Onset Of Febrile Neutropenia Research Articles

Prognostic indicators predictive of chemotherapy-induced febrile neutropenia outcomes in adult cancer patients: a systematic review.

Review question/objective What are the prognostic indicators predictive of chemotherapy-induced febrile neutropenia outcomes among adult cancer patients? Inclusion criteria Types of participants The participants of interest include adults, 18 years old and above with cancer, who developed febrile neutropenia as a result of myelosuppressive systemic chemotherapy either in an in-patient or outpatient setting. Types of intervention(s)/phenomena of interest The focus of this systematic review is on the prognostic indicators predictive of chemotherapy-induced febrile neutropenia outcomes in adult cancer patients. Types of Outcome(s) The primary outcome of this review is to identify the indicators predictive of FN outcomes (favourable or unfavourable) that influence the incidence of morbidity and mortality of adult cancer patients related to FN

Prognostic indicators predictive of chemotherapy-induced febrile neutropenia outcomes in adult cancer patients: a systematic review

Prognostic indicators predictive of chemotherapy-induced febrile neutropenia outcomes in adult cancer patients: a systematic review

Predicting febrile neutropenic patients at low risk using the MASCC score: does bacteremia matter?

Febrile neutropenic cancer patients represent a heterogeneous population with a limited proportion at risk of serious medical complications. The Multinational Association for Supportive Care in Cancer (MASCC) score has been developed and validated for identifying low-risk patients at the onset of febrile neutropenia. Since bacteremia, although not documented at baseline, is a predictor of pejorative outcome, the purpose of this study was to investigate the possible interaction between the MASCC score and bacteremic status and to assess whether, assuming that bacteremic status could be predicted at onset of febrile neutropenia, adding bacteremia as a covariate in a risk model would improve the accuracy of low-risk patients identification. Two consecutive multicentric observational studies were carried out from 1994 till 2005 involving 2,142 febrile neutropenic patients. The study data bases were retrospectively used for the present analysis. A predictive value was found for the MASCC score in all strata obtained by stratification for the bacteremic status with odds ratios for successful outcome being, in patients with a score ≥21, respectively, 6.06 (95%CI: 4.51-8.15), 3.42 (95%CI: 1.95-5.98), and 6.04 (95%CI: 3.01-12.09) in patients without bacteremia, gram-positive bacteremia, and gram-negative bacteremia. No interaction between the MASCC score and the bacteremic status was present. A clinical prediction rule integrating the MASCC score and the bacteremic status was not helpful in improving the identification of low-risk patients. This rule may then be used in a general population of patients with febrile neutropenia without having concerns for a lower predictive value in bacteremic patients. Our results suggest that the knowledge, provided we could find a model to predict it at fever onset, of a bacteremic etiology of the fever would be of little additional value to the MASCC score when attempting to identify low-risk patients.

Randomized Control Trial Comparing Oral Amoxicillin-clavulanate and Ofloxacin With Intravenous Ceftriaxone and Amikacin as Outpatient Therapy in Pediatric Low-risk Febrile Neutropenia

Outpatient oral therapy is infrequently used in pediatric low-risk febrile neutropenia (LRFN) as there is insufficient data regarding its equivalence as compared with parenteral therapy. This is a single institutional, randomized control trial in pediatric LRFN aged 2 to 15 years, in which 123 episodes in 88 patients were randomized to outpatient oral ofloxacin 7.5 mg/kg 12 hourly and amoxycillin-clavulanate 12.5 mg/kg 8 hourly or outpatient intravenous (IV) ceftriaxone 75 mg/kg and amikacin 15 mg/kg once daily after blood cultures. Out of 119 evaluable episodes, one-third were leukemia patients in maintenance and rest were solid tumors. Success was achieved in 55/61 (90.16%) and 54/58 (93.1%) in oral and IV arms, respectively, (P=0.56). There were 3 hospitalizations but no mortality. Median days to resolution of fever, absolute neutrophil count >500/mm(3) and antibiotic use were 3, 5, and 6 days in both arms. There were 5 blood culture isolates (3 gram-positive and 2 gram-negative bacteria). Failure of outpatient therapy was associated with perianal infections, bacteremia, febrile neutropenia onset before day 9 of chemotherapy in solid tumors and Vincristine, actinomycin-D, and cyclophosphamide chemotherapy for rhabdomyosarcoma. All gram-positive isolates were successes, whereas both gram-negative isolates were failures. Diarrhea in IV arm and Vincristine, actinomycin-D, and cyclophosphamide chemotherapy in the oral arm predicted failure in subgroup analysis. Outpatient therapy is efficacious and safe in pediatric LRFN. There was no difference in outcome in oral versus IV outpatient therapy. Amoxycillin-clavulanate and ofloxacin may be the oral regimen of choice.

