Risk factors for febrile neutropenia during chemotherapy for HIV-related lymphoma.

PubMed

Park, Jinyong; Kim, Tae Min; Hwang, Jeong-Hwan; Kim, Nak-Hyun; Choe, Pyoeng Gyun; Song, Kyoung-ho; Kim, Eu Suk; Park, Sang-Won; Kim, Hong Bin; Kim, Nam Joong; Park, Wan Beom; Oh, Myoung-don

2012-12-01

We evaluated risk factors for neutropenic fever and febrile prolonged neutropenia during vincristine-including chemotherapy to treat HIV-related lymphoma to investigate whether protease inhibitor (PI) treatment is associated with infectious complications due to drug interactions with chemotherapeutic agents. We included all HIV patients who received chemotherapy including vincristine for lymphoma at a single referral center in 1999-2010. Neutropenic fever was defined as absolute neutrophil count < 500 cells/µL with body temperature over 38℃; and prolonged neutropenia was defined if it persisted over 7 days. CODOX-M/IVAC and Stanford regimens were considered high-risk regimens for prolonged neutropenia. We analyzed 48 cycles of chemotherapy in 17 HIV patients with lymphoma. There were 22 neutropenic fever and 12 febrile prolonged neutropenia events. In multivariate analysis, neutropenic fever was associated with old age and low CD4 cell count, but not with PI use or ritonavir-boosted PI use. Low CD4 cell count and high-risk regimens were associated with febrile prolonged neutropenia. Neutropenic fever and febrile prolonged neutropenia is associated with old age, low CD4 cell count, and high-risk regimens, but not PI use, in HIV patients undergoing chemotherapy including vincristine for lymphoma.

Comorbidities among patients with cancer who do and do not develop febrile neutropenia during the first chemotherapy cycle.

PubMed

Li, Xiaoyan; Luthra, Rakesh; Morrow, Phuong K; Fisher, Maxine D; Reiner, Maureen; Barron, Richard L; Langeberg, Wendy J

2016-10-01

Patients receiving myelosuppressive chemotherapy with certain comorbidities are at increased risk of febrile neutropenia. A comprehensive evaluation of febrile neutropenia-related comorbidities across cancers is needed. This study compared comorbidity prevalence among patients with cancer who did and did not develop febrile neutropenia during the first chemotherapy cycle. This case-control study used administrative claims from adult patients with non-Hodgkin lymphoma or breast, lung, colorectal, ovarian, or gastric cancer who received chemotherapy between 2007 and 2012. Each patient who developed febrile neutropenia (case) was matched with up to four patients without febrile neutropenia (controls) by cancer type, metastasis, chemotherapy regimen, age group, and sex. For each comorbidity (identified in the year before chemotherapy began), the adjusted odds ratio (aOR) for febrile neutropenia by cancer type was evaluated using conditional logistic regression models adjusted for potential confounding factors. Of 31,331 eligible patients, 672 developed febrile neutropenia in the first chemotherapy cycle. A total of 3312 febrile neutropenia cases and matched controls were analyzed. Across tumor types, comorbidity prevalence was higher in patients who developed febrile neutropenia than in those without febrile neutropenia. Among patients with breast cancer, osteoarthritis was more prevalent in patients with febrile neutropenia (aOR, 1.85; 95% CI, 1.07 to 3.18). Among patients with non-Hodgkin lymphoma, renal disease was more prevalent in patients with febrile neutropenia (aOR, 2.25; 95% CI, 1.23 to 4.11). Patients who developed febrile neutropenia in the first chemotherapy cycle presented with comorbidities more often than otherwise similar patients who did not develop febrile neutropenia. These findings warrant further investigation and support the inclusion of comorbidities into febrile neutropenia risk models. © The Author(s) 2015.

Risk Factors for Febrile Neutropenia during Chemotherapy for HIV-Related Lymphoma

PubMed Central

Park, Jinyong; Kim, Tae Min; Hwang, Jeong-Hwan; Kim, Nak-Hyun; Choe, Pyoeng Gyun; Song, Kyoung-ho; Kim, Eu Suk; Park, Sang-Won; Kim, Hong Bin; Kim, Nam Joong; Oh, Myoung-don

2012-01-01

We evaluated risk factors for neutropenic fever and febrile prolonged neutropenia during vincristine-including chemotherapy to treat HIV-related lymphoma to investigate whether protease inhibitor (PI) treatment is associated with infectious complications due to drug interactions with chemotherapeutic agents. We included all HIV patients who received chemotherapy including vincristine for lymphoma at a single referral center in 1999-2010. Neutropenic fever was defined as absolute neutrophil count < 500 cells/µL with body temperature over 38℃; and prolonged neutropenia was defined if it persisted over 7 days. CODOX-M/IVAC and Stanford regimens were considered high-risk regimens for prolonged neutropenia. We analyzed 48 cycles of chemotherapy in 17 HIV patients with lymphoma. There were 22 neutropenic fever and 12 febrile prolonged neutropenia events. In multivariate analysis, neutropenic fever was associated with old age and low CD4 cell count, but not with PI use or ritonavir-boosted PI use. Low CD4 cell count and high-risk regimens were associated with febrile prolonged neutropenia. Neutropenic fever and febrile prolonged neutropenia is associated with old age, low CD4 cell count, and high-risk regimens, but not PI use, in HIV patients undergoing chemotherapy including vincristine for lymphoma. PMID:23255844

Factors Associated with Hospital Length of Stay among Cancer Patients with Febrile Neutropenia

PubMed Central

Rosa, Regis G.; Goldani, Luciano Z.

2014-01-01

Purpose This study sought to evaluate factors associated with hospital length of stay in cancer patients with febrile neutropenia. Methods A prospective cohort study was performed at a single tertiary referral hospital in southern Brazil from October 2009 to August 2011. All adult cancer patients with febrile neutropenia admitted to the hematology ward were evaluated. Stepwise random-effects negative binomial regression was performed to identify risk factors for prolonged length of hospital stay. Results In total, 307 cases of febrile neutropenia were evaluated. The overall median length of hospital stay was 16 days (interquartile range 18 days). According to multiple negative binomial regression analysis, hematologic neoplasms (P = 0.003), high-dose chemotherapy regimens (P<0.001), duration of neutropenia (P<0.001), and bloodstream infection involving Gram-negative multi-drug-resistant bacteria (P = 0.003) were positively associated with prolonged hospital length of stay in patients with febrile neutropenia. The condition index showed no evidence of multi-collinearity effect among the independent variables. Conclusions Hematologic neoplasms, high-dose chemotherapy regimens, prolonged periods of neutropenia, and bloodstream infection with Gram-negative multi-drug-resistant bacteria are predictors of prolonged length hospital of stay among adult cancer patients with febrile neutropenia. PMID:25285790

Parental perspectives on inpatient versus outpatient management of pediatric febrile neutropenia.

PubMed

Diorio, Caroline; Martino, Julia; Boydell, Katherine Mary; Ethier, Marie-Chantal; Mayo, Chris; Wing, Richard; Teuffel, Oliver; Sung, Lillian; Tomlinson, Deborah

2011-01-01

To describe parent preference for treatment of febrile neutropenia and the key drivers of parental decision making, structured face-to-face interviews were used to elicit parent preferences for inpatient versus outpatient management of pediatric febrile neutropenia. Parents were presented with 4 different scenarios and asked to indicate which treatment option they preferred and to describe reasons for this preference during the face-to-face interview. Comments were recorded in writing by research assistants. A consensus approach to thematic analysis was used to identify themes from the written comments of the research assistants. A total of 155 parents participated in the study. Of these, 80 (51.6%) parents identified hospital-based intravenous treatment as the most preferred treatment scenario for febrile neutropenia. The major themes identified included convenience/disruptiveness, physical health, emotional well-being, and modifiers of parental decision making. Most parents preferred hospital-based treatment for febrile neutropenia. An understanding of issues that influence parental decision making may assist health care workers in planning program implementation and further support families in their decision-making process.

[Epidemiology of febrile neutropenia in patients with hematological disease-a prospective multicentre survey in China].

PubMed

Yan, C H; Xu, T; Zheng, X Y; Sun, J; Duan, X L; Gu, J L; Zhao, C L; Zhu, J; Wu, Y H; Wu, D P; Hu, J D; Huang, H; Jiang, M; Li, J; Hou, M; Wang, C; Shao, Z H; Liu, T; Hu, Y; Huang, X J

2016-03-01

To investigate the incidence, clinical and microbiological features of febrile, and risk factors during neutropenia periods in patients with hematological diseases. From October 20, 2014 to March 20, 2015, consecutive patients who had hematological diseases and developed neutropenia during hospitalization were enrolled in the prospective, multicenter and observational study. A total of 784 episodes of febrile occurred in 1 139 neutropenic patients with hematological diseases. The cumulative incidence of febrile was 81.9% at 21 days after neutropenia. Multivariate analysis suggested that central venous catheterization (P<0.001, HR=3.407, 95% CI 2.276-4.496), gastrointestinal mucositis (P<0.001, HR=10.548, 95% CI 3.245-28.576), previous exposure to broad-spectrum antibiotics within 90 days (P<0.001, HR=3.582, 95% CI 2.387-5.770) and duration of neutropenia >7 days (P<0.001,HR=4.194, 95% CI 2.572-5.618) were correlated with higher incidence of febrile during neutropenia. With the increase of the risk factors, the incidence of febrile increased gradually (35.4%, 69.2%, 86.1%, 95.6%, P<0.001). Of 784 febrile cases, 253 (32.3%) were unknown origin, 429 (54.7% )of clinical documented infections and 102(13.0%) of microbiological documented infections. The most common sites of infection were pulmonary (49.5%), upper respiratory (16.0%), crissum (9.8%), blood stream (7.7%). The most common pathogens were gram-negative bacteria (44.54%), followed by gram-positive bacteria (37.99% ) and fungi (17.47% ). There was no significant difference in mortality rates between cases with febrile and cases without febrile (9.2% vs 4.8%, P=0.099). Multivariate analysis also suggested that >40 years old (P=0.047, HR=5.000, 95% CI 0.853-28.013), hemodynamic instability (P=0.001, HR=13.185, 95% CI 2.983-54.915), prior colonization or infection by resistant pathogens (P=0.005, HR=28.734, 95% CI 2.921-313.744), blood stream infection (P=0.038, HR=9.715, 95% CI 1.110-81.969) and pulmonary

Safety of early discharge for low-risk patients with febrile neutropenia: a multicenter randomized controlled trial.

PubMed

Talcott, James A; Yeap, Beow Y; Clark, Jack A; Siegel, Robert D; Loggers, Elizabeth Trice; Lu, Charles; Godley, Paul A

2011-10-20

Febrile neutropenia commonly complicates cancer chemotherapy. Outpatient treatment may reduce costs and improve patient comfort but risk progression of undetected medical problems. By using our validated algorithm, we identified medically stable inpatients admitted for febrile neutropenia (neutrophils < 500/μL) after chemotherapy and randomly assigned them to continued inpatient antibiotic therapy or early discharge to receive identical antibiotic treatment at home. Our primary outcome was the occurrence of any serious medical complication, defined as evidence of medical instability requiring urgent medical attention. We enrolled 117 patients with 121 febrile neutropenia episodes before study termination for poor accrual. We excluded five episodes as ineligible and three because of inadequate documentation of the study outcome. Treatment groups were clinically similar, but sociodemographic imbalances occurred because of block randomization. The median presenting absolute neutrophil count was 100/μL. Hematopoietic growth factors were used in 38% of episodes. The median neutropenia duration was 4 days (range, 1 to 15 days). Five outpatients were readmitted to the hospital. Major medical complications occurred in five episodes (8%) in the hospital arm and four (9%) in the home arm (95% CI for the difference, -10% to 13%; P = .56). No study patient died. Patient-reported quality of life was similar on both arms. We found no evidence of adverse medical consequences from home care, despite a protocol designed to detect evidence of clinical deterioration. These results should reassure clinicians who elect to treat rigorously characterized low-risk patients with febrile neutropenia in suitable outpatient settings with appropriate surveillance for unexpected clinical deterioration.

Prospective cohort study of febrile neutropenia in breast cancer patients with neoadjuvant and adjuvant chemotherapy: CSPOR-BC FN study.

PubMed

Ishikawa, Takashi; Sakamaki, Kentaro; Narui, Kazutaka; Kaise, Hiroshi; Tsugawa, Koichiro; Ichikawa, Yasushi; Mukai, Hirofumi

2016-07-01

With the increasing use of adjuvant chemotherapy for treating early breast cancer, febrile neutropenia management has become crucial. Guidelines for febrile neutropenia management are mostly based on a Caucasian population survey although ethnic differences are reported in terms of adverse events. We survey the current status of febrile neutropenia and risk factors in Japanese female breast cancer patients receiving neoadjuvant and adjuvant chemotherapy regimens potential for febrile neutropenia. Subsequently, we plan to conduct a multicenter prospective cohort study involving 1000 patients with operable breast cancer. With the current state of oral antibiotics being routinely prescribed without hematology tests, we survey febrile neutropenia based on two different definitions, namely, true febrile neutropenia: ≥37.5°C and Grade 4 neutropenia, and surrogate febrile neutropenia: ≥37.5°C and oral antibiotic and antipyretic intake. The comparison of true febrile neutropenia and surrogate febrile neutropenia incidences is anticipated to provide information on the safety and feasibility of chemotherapy management without performing blood tests. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Febrile neutropenia: outline of management.

PubMed

Oberoi, Sapna; Suthar, Renu; Bansal, Deepak; Marwaha, R K

2013-02-01

Febrile neutropenia is a common emergency encountered in children receiving chemotherapy for a malignancy. Left untreated, it can lead to serious morbidity and mortality. Febrile neutropenia is suspected in any patient on chemotherapy who presents with fever. Prompt evaluation and management by the primary contact pediatrician is essential for a successful outcome. A detailed history and physical examination is warranted to identify source of infection, although two thirds of them may not have localizing symptoms or signs. Risk stratification is valuable in categorizing the severity and guiding therapy. Initial stabilization, prompt initiation of appropriate antibiotics and adequate supportive care are the cornerstone of treatment. Knowledge of the locally prevailing bacteriological profile and antimicrobial susceptibility data is crucial for each hospital/unit to frame and periodically modify guidelines for the choice of antimicrobials. Delay in initiating antimicrobials significantly worsens the outcome. Education of the family as well as the members of the treating unit is important in this regard. Pro-active steps must be taken to reduce incidence of hospital acquired sepsis. Diagnosis and management in relevance to the emergency room is reviewed and institutional practice is shared.

Impact of a clinical pathway on appropriate empiric vancomycin use in cancer patients with febrile neutropenia.

PubMed

Vicente, Mildred; Al-Nahedh, Mohammad; Parsad, Sandeep; Knoebel, Randall W; Pisano, Jennifer; Pettit, Natasha N

2017-12-01

Objectives Febrile neutropenia management guidelines recommend the use of vancomycin as part of an empiric antimicrobial regimen when specific criteria are met. Often, vancomycin use among patients with febrile neutropenia is not indicated and may be over utilized for this indication. We sought to evaluate the impact of implementing a febrile neutropenia clinical pathway on empiric vancomycin use for febrile neutropenia and to identify predictors of vancomycin use when not indicated. Methods Adult febrile neutropenia patients who received initial therapy with an anti-pseudomonal beta-lactam with or without vancomycin were identified before (June 2008 to November 2010) and after (June 2012 to June 2013) pathway implementation. Patients were assessed for appropriateness of therapy based on whether the patient received vancomycin consistent with guideline recommendations. Using a comorbidity index used for risk assessment in high risk hematology/oncology patients, we evaluated whether specific comorbidities are associated with inappropriate vancomycin use in the setting of febrile neutropenia. Results A total of 206 patients were included in the pre-pathway time period with 35.9% of patients receiving vancomycin therapy that was inconsistent with the pathway. A total of 131 patients were included in the post-pathway time period with 11.4% of patients receiving vancomycin inconsistent with the pathway ( p = 0.001). None of the comorbidities assessed, nor the comorbidity index score were found to be predictors of vancomycin use inconsistent with guideline recommendations. Conclusion Our study has demonstrated that implementation of a febrile neutropenia pathway can significantly improve adherence to national guideline recommendations with respect to empiric vancomycin utilization for febrile neutropenia.

Safety of Early Discharge for Low-Risk Patients With Febrile Neutropenia: A Multicenter Randomized Controlled Trial

PubMed Central

Talcott, James A.; Yeap, Beow Y.; Clark, Jack A.; Siegel, Robert D.; Loggers, Elizabeth Trice; Lu, Charles; Godley, Paul A.

