies. A comparative cost-analytic model was applied from a hospital perspective. The costs of primary therapy, hospitalisation, laboratory tests, routine patient care and treating ADRs were calculated, as were future costs. Monotherapy with ceftazidime was associated with an overall response rate of 63.5% and mean per-patient costs of $Can12,000 to $Can14,000. In comparison, regimen AP was associated with an overall response rate of 58.8% and mean costs of $Can13,000 to $Can16,000 per patient. The overall response rate in patients receiving CAP was 75.3%, and the mean cost per patient was $Can11,000 to $Can12,000. Thus, regimen CAP was the most cost-effective therapy from a hospital perspective.

Febrile neutropenia in cancer patients in Kuwait: microbial spectrum and outcome.

A sample of 100 consecutive febrile neutropenic episodes in cancer patients in Kuwait was studied. Acute leukaemias (44%) and lymphomas (29%) were the most frequent underlying cancers; 21 bacteraemis (gram-positive 10, gram-negative 9, polymicrobial 2) were encountered. Staphylococcous epidermidis and Escherichia coli were the commonest organisms. Urinary tract infection occurred in 30% of the microbiologically documented cases. A total of 84 episodes responded to therapy and 9 of the 14 deaths were secondary to infection.