Successful treatment with Protein C of febrile neutropenia in pediatric patients during cancer therapy

Febrile Neutropenia (FN) is a complication of chemotherapy in childhood cancer and at the same time secondary deficit of Protein C (PC) is often present during sepsis in children with cancer. In this study we have compared the clinical outcome of two different groups. At the onset of FN during chemotherapy the first group (patients with a secondary deficit of PC) received Protein C Concentrate (PCC) replacement while the other group without PC deficiency received only symptomatic therapies. We report that PC replacement could shorten duration of FN and improve the clinical outcome. The administration of PCC was safe and without any complications.

Evaluation of the risk factors for febrile neutropenia associated with hematological malignancy

Febrile neutropenia (FN) can frequently become a very serious problem. In 2002, Klastersky and colleagues established the Multinational Association for Supportive Care in Cancer (MASCC) score, which consisted of risk factors for conditions that included solid tumors. However, hematopoietic tumors, in comparison to solid tumors, are plagued by such problems as the quantity and quality of abnormalities associated with leukocytes and neutrophils and the requirement for higher dosages of both radio- and chemotherapy. FN is a complication associated with hematological malignancies that can lead to a fatal outcome, but it is avoidable if the appropriate preventive treatment is performed at an early stage. The subjects of the present study consisted of 354 patients with hematopoietic malignancies who were treated at the Japanese Red Cross Medical Center Hospital, Tokyo, between August 2000 and September 2004. They were retrospectively evaluated for the risk factors of FN by applying Wilcoxon's rank sum test. A scoring index was defined and the patients were classified into high- and low-risk groups before evaluation. The following nine risk factors, which may significantly influence the relationship between the time required for defervescence and the duration of neutropenia - age; hematological diseases; the leukocyte count during the febrile period; the reduction in leukocyte count per day before the onset of FN; the prophylactic administration of antimycotic agents; sterilization of the intestinal tract; and urine albumin content, creatine level, and C-reactive protein (CRP) level - were expressed in points and their sum was termed risk points. The range of risk points was classified as 0-3 and 4-9. The time required for defervescence was 5.1 days when the risk points were in the range of 0-3 and 8.1 days when the points were in the range of 4-9. These figures were distributed normally and there was a significant difference between the two groups (P = 0.0016). FN associated with hematological malignancies is somewhat different from that related to other malignancies; it is therefore associated with unique risk factors. Most of the risk factors used in the present study can be evaluated objectively. At the onset of FN, they were expressed in points for evaluation. Further prospective studies are needed to determine whether these risk factors are suitable for use in actual cases.

Febrile Neutropenia Following Autologous Stem Cell Transplantation in Patients with Lymphoma

Background: Infections remain a major cause of morbidity and mortality in patients with lymphoma treated with autologous hematopoietic stem cell transplantation. Knowledge of local microbiological epidemiology and patients' risk factors are essential for optimal management of these infections.Aims: to determine incidence of febrile neutropenia (FN) in patients with lymphoma treated with autologous peripheral blood stem cell transplantation (PBSCT) and to investigate correlations of a number of variables available on the day of FN onset with the severity of infection.Patients and Methods: 102 consecutive patients (median age 44, range 19–68 yrs, 58M/44F) with relapsed or refractory Non-Hodgkin's Lymphoma (NHL, n=78) and Hodgkin's Disease (HD, n=24) treated with PBSCT in a single center have been evaluated for infectious complications following transplantation.Results: Febrile neutropenia occurred in 67 (65.7%) patients at a mean of 6 days after transplantation (range 1–9, SD 1.71). Microbiological work-up was done and empirical antibiotic therapy with piperacillin-tazobactam was initiated in all but 15 patients who received a carbapenem. Empirical therapy was modified in 31 (46.3%) patients. Vancomycin was added in 22 patients (32.8%), a sistemic antifungal in 4 (6.0%) and both in 6 (9.0%) patients. Three patiens died as a consequence of sepsis (TRM=2.9%). Twenty two patients (32.8%) had proven bacteremias while 27 (40.3%) had other microbiologically documented infections (MDIs). Gram+ microorganisms were responsible for the majority of all documented infections (63.6% of bacteremias and 54.5% of other MDIs). Correlations of a number of variables available at time of FN onset with the duration of febrile episode have been investigated. Patients with higher CRP levels at FN onset and those with earlier onset of fever following PBSCT had significantly longer (p=0.047 and p=0.0066, respectively) duration of fever. Other variables, including age, No. of previous lines of therapy, No. of stem cells reinfused, ANC and monocyte counts as well as peak temperature values at day of fever onset did not show statistically significant correlations with duration of fever. All patients with diabetes developed FN and, although not reaching statistical significance (p=0.09), its duration was longer in comparison to other patients.Conclusions: Infections are serious but manageable complications of PBSCT. Gram+ microorganisms remain the major cause of documented infections. Early empirical antimicrobial therapy, tailored according to local microbiological epidemiology is essential for their optimal treatment.