2011-01-01

Purpose Febrile neutropenia commonly complicates cancer chemotherapy. Outpatient treatment may reduce costs and improve patient comfort but risk progression of undetected medical problems. Patients and Methods By using our validated algorithm, we identified medically stable inpatients admitted for febrile neutropenia (neutrophils < 500/μL) after chemotherapy and randomly assigned them to continued inpatient antibiotic therapy or early discharge to receive identical antibiotic treatment at home. Our primary outcome was the occurrence of any serious medical complication, defined as evidence of medical instability requiring urgent medical attention. Results We enrolled 117 patients with 121 febrile neutropenia episodes before study termination for poor accrual. We excluded five episodes as ineligible and three because of inadequate documentation of the study outcome. Treatment groups were clinically similar, but sociodemographic imbalances occurred because of block randomization. The median presenting absolute neutrophil count was 100/μL. Hematopoietic growth factors were used in 38% of episodes. The median neutropenia duration was 4 days (range, 1 to 15 days). Five outpatients were readmitted to the hospital. Major medical complications occurred in five episodes (8%) in the hospital arm and four (9%) in the home arm (95% CI for the difference, −10% to 13%; P = .56). No study patient died. Patient-reported quality of life was similar on both arms. Conclusion We found no evidence of adverse medical consequences from home care, despite a protocol designed to detect evidence of clinical deterioration. These results should reassure clinicians who elect to treat rigorously characterized low-risk patients with febrile neutropenia in suitable outpatient settings with appropriate surveillance for unexpected clinical deterioration. PMID:21931024

Temperature management in haematology patients with febrile neutropenia: a practice survey.

PubMed

Weinkove, Robert; Clay, Jennifer; Wood, Catherine

2013-04-19

To assess the attitudes of clinicians to temperature management in haematology patients with febrile neutropenia. An online scenario-based survey was circulated to consultant members of the New Zealand branch of the Haematology Society of Australia and New Zealand, to haematology advanced trainees, and to nursing representatives at each haematology department in New Zealand. Eighty-eight responses were obtained, from 34 doctors and 54 nurses. Most respondents would advise a neutropenic patient to take paracetamol as needed for pain. Median temperature intervention threshold for an asymptomatic patient with febrile neutropenia was higher for doctors than for nurses (38.5 versus 38.0 degrees Celcius), despite considerable heterogeneity. Both groups indicated they would intervene at a median 38.0 degrees Celcius for a patient with rigors. Paracetamol was the preferred first-line cooling measure, with physical methods second-line, and pethidine third-line. All respondents favoured oral over intravenous or rectal paracetamol. Most believed a clinical trial of antipyretic treatment for febrile neutropenia was warranted, and indicated willingness to enrol their patients in such a study. This survey documents clinicians' preferred temperature intervention thresholds and methods for haematology patients with neutropenic fever, and shows considerable variation in practice. Most respondents supported a trial of antipyretic management in febrile neutropenia.

Clozapine-Induced Febrile Neutropenia and Cellulitis.

PubMed

Yaylaci, Selcuk; Yilmaz, Emine Ulku; Guclu, Ertugrul; Kumsar, Neslihan Akkisi; Tamer, Ali; Karabay, Oguz

2014-03-01

Clozapine is one of the atypical antipsychotics and is frequently prescribed to patients with treatment-resistant schizophrenia. Agranulocytosis is a major side effect that may lead to death, which limits its use. This is a case report of a patient that developed febrile neutropenia and cellulitis after treatment with clozapine for 20 weeks.

Bacterial infection profiles in lung cancer patients with febrile neutropenia.

PubMed

Lanoix, Jean-Philippe; Pluquet, Emilie; Lescure, Francois Xavier; Bentayeb, Houcine; Lecuyer, Emmanuelle; Boutemy, Marie; Dumont, Patrick; Jounieaux, Vincent; Schmit, Jean Luc; Dayen, Charles; Douadi, Youcef

2011-06-27

The chemotherapy used to treat lung cancer causes febrile neutropenia in 10 to 40% of patients. Although most episodes are of undetermined origin, an infectious etiology can be suspected in 30% of cases. In view of the scarcity of data on lung cancer patients with febrile neutropenia, we performed a retrospective study of the microbiological characteristics of cases recorded in three medical centers in the Picardy region of northern France. We analyzed the medical records of lung cancer patients with neutropenia (neutrophil count < 500/mm(3)) and fever (temperature > 38.3°C). The study included 87 lung cancer patients with febrile neutropenia (mean age: 64.2). Two thirds of the patients had metastases and half had poor performance status. Thirty-three of the 87 cases were microbiologically documented. Gram-negative bacteria (mainly enterobacteriaceae from the urinary and digestive tracts) were identified in 59% of these cases. Staphylococcus species (mainly S. aureus) accounted for a high proportion of the identified Gram-positive bacteria. Bacteremia accounted for 60% of the microbiologically documented cases of fever. 23% of the blood cultures were positive. 14% of the infections were probably hospital-acquired and 14% were caused by multidrug-resistant strains. The overall mortality rate at day 30 was 33% and the infection-related mortality rate was 16.1%. Treatment with antibiotics was successful in 82.8% of cases. In a multivariate analysis, predictive factors for treatment failure were age >60 and thrombocytopenia < 20000/mm(3). Gram-negative species were the most frequently identified bacteria in lung cancer patients with febrile neutropenia. Despite the success of antibiotic treatment and a low-risk neutropenic patient group, mortality is high in this particular population.

INVASIVE FUNGAL INFECTION AMONG FEBRILE PATIENTS WITH CHEMOTHERAPY-INDUCED NEUTROPENIA IN THAILAND.

PubMed

Phikulsod, Ployploen; Suwannawiboon, Bundarika; Chayakulkeeree, Methee

2017-01-01

Invasive fungal infections (IFI) can cause serious morbidity and mortality among febrile patients with chemotherapy-induced neutropenia (CIN). In order to evaluate the incidence, treatment outcome and factors associated with IFI in this patient population in Thailand, we retrospectively reviewed the medical record of patients admitted to Siriraj Hospital from January 2008 to June 2010. Criteria used to diagnosed IFI were those of the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases/Mycoses Study Group (EORTC/MSG) consensus 2008 criteria. Three hundred ten episodes of chemotherapy-induced neutropenia occurred in 233 patients. IFI were found in 37 episodes (12%) and occurred only in patients who received chemotherapy for hematological malignancies. The incidence of IFI among patients with hematologic malignancies was 14%. Most commonly occurred in AML patients (17%). Patients who received aggressive induction chemotherapy regimens for AML had the highest incidence of IFI (20.5%). Of the 37 episodes, 12 were candidiasis, 5 were aspergillosis, 1 was zygomycosis, 1 was fusariosis, 10 were probable and 9 were possible IFI. The IFI-related mortality was 35%. The clinical factor associated with IFI was a temperature > 39 °C during febrile neutropenia. A higher mortality rate was seen in patients aged > 40 years and those with a serum albumin level < 3 g/dl.

Clinical factors predicting bacteremia in low-risk febrile neutropenia after anti-cancer chemotherapy.

PubMed

Ha, Young Eun; Song, Jae-Hoon; Kang, Won Ki; Peck, Kyong Ran; Chung, Doo Ryeon; Kang, Cheol-In; Joung, Mi-Kyong; Joo, Eun-Jeong; Shon, Kyung Mok

2011-11-01

Bacteremia is an important clinical condition in febrile neutropenia that can cause clinical failure of antimicrobial therapy. The purpose of this study was to investigate the clinical factors predictive of bacteremia in low-risk febrile neutropenia at initial patient evaluation. We performed a retrospective cohort study in a university hospital in Seoul, Korea, between May 1995 and May 2007. Patients who met the criteria of low-risk febrile neutropenia at the time of visit to emergency department after anti-cancer chemotherapy were included in the analysis. During the study period, 102 episodes of bacteremia were documented among the 993 episodes of low-risk febrile neutropenia. Single gram-negative bacteremia was most frequent. In multivariate regression analysis, initial body temperature ≥39°C, initial hypotension, presence of clinical sites of infection, presence of central venous catheter, initial absolute neutrophil count <50/mm(3), and the CRP ≥10 mg/dL were statistically significant predictors for bacteremia. A scoring system using these variables was derived and the likelihood of bacteremia was well correlated with the score points with AUC under ROC curve of 0.785. Patients with low score points had low rate of bacteremia, thus, would be candidates for outpatient-based or oral antibiotic therapy. We identified major clinical factors that can predict bacteremia in low-risk febrile neutropenia.

Treatment of Febrile Neutropenia and Prophylaxis in Hematologic Malignancies: A Critical Review and Update

PubMed Central

Villafuerte-Gutierrez, Paola; Villalon, Lucia; Losa, Juan E.; Henriquez-Camacho, Cesar

2014-01-01

Febrile neutropenia is one of the most serious complications in patients with haematological malignancies and chemotherapy. A prompt identification of infection and empirical antibiotic therapy can prolong survival. This paper reviews the guidelines about febrile neutropenia in the setting of hematologic malignancies, providing an overview of the definition of fever and neutropenia, and categories of risk assessment, management of infections, and prophylaxis. PMID:25525436

Bacterial infection profiles in lung cancer patients with febrile neutropenia

PubMed Central

2011-01-01

Background The chemotherapy used to treat lung cancer causes febrile neutropenia in 10 to 40% of patients. Although most episodes are of undetermined origin, an infectious etiology can be suspected in 30% of cases. In view of the scarcity of data on lung cancer patients with febrile neutropenia, we performed a retrospective study of the microbiological characteristics of cases recorded in three medical centers in the Picardy region of northern France. Methods We analyzed the medical records of lung cancer patients with neutropenia (neutrophil count < 500/mm3) and fever (temperature > 38.3°C). Results The study included 87 lung cancer patients with febrile neutropenia (mean age: 64.2). Two thirds of the patients had metastases and half had poor performance status. Thirty-three of the 87 cases were microbiologically documented. Gram-negative bacteria (mainly enterobacteriaceae from the urinary and digestive tracts) were identified in 59% of these cases. Staphylococcus species (mainly S. aureus) accounted for a high proportion of the identified Gram-positive bacteria. Bacteremia accounted for 60% of the microbiologically documented cases of fever. 23% of the blood cultures were positive. 14% of the infections were probably hospital-acquired and 14% were caused by multidrug-resistant strains. The overall mortality rate at day 30 was 33% and the infection-related mortality rate was 16.1%. Treatment with antibiotics was successful in 82.8% of cases. In a multivariate analysis, predictive factors for treatment failure were age >60 and thrombocytopenia < 20000/mm3. Conclusion Gram-negative species were the most frequently identified bacteria in lung cancer patients with febrile neutropenia. Despite the success of antibiotic treatment and a low-risk neutropenic patient group, mortality is high in this particular population. PMID:21707992

Efficacy of granulocyte colony stimulating factor as a secondary prophylaxis along with full-dose chemotherapy following a prior cycle of febrile neutropenia.

PubMed

Gupta, Seema; Singh, Pankaj K; Bhatt, Madan L B; Pant, Mohan C; Gupta, Rajeev; Negi, Mahendra P S

2010-10-01

Secondary prophylaxis with recombinant human granulocyte colony stimulating factor (G-CSF) is recommended where patients have experienced febrile neutropenia in an earlier chemotherapy cycle and for whom the maintenance of chemotherapy dose intensity is important; or where febrile neutropenia has not occurred but prolonged neutropenia is causing excessive dose delay or reduction, where maintenance of dose intensity is important. The objective of this study was to determine the efficacy and feasibility of G-CSF as secondary prophylaxis when used along with full dose moderately myelotoxic chemotherapy following a prior cycle with febrile-neutropenia. Fifty-two patients aged 22-75 years with febrile neutropenia that required intravenous antibiotics following moderately myelotoxic chemotherapy were included. These patients received the next cycle of the same chemotherapy regime without dose modification but with support of filgrastim 24 h after completion of chemotherapy (300 μg/day/subcutaneously (s.c.) for weight < 60 kg, 480 μg/day/s.c. for weight > 60 kg, for at least 10 consecutive days), patients in whom neutropenia was associated with a life-threatening infection and those who developed prolonged myelosuppression were excluded. The use of the hematopoietic growth factor G-CSF was shown to shorten the neutrophil recovery time, resulting in significant reduction of incidence of febrile neutropenia, hospitalization and use of broad spectrum antibiotics. There was no drug related death or adverse events associated with either cycle. In conclusion, recombinant human G-CSF is effective and relatively safe as a secondary prophylaxis with full dose chemotherapy in patients who develop febrile neutropenia following prior cycles of moderately myelotoxic chemotherapy.

Management of Breast Cancer Patients with Chemotherapy-Induced Neutropenia or Febrile Neutropenia

PubMed Central

Fontanella, Caterina; Bolzonello, Silvia; Lederer, Bianca; Aprile, Giuseppe

2014-01-01

Summary Chemotherapy-induced neutropenia (CIN) is a common toxicity caused by the administration of anticancer drugs. This side effect is associated with life-threatening infections and may alter the chemotherapy schedule, thus impacting on early and long-term outcomes. Elderly breast cancer patients with impaired health status or advanced disease as well as patients undergoing dose-dense anthracycline/taxane- or docetaxel-based regimens have the highest risk of CIN. A careful assessment of the baseline risk for CIN allows the selection of patients who need primary prophylaxis with granulocyte colony-stimulating factor (G-CSF) and/or antimicrobial agents. Neutropenic cancer patients may develop febrile neutropenia and CIN-related severe medical complications. Specific risk assessment scores, along with comprehensive clinical evaluation, are able to define a group of febrile patients with low risk for complications who can be safely treated as outpatients. Conversely, patients with higher risk of severe complications should be hospitalized and should receive intravenous antibiotic therapy with or without G-CSF. PMID:25404882

IL-8 predicts pediatric oncology patients with febrile neutropenia at low risk for bacteremia.

PubMed

Cost, Carrye R; Stegner, Martha M; Leonard, David; Leavey, Patrick

2013-04-01

Despite a low bacteremia rate, pediatric oncology patients are frequently admitted for febrile neutropenia. A pediatric risk prediction model with high sensitivity to identify patients at low risk for bacteremia is not available. We performed a single-institution prospective cohort study of pediatric oncology patients with febrile neutropenia to create a risk prediction model using clinical factors, respiratory viral infection, and cytokine expression. Pediatric oncology patients with febrile neutropenia were enrolled between March 30, 2010 and April 1, 2011 and managed per institutional protocol. Blood samples for C-reactive protein and cytokine expression and nasopharyngeal swabs for respiratory viral testing were obtained. Medical records were reviewed for clinical data. Statistical analysis utilized mixed multiple logistic regression modeling. During the 12-month period, 195 febrile neutropenia episodes were enrolled. There were 24 (12%) episodes of bacteremia. Univariate analysis revealed several factors predictive for bacteremia, and interleukin (IL)-8 was the most predictive variable in the multivariate stepwise logistic regression. Low serum IL-8 predicted patients at low risk for bacteremia with a sensitivity of 0.9 and negative predictive value of 0.98. IL-8 is a highly sensitive predictor for patients at low risk for bacteremia. IL-8 should be utilized in a multi-institution prospective trial to assign risk stratification to pediatric patients admitted with febrile neutropenia.

A prospectively validated nomogram for predicting the risk of chemotherapy-induced febrile neutropenia: a multicenter study.

PubMed

Bozcuk, H; Yıldız, M; Artaç, M; Kocer, M; Kaya, Ç; Ulukal, E; Ay, S; Kılıç, M P; Şimşek, E H; Kılıçkaya, P; Uçar, S; Coskun, H S; Savas, B

2015-06-01

There is clinical need to predict risk of febrile neutropenia before a specific cycle of chemotherapy in cancer patients. Data on 3882 chemotherapy cycles in 1089 consecutive patients with lung, breast, and colon cancer from four teaching hospitals were used to construct a predictive model for febrile neutropenia. A final nomogram derived from the multivariate predictive model was prospectively confirmed in a second cohort of 960 consecutive cases and 1444 cycles. The following factors were used to construct the nomogram: previous history of febrile neutropenia, pre-cycle lymphocyte count, type of cancer, cycle of current chemotherapy, and patient age. The predictive model had a concordance index of 0.95 (95 % confidence interval (CI) = 0.91-0.99) in the derivation cohort and 0.85 (95 % CI = 0.80-0.91) in the external validation cohort. A threshold of 15 % for the risk of febrile neutropenia in the derivation cohort was associated with a sensitivity of 0.76 and specificity of 0.98. These figures were 1.00 and 0.49 in the validation cohort if a risk threshold of 50 % was chosen. This nomogram is helpful in the prediction of febrile neutropenia after chemotherapy in patients with lung, breast, and colon cancer. Usage of this nomogram may help decrease the morbidity and mortality associated with febrile neutropenia and deserves further validation.

Infusional β-lactam antibiotics in febrile neutropenia: has the time come?

PubMed

Abbott, Iain J; Roberts, Jason A

2012-12-01

Febrile neutropenia presents a clinical challenge in which timely and appropriate antibiotic exposure is crucial. In the context of altered pharmacokinetics and rising bacterial resistance, standard antibiotic doses are unlikely to be sufficient. This review explores the potential utility of altered dosing approaches of β-lactam antibiotics to optimize treatment in febrile neutropenia. There is a dynamic relationship between the antibiotic, the infecting pathogen, and the host. Great advancements have been made in the understanding of the pharmacokinetic changes in critical illness and the pharmacodynamic relationships of antibiotics in these settings. Antibiotic treatment in febrile neutropenia is becoming increasingly difficult. Patients are of higher acuity, receive more intensive chemotherapy regimens leading to prolonged neutropenia, and are often exposed to multiple antibiotic courses. These patients display significant variability in antibiotic clearances and increases in volume of distribution compared with standard ward-based patients. Rising antibiotic resistance and a lack of new antibiotics in production have prompted alternative dosing strategies based on pharmacokinetic/pharmacodynamic data, such as extended or continuous infusions of β-lactam antibiotics, to maximize the likelihood of treatment success. A definitive study that describes a mortality benefit of such dosing regimens remains elusive and the theoretical advantages require testing in well designed clinical trials.