Bloodstream infections in cancer patients with febrile neutropenia

Bloodstream infections (bacteraemia) account for approximately 25–30% of febrile episodes in patients with febrile neutropenia (FN). In developed countries, Gram-positive pathogens predominate. Mortality is higher in Gram-negative bacteraemia. A recent study involving 2142 patients with FN was reviewed, including 168 patients with Gram-negative bacteraemia (mortality 18%), 283 patients with Gram-positive bacteraemia (mortality 5%) and 48 patients with polymicrobial bacteraemia (mortality 13%). Among patients who received prophylactic antibiotics, Gram-positive bacteraemia was far more common than Gram-negative bacteraemia (75% vs. 25%), compared with approximately 50% of each in patients without prophylactic antibiotics. Patients with a Multinational Association for Supportive Care in Cancer (MASCC) score <15 had a 36% mortality compared with 3% if the MASCC score was >21. The MASCC score may help risk stratification of patients with FN and bacteraemia, although these data require confirmation. In two series of patients from developing countries (Lebanon and Malaysia), Gram-negative bacteraemia was more common and mortality was higher. In developing countries, Gram-negative bacteraemia may be more frequent due to less use of prophylactic antibiotics and central lines. Laboratory markers may have predictive and prognostic value for bacteraemia in patients at the onset of FN, including mannose-binding lectin, interleukin (IL)-6, IL-8 and procalcitonin, but further studies are required before they can be recommended. New therapies are required to lower the mortality in patients with FN with a high risk for bacteraemia.

Costs related to febrile neutropenia (FN) in patients with acute leukemia (AL) or in autologous stem cell transplantation (ASCT) recipients treated in German hospitals

18023 Background: This study assesses treatment patterns, resource consumption and costs related to FN in patients with AL receiving chemotherapy (CT) or in ASCT recipients. Methods: This is a multicentre observational,cost study. Interim results are presented for consecutive adult patients receiving CT or ASCT between 01–11/2006 at 4 academic hospitals. FN was defined as absolute neutrophil count <0.5×109/L, fever ≥38ºC and no hint of a non-infectious fever origin. Resource use was extracted from medical charts. FN related costs for medication, diagnostics, blood products and re-hospitalization are presented from provider perspective. Costs for prolonged inpatient stay due to FN are excluded (under investigation). Results: Of 86 cases, 46 received CT and 40 ASCT. Most common disease in CT pts was AML (78%) and in ASCT pts multiple myeloma (50%) and NHL (40%). Mean±SD age was 55±17 yrs (CT) and 57±11 yrs (ASCT). 96% (CT) and 98% (ASCT) of cases respectively received neutropenia/infection prophylaxes (G-CSF, GM-CSF, anti-infectives). Mean onset of FN was 25.3±37.5 and 6.8±2.7 days following start of CT or ASCT. Mean duration of FN episodes was 5.7±4.8 days (CT) and 3.7±2.3 days (ASCT); mean treatment duration of FN was 13.3±8.2 days (CT) and 9.2±3.2 days (ASCT). Two CT pts were re-hospitalized, all other were inpatients at onset of FN. 91% (CT) and 95% (ASCT) received antibiotics, 46% (CT) and 28% (ASCT) received antifungal agents. 83% (CT) and 85% (ASCT) of cases received blood products. Mean treatment cost per FN episode was €4,740±6,914 (Range: 0–32,455) for CT cases and €1,656±1,225 (range: 0–5,721) for ASCT cases. Main cost drivers were anti-infective drugs (CT 62% of cost, ASCT 43% of cost). Conclusions: FN induces significant costs with highest average cost for patients with AL receiving chemotherapy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen GmbH Amgen GmbH

Febrile neutropenia: a prospective study to validate the Multinational Association of Supportive Care of Cancer (MASCC) risk-index score.

The objective of this study was to prospectively validate the Multinational Association of Supportive Care of Cancer (MASCC) risk-index score in an attempt to accurately predict on presentation with febrile neutropenia those cancer patients who are at low- or high-risk for development of serious medical complications during the episode. Patients who presented with febrile neutropenia during November 2000 and July 2002 were prospectively enrolled in the protocol. All patients were hospitalized until recovery or outcome of the event and were treated with broad-spectrum, empiric, intravenous antibiotic therapy. The MASCC risk-index score (based on seven independent factors present at onset of febrile neutropenia) was calculated in 64 patients with 80 febrile neutropenic episodes. Patients with a score of > or =21 were regarded as low risk; patients with a score of <21 were regarded as high risk. Of the 80 febrile neutropenic episodes, 58 were classified as low-risk and 22 as high-risk patients. Fifty-seven (98.3%) of the 58 low-risk patients recovered without complications, and three (13.6%) of the 22 high-risk patients did not develop medical complications. One low-risk patient developed a fungal infection but recovered completely in comparison to 11 high-risk patients (50%) who developed serious medical complications ( p<0.001). None of the low-risk patients died. However, eight (36.4%) of the 22 high-risk patients died during the febrile neutropenic episode ( p<0.001), six as a consequence of sepsis and two due to rapidly uncontrolled cancer. We correctly predicted 98.3% of low-risk patients and 86.3% of high-risk patients. This study had a positive predictive value of 98.3% and a negative predictive value of 86.4% with both a sensitivity and specificity of 95%. The MASCC risk-index score correctly identifies low- and high-risk patients at presentation with febrile neutropenia.

Efficacy of granulocyte transfusions for neutropenia-related infections: retrospective analysis of predictive factors.

The transfusion of G-CSf-primed granulocytes (GTX) might represent an important treatment option for neutropenia-related infections unresponsive to conventional antimicrobial therapies and to recombinant hematopoietic growth factors. However, few studies to date have identified the factors that can predict clinical outcome and the patient populations who are likely to benefit most from GTX. The primary endpoint of the present retrospective study was to evaluate the efficacy of GTX in 22 patients with hematological malignancies who developed neutropenia-related bacterial and fungal infections that were unresponsive to appropriate antimicrobial therapies. Peripheral blood granulocytes were collected by continuous-flow leukapheresis from HLA-identical siblings after priming with G-CSF. The response to GTX was classified as 'favorable' if clinical symptoms and signs of infection resolved or 'unfavorable' if clinical symptoms and signs of infection were unchanged or worsened. Control of infection at Day 30 after the enrollment in the GTX program was considered as the outcome variable in multiple regression analysis. Two patients died of infection before receiving the granulocyte concentrates. Bacterial infections (monomicrobial or mixed bacteremias) were documented in 11 patients, whereas fungal infections (fungemia or focal fungal infections) were diagnosed in seven patients. In two patients, no infecting agent could be isolated (clinical infection). Control of infection at Day 30 after the first GTX was achieved in 10 of 20 assemble patients. Overall, 54% of patients with bacterial infections had a favorable response, compared with 57% of patients with fungal infections. No differences in terms of survival were found when comparing patients with bacterial and those with fungal infections at a median follow-up 90 days from the first GTX. In univariate analysis, disease status before GTX, e.g., complete or partial remission, and spontaneous recovery of the neutrophil count were significantly associated with control of infection. when multivariate regression models were formed, the recovery 0.5 x 10 (9)/L PMN was the only parameter that significantly and independently correlated with a favorable response to GTX. GTX can be used to successfully treat bacterial as well as fungal infections in severely neutropenic patients when administered early after the onset of febrile neutropenia in patients with remission of the underlying disease and who are likely to recover marrow function.