G-CSF in solid tumor chemotherapy: a tailored regimen reduces febrile neutropenia, treatment delays and direct costs.

PubMed

Tsavaris, Nicolas; Kosmas, Christos; Gouveris, Panagiotis; Vadiak, Maria; Dimitrakopoulos, Antonis; Karadima, Dimitra; Pagouni, Efterpi; Panagiotakopoulos, George; Tzima, Evanthia; Ispoglou, Sevasti; Sakelariou, Dimitris; Koufos, Christos

2004-02-01

Current guidelines do not recommend G-CSF for patients with risk factors for neutropenia. One-hundred patients undergoing chemotherapy were randomized to treatment with G-CSF at 5 Kg/kg for established febrile neutropenia (ANC <1000/microl) (Group A) or G-CSF at 263 Kg/day if ANC was 1500/microl or less on the day of the expected nadir, with the duration of treatment determined by the severity of neutropenia (Group B). The number of doses of G-CSF was similar in the two groups. There were 34 cases of febrile neutropenia in Group A, but none in Group B (p=0.0001). Hospital admission for febrile neutropenia, antibiotic use and delays in chemotherapy were all significantly more common in Group A. Total direct costs were estimated to be 66, 646 for Group A and 47, 119 for Group B. Tailoring treatment does not increase G-CSF use, but significantly reduces febrile neutropenia and treatment delays and lowers direct costs.

[A pilot study of antibiotic cycling for the treatment of febrile neutropenia patients with hematological diseases].

PubMed

Ikegaya, Satoshi; Iwasaki, Hiromichi; Kinoshita, Keiichi; Urasaki, Yoshimasa; Tsutani, Hiroshi; Ueda, Takanori

2004-03-01

Two antibiotics recommended by the guideline of Infectious Diseases Society of America (IDSA) were selected for treatment of febrile neutropenia, and these paired antibiotics were changed periodically three times. The clinical efficacy of each antibiotic was retrospectively evaluated at the end of the final period. There was no significant difference about efficacy rate between two kinds of antibiotics in the same sequential period. However, the efficacy rate has been rising and febrile duration has been shortening by degrees. Only a few drug resistant bacteria were recognized by the surveillance culture during antibiotic cycling. Recently, antibiotic cycling therapy has attracted attention especially in the ICU. However, a clinical study of treatment for febrile neutropenia has not been reported. Our trial suggests that cycling therapy may be useful for febrile neutropenia. However, Some deviation in the patients characteristics of each period may affect the result. It seems that further examination is necessary about usefullness of the cycling therapy for febrile neutropenia.

Extended versus Bolus Infusion of Broad Spectrum β-Lactams for Febrile Neutropenia: an Unblinded Randomized Trial.

PubMed

Ram, Ron; Halavy, Yael; Amit, Odelia; Paran, Yael; Katchman, Eugene; Yachini, Bruria; Kor, Svetlana; Avivi, Irit; Ben-Ami, Ronen

2018-03-28

Febrile neutropenia may be a sign of severe infection, and is associated with significant morbidity and mortality in high-risk patients with hematologic malignancies. Extended infusion of β-lactam antibiotics is associated with greater clinical response than is bolus infusion in non-neutropenic critically ill patients, but data are lacking for febrile neutropenic patients. We designed a single-center, non-blinded randomized trial comparing extended infusion (4 hours) and bolus infusion (30 minutes) of piperacillin-tazobactam or ceftazidime in high-risk patients with febrile neutropenia. The primary end-point was overall response on day 4, defined as the combination of resolution of fever, sterile blood cultures, resolution of clinical signs and symptoms, and no need for a change in the antibiotic regimen. Outcome was adjudicated by investigators blinded to treatment allocation. Of 123 enrolled patients, 105 had febrile neutropenia and were included in the intention-to-treat analysis: 47 in the extended infusion arm and 58 in the bolus infusion arm. Overall response occurred in 35 (74.4%) patients treated with extended infusion and 32 (55.1%) patients treated with bolus infusion (P=0.044). The superiority of extended infusion compared with bolus infusion was greatest for patients with clinically documented infections (overall response, 68.4% [13/19] versus 35.7% [10/28]; P=0.039), and specifically for those with pneumonia (80% [4/5] versus 0% [0/8]; P=0.007). Extended infusion of β-lactams is associated with superior treatment outcomes as compared with bolus infusion for high-risk patients with febrile neutropenia. The benefit of extended β-lactam infusion may be greatest for patients with pulmonary infections.

[Pathophysiology and diagnosis of cancer patients with febrile neutropenia].

PubMed

Saito, Takeshi; Aiba, Keisuke

2013-06-01

Exogenous pyrogens induce several cytokines which activate immune responses, and produce fever. In Japan, febrile neutropenia is defined as having an axillary temperature of>37. 5°C, and neutropenia showing an absolute neutrophil count (ANC)of<500 cells/mL or an ANC that is expected to reduce to<500 cells/mL during the next 48 hours. Signs and symptoms of inflammation are often attenuated or absent in neutropenic patients. Therefore, careful physical examination is required to detect subtle symptoms and signs of infection. As an initial assessment, laboratory tests should include the following: a ) complete blood cell count with differential leukocyte count and platelet count, b ) measurement of serum levels of creatinine, electrolytes, and hepatic transaminase enzymes, c ) serologic assay for fungal infection, and d ) at least 2 sets of blood cultures. Radiographical approaches are also important for detecting the focus of infection. Proper risk classification should be performed using the Multinational Association for Supportive Care in Cancer(MASCC)scoring system to distinguish high-risk and low-risk patients with febrile neutropenia.

Can complications in febrile neutropenia be predicted? Report from a developing country.

PubMed

Oberoi, Sapna; Das, Anirban; Trehan, Amita; Ray, Pallab; Bansal, Deepak

2017-11-01

Febrile neutropenia (FN) is an important cause of morbidity and mortality in children with acute lymphoblastic leukemia (ALL). We aimed to look at complications in febrile neutropenia and to derive a risk model for developing complications from the variables predicting complications. Children on treatment for ALL, presenting with FN, were prospectively enrolled over a period of 1 year. Their clinical presentation, course during hospital stay, and outcomes were recorded. Complications recorded included septic shock, pneumonia requiring invasive or non-invasive ventilation, renal failure, neutropenic enterocolitis, encephalopathy, congestive heart failure, and bleeding manifestations. There were 320 episodes of FN among 176 patients. Complications occurred during 73 (22.8%) episodes. Time since last chemotherapy ≤7 days [OR 2.2 (1-4.5)], clinical focus of infection [OR 2.7 (1.3-5.5)], undernutrition [OR 2.5 (1.1-5.5)], absolute neutrophil count (ANC) ≤ 100/μL [OR 2.8 (1.3-5.9)], and C-reactive protein (CRP) > 60 mg/L at admission [OR 13.3 (5.2-33.8)] were independent predictors of complications. A risk model (total score = 13) was developed based on these predictors. Children with score of ≥7 had 17.2 (7.7-38.6) odds of developing complications as compared to those with score <7. Score of <7 predicted children at lower risk of complications [sensitivity 88% (78.2-93.8%), specificity 72.5% (65.7-78.4%), PPV 53.6% (44.3-62.6%), NPV 94.4% (89.3-97.1%)]. Complications during febrile neutropenia are high in a developing country setup. A risk score model based on identified risk factors can possibly help in recognizing low-risk febrile neutropenic children at admission.

Colony-stimulating factor use and impact on febrile neutropenia among patients with newly diagnosed breast, colorectal, or non-small cell lung cancer who were receiving chemotherapy.

PubMed

McCune, Jeannine S; Sullivan, Sean D; Blough, David K; Clarke, Lauren; McDermott, Cara; Malin, Jennifer; Ramsey, Scott

2012-01-01

To determine the impact of primary prophylactic colony-stimulating factor (CSF) use on febrile neutropenia in a large patient population receiving contemporary chemotherapy regimens to treat breast cancer, colorectal cancer, or non-small cell lung cancer (NSCLC). Retrospective claims analysis. The Surveillance, Epidemiology, and End Results (SEER)-Puget Sound cancer registry and insurance claims records. A total of 2728 patients aged 25 years or older who received a diagnosis of breast cancer (998 patients), colorectal cancer (688 patients), or NSCLC (1042 patients) between January 1, 2002, and December 31, 2005, and received chemotherapy. Initial chemotherapy regimen, CSF use (filgrastim or pegfilgrastim), and febrile neutropenia events were evaluated after the first chemotherapy administration. Subsequently, febrile neutropenia rates in patients receiving primary prophylactic CSF were compared with febrile neutropenia rates in patients receiving CSF in settings other than primary prophylaxis or not at all. The impact of primary prophylactic CSF could not be assessed for patients with colorectal cancer or NSCLC because only 1 and 18 febrile neutropenia events, respectively, occurred in those receiving primary prophylactic CSF. Of the 998 patients with breast cancer, 72 (7.2%) experienced febrile neutropenia, 28 of whom received primary prophylactic CSF. In the patients with breast cancer, we observed that primary prophylactic CSF use was associated with reduced febrile neutropenia rates; however, the analysis may have been confounded by unmeasured factors associated with febrile neutropenia. The impact of primary prophylactic CSFs on febrile neutropenia rates could not be demonstrated. Given the substantive cost of CSFs to pharmacy budgets, there are numerous opportunities for pharmacists to optimize CSF use. Research studies are needed to evaluate if guideline-directed prescribing of primary prophylactic CSFs can improve clinical outcomes. © 2012

Colony-stimulating factors for chemotherapy-induced febrile neutropenia.

PubMed

Mhaskar, Rahul; Clark, Otavio Augusto Camara; Lyman, Gary; Engel Ayer Botrel, Tobias; Morganti Paladini, Luciano; Djulbegovic, Benjamin

2014-10-30

Febrile neutropenia is a frequent adverse event experienced by people with cancer who are undergoing chemotherapy, and is a potentially life-threatening situation. The current treatment is supportive care plus antibiotics. Colony-stimulating factors (CSFs), such as granulocyte-CSF (G-CSF) and granulocyte-macrophage CSF (GM-CSF), are cytokines that stimulate and accelerate the production of one or more cell lines in the bone marrow. Clinical trials have addressed the question of whether the addition of a CSF to antibiotics could improve outcomes in individuals diagnosed with febrile neutropenia. However, the results of these trials are conflicting. To evaluate the safety and efficacy of adding G-CSF or GM-CSF to standard treatment (antibiotics) when treating chemotherapy-induced febrile neutropenia in individuals diagnosed with cancer. We conducted the search in March 2014 and covered the major electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS, and SCI. We contacted experts in hematology and oncology and also scanned the citations from the relevant articles. We searched for randomized controlled trials (RCTs) that compared CSF plus antibiotics versus antibiotics alone for the treatment of chemotherapy-induced febrile neutropenia in adults and children. We used the standard methodological procedures expected by The Cochrane Collaboration. We performed meta-analysis of the selected studies using Review Manager 5 software. Fourteen RCTs (15 comparisons) including a total of 1553 participants addressing the role of CSF plus antibiotics in febrile neutropenia were included. Overall mortality was not improved by the use of CSF plus antibiotics versus antibiotics alone (hazard ratio (HR) 0.74 (95% confidence interval (CI) 0.47 to 1.16) P = 0.19; 13 RCTs; 1335 participants; low quality evidence). A similar finding was seen for infection-related mortality (HR 0.75 (95% CI 0.47 to 1.20) P = 0.23; 10 RCTs; 897

IL-10 combined with procalcitonin improves early prediction of complications of febrile neutropenia in hematological patients.

PubMed

Vänskä, Matti; Koivula, Irma; Jantunen, Esa; Hämäläinen, Sari; Purhonen, Anna-Kaisa; Pulkki, Kari; Juutilainen, Auni

2012-12-01

Early diagnosis of complicated course in febrile neutropenia is cumbersome due to the non-specificity of clinical and laboratory signs of severe infection. This prospective study included 100 adult hematological patients with febrile neutropenia after intensive chemotherapy at the onset of fever (d0) and for 3 days (d1-d3) thereafter. The study aim was to find early predictors for complicated course of febrile neutropenia, defined as bacteremia or septic shock. Interleukin 6 (IL-6), interleukin 10 (IL-10), procalcitonin (PCT) and C-reactive protein (CRP) all predicted complicated course of febrile neutropenia on d0, but only PCT was predictive throughout the study period. For IL-10 on d0-1 with cut-off 37 ng/L, sensitivity was 0.71, specificity 0.82, positive predictive value 0.52 and negative predictive value 0.92. For PCT on d0-1 with cut-off 0.13 μg/L, the respective measures were 0.95, 0.53, 0.36, and 0.98. For the combination of IL-10 and PCT on d0-1 with the same cut-offs, specificity improved to 0.85 and positive predictive value to 0.56. In conclusion, the present study confirms the high negative predictive value of PCT and provides new evidence for IL-10 as an early predictor for complicated course of febrile neutropenia in hematological patients. Combining IL-10 with PCT improves the early prediction for complicated course of febrile neutropenia. Copyright © 2012 Elsevier Ltd. All rights reserved.

Predictors of chemoradiation related febrile neutropenia prophylaxis in older adults - Experience from a limited resource setting.

PubMed

Gangopadhyay, Aparna

2018-01-01

To identify risk factors that lower efficacy of antibiotic prophylaxis of febrile neutropenia among older patients on chemoradiation. Audit of institutional data showed that older adults are at higher risk of febrile neutropenia during chemoradiation. In limited resource settings widespread use of Granulocyte-Colony Stimulating Factor (G-CSF) is not economically feasible and antibiotics are used commonly. Despite compliance with antibiotics, prophylaxis is inadequate in many patients owing to patient and tumor related factors. Data from records of 219 older patients receiving antibiotic prophylaxis during chemoradiation were studied. Baseline assessment data and predisposing factors for febrile neutropenia were recorded. All patients received prophylactic fluoroquinolones. Incidence of febrile neutropenia and association with predisposing factors at baseline was analyzed by multiple logistic regression. 38.4% developed febrile neutropenia despite compliance. Multiple logistic regression revealed geriatric assessment (G8) score and tumor stage to be significant predictors of febrile neutropenia while on antibiotics ( p  < 0.0001). Odds ratios for two significant predictors G8 score and tumor stage, respectively, were 2.9 (95% CI 1.8036-4.6815) and 2.7 (95% CI 1.7501-4.1318). Correlation between these two significant predictors was found to be low in our cohort (Spearman's coefficient of rank correlation (rho) - 0.431, p  < 0.0001). G8 score and tumor burden are significant predictors of efficacy of antibiotic prophylaxis among older adults receiving chemoradiation. In older patients having poor G8 scores and advanced tumors, antibiotic prophylaxis is unsuitable. Interestingly, co-morbidities and poor performance status did not impact efficacy of antibiotic prophylaxis among our elderly patients.

The incidence and risk factors of febrile neutropenia in chemotherapy-naïve lung cancer patients receiving etoposide plus platinum.

PubMed

Fujiwara, Takumi; Kenmotsu, Hirotsugu; Naito, Tateaki; Kawamura, Takahisa; Mamesaya, Nobuaki; Kotake, Mie; Kobayashi, Haruki; Omori, Shota; Nakashima, Kazuhisa; Wakuda, Kazushige; Ono, Akira; Taira, Tetsuhiko; Murakami, Haruyasu; Omae, Katsuhiro; Mori, Keita; Endo, Masahiro; Takahashi, Toshiaki

2017-06-01

This study was to determine the incidence and risk factors of febrile neutropenia in chemotherapy-naïve Japanese patients treated systemically with etoposide plus platinum for lung cancer. The study was a retrospective analysis of 244 patients who were monitored for febrile neutropenia through multiple cycles of the combination of etoposide with platinum, and the associations between incidence of febrile neutropenia and patient characteristics were evaluated. Eighty-eight patients were treated with etoposide plus cisplatin and 156 were treated with etoposide plus carboplatin. Of the 244 patients treated, 198 (81.1%) completed 4 cycles for chemotherapy. Febrile neutropenia was observed in 48 of 244 patients (19.7%), including 18 of 88 (20.5%) patients who received etoposide plus cisplatin and 30 of 156 (19.2%) patients who received etoposide plus carboplatin. Grade 3 or 4 of neutropenia was experienced by a total of 208 patients (85.2%); 79 of 88 (89.8%) receiving etoposide plus cisplatin and 129 of 156 (82.7%) receiving etoposide plus carboplatin. Male gender and previous radiotherapy were identified by multivariate analysis as independent risk factors for febrile neutropenia. These results contrast with findings in Western patients and suggest that ethnic differences exist in the incidence of febrile neutropenia in patients receiving etoposide plus platinum chemotherapy. In addition, our results suggest that primary prophylaxis with granulocyte colony-stimulating factor should be considered for patients with these risk factors for febrile neutropenia prior to treatment with etoposide plus platinum.

Time to antibiotics and outcomes in cancer patients with febrile neutropenia

PubMed Central

2014-01-01

Background Febrile neutropenia is an oncologic emergency. The timing of antibiotics administration in patients with febrile neutropenia may result in adverse outcomes. Our study aims to determine time-to- antibiotic administration in patients with febrile neutropenia, and its relationship with length of hospital stay, intensive care unit monitoring, and hospital mortality. Methods The study population was comprised of adult cancer patients with febrile neutropenia who were hospitalized, at a tertiary care hospital, between January 2010 and December 2011. Using Multination Association of Supportive Care in Cancer (MASCC) risk score, the study cohort was divided into high and low risk groups. A multivariate regression analysis was performed to assess relationship between time-to- antibiotic administration and various outcome variables. Results One hundred and five eligible patients with median age of 60 years (range: 18–89) and M:F of 43:62 were identified. Thirty-seven (35%) patients were in MASCC high risk group. Median time-to- antibiotic administration was 2.5 hrs (range: 0.03-50) and median length of hospital stay was 6 days (range: 1–57). In the multivariate analysis time-to- antibiotic administration (regression coefficient [RC]: 0.31 days [95% CI: 0.13-0.48]), known source of fever (RC: 4.1 days [95% CI: 0.76-7.5]), and MASCC high risk group (RC: 4 days [95% CI: 1.1-7.0]) were significantly correlated with longer hospital stay. Of 105 patients, 5 (4.7%) died & or required ICU monitoring. In multivariate analysis no variables significantly correlated with mortality or ICU monitoring. Conclusions Our study revealed that delay in antibiotics administration has been associated with a longer hospital stay. PMID:24716604

Increased interleukin-10 levels correlate with bacteremia and sepsis in febrile neutropenia pediatric oncology patients.

PubMed

Urbonas, Vincas; Eidukaitė, Audronė; Tamulienė, Indrė

2012-03-01

Early diagnosis of bacteremia and sepsis in pediatric oncology patients with febrile neutropenia still remains unresolved task due to lack of sensitive and specific laboratory markers particularly at the beginning of the infectious process. The objective of our study was to assess the potentiality of interleukin-10 (IL-10) to predict or exclude bacteremia or sepsis at the beginning of febrile episode in childhood oncology patients. A total of 36 febrile neutropenic episodes in 24 children were studied. Serum samples were collected after confirmation of febrile neutropenia and analyzed using automated random access analyzer. The sensitivity of IL-10 was 73% and specificity - 92% (cut-off=18pg/ml, area under the curve - 0.87, 95% CI for sensitivity 39-94%, 95% CI for specificity 74-99%) with negative predictive value (NPV) - 83%. IL-10 evaluation might be used as an additional diagnostic tool for clinicians in excluding bacteremia or clinical sepsis in oncology patients with febrile neutropenia because of high NPV and specificity. Copyright © 2011 Elsevier Ltd. All rights reserved.

Moxifloxacin is more effective than tosufloxacin in reducing chemotherapy-induced febrile neutropenia in patients with hematological malignancies.

PubMed

Shinohara, Akihito; Yoshiki, Yumiko; Masamoto, Yosuke; Hangaishi, Akira; Nannya, Yasuhito; Kurokawa, Mineo

2013-04-01

Recent studies have shown the prophylactic efficacy of fluoroquinolones against infections in patients with chemotherapy-induced neutropenia. However, little is known about the differences between fluoroquinolones, and there are some concerns about the emergence of resistant bacteria. In this retrospective study, we compared the prophylactic efficacy of moxifloxacin (MFLX) and tosufloxacin (TFLX) for chemotherapy-induced febrile neutropenia. The cumulative incidences of febrile neutropenia were 74.7% (59 of 79) in the MFLX group and 81.1% (219 of 270) in the TFLX group (log-rank test p = 0.044). Subgroup analysis revealed a more prominent prophylactic advantage of MFLX in patients with acute myeloid leukemia (AML) or long duration of neutropenia (p = 0.013 and 0.008, respectively). There were no significant differences in the incidences of adverse events and fluoroquinolone resistant bacteria in both groups. This study indicates that prophylaxis with MFLX is more beneficial to reduce febrile neutropenia episodes than TFLX, especially in patients with high-risk disease.

Advances in the treatment of neutropenia.

PubMed

Dale, David C

2009-09-01

The present review updates treatment of neutropenia from articles published from January 2008 through April 2009. Chemotherapy-induced neutropenia occurs most commonly in the first cycle of treatment. Older patients, patients with multiple comorbidities, and those receiving more myelotoxic drugs are prone to develop neutropenia and its complications. Current guidelines recommend the prophylactic use of the myeloid growth factors for the first cycle of chemotherapy for patients with more than a 20% risk of febrile neutropenia. Meta analysis from randomized trials shows that granulocyte colony-stimulating factor prophylaxis is associated with patients receiving more intensive chemotherapy, having better survival, but also having a higher risk of secondary acute myeloid leukemia. Antibiotics are standard treatment of febrile neutropenia and are increasingly used for prophylaxis in 'low-risk' patients. The myeloid growth factor granulocyte colony-stimulating factor has radically changed our approach to the prevention of febrile neutropenia. Antibiotics remain the mainstay of treatment of febrile neutropenia.

Frequent Respiratory Viral Infections in Children with Febrile Neutropenia - A Prospective Follow-Up Study.

PubMed

Söderman, Martina; Rhedin, Samuel; Tolfvenstam, Thomas; Rotzén-Östlund, Maria; Albert, Jan; Broliden, Kristina; Lindblom, Anna

2016-01-01

Febrile neutropenia is common in children undergoing chemotherapy for the treatment of malignancies. In the majority of cases, the cause of the fever is unknown. Although respiratory viruses are commonly associated with this condition, the etiologic significance of this finding remains unclear and is therefore the subject of this study. Nasopharyngeal aspirates were collected during 87 episodes of febrile neutropenia in children age 0-18 years, being treated at a children's oncology unit between January 2013 and June 2014. Real-time polymerase chain reaction was used to determine the presence of 16 respiratory viruses. Follow-up samples were collected from children who tested positive for one or more respiratory viruses. Rhinoviruses were genotyped by VP4/VP2 sequencing. Fisher's exact test and Mann-Whitney U test were used for group comparisons. At least one respiratory virus was detected in samples from 39 of 87 episodes of febrile neutropenia (45%), with rhinoviruses the most frequently detected. Follow-up samples were collected after a median of 28 days (range, 9-74 days) in 32 of the 39 virus-positive episodes. The respiratory viral infection had resolved in 25 episodes (78%). The same virus was detected at follow-up in one coronavirus and six rhinovirus episodes. Genotyping revealed a different rhinovirus species in two of the six rhinovirus infections. The frequency of respiratory viral infections in this group of patients suggests an etiologic role in febrile neutropenia. However, these findings must be confirmed in larger patient cohorts.

Frequent Respiratory Viral Infections in Children with Febrile Neutropenia - A Prospective Follow-Up Study

PubMed Central

Söderman, Martina; Rhedin, Samuel; Tolfvenstam, Thomas; Rotzén-Östlund, Maria; Albert, Jan; Broliden, Kristina; Lindblom, Anna

2016-01-01

Objective Febrile neutropenia is common in children undergoing chemotherapy for the treatment of malignancies. In the majority of cases, the cause of the fever is unknown. Although respiratory viruses are commonly associated with this condition, the etiologic significance of this finding remains unclear and is therefore the subject of this study. Study design Nasopharyngeal aspirates were collected during 87 episodes of febrile neutropenia in children age 0–18 years, being treated at a children’s oncology unit between January 2013 and June 2014. Real-time polymerase chain reaction was used to determine the presence of 16 respiratory viruses. Follow-up samples were collected from children who tested positive for one or more respiratory viruses. Rhinoviruses were genotyped by VP4/VP2 sequencing. Fisher’s exact test and Mann-Whitney U test were used for group comparisons. Results At least one respiratory virus was detected in samples from 39 of 87 episodes of febrile neutropenia (45%), with rhinoviruses the most frequently detected. Follow-up samples were collected after a median of 28 days (range, 9–74 days) in 32 of the 39 virus-positive episodes. The respiratory viral infection had resolved in 25 episodes (78%). The same virus was detected at follow-up in one coronavirus and six rhinovirus episodes. Genotyping revealed a different rhinovirus species in two of the six rhinovirus infections. Conclusion The frequency of respiratory viral infections in this group of patients suggests an etiologic role in febrile neutropenia. However, these findings must be confirmed in larger patient cohorts. PMID:27309354

Febrile Neutropenia Rates According to Body Mass Index and Dose Capping in Women Receiving Chemotherapy for Early Breast Cancer.

PubMed

Lote, H; Sharp, A; Redana, S; Papadimitraki, E; Capelan, M; Ring, A

2016-09-01

Studies suggest worse outcomes in obese women with breast cancer than in non-obese women. One potential reason may be that oncologists 'dose cap' adjuvant chemotherapy in obese patients in order to avoid excessive toxicity. Reductions from standard dosing may compromise survival outcomes in the curative setting. Here we describe the body mass index (BMI) distribution of patients in a non-trial population, the frequency with which oncologists dose cap and its effect on febrile neutropenia chemotherapy toxicity. In this non-randomised study, electronic patient records retrospectively identified patients with early breast cancer who initiated neoadjuvant or adjuvant chemotherapy at the Royal Marsden Hospital between 1 January and 31 December 2013. Baseline data included age, BMI, performance status, tumour characteristics, granulocyte colony-stimulating factor and comorbidities. Chemotherapy doses, rates of dose capping across BMI groups and rates of febrile neutropenia were reported. In total, 325 patients were eligible: 79 (24.5%) were obese (BMI ≥ 30), 109 (33.5%) were overweight (BMI ≥25 - <30) and 137 (42%) were normal bodyweight (BMI < 25). Sixteen patients (20.5%) in the obese group received dose-capped chemotherapy. Overall, 62 patients (19%) had an episode of febrile neutropenia. Obese patients receiving uncapped chemotherapy did not experience a significant difference in febrile neutropenia rates when compared with overweight or normal bodyweight groups (P = 0.5798). The febrile neutropenia rate in obese patients receiving capped chemotherapy was 6.5%, compared with 24% in obese patients receiving uncapped chemotherapy (P = 0.1216). In a non-trial population of obese patients, dose capping is frequently used. Obese patients receiving uncapped chemotherapy do not experience increased febrile neutropenia rates when compared with uncapped overweight or normal bodyweight patients. Furthermore, dose capping was associated with a trend towards lower

Implementation of an evidence-based order set to impact initial antibiotic time intervals in adult febrile neutropenia.

PubMed

Best, Janie T; Frith, Karen; Anderson, Faye; Rapp, Carla Gene; Rioux, Lisa; Ciccarello, Christina

2011-11-01

To evaluate the impact of the implementation of a standardized order set on the time interval in initiation of antibiotic therapy for adult patients with cancer and febrile neutropenia. Practice change. The oncology unit of an urban hospital in the south-eastern United States. Adult patients with cancer and febrile neutropenia admitted six months prior to (n = 30) or during the three months following (n = 23) implementation of the order set. Literature regarding febrile neutropenia, use of order sets, and change process was reviewed. In addition, a retrospective and concurrent chart review was conducted for adult patients admitted with febrile neutropenia. Time intervals were analyzed using SPSS® software, version 18. Initial antibiotic times, order-set use, and length of stay. An overall reduction in time intervals for initiation of antibiotic therapy was observed for presentation (t = 2.25; degrees of freedom [df] = 37; p = 0.031) and order (t = 2.67; df = 40.17; p = 0.012) to antibiotic administration, with an order-set usage of 31% in the inpatient unit and 71% in the emergency department. Findings in the presence of low order-set usage suggest that staff education and placement of the order-set antibiotics in unit-based medication dispensing machines helped reduce time intervals for initial antibiotic therapy. The use of an evidence-based approach to nursing care is essential to achieving the best outcomes for patients with febrile neutropenia. Incorporation of current evidence into an order set to guide clinical practice and comprehensive nurse, pharmacy, and physician education are needed for the successful implementation of evidence-based practice changes.

History and Outcome of Febrile Neutropenia Outside the Oncology Setting: A Retrospective Study of 76 Cases Related to Non-Chemotherapy Drugs

PubMed Central

Andrès, Emmanuel; Mourot-Cottet, Rachel; Maloisel, Frédéric; Keller, Olivier; Vogel, Thomas; Séverac, François; Tebacher, Martine; Gottenberg, Jacques-Eric; Weber, Jean-Christophe; Kaltenbach, Georges; Goichot, Bernard; Sibilia, Jean; Korganow, Anne-Sophie; Herbrecht, Raoul

2017-01-01

patients exhibiting severe pneumonia, septicemia, and septic shock, with a mortality rate of 10%. Like in febrile, chemotherapy-related neutropenia, modern and timely management (immediate broad spectrum antibiotherapy, hematopoietic growth factors) may reduce infection-related mortality. All practitioners should be aware of this potential side-effect that may even occur in the event of “daily medication” exposure. PMID:28954408

Outpatient management of febrile neutropenia: time to revise the present treatment strategy.

PubMed

Carstensen, Mads; Sørensen, Jens Benn

2008-01-01

We reviewed medical literature on the efficacy and safety of outpatient versus hospital-based therapy of low-risk febrile neutropenia in adult cancer patients. A PubMed search for all studies evaluating the outpatient treatment of adults diagnosed with solid tumors who suffered from low-risk febrile neutropenia was completed; reference lists from identified articles also were used. In all, 10 trials were included in the analysis, which showed no significant difference in clinical failure rates and mortality for ambulatory regimens and standard hospital-based therapy. Subgroup analysis according to the type of fever episode showed no significant differences in clinical failure rates for fever of unknown origin and fever due to documented infections. Subgroup analyses in two independent trials identified an absolute neutrophil count < 100 cells/ mm3 as being predictive of outpatient treatment failure (P < 0.04). These findings need to be confirmed by further trials. Thus, outpatient management of adult cancer patients with low-risk febrile neutropenia is safe, effective, and comparable to standard hospital-based therapy. Patients at low risk are outpatients and are hemodynamically stable; they have no organ failure, they are able to take oral medications, and they do not suffer from acute leukemia. Low-risk prediction also may be based on the Multinational Association for Supportive Care in Cancer risk index.

Validation of MASCC Score for Risk Stratification in Patients of Hematological Disorders with Febrile Neutropenia.

PubMed

Taj, M; Nadeem, M; Maqsood, S; Shah, T; Farzana, T; Shamsi, T S

2017-09-01

The purpose of this study is to evaluate the association of MASCC score (Multinational Association for Supportive Care in Cancer Score) in patients with febrile neutropenia (as resultant treatment of hematological disorders) for risk assessment of morbidity and mortality. Patients presenting with Febrile Neutropenia from November 2011 till December 2013 were enrolled in the study. Initially all patients were hospitalized and their MASCC score was calculated, however those with high risk stayed in hospital till full ANC recovery while low risk group was discharged earlier and keenly followed as out-patient while being on prophylactic oral antibiotics. The MASCC risk-index score was calculated and patients with risk score >21 were regarded as low-risk while <21 were labeled as high-risk. On the basis of 226 febrile neutropenia patient 132(58.4 %) were categorized as low risk while 94(41.5 %) as high risk patients according to MASCC risk index score. In low risk group 123(93 %) had uncomplicated infection while 9(7 %) had complicated infections. There was no mortality documented in low risk group while eight patients died in high risk group. In this study we correctly predicted outcome of 123(93 %) low risk group patients. The study had positive predictive value of 93 % with both sensitivity and specificity of 65 and 75 % respectively. The MASCC risk score is a valuable tool in determining the outcome in patients with febrile neutropenia.

Colony-stimulating factors: clinical evidence for treatment and prophylaxis of chemotherapy-induced febrile neutropenia.

PubMed

Gómez Raposo, César; Pinto Marín, Alvaro; González Barón, Manuel

2006-10-01

The hematopoietic growth factors (HGFs) are a family of glycoproteins which plays a major role in the proliferation, differentiation, and survival of primitive hematopoietic stem and progenitor cells, and in the functions of some mature cells. More than 20 different molecules of HGF have been identified. Among them, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been demostrated to be effective in reducing the incidence of febrile neutropenia when administered inmediately after chemotherapy and as supportive therapy in patients undergoing bone marrow transplantation. Chemotherapy used for treatment of cancer often causes neutropenia, which may be profound, requiring hospitalization, and leading to potentially fatal infection. The uses of the recombinant human hematopoietic colony-stimulating factors G-CSF and GM-CSF for treatment and prophylaxis of chemotherapy-induced febrile neutropenia will be reviewed here.

Febrile Neutropenia following Parvovirus B19 Infection and Cross Anti-Kell Reaction to E. Coli in Pregnancy.

PubMed

Brandão, Pedro; Freixo, Marília; Soares, Elisa; Estevinho, Catarina; Carvalho, Ana Sofia Portela; Melo, Anabela

2018-06-20

Parvovirus B19 has tropism for red line blood cells, causing immune hydrops during pregnancy. A positive anti-Kell Coombs reaction usually happens during pregnancy when there is production of antibodies that target Kell antigens, but cross reactions to other antigens may occur. A 24-year-old Gypsy primigravida, 0 Rhesus positive, presented with persistent isolated hyperthermia for 2 weeks and a positive indirect Coombs test result with anti-Kell antibodies at routine tests. She had a 19-week live fetus. The blood tests revealed bicytopenia with iron deficiency anemia, leucopoenia with neutropenia, and elevated C-reactive protein. She was medicated with imipenem, and had a slow clinical recovery. Blood, urine and sputum samples were taken to perform cultures and to exclude other systemic infections. Escherichia coli was isolated in the urine, which most probably caused a transient cross anti-Kell reaction. Haemophilus influenza in the sputum and seroconversion to parvovirus B19 was confirmed, causing unusual deficits in the white cells, culminating in febrile neutropenia. Despite the patient's lack of compliance to the medical care, both maternal and fetal/neonatal outcomes were good. This a rare case report of 2 rare phenomena, a cross anti-Kell reaction to E. coli and parvovirus B19 infection with tropism for white cells causing febrile neutropenia, both events occurring simultaneously during pregnancy. Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.

[Results of a post-marketing surveillance of meropenem for febrile neutropenia].

PubMed

Wakisaka, Koji; Tani, Shunsuke; Ishibashi, Kazuo; Nukui, Kazuhiko; Nagao, Munehiko

2015-08-01

The post-marketing surveillance of meropenem (Meropen) for febrile neutropenia (FN) was conducted between July 2010 and June 2012 to evaluate safety and efficacy under actual clinical use. There were 1191 and 1124 evaluable cases for safety and efficacy respectively, of 1207 case cards collected from 180 institutions. In safety analysis, the incidence of adverse drug reactions (ADRs) associated with use of meropenem (including abnormal laboratory findings) was 15.7% (187/1191 cases), and the main ADRs were alanine aminotransferase increased, aspartate aminotransferase increased, blood alkaline phosphatase increased, hepatic function abnormal, and liver disorder, which were similar to these observed in the clinical study for FN or post marketing surveillances of meropenem conducted before. In efficacy analysis, the overall efficacy was 81.8% (919/1124 cases). Also, it was 79.2% (708/894 cases) for hematological malignancy and 91.8% (213/232 cases) for solid cancer. These results confirmed meropenem (Meropen) is one of the well-tolerated and potent antimicrobial agents for febrile neutropenia.

Prevention of febrile neutropenia: use of prophylactic antibiotics.

PubMed

Cullen, M; Baijal, S

2009-09-01

Febrile neutropenia (FN) causes significant morbidity and mortality in patients receiving cytotoxic chemotherapy and can lead to reduced chemotherapy dose intensity and increased overall treatment costs. Antibiotic prophylaxis reduces the incidence of FN. Recent research and meta-analyses confirm that prophylactic fluoroquinolones decrease FN and infection-related mortality in patients with acute leukaemia and those receiving high-dose chemotherapy. Fluoroquinolone prophylaxis also lowers the incidence of FN and all-cause mortality following the first cycle of myelosuppressive chemotherapy for solid tumours. Levofloxacin has been the agent studied most thoroughly in this context. Although there is no convincing evidence that colonisation of individuals with resistant organisms due to antibiotic prophylaxis increases FN or mortality, such concerns must be taken seriously and the use of prophylaxis should be limited responsibly for patients with the greatest chance of benefit. Fluoroquinolone prophylaxis is well tolerated and cost-effective and should be offered to patients receiving chemotherapy for haematological malignancies and high-dose chemotherapy for solid tumours in which prolonged (>7 days) neutropenia is expected. It should also be considered for those receiving chemotherapy for solid tumours and lymphomas during the first cycle of chemotherapy when grade 4 neutropenia is anticipated.

Prevention of febrile neutropenia: use of prophylactic antibiotics

PubMed Central

Cullen, M; Baijal, S

2009-01-01

Febrile neutropenia (FN) causes significant morbidity and mortality in patients receiving cytotoxic chemotherapy and can lead to reduced chemotherapy dose intensity and increased overall treatment costs. Antibiotic prophylaxis reduces the incidence of FN. Recent research and meta-analyses confirm that prophylactic fluoroquinolones decrease FN and infection-related mortality in patients with acute leukaemia and those receiving high-dose chemotherapy. Fluoroquinolone prophylaxis also lowers the incidence of FN and all-cause mortality following the first cycle of myelosuppressive chemotherapy for solid tumours. Levofloxacin has been the agent studied most thoroughly in this context. Although there is no convincing evidence that colonisation of individuals with resistant organisms due to antibiotic prophylaxis increases FN or mortality, such concerns must be taken seriously and the use of prophylaxis should be limited responsibly for patients with the greatest chance of benefit. Fluoroquinolone prophylaxis is well tolerated and cost-effective and should be offered to patients receiving chemotherapy for haematological malignancies and high-dose chemotherapy for solid tumours in which prolonged (>7 days) neutropenia is expected. It should also be considered for those receiving chemotherapy for solid tumours and lymphomas during the first cycle of chemotherapy when grade 4 neutropenia is anticipated. PMID:19756000

[Fever profile of febrile neutropenia in patients treated with cancer chemotherapy for hematological malignancies].

PubMed

Tamai, Yotaro; Imataki, Osamu; Kawakami, Kimihiro

2010-05-01

It is important to diagnose infectious events in cancer patients during chemotherapy. Since many of them have complications of febrile neutropenia (FN), determining its cause is critical for their treatment course. We analyzed all febrile events (>38.0 degrees C, single axillary temperature) in hospitalized cancer patients treated at Shizuoka Cancer Center over a period of 8 months. Based on the clinical presentation at the onset, we estimated the cause of fever and classified it as infection, tumor fever, immunologic reaction or unknown. Clinical presentations found at the onset of FN were categorized into 4 groups: (1) oral mucositis, and (2) respiratory, (3) gastrointestinal and (4) cutaneous findings. We detected 85 febrile episodes (median age 58, range 26 approximately 86; 37 males and 48 females). Neutropenia was observed (500/mL) in 52. 9% (45/85) of the patients and clinical symptoms were detected in 74.1% (63/85). In eleven of 18 infection-proven cases, we successfully predicted the infection focus at the onset of fever. Multivariate analysis revealed that initial high fever, antimicrobial prophylaxis, cutaneous findings and severe neutropenia were important influencing factors in predicting infectious disease during FN. Physical examination can support the diagnosis of the cause of fever in FN patients.

Evaluation of empiric antibiotic de-escalation in febrile neutropenia.

PubMed

Kroll, Amanda L; Corrigan, Patricia A; Patel, Shejal; Hawks, Kelly G

2016-10-01

Up until 2010, the recommended duration of empiric broad-spectrum antibiotics for febrile neutropenia was until absolute neutrophil count (ANC) recovery. An updated guideline on the use of antimicrobial agents in neutropenic patients with cancer indicates that patients who have completed an appropriate treatment course of broad-spectrum antibiotics, with resolution of signs and symptoms of infection but persistent neutropenia, can be de-escalated to oral fluoroquinolone prophylaxis until ANC recovery. The primary objective of this retrospective investigation was to evaluate the safety and efficacy of de-escalating broad-spectrum antibiotics in patients remaining neutropenic after at least 14 days of empiric broadspectrum antibiotics for febrile neutropenia compared to patients continuing broad-spectrum antibiotics until ANC recovery. There were 16 patients (61.5%) in the comparator group who met the primary endpoint of remaining afebrile and without escalation of antibiotics for at least 72 hours after 14 days of broad-spectrum antibiotics and 21 patients (80.7%) in the de-escalation group who met the primary endpoint of remaining afebrile and without reinitiation of broad-spectrum antibiotics for at least 72 hours after de-escalation to levofloxacin therapy (p = 0.11). Mean total duration of broad-spectrum antibiotic therapy was 23.5 ± 1.5 days in the comparator group versus 22.2 ± 1.43 days in the de-escalation group (p = 0.39). Results of this investigation indicate that broad-spectrum antibiotics can be safely de-escalated to levofloxacin prophylaxis prior to ANC recovery in select patients. This practice may decrease the duration of broad-spectrum antibiotic exposure and associated complications. © The Author(s) 2015.

Diagnostic value of sTREM-1, IL-8, PCT, and CRP in febrile neutropenia after autologous stem cell transplantation.

PubMed

Michel, C S; Teschner, D; Wagner, E M; Theobald, M; Radsak, Markus P

2017-12-01

Infections and infectious complications are the major cause of morbidity and mortality in febrile neutropenic patients after autologous stem cell transplantation. Laboratory biomarkers are helpful for early identification of critically ill patients and optimal therapy management. Several studies in adult non-neutropenic patients proposed sTREM-1 as a superior biomarker for identification of septic patients as well as a predictor for survival in these patients compared with procalcitonin (PCT), C-reactive protein (CRP), or interleukin-8 (IL-8). Here, to assess the utility of PCT, CRP, IL-8, and sTREM-1 in febrile neutropenia, 44 patients presenting with febrile neutropenia after autologous stem cell transplantation were recruited in a single-center prospective pilot study. We analyzed PCT and CRP as well as IL-8 and sTREM-1 levels pre- and post-transplantation at defined time points. In 20 of 44 patients, concentration of sTREM-1 was under the detection level at appearance of febrile neutropenia. Mean levels of PCT, IL-8, and CRP were significantly increased in infections of critically ill patients who by dysfunction or failure of one or more organs/system depend on survival from advanced instruments of monitoring and therapy. However, all tested biomarkers could not distinguish between presence and absence of bloodstream infection. The combination of the biomarkers PCT and IL-8 achieved a high sensitivity of 90% and specificity of 74% for the identification of serious complications in febrile neutropenia, whereas the combination of CRP and PCT or IL-8 achieved a high sensitivity of 100%, but with the addition of a low specificity of 47or 41%. In conclusion, we found that the measurement of sTREM-1 concentration at presentation of febrile neutropenia is not useful to identify bacterial bloodstream infections and critically ill patients. PCT and IL-8 are useful biomarkers for the early identification of critically ill patients, compared to CRP and sTREM-1 in febrile

Prognostic factors for risk stratification of adult cancer patients with chemotherapy-induced febrile neutropenia: a systematic review and meta-analysis.

PubMed

Lee, Yee Mei; Lang, Dora; Lockwood, Craig

Increasing numbers of studies identify new prognostic factors for categorising chemotherapy-induced febrile neutropenia adult cancer patients into high- or low-risk groups for adverse outcomes. These groupings are used to tailor therapy according to level of risk. However many emerging factors with prognostic significance remain controversial, being based on single studies only. A systematic review was conducted to determine the strength of association of all identified factors associated with the outcomes of chemotherapy-induced febrile neutropenia patients. The participants included were adults of 15 years old and above, with a cancer diagnosis and who underwent cancer treatment.The review focused on clinical factors and their association with the outcomes of cancer patients with chemotherapy-induced febrile neutropenia at presentation of fever.All quantitative studies published in English which investigated clinical factors for risk stratification of adult cancer patients with chemotherapy-induced febrile neutropenia were considered.The primary outcome of interest was to identify the clinical factors for risk stratification of adult cancer patients with chemotherapy-induced febrile neutropenia. Electronic databases searched from their respective inception date up to December 2011 include MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Science-Direct, Scopus and Mednar. The quality of the included studies was subjected to assessment by two independent reviewers. The standardised critical appraisal tool from the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) was used to assess the following criteria: representativeness of study population; clearly defined prognostic factors and outcomes; whether potential confounders were addressed and appropriate statistical analysis was undertaken for the study design. Data extraction was performed using a modified version of

Cost-effectiveness of filgrastim and pegfilgrastim as primary prophylaxis against febrile neutropenia in lymphoma patients.

PubMed

Lathia, Nina; Isogai, Pierre K; De Angelis, Carlo; Smith, Thomas J; Cheung, Matthew; Mittmann, Nicole; Hoch, Jeffrey S; Walker, Scott

2013-08-07

Febrile neutropenia is a serious toxicity of cancer chemotherapy that is usually treated in hospital. We assessed the cost-effectiveness of filgrastim and pegfilgrastim as primary prophylaxis against febrile neutropenia in diffuse large B-cell lymphoma (DLBCL) patients undergoing chemotherapy. We used a Markov model that followed patients through induction chemotherapy to compare the three prophylaxis strategies: 1) no primary prophylaxis against febrile neutropenia; 2) primary prophylaxis with 10 days of filgrastim therapy; and 3) primary prophylaxis with a single dose of pegfilgrastim. The target population was a hypothetical cohort of 64-year-old men and women with DLBCL. Data sources included published literature and current clinical practice. The analysis was conducted from a publicly funded health-care system perspective. The main outcome measures included costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). In the base-case analysis, costs associated with no primary prophylaxis, primary prophylaxis with 10 days of filgrastim, and primary prophylaxis with pegfilgrastim were CaD $7314, CaD $13947, and CaD $16290, respectively. The QALYs associated with the three strategies were 0.2004, 0.2015, and 0.2024, respectively. The ICER for the filgrastim vs no primary prophylaxis strategy was CaD $5796000 per QALY. The ICER for the pegfilgrastim vs filgrastim primary prophylaxis strategy was CaD $2611000 per QALY. All one-way sensitivity analyses yielded ICERs greater than CaD $400000 per QALY. Cost-effectiveness acceptability curves show that 20.0% of iterations are cost-effective at a willingness-to-pay threshold of CaD $1595000 for the filgrastim strategy and CaD $561000 for the pegfilgrastim strategy. Primary prophylaxis against febrile neutropenia with either filgrastim or pegfilgrastim is not cost-effective in DLBCL patients.

Dengue fever causing febrile neutropenia in children with acute lymphoblastic leukemia: an unknown entity.

PubMed

Ramzan, Mohammed; Yadav, Satya Prakash; Dinand, Veronique; Sachdeva, Anupam

2013-06-01

Dengue fever is endemic in many parts of the world but it has not been described as a cause of febrile neutropenia. We describe here clinical features, laboratory values and outcome in 10 children with acute lymphoblastic leukemia (ALL) and with dengue fever as a cause of febrile neutropenia. These data are compared to an age-matched control population of 22 children with proven dengue infection without ALL. Except for fever in all patients and plethoric face in one patient, typical symptoms of dengue such as abdominal pain, myalgias, and headaches, were absent. Mean duration of hospital stay was 6.3±2.0 days in ALL patients vs. 5.0±2.0 in controls (p=0.096). Median platelet count was 13,000/cmm (range 1000-28,000) in cases vs. 31,500 (range 13,000-150,000) in controls (p=0.018). Mean time for recovery for platelet was 6.0±1.3days in ALL patients vs. 2.5±0.9days in controls (p<0.001). All 10 patients survived. In endemic areas, high suspicion of dengue fever should be maintained in children with ALL and febrile neutropenia although typical symptoms may be lacking. Platelet recovery may be significantly delayed. Copyright © 2013 King Faisal Specialist Centre & Research Hospital. Published by Elsevier B.V. All rights reserved.

A Comparison of Brand and Biosimilar Granulocyte-Colony Stimulating Factors for Prophylaxis of Chemotherapy-Induced Febrile Neutropenia.

PubMed

Douglas, Andrea G; Schwab, Phil; Lane, Daniel; Kennedy, Kenneth; Slabaugh, S Lane; Bowe, Andy

2017-12-01

Filgrastim-sndz, a granulocyte-colony stimulating factor (G-CSF), was introduced as a biosimilar to filgrastim in 2015, but real-world comparative effectiveness for filgrastim versus filgrastim-sndz has not been reported to date. To (a) compare the incidence of febrile neutropenia for patients taking filgrastim versus those taking filgrastim-sndz and (b) compare the incidence of a potential serious adverse event for filgrastim versus filgrastim-sndz. This retrospective cohort study identified patients receiving a G-CSF following chemotherapy, using administrative claims from the Humana Research Database. Patients enrolled in a Medicare Advantage Prescription Drug plan with a claim for a G-CSF from October 1, 2015, through September 30, 2016, were identified. G-CSF use had to occur within 6 days of exposure to chemotherapy and without any subsequent chemotherapy within 14 days after G-CSF use. Febrile neutropenia requiring hospitalization was defined as hospitalization within 14 days after G-CSF use with (a) diagnosis of infection and/or neutropenia (broad definition) or (b) infection and neutropenia diagnoses (narrow definition). Serious adverse drug events (spleen rupture, acute respiratory syndrome, serious allergic reactions, capillary leak syndrome, thrombocytopenia, leukocytosis, cutaneous vasculitis, or bones and muscle ache) were also identified within 14 days after G-CSF use. An incidence difference of < 1% with 90% CI crossing zero qualified as support for noninferiority. Two-tailed chi-square tests were also used to investigate differences. A total of 88 filgrastim and 101 filgrastim-sndz patients were identified. Filgrastim and filgrastim-sndz met the criteria for noninferiority based on an incidence difference of -0.6% (90% CI = -5.1%-4.0%; P = 0.84) for the broad definition of febrile neutropenia and a difference of -0.8% (90% CI = -3.8%-2.1%; P = 0.64) for the narrow definition. For the analysis of serious adverse events, an incidence difference of -2

Oral versus intravenous antibiotics in treatment of paediatric febrile neutropenia.

PubMed

Vedi, Aditi; Cohn, Richard

2013-03-01

The purpose of this study is to determine whether, in low-risk febrile neutropenic paediatric populations, oral antibiotics are as effective as intravenous antibiotics in obtaining resolution of the febrile neutropenic episode. A comprehensive literature search of MEDLINE, EMBASE and CENTRAL identified prospective, randomised controlled trials comparing oral antibiotics with intravenous antibiotics in the treatment of febrile neutropenic episodes in low-risk paediatric oncology patients. Outcomes assessed were mortality, rate of treatment failure, length of the febrile neutropenic episode and adverse events. The random effects model was used to calculate risk ratios (RRs) for dichotomous data and mean difference with standard deviation for continuous data. Seven trials were included in the overall analysis, which included 934 episodes of febrile neutropenia in 676 patients aged between 9 months and 20 years. The overall treatment failure rates were not significantly different between oral and intravenous antibiotics (RR: 1.02, 95% confidence interval 0.78-1.32, P= 0.91). In carefully selected low-risk febrile neutropenic children, empiric treatment with oral antibiotics is a safe and effective alternative to intravenous antibiotics as they lower the cost of treatment as well as psychosocial burden on these children and their families. © 2011 The Authors. Journal of Paediatrics and Child Health © 2011 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Efficacy and safety of tazobactam/piperacillin as an empirical treatment for the patients of adult and child with febrile neutropenia in Japan.

PubMed

Tamura, Kazuo; Akiyama, Nobu; Kanda, Yoshinobu; Saito, Masahiro

2015-09-01

Tazobactam/piperacillin (4.5 g for adults and 90 mg/kg body weight for children, every 6 h) was administered to Japanese patients with febrile neutropenia to evaluate its defervescence and clinical efficacy and safety. The pharmacokinetics in children were also examined. Defervescence efficacy at day 4 of the treatment was achieved in 50.0% of 94 adult and 62.5% of 8 pediatric patients, respectively. The defervescence efficacy rate in relation to the neutrophil count in adults was 37.5% for the patients with a neutrophil count of less than 100/μL and 62.5% for that between 100 and 500/μL. The clinical efficacy rate at day 7 and at the end or discontinuation of the treatment was 79.6% and 59.1% in adult patients, respectively, and 57.1% and 75.0% in pediatric patients, respectively. Fifteen strains of causative bacteria were isolated in 13 adult patients at baseline. All strains were eradicated within 4 days of the treatment. The side effects that occurred in adult and pediatric patients during the treatment were all known and not specific to febrile neutropenia patients. The pharmacokinetics profiles of tazobactam/piperacillin in children with febrile neutropenia are unlikely to be different from those in children with a common bacterial infection and without any immunosuppressive conditions. The study results in Japanese patients with febrile neutropenia demonstrate that tazobactam/piperacillin treatment is efficacious and safe in adults. As for pediatric patients, given the limited number of cases studied, further investigation is needed (Clinical trial number: Japic CTI-121728). Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Diagnostic Value of PCR Analysis of Bacteria and Fungi from Blood in Empiric-Therapy-Resistant Febrile Neutropenia ▿

PubMed Central

Nakamura, Akiko; Sugimoto, Yuka; Ohishi, Kohshi; Sugawara, Yumiko; Fujieda, Atsushi; Monma, Fumihiko; Suzuki, Kei; Masuya, Masahiro; Nakase, Kazunori; Matsushima, Yoshiko; Wada, Hideo; Katayama, Naoyuki; Nobori, Tsutomu

2010-01-01

This study aimed to assess the clinical utility of PCR for the analysis of bacteria and fungi from blood for the management of febrile neutropenic patients with hematologic malignancies. Using a PCR system able to detect a broad range of bacteria and fungi, we conducted a prospective pilot study of periodic analyses of blood from patients following intensive chemotherapy. When fever occurred, it was treated with empirical antibiotic therapy, basically without knowledge of the PCR results. In 23 febrile episodes during the neutropenic period, bacteria were detected by PCR in 11 cases, while the same species were identified by blood culture in 3 cases. In 10 out of 11 PCR-positive cases, fever could be managed by empirical therapy. In the empirical-therapy-resistant case, the identification of Stenotrophomonas maltophilia by PCR led to improvement of fever. No fungi were detected by PCR in febrile cases, while Aspergillus fumigatus was detected in one afebrile patient, several days before a clinical diagnosis was made. In subsequent sporadic PCR analyses in 15 cases of febrile neutropenia, bacteria were detected by both PCR and blood culture in 7 cases and by PCR alone in 6. Fungi were not detected. While fever was improved by empirical therapy in 12 out of the 13 PCR-positive cases, the identification of Pseudomonas aeruginosa by PCR in one therapy-resistant case contributed to the successful treatment of persistent fever. Our results indicate that PCR analysis of bacteria from blood provides essential information for managing empirical-therapy-resistant febrile neutropenia. PMID:20392911

Consensus on diagnosis and empiric antibiotic therapy of febrile neutropenia

PubMed Central

Giurici, Nagua; Zanazzo, Giulio A.

2011-01-01

Controversial issues on the management of empiric therapy and diagnosis of febrile neutropenia (FN) were faced by a Consensus Group of the Italian Association of Pediatric Hematology-Oncology (AIEOP). In this paper we report the suggestions of the consensus process regarding the role of aminoglycosides, glycopeptides and oral antibiotics in empiric therapy of FN, the rules for changing or discontinuing the therapy as well as the timing of the blood cultures. PMID:21647277

Bacteria causing bacteremia in pediatric cancer patients presenting with febrile neutropenia--species distribution and susceptibility patterns.

PubMed

Miedema, Karin G E; Winter, Rik H L J; Ammann, Roland A; Droz, Sara; Spanjaard, Lodewijk; de Bont, Eveline S J M; Kamps, Willem A; van de Wetering, Marianne D; Tissing, Wim J E

2013-09-01

Infections are a major cause of morbidity and mortality in pediatric cancer patients. The aim of this study was to establish the microbiological spectrum and the susceptibility patterns of bacteremia-causing bacteria in pediatric cancer patients with febrile neutropenia in relation to the use of prophylactic and empirical antibiotics. We analyzed positive blood cultures of pediatric cancer patients presenting with febrile neutropenia between 2004 and 2011 in Groningen and Amsterdam (the Netherlands) and in Bern (Switzerland), using different antibiotic prophylactic and empirical regimens. A total of 156 patients with 202 bacteremias, due to 248 bacteria species, were enrolled. The majority (73%) of bacteremias were caused by Gram-positive bacteria. Gram-negative bacteria, especially Pseudomonas aeruginosa, were observed significantly more often in Bern, where no fluoroquinolone prophylaxis was used. Ciprofloxacin-resistant bacteria were cultured more often from patients who did receive ciprofloxacin prophylaxis, compared to the patients who did not (57 versus 11%, p = 0.044). Gram-positive bacteria predominated in this study. We showed that the use of prophylactic antibiotics in pediatric cancer patients was associated with increased resistance rates, which needs further study. The strategy for empiric antimicrobial therapy for febrile neutropenia should be adapted to local antibiotic resistance patterns.

Antibiotic prophylaxis with teicoplanin on alternate days reduces rate of viridans sepsis and febrile neutropenia in pediatric patients with acute myeloid leukemia.

PubMed

Boztug, Heidrun; Mühlegger, Nora; Pötschger, Ulrike; Attarbaschi, Andishe; Peters, Christina; Mann, Georg; Dworzak, Michael

2017-01-01

Intensive chemotherapy directed against acute myeloid leukemia of childhood is followed by profound neutropenia and high risk for bacterial and fungal infections, including viridans group streptococci as a common cause for gram-positive septicemia. Few retrospective studies have shown the efficacy of various antibiotic prophylactic regimens in children. We retrospectively studied 50 pediatric patients treated on the AML-BFM 2004 protocol between 2005 and 2015 at St. Anna Children's Hospital and assessed the effect of antibiotic prophylaxis on the frequency of febrile neutropenia and bacterial sepsis. Fifty pediatric patients underwent 199 evaluable chemotherapy cycles. Viridans sepsis occurred after none of 98 cycles with prophylactic administration of teicoplanin/vancomycin in comparison to 12 cases of viridans sepsis among 79 cycles without systemic antibacterial prophylaxis (0 vs. 15 %, p < 0.0001). In addition, there were significantly fewer episodes of febrile neutropenia in the teicoplanin/vancomycin group (44 % vs. no prophylaxis 82 %, p < 0.0001). Severity of infection seemed to be worse when no antibiotic prophylaxis had been administered with a higher rate of intensive care unit treatment (0/98, 0 %, vs. 4/79, 5 %, p = 0.038). So far, no increase of vancomycin-resistant enterococcus isolates in surveillance cultures was noticed. Antibiotic prophylaxis with teicoplanin (or vancomycin) appears safe and feasible and resulted in eradication of viridans sepsis and decreased incidence of febrile neutropenia in pediatric AML patients. The possibility to administer teicoplanin on alternate days on an outpatient basis or at home could contribute to patient's quality of life and decrease health care costs.

Imbalances in serum angiopoietin concentrations are early predictors of septic shock development in patients with post chemotherapy febrile neutropenia

PubMed Central

2010-01-01

Background Febrile neutropenia carries a high risk of sepsis complications, and the identification of biomarkers capable to identify high risk patients is a great challenge. Angiopoietins (Ang -) are cytokines involved in the control microvascular permeability. It is accepted that Ang-1 expression maintains endothelial barrier integrity, and that Ang-2 acts as an antagonizing cytokine with barrier-disrupting functions in inflammatory situations. Ang-2 levels have been recently correlated with sepsis mortality in intensive care units. Methods We prospectively evaluated concentrations of Ang-1 and Ang-2 at different time-points during febrile neutropenia, and explored the diagnostic accuracy of these mediators as potential predictors of poor outcome in this clinical setting before the development of sepsis complications. Results Patients that evolved with septic shock (n = 10) presented higher levels of Ang-2 measured 48 hours after fever onset, and of the Ang-2/Ang-1 ratio at the time of fever onset compared to patients with non-complicated sepsis (n = 31). These levels correlated with sepsis severity scores. Conclusions Our data suggest that imbalances in the concentrations of Ang-1 and Ang-2 are independent and early markers of the risk of developing septic shock and of sepsis mortality in febrile neutropenia, and larger studies are warranted to validate their clinical usefulness. Therapeutic strategies that manipulate this Ang-2/Ang-1 imbalance can potentially offer new and promising treatments for sepsis in febrile neutropenia. PMID:20509945

Evaluation of malnutrition as a predictor of adverse outcomes in febrile neutropenia associated with paediatric haematological malignancies.

PubMed

Chaudhuri, Jasodhara; Biswas, Tamoghna; Datta, Jyotishka; Sabui, Tapas Kumar; Chatterjee, Sukanta; Ray, Somosri; Raychaudhuri, Dibyendu; Mandal, Kalyanbrata; Chatterjee, Kaushani; Chakraborty, Swapna

2016-07-01

Malnutrition has been reported in the literature to be adversely associated with outcomes in paediatric malignancies. Our objective in this paper was to evaluate malnutrition as a potential predictor for adverse outcomes in febrile neutropenia associated with haematological malignancies. A prospective observational study was performed in a tertiary care teaching hospital of Kolkata, India. Forty-eight participants, suffering from haematological malignancy, were included. Participants were included if they experienced at least one episode of febrile neutropenia. For children aged <5 years, weight for height, height for age and weight for age were used as criteria for defining malnutrition, while body mass index for age was used in children ≥5 years. A total of 162 episodes of febrile neutropenia were studied. Thirty patients (30/48, 62.5%) included in the study had malnutrition. In bivariate analyses at patient level, there is a strong association between malnutrition and death (odds ratio (OR) 7.286, 95% confidence interval (CI) 0.838-63.345, one-tailed P = 0.044), and life-threatening complications show a moderate trend towards significance (OR 3.333, 95% CI 0.791-14.052, one-tailed P = 0.084). Survival functions were significantly different between malnourished and non-malnourished children (log rank test χ(2)  = 4.609, degree of freedom = 1, P = 0.032). Wasting was associated with life-threatening complications in children aged <5 years (OR 14, 95% CI 1.135-172.642, one-tailed P = 0.036). Logistic regression analyses at episode level revealed that phase of treatment and respiratory system involvement were significant predictors of death, while malnutrition was not. Malnutrition may be a potential predictor of mortality in febrile neutropenia. © 2016 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

[Oncological emergencies in chemotherapy : Febrile neutropenia, tumor lysis syndrome, and extravasation].

PubMed

von Amsberg, G

2018-05-01

Uro-oncological emergencies can be caused by the tumor, treatment complications, or non-oncological diseases. This review focuses on chemotherapy-associated emergencies, especially febrile neutropenia (FN), tumor lysis syndrome (TLS), and extravasations. The goal is to provide an overview on the most relevant chemotherapy-associated emergencies and treatment methods. The ESMO (European Society of Medical Oncology), EORTC (European Organization for Research and Treatment of Cancer), and S3 guidelines were used for the preparation of this review and a PubMed search was performed for "febrile neutropenia", "extravasation", and "tumor lysis syndrome". A selection of the most relevant articles was included. A comprehensive medical history and examination are prerequisite for optimal treatment of chemotherapy-associated emergencies. The following aspects are of special interest: the malignant disease (tumor proliferation rate and burden); the applied medication (e. g., risk of FN, tissue damaging potential); the physical condition of the patient; age and relevant concomitant diseases (e. g., cardiovascular disease). Based on the diagnosis and the individual risk profile, therapeutic procedures are initiated. Distinct complications require an interdisciplinary treatment strategy. New treatment options such as checkpoint inhibitors complicate diagnosis and treatment of uro-oncological emergencies. Thus, improved diagnostic tools are required to draw the right conclusions in an emergency.

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

PubMed

Ahmed, Nabil; El-Mahallawy, Hadir A; Ahmed, Ibrahim A; Nassif, Shimaa; El-Beshlawy, Aamal; El-Haddad, Alaa

2007-11-01

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. (c) 2007 Wiley-Liss, Inc.

Assessment and management of febrile neutropenia in emergency departments within a regional health authority—a benchmark analysis

PubMed Central

Szwajcer, D.; Czaykowski, P.; Turner, D.

2011-01-01

Objectives Febrile neutropenia is considered an oncologic emergency, for which prompt initiation of antibiotics is essential. Methods We conducted a retrospective cohort study for the 2006 calendar year involving all adult oncology patients presenting with febrile neutropenia to a regional health authority’s emergency departments. The objective was to determine the time from triage to antibiotic administration and its impact on patient outcomes. Results We identified 68 patients presenting with febrile neutropenia, most of whom (76%) were seen in tertiary care centers. Of those patients, 65% were triaged to be seen within 15 minutes of arrival in the emergency room; however, the median time to reassessment was 57 minutes. The median time from triage to antibiotic administration was 5 hours (range: 1.23–22.8 hours). No increased risk of death or increased length of hospital stay was associated with delayed antibiotic administration. Older patients and patients without caregiver support were more likely to experience delayed antibiotic administration (odds ratio: 3.8 and 12.7 respectively). Conclusions We were not able to show a deleterious effect of delay in antibiotic administration, but our analysis identified several points at which patient flow through the emergency room could be improved. PMID:22184489

Asymmetric dimethylarginine in the assessment of febrile neutropenia in hematological patients.

PubMed

Lappalainen, Marika; Hämäläinen, Sari; Juutilainen, Auni; Koivula, Irma; Pulkki, Kari; Jantunen, Esa

2017-04-01

Asymmetric dimethylarginine (ADMA) has been recognized as an independent prognostic factor for sepsis mortality in intensive care units. No data are available on kinetics or prognostic value of ADMA in hematological patients. We evaluated the ability of ADMA to act as a predictor for complicated course of febrile neutropenia, defined as bacteremia and/or septic shock in adult hematological patients receiving intensive chemotherapy. This prospective study included 87 adult hematological patients with febrile neutropenia after an intensive chemotherapy for acute myeloid leukemia (AML) or after an autologous stem cell transplantation (ASCT). Plasma ADMA and serum C-reactive protein (CRP) levels were measured from the onset of fever (d0) and for 2 days (d1-d2) thereafter. The levels of ADMA were stable or had only minimal changes during the study period. There was no difference between the levels at any time-point in patients having complicated course compared to those without it. On the other hand, CRP levels were significantly higher on d1 (p = 0.016) in patients with bacteremia and/or septic shock than in those without. ADMA was not able to differentiate hematological patients with a complicated course from those without complications. Elevated ADMA levels are probably associated with organ dysfunction, which is rare in this group of patients, of whom about 95% can be successfully managed at the hematology ward.

Microbial etiology of febrile neutropenia.

PubMed

Swati, Mudshingkar; Gita, Nataraj; Sujata, Baveja; Farah, Jijina; Preeti, Mehta

2010-06-01

Bacterial and fungal infections are a major cause of morbidity and mortality among neutropenic patients. The choice of empiric antimicrobial regimen is based on susceptibility pattern of locally prevalent pathogens. From 64 febrile neutropenic patients with clinical sepsis, blood and other appropriate clinical specimens were processed to determine bacterial and fungal spectrum and their antimicrobial susceptibility pattern. Risk factors for developing sepsis were determined by case-control study. 68 organisms were recovered. Fifteen (22.05%) were Gram-positive cocci with predominance of methicillin Sensitive S. aureus (10.29%), 47 (69.11%) were Gram-negative rods with predominance of Klebsiella pneumoniae (30.88%) and four were Non albicans Candida. 81% and 60% of Klebsiella and E. coli were ESBL producers. All species of Candida were sensitive to amphoterecin B and voriconazole. Duration and extent of neutropenia, chemotherapy, immunosuppressive therapy, altered mucosal barriers and presence of central venous lines were statistically significant risk factors for developing sepsis. Gram-negative bacteria were the predominant isolates. The choice of therapy in neutropenic patients should be formulated based on local spectrum of microbes and local and regional resistance patterns.

Microbial Etiology of Febrile Neutropenia

PubMed Central

Gita, Nataraj; Sujata, Baveja; Farah, Jijina; Preeti, Mehta

2010-01-01

Bacterial and fungal infections are a major cause of morbidity and mortality among neutropenic patients. The choice of empiric antimicrobial regimen is based on susceptibility pattern of locally prevalent pathogens. From 64 febrile neutropenic patients with clinical sepsis, blood and other appropriate clinical specimens were processed to determine bacterial and fungal spectrum and their antimicrobial susceptibility pattern. Risk factors for developing sepsis were determined by case–control study. 68 organisms were recovered. Fifteen (22.05%) were Gram-positive cocci with predominance of methicillin Sensitive S. aureus (10.29%), 47 (69.11%) were Gram-negative rods with predominance of Klebsiella pneumoniae (30.88%) and four were Non albicans Candida. 81% and 60% of Klebsiella and E. coli were ESBL producers. All species of Candida were sensitive to amphoterecin B and voriconazole. Duration and extent of neutropenia, chemotherapy, immunosuppressive therapy, altered mucosal barriers and presence of central venous lines were statistically significant risk factors for developing sepsis. Gram-negative bacteria were the predominant isolates. The choice of therapy in neutropenic patients should be formulated based on local spectrum of microbes and local and regional resistance patterns. PMID:21629636

Piperacillin-tazobactam vs. imipenem-cilastatin as empirical therapy in hematopoietic stem cell transplantation recipients with febrile neutropenia.

PubMed

Jing, Yu; Li, Jian; Yuan, Lei; Zhao, Xiaoli; Wang, Quanshun; Yu, Li; Zhou, Daobin; Huang, Wenrong

2016-03-01

This randomized, dual-center study compared the efficacy and safety of piperacillin-tazobactam (PTZ) and imipenem-cilastatin (IMP) in hematopoietic stem cell transplantation (HSCT) recipients with febrile neutropenia. HSCT recipients with febrile neutropenia were randomized into two groups receiving either PTZ or IMP as initial empiric antibiotic. Endpoints were defervescence rate after empiric antibiotic for 48 h, success at end of therapy, and side effects. Defervescence within 48 h after empiric antibiotic was observed in 46 patients with PTZ (75.4%) and 59 patients with IMP (95.2%) (p = 0.002). Ten patients (10/46) in the PTZ group and two patients (2/59) in the IMP group switched empiric antibiotics due to recurrent fever (p = 0.005). Success of initial antibiotic with modification was achieved in 34 patients with PTZ (55.7%) and 53 patients with IMP (85.5%) at the end of therapy (p = 0.001). To treat the bacteremia, seven of 10 patients in the PTZ group and one of eight patients in the IMP group needed to switch the empiric antibiotic (p = 0.025). Compared with PTZ, IMP had more gastrointestinal adverse events (p = 0.045). This study demonstrates that IMP had better efficacy than PTZ as an empiric antibiotic for febrile neutropenia in the HSCT setting, but with more gastrointestinal side reactions. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A de-escalation protocol for febrile neutropenia cases and its impact on carbapenem resistance: A retrospective, quasi-experimental single-center study.

PubMed

Alshukairi, Abeer; Alserehi, Haleema; El-Saed, Aiman; Kelta, Mouhammed; Rehman, Jalil U; Khan, Farrukh A; Alsalmi, Hanadi; Alattas, Majda; Aslam, Muhammad

2016-01-01

Our objective was to evaluate the impact of using an imipenem de-escalation protocol for empiric febrile neutropenia on the development of carbapenem resistance. A pre-post intervention design was used. The intervention was adopting the imipenem de-escalation approach, which began on January 1, 2012. A retrospective chart review of cases of febrile neutropenia bacteremia was performed one year before and one year after the intervention. We compared the development of carbapenem resistance between the two study periods. Seventy-five episodes of febrile neutropenia bacteremia were included in the study. They had similar demographics, clinical features and outcomes. There were 78 and 12 pathogens in the primary and follow-up blood cultures, respectively. Approximately 61% and 66% of the primary and follow-up blood cultures, respectively, were gram-negative bacteria with similar carbapenem resistance profiles in the two study periods. In our study population, 57% of the gram-negative bacteria were ESBL pathogens. The resistance of the gram-negative bacteria to piperacillin/tazobactam (72% versus 53%, p=0.161), imipenem (16% versus 11%, p=0.684), and meropenem (8% versus 16%, p=0.638) did not significantly change after our policy change. In conclusion, the use of the carbapenem de-escalation approach for febrile neutropenia in our institution was not associated with an increase in carbepenem resistance. Future prospective multi-center studies are recommended to further confirm the current findings. Copyright © 2015 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

Biomarker candidates for the detection of an infectious etiology of febrile neutropenia.

PubMed

Richter, Martin E; Neugebauer, Sophie; Engelmann, Falco; Hagel, Stefan; Ludewig, Katrin; La Rosée, Paul; Sayer, Herbert G; Hochhaus, Andreas; von Lilienfeld-Toal, Marie; Bretschneider, Tom; Pausch, Christine; Engel, Christoph; Brunkhorst, Frank M; Kiehntopf, Michael

2016-04-01

Infections and subsequent septicemia are major complications in neutropenic patients with hematological malignancies. Here, we identify biomarker candidates for the early detection of an infectious origin, and monitoring of febrile neutropenia (FN). Proteome, metabolome, and conventional biomarkers from 20 patients with febrile neutropenia without proven infection (FNPI) were compared to 28 patients with proven infection, including 17 patients with bacteremia. Three peptides (mass to charge ratio 1017.4-1057.3; p-values 0.011-0.024), six proteins (mass to charge ratio 6881-17,215; p-values 0.002-0.004), and six phosphatidylcholines (p-values 0.007-0.037) were identified that differed in FNPI patients compared to patients with infection or bacteremia. Seven of these marker candidates discriminated FNPI from infection at fever onset with higher sensitivity and specificity (ROC-AUC 0.688-0.824) than conventional biomarkers i.e., procalcitonin, C-reactive protein, or interleukin-6 (ROC-AUC 0.535-0.672). In a post hoc analysis, monitoring the time course of four lysophosphatidylcholines, threonine, and tryptophan allowed for discrimination of patients with or without resolution of FN (ROC-AUC 0.648-0.919) with higher accuracy compared to conventional markers (ROC-AUC 0.514-0.871). Twenty-one promising biomarker candidates for the early detection of an infectious origin or for monitoring the course of FN were found which might overcome known shortcomings of conventional markers.

Is the addition of aminoglycosides to beta-lactams in cancer patients with febrile neutropenia needed?

PubMed

Contreras, Valeria; Sepúlveda, Sebastián; Heredia, Ana

2016-02-24

It is still controversial if the combined use of beta-lactam antibiotics and aminoglycosides has advantages over broad-spectrum beta-lactam monotherapy for the empirical treatment of cancer patients with febrile neutropenia. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified three systematic reviews including 14 pertinent randomized trials. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded the combination of beta-lactam antibiotics and aminoglycosides probably does not lead to a reduced mortality in febrile neutropenic cancer patients and it might increase nephrotoxicity.

Technical evaluation of methods for identifying chemotherapy-induced febrile neutropenia in healthcare claims databases.

PubMed

Weycker, Derek; Sofrygin, Oleg; Seefeld, Kim; Deeter, Robert G; Legg, Jason; Edelsberg, John

2013-02-13

Healthcare claims databases have been used in several studies to characterize the risk and burden of chemotherapy-induced febrile neutropenia (FN) and effectiveness of colony-stimulating factors against FN. The accuracy of methods previously used to identify FN in such databases has not been formally evaluated. Data comprised linked electronic medical records from Geisinger Health System and healthcare claims data from Geisinger Health Plan. Subjects were classified into subgroups based on whether or not they were hospitalized for FN per the presumptive "gold standard" (ANC <1.0×10(9)/L, and body temperature ≥38.3°C or receipt of antibiotics) and claims-based definition (diagnosis codes for neutropenia, fever, and/or infection). Accuracy was evaluated principally based on positive predictive value (PPV) and sensitivity. Among 357 study subjects, 82 (23%) met the gold standard for hospitalized FN. For the claims-based definition including diagnosis codes for neutropenia plus fever in any position (n=28), PPV was 100% and sensitivity was 34% (95% CI: 24-45). For the definition including neutropenia in the primary position (n=54), PPV was 87% (78-95) and sensitivity was 57% (46-68). For the definition including neutropenia in any position (n=71), PPV was 77% (68-87) and sensitivity was 67% (56-77). Patients hospitalized for chemotherapy-induced FN can be identified in healthcare claims databases--with an acceptable level of mis-classification--using diagnosis codes for neutropenia, or neutropenia plus fever.

Quest for certainty regarding early discharge in paediatric low-risk febrile neutropenia: a multicentre qualitative focus group discussion study involving patients, parents and healthcare professionals in the UK

PubMed Central

Phillips, Bob; Stewart, Lesley A; Atkin, Karl

2018-01-01

Objectives A systematic review of paediatric low-risk febrile neutropenia found that outpatient care is safe, with low rates of treatment failure. However, this review, and a subsequent meta-ethnography, suggested that early discharge of these patients may not be acceptable to key stakeholders. This study aimed to explore experiences and perceptions of patients, parents and healthcare professionals involved in paediatric febrile neutropenia care in the UK. Setting Three different centres within the UK, purposively selected from a national survey on the basis of differences in their service structure and febrile neutropenia management. Participants Thirty-two participants were included in eight focus group discussions. Primary outcomes Experiences and perceptions of paediatric febrile neutropenia care, including possible future reductions in therapy. Results Participants described a quest for certainty, in which they attempted to balance the uncertainty involved in understanding, expressing and negotiating risk with the illusion of certainty provided by strict protocols. Participants assessed risk using both formal and informal stratification tools, overlaid with emotional reactions to risk and experiences of risk within other situations. The benefits of certainty provided by protocols were counterbalanced by frustration at their strict constraints. The perceived benefits and harms of previous inpatient care informed participants’ appraisals of future treatment strategies. Conclusions This study highlighted the previously underestimated harms of admission for febrile neutropenia and the paternalistic nature of decision making, along with the frustrations and challenges for all parties involved in febrile neutropenia care. It demonstrates how the same statistics, generated by systematic reviews, can be used by key stakeholders to interpret risk differently, and how families in particular can view the harms of therapeutic options as different from the outcomes used

Improving early diagnosis of pulmonary infections in patients with febrile neutropenia using low-dose chest computed tomography.

PubMed

Gerritsen, M G; Willemink, M J; Pompe, E; van der Bruggen, T; van Rhenen, A; Lammers, J W J; Wessels, F; Sprengers, R W; de Jong, P A; Minnema, M C

2017-01-01

We performed a prospective study in patients with chemotherapy induced febrile neutropenia to investigate the diagnostic value of low-dose computed tomography compared to standard chest radiography. The aim was to compare both modalities for detection of pulmonary infections and to explore performance of low-dose computed tomography for early detection of invasive fungal disease. The low-dose computed tomography remained blinded during the study. A consensus diagnosis of the fever episode made by an expert panel was used as reference standard. We included 67 consecutive patients on the first day of febrile neutropenia. According to the consensus diagnosis 11 patients (16.4%) had pulmonary infections. Sensitivity, specificity, positive predictive value and negative predictive value were 36%, 93%, 50% and 88% for radiography, and 73%, 91%, 62% and 94% for low-dose computed tomography, respectively. An uncorrected McNemar showed no statistical difference (p = 0.197). Mean radiation dose for low-dose computed tomography was 0.24 mSv. Four out of 5 included patients diagnosed with invasive fungal disease had radiographic abnormalities suspect for invasive fungal disease on the low-dose computed tomography scan made on day 1 of fever, compared to none of the chest radiographs. We conclude that chest radiography has little value in the initial assessment of febrile neutropenia on day 1 for detection of pulmonary abnormalities. Low-dose computed tomography improves detection of pulmonary infiltrates and seems capable of detecting invasive fungal disease at a very early stage with a low radiation dose.

Improving early diagnosis of pulmonary infections in patients with febrile neutropenia using low-dose chest computed tomography

PubMed Central

Pompe, E.; van der Bruggen, T.; van Rhenen, A.; Lammers, J. W. J.; Wessels, F.; Sprengers, R. W.; de Jong, P. A.; Minnema, M. C.

2017-01-01

We performed a prospective study in patients with chemotherapy induced febrile neutropenia to investigate the diagnostic value of low-dose computed tomography compared to standard chest radiography. The aim was to compare both modalities for detection of pulmonary infections and to explore performance of low-dose computed tomography for early detection of invasive fungal disease. The low-dose computed tomography remained blinded during the study. A consensus diagnosis of the fever episode made by an expert panel was used as reference standard. We included 67 consecutive patients on the first day of febrile neutropenia. According to the consensus diagnosis 11 patients (16.4%) had pulmonary infections. Sensitivity, specificity, positive predictive value and negative predictive value were 36%, 93%, 50% and 88% for radiography, and 73%, 91%, 62% and 94% for low-dose computed tomography, respectively. An uncorrected McNemar showed no statistical difference (p = 0.197). Mean radiation dose for low-dose computed tomography was 0.24 mSv. Four out of 5 included patients diagnosed with invasive fungal disease had radiographic abnormalities suspect for invasive fungal disease on the low-dose computed tomography scan made on day 1 of fever, compared to none of the chest radiographs. We conclude that chest radiography has little value in the initial assessment of febrile neutropenia on day 1 for detection of pulmonary abnormalities. Low-dose computed tomography improves detection of pulmonary infiltrates and seems capable of detecting invasive fungal disease at a very early stage with a low radiation dose. PMID:28235014

Could Neutrophil CD64 Expression Be Used as a Diagnostic Parameter of Bacteremia in Patients with Febrile Neutropenia?

PubMed

Efe İris, Nur; Yıldırmak, Taner; Gedik, Habip; Şimşek, Funda; Aydın, Demet; Demirel, Naciye; Yokuş, Osman

2017-06-05

The aim of this study is to investigate if neutrophil CD64 expression in febrile neutropenia patients could be used as an early indicator of bacteremia. All consecutive patients older than 18 years of age who had developed febrile neutropenia episodes due to hematological malignancies were included in the study. Those patients who had significant growth in their blood cultures constituted the case group, while those who had febrile neutropenia without any growth in their cultures and who did not have any documented infections formed the control group. Blood culture bottles were incubated in the Bact ALERT 3D system (bioMerieux, France), identification and susceptibility testing were performed using an automated broth microdilution method (VITEK 2, bioMerieux), and CD64 expression analysis was performed by the flow cytometry method. C-reactive protein (CRP) was measured by turbidimetric methods (Biosystems, Spain) and erythrocyte sedimentation rate (ESR) was measured by the Wintrobe method. In total, we prospectively evaluated 31 febrile episodes. The case group consisted of 17 patients while the control group included 14 patients. CD64 was found on neutrophils of the case group patients with a mean count of 8006 molecules/cell and of control group with a mean count of 2786 molecules/cell. CD64 levels of the case group were significantly higher than those of the control group (p=0.005). In the differentiation of the case group from the control group, a 2500 cut-off value for CD64 had significant [AUC=0.792 (0.619-0.965)] predictive value (p=0.001). In the prediction of patients with a 2500 cut-off value for CD64, sensitivity was 94.1%, positive predictive value was 76.2%, specificity was 64.3%, and negative predictive value was 90.0%. CRP levels and ESR values did not differ significantly between the groups (p=0.005). Neutrophil CD64 expression could be a good predictor as an immune parameter with high sensitivity and a negative predictive value for bacteremia in

High-risk febrile neutropenia in Auckland 2003-2004: the influence of the microbiology laboratory on patient treatment and the use of pathogen-specific therapy.

PubMed

Ritchie, S; Palmer, S; Ellis-Pegler, R

2007-01-01

International guidelines recommend routine microbiological assessment of patients with febrile neutropenia, but do not recommend a change from broad-spectrum antibiotic therapy to pathogen-specific therapy when a clinically relevant organism has been isolated. The aim of the study was to determine the aetiology of febrile neutropenia in adult haematology patients at Auckland City Hospital, to document the changes in treatment made following isolation of a clinically relevant organism and to assess adverse outcomes in any patient who received pathogen-specific therapy after a positive culture result. The results of all microbiological tests together with antibiotic therapy were recorded from consecutive patients with fever and a neutrophil count <0.5 x 10(9)/L over 1 year beginning in May 2003. One thousand one hundred and ninety-six specimens were collected from 81 patients during 116 episodes of febrile neutropenia. A pathogen was isolated from blood cultures in 40 episodes: Gram-positive cocci accounted for 46% of isolates and Gram-negative bacilli for 35%. Isolation of a pathogen from blood cultures resulted in a change of treatment in 25 of 40 (62.5%, 95%CI 46-77%) episodes. In 12 of these episodes, antibiotic therapy was optimized to a single pathogen-specific agent. No adverse events or subsequent changes in antibiotic therapy occurred in any of these 12 patients. Isolation of a pathogen from specimens other than blood seldom led to a change in therapy. Isolation of a pathogen from blood cultures often allows antibiotic therapy to be simplified to a pathogen-specific regimen. Further study of this approach is warranted.

Technical evaluation of methods for identifying chemotherapy-induced febrile neutropenia in healthcare claims databases

PubMed Central

2013-01-01

Background Healthcare claims databases have been used in several studies to characterize the risk and burden of chemotherapy-induced febrile neutropenia (FN) and effectiveness of colony-stimulating factors against FN. The accuracy of methods previously used to identify FN in such databases has not been formally evaluated. Methods Data comprised linked electronic medical records from Geisinger Health System and healthcare claims data from Geisinger Health Plan. Subjects were classified into subgroups based on whether or not they were hospitalized for FN per the presumptive “gold standard” (ANC <1.0×109/L, and body temperature ≥38.3°C or receipt of antibiotics) and claims-based definition (diagnosis codes for neutropenia, fever, and/or infection). Accuracy was evaluated principally based on positive predictive value (PPV) and sensitivity. Results Among 357 study subjects, 82 (23%) met the gold standard for hospitalized FN. For the claims-based definition including diagnosis codes for neutropenia plus fever in any position (n=28), PPV was 100% and sensitivity was 34% (95% CI: 24–45). For the definition including neutropenia in the primary position (n=54), PPV was 87% (78–95) and sensitivity was 57% (46–68). For the definition including neutropenia in any position (n=71), PPV was 77% (68–87) and sensitivity was 67% (56–77). Conclusions Patients hospitalized for chemotherapy-induced FN can be identified in healthcare claims databases--with an acceptable level of mis-classification--using diagnosis codes for neutropenia, or neutropenia plus fever. PMID:23406481

Association of ABCB1 and SLC22A16 Gene Polymorphisms with Incidence of Doxorubicin-Induced Febrile Neutropenia: A Survey of Iranian Breast Cancer Patients.

PubMed

Faraji, Abolfazl; Dehghan Manshadi, Hamid Reza; Mobaraki, Maryam; Zare, Mahkameh; Houshmand, Massoud

2016-01-01

Breast cancer is the most common cancer in women worldwide. Doxorubicin-based chemotherapy is used to treat breast cancer patients; however, neutropenia is a common hematologic side effect and can be life-threatening. The ABCB1 and SLC22A16 genes encode proteins that are essential for doxorubicin transport. In this study, we explored the effect of 2 common polymorphisms in ABCB1 (rs10276036 C/T) and SLC22A16 (rs12210538 A/G) on the development of grade 3/4 febrile neutropenia in Iranian breast cancer patients. Our results showed no significant association between these polymorphisms and grade 3/4 febrile neutropenia; however, allele C of ABCB1 (rs10276036 C/T) (p = 0.315, OR = 1.500, 95% CI = 0.679-3.312) and allele A of SLC22A16 (rs12210538 A/G) (p = 0.110, OR = 2.984, 95% CI = 0.743-11.988) tended to have a greater association with grade 3/4 febrile neutropenia, whereas allele T of ABCB1 (rs10276036) (p = 0.130, OR = 0.515, 95% CI = 0.217-1.223) and allele G of SLC22A16 (rs12210538) (p = 0.548, OR = 0.786, 95% CI = 0.358-1.726) tended to protect against this condition. In addition to breast cancer, a statistically significant association was also observed between the development of grade 3/4 febrile neutropenia and other clinical manifestations such as stage IIIC cancer (p = 0.037) and other diseases (p = 0.026). Our results indicate that evaluation of the risk of grade 3/4 neutropenia development and consideration of molecular and clinical findings may be of value when screening for high-risk breast cancer patients.

Multicentre, Prospective Observational Study of Pegfilgrastim Primary Prophylaxis in Patients at High Risk of Febrile Neutropenia in Poland: PROFIL Study

PubMed Central

Jurczak, Wojciech; Kalinka-Warzocha, Ewa; Chmielowska, Ewa; Duchnowska, Renata; Wojciechowska-Lampka, Elzbieta

2015-01-01

Aim of the study PROFIL was a prospective observational study conducted to investigate physicians’ evaluation of febrile neutropenia (FN) risk and reasons for giving pegfilgrastim primary prophylaxis (PP) in routine clinical practice in Poland. Material and methods Adult cancer patients treated with chemotherapy (CT), assessed by investigators as having high overall FN risk, and who received pegfilgrastim in cycle 1 were enrolled between 03/2009 and 09/2010. Investigators assessed FN risk of the CT regimen, individual risk factors, and overall FN risk, and were asked to provide the most important reasons for providing pegfilgrastim PP. Investigator-assessed CT FN risk was compared with guideline classification. Results Data were analysed from 1006 breast, ovarian, and lung cancer, and non-Hodgkin (NHL) and Hodgkin lymphoma (HL) patients. The most important reasons for using pegfilgrastim PP were high CT FN risk and advanced disease; these were consistent across tumour types and treatment intent. The investigators generally assessed high CT FN risk in agreement with guideline classification. Febrile neutropenia occurred in 4% of patients, most commonly in HL, NHL, and patients with advanced disease. Conclusions High CT FN risk and advanced stage of disease were found to be the most important reasons for providing pegfilgrastim PP by physicians in Poland. PMID:26557762

Febrile neutropenia in cats treated with chemotherapy.

PubMed

Pierro, J; Krick, E; Flory, A; Regan, R; DeRegis, C; Boudreaux, B; Barber, L; Saam, D; Saba, C

2017-06-01

The purpose of this study was to describe the clinical presentation, potential causative agents, treatment and outcome of febrile neutropenia (FN) in chemotherapy-treated cats. Medical records from eight institutions were retrospectively reviewed. A total of 22 FN events in 20 cats were evaluated. Lymphoma was the most common cancer diagnosis; lomustine and vinca alkaloids were the most frequently implicated causative agents. Presenting clinical signs included decreased appetite, lethargy, vomiting and diarrhoea. Median body temperature and absolute neutrophil count at presentation were 104.1 °F; 40 °C (range: 103.1-105.1 °F; 39.5-40.6 °C) and 246 mL -1 (range: 0-1600 mL -1 ), respectively. Median number of days between chemotherapy administration and FN onset was 5 (range: 4-25 days). All but one cat were treated with intravenous fluids and broad spectrum antibiotics. Fevers resolved in all cases and absolute neutrophil counts returned to normal in 19 cats. Clinical presentation of cats with FN appears similar to that of dogs. © 2016 John Wiley & Sons Ltd.

The diagnostic value of CRP, IL-8, PCT, and sTREM-1 in the detection of bacterial infections in pediatric oncology patients with febrile neutropenia.

PubMed

Miedema, Karin G E; de Bont, Eveline S J M; Elferink, Rob F M Oude; van Vliet, Michel J; Nijhuis, Claudi S M Oude; Kamps, Willem A; Tissing, Wim J E

2011-10-01

In this study, we evaluated C-reactive protein (CRP), interleukin (IL)-8, procalcitonin (PCT), and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as predictors for bacterial infection in febrile neutropenia, plus their usefulness in febrile neutropenia during chemotherapy-induced gastrointestinal mucositis. Plasma was obtained from pediatric oncology patients at presentation with febrile neutropenia (n = 43) and 24-48 h later (n = 17). The patients were classified as having or not having a bacterial infection. Plasma was also obtained of patients in the absence and in the presence of mucositis (n = 26). At presentation with febrile neutropenia, median IL-8 and PCT levels were significantly increased in patients with a bacterial infection, in contrast to CRP and sTREM-1. IL-8 was the most sensitive marker for the early detection of bacterial infection, in combination with clinical parameters or PCT the sensitivity reached 100%. After 24-48 h, only PCT was significantly elevated during bacterial infection. IL-8 levels were significantly increased during mucositis. Mucositis did not cause considerable changes in PCT levels. IL-8 is the most useful marker for the early detection of bacterial infections, compared with CRP, PCT, and sTREM-1. IL-8 in combination with clinical parameters or PCT might be even more useful. Gastrointestinal mucositis alone does not affect PCT levels, in contrast to IL-8 levels, and therefore, PCT might be more useful for the detection of bacterial infections during mucositis than IL-8.

Plasma presepsin level is an early diagnostic marker of severe febrile neutropenia in hematologic malignancy patients.

PubMed

Koizumi, Yusuke; Shimizu, Kaoru; Shigeta, Masayo; Okuno, Takafumi; Minamiguchi, Hitoshi; Kito, Katsuyuki; Hodohara, Keiko; Yamagishi, Yuka; Andoh, Akira; Fujiyama, Yoshihide; Mikamo, Hiroshige

2017-01-05

Febrile neutropenia (FN) is a common infectious complication in chemotherapy. The mortality of FN is higher in hematologic malignancy patients, and early diagnostic marker is needed. Presepsin is a prompt and specific marker for bacterial sepsis, but its efficacy in severe febrile neutropenia (FN) is not well confirmed. We tried to clarify whether it is a useful maker for early diagnosis of FN in patients during massive chemotherapy. We measured plasma presepsin levels every 2-3 day in FN cases and evaluated its change during the course of massive chemotherapy. The patients had hematologic malignancy or bone marrow failure, and in all cases, neutropenia was severe during the episode. The baseline levels, onset levels, increase rate at FN onset, and onset / baseline ratio were evaluated for their efficacy of early FN diagnosis. Eleven episodes of bacteremia (six gram negatives and five gram positives) in severe neutropenia were analyzed in detail. While plasma presepsin level was strongly associated to the CRP level (r = 0.61, p < 0.01), it was not associated with the absolute WBC count (r = -0.19, p = 0.19), absolute neutrophil count (r = -0.11, p = 0.41) or absolute monocyte count (r = -0.12, p = 0.40). The average of onset presepsin level was 638 ± 437 pg/mL and the cutoff value (314 pg/mL) has detected FN onset in 9 of 11 cases. The two cases undetected by presepsin were both Bacillus species bacteremia. Plasma presepsin level is a reliable marker of FN even in massive chemotherapy with very low white blood cell counts. Closer monitoring of this molecule could be a help for early diagnosis in FN. But bacteremia caused by Bacillus species was an exception in our study.

Pentraxin 3 predicts complicated course of febrile neutropenia in haematological patients, but the decision level depends on the underlying malignancy.

PubMed

Juutilainen, Auni; Vänskä, Matti; Pulkki, Kari; Hämäläinen, Sari; Nousiainen, Tapio; Jantunen, Esa; Koivula, Irma

2011-11-01

This study aimed at assessing the cut-off levels for pentraxin 3 (PTX3) in predicting complications of neutropenic fever (bacteraemia, septic shock) in haematological patients. A prospective study during 2006-2009 was performed at haematology ward in Kuopio University Hospital. A patient was eligible for the study if having neutropenic fever after intensive therapy for acute myeloid leukaemia (AML) (n = 32) or non-Hodgkin lymphoma (NHL) (n = 35). Blood cultures were taken, and maximal PTX3 and C-reactive protein (CRP) were evaluated during d0 to d3 from the beginning of fever onset. The level of PTX3 was associated with both the underlying malignancy and the presence of complications, with highest level in NHL patients with complicated course of febrile neutropenia and lowest in AML patients with non-complicated course. The cut-off level of PTX3 to predict complications was ten-fold in patients with NHL (115 μg/L) in comparison with patients with AML (11.5 μg/L). In combined analysis based on separate cut-offs, PTX3 predicted complications of febrile neutropenia with sensitivity of 0.86, specificity of 0.83, positive predictive value of 0.57 and negative predictive value of 0.96.   PTX3 was superior to CRP in predicting complicated course of febrile neutropenia, but only when the effect of the underlying malignancy had been taken into account. © 2011 John Wiley & Sons A/S.

Effects of Traditional Chinese Medicine on Chemotherapy-Induced Myelosuppression and Febrile Neutropenia in Breast Cancer Patients

PubMed Central

Tian, Huan; Qin, Wei; Wu, Wenjing; Guo, Pi; Lu, Yong; Liu, Pengxi; Liu, Qiang; Su, Fengxi

2015-01-01

Title. Chemotherapy-induced myelosuppression lowers the quality of life in breast cancer patients and causes many complications. Traditional Chinese Medicine (TCM) is a widely used complementary and alternative medicine therapies. Objective. To study whether TCM can reduce the incidence of chemotherapy-induced leukopenia, neutropenia, and febrile neutropenia (FN) in breast cancer patients. Methods. The data were analyzed retrospectively between patients who received TCM treatment (group 1, n = 453) and patients who did not receive TCM treatment (group 2, n = 359). Significant risk factors associated with the occurrence of chemotherapy-induced leukopenia, neutropenia, and FN were identified using multivariate analysis. Propensity score-matched patients were analyzed to adjust for any baseline differences. Results. Group 1 patients had a significantly lower rate of chemotherapy-induced severe leukopenia, neutropenia, and FN, compared with group 2 (43% versus 71%, P < 0.0001, 72% versus 78%, P = 0.005, 6% versus 24%, P < 0.0001, resp.). Multivariate analysis revealed that chemotherapy regimens containing anthracyclines combined with paclitaxel or docetaxel were the most significant predictor. Subgroup analysis indicated that TCM treatment showed benefit in relieving chemotherapy-induced leukopenia and FN in most chemotherapy regimens. Conclusions. TCM treatment could lower the risk of severe chemotherapy-induced leukopenia, neutropenia, and FN in breast cancer patients. PMID:26347793

Antimicrobial agent prescription patterns for chemotherapy-induced febrile neutropenia in patients with hematological malignancies at Sultan Qaboos University Hospital, Oman.

PubMed

Al Balushi, K A; Balkhair, A; Ali, B H; Al Rawas, N

2013-06-01

The aim of this study was to describe the antimicrobial prescription patterns of patients with hematological malignancies who developed febrile neutropenia (FN) at Sultan Qaboos University Hospital (SQUH) in Oman. This was a retrospective observational study covering a period of 3 years (January 2007-February 2010). FN episodes were studied in patients with hematological malignancies in three different wards at SQUH. A total of 176 FN episodes were analyzed. Overall, 64% of the 107 patients studied experienced at least 2 episodes during the analysis period. Approximately, 69% of the febrile neutropenia episodes had severe neutropenia. The duration of neutropenia was less than 1 week in the majority of the episodes (57%). The mean duration of treatment was approximately 7 days, with no significant difference between specialties or different types of malignancies. Only 34 (19%) episodes had positive cultures, and most of these were from blood samples (30 episodes, 88%). The majority of isolates were gram-negative organisms (63%). The initial empirical treatment included monotherapy (37%), dual therapy (60%) and triple therapy (3%). This study demonstrates that there is a large variation in the antimicrobial treatment of FN episodes in patients with hematological malignancies at SQUH. All chosen drugs were within international guideline recommendations. Copyright © 2013 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

G-CSF and GM-CSF in Neutropenia

PubMed Central

Mehta, Hrishikesh M.; Malandra, Michael; Corey, Seth J.

2015-01-01

Granulocyte Colony Stimulating Factor (G-CSF) and Granulocyte/Macrophage Colony Stimulating Factor (GM-CSF) are used widely to promote the production of granulocytes or antigen presenting cells (APC). The Food and Drug Administration approved G-CSF (filgrastim) for the treatment of congenital and acquired neutropenias and for mobilization of peripheral hematopoietic progenitor cells for stem cell transplantation. A polyethylene glycol modified (PEGylated) form of G-CSF is approved for the treatment of neutropenias. Clinically significant neutropenia, rendering an individual immunocompromised, occurs when their number is less than 1500/µl. Current guidelines recommend their use when the risk of febrile neutropenia is greater than 20%. GM-CSF (sargramostim) is approved for neutropenia associated with stem cell transplantation. Because of its promotion of APC function, GM-CSF is being evaluated as an immunostimulatory adjuvant in a number of clinical trials. More than 20 million persons have benefited worldwide, and more than $5 billion sales occur annually in the United States. PMID:26254266

The predictive value of soluble biomarkers (CD14 subtype, interleukin-2 receptor, human leucocyte antigen-G) and procalcitonin in the detection of bacteremia and sepsis in pediatric oncology patients with chemotherapy-induced febrile neutropenia.

PubMed

Urbonas, Vincas; Eidukaitė, Audronė; Tamulienė, Indrė

2013-04-01

Prediction of bacteremia/sepsis in childhood oncology patients with febrile neutropenia still remains a challenge for the medical community due to the lack of reliable biomarkers, especially at the beginning of infectious process. The objective of this study was to evaluate diagnostic value of soluble biomarkers (CD14 subtype, interleukin-2 receptor, HLA-G) and procalcitonin (PCT) in the identification of infectious process at the beginning of a febrile episode in pediatric oncology patients. A total of 62 episodes of febrile neutropenia in 37 childhood oncology patients were enrolled in this study. Serum samples were collected at presentation after confirmation of febrile neutropenia and analyzed according to recommendations