229 A randomized study of interventional G-CSF therapy in patients with febrile neutropenia following chemotherapy

Febrile neutropenia (FN) following chemotherapy carries considerable patient (pt) welfare and resource use implications. It remains unclear whether cytokines commenced with antibiotic therapy hasten recovery from the septic episode. In a double blind study, 186 paediatric pts (median age 5 yrs) commencing antibiotics for FN (neutrophils ≤0.5×10⁹/1) were randomized to also receive G-CSF (Amgen) 5μg/kg/d or placebo. Study guidelines required neutrophils at least 0.2 for hospital discharge. G-CSF/placebo was stopped at withdrawal of antibiotics or if neutrophils reached 1.0. Patients received a total G-CSF dose of 603μg over 5.2 days. G-CSF treated pts had more rapid neutrophil recovery to ≥0.5 (median 3d vs 5d; <i>P</i>=.03; Mann-Whitney), less use of antibiotics (median 5d vs 6d; <i>P</i>=.02) and shorter hospital stay (median 5d vs 7d; <i>P</i>=.04). Fever duration (2d vs 3d) and neutrophil recovery to 0.2 (3d vs 4d) for G-CSF and placebo-treated pts respectively were not significantly different. No G-CSF-related symptomatic or haematological toxicity was seen. This study indicates that G-CSF therapy, initiated after the onset of FN in paediatric pts, accelerates neutrophil recovery and reduces the duration of both antibiotic usage and hospitalization.

American Society of Clinical Oncology. Recommendations for the use of hematopoietic colony-stimulating factors: evidence-based, clinical practice guidelines.

Standard practice in protecting against chemotherapy-associated infection has been chemotherapy dose modification or dose delay, administration of progenitor-cell support, or selective use of prophylactic antibiotics. Therapy of chemotherapy-associated neutropenic fever or infection has customarily involved treatment with intravenous antibiotics, usually accompanied by hospitalization. The hematopoietic colony-stimulating factors (CSFs) have been introduced into clinical practice as additional supportive measures that can reduce the likelihood of neutropenic complications due to chemotherapy. Clinical benefit has been shown, but the high cost of CSFs has led to concern about their appropriate use. The American Society of Clinical Oncology (ASCO) wishes to establish evidence-based, clinical practice guidelines for the use of CSFs in patients who are not enrolled on clinical trials. An expert multidisciplinary panel reviewed the clinical data documenting the activity of CSFs. For each common clinical situation, the Panel formulated a guideline to encourage reasonable use of CSFs to preserve effectiveness but discourage excess use when little marginal benefit is anticipated. Consensus was reached after critically appraising the available evidence. Guidelines were validated by comparing them with recommendations for CSF use developed in other countries and by several academic institutions. Outcomes considered in evaluating CSF benefit included duration of neutropenia, incidence of febrile neutropenia, incidence and duration of antibiotic use, frequency and duration of hospitalization, infectious mortality, chemotherapy dose-intensity, chemotherapy efficacy, quality of life, CSF toxicity, and economic impact. To the extent that these data were available, the Panel placed greatest value on survival benefit, reduction in rates of febrile neutropenia, decreased hospitalization, and reduced costs. Lesser value was placed on alterations in absolute neutrophil counts (ANC). CSFs are recommended in some situations, eg, to reduce the likelihood of febrile neutropenia when the expected incidence is > or = 40%; after documented febrile neutropenia in a prior chemotherapy cycle to avoid infectious complications and maintain dose-intensity in subsequent treatment cycles when chemotherapy dose-reduction is not appropriate; and after high-dose chemotherapy with autologous progenitor-cell transplantation. CSFs are also effective in the mobilization of peripheral-blood progenitor cells. Therapeutic initiation of CSFs in addition to antibiotics at the onset of febrile neutropenia should be reserved for patients at high risk for septic complications. CSF use in patients with myelodysplastic syndromes may be reasonable if they are experiencing neutropenic infections. Administration of CSFs after initial chemotherapy for acute myeloid leukemia does not appear to be detrimental, but clinical benefit has been variable and caution is advised. Available data support use of CSFs in pediatric cancer patients similar to that recommended for adult patients. Outside of clinical trials, CSFs should not be used concurrently with chemotherapy and radiation, or to support increasing chemotherapy dose-intensity. Further research is warranted as a means to improve the cost-effective administration of the CSFs and identify clinical predictors of infectious complications that may direct their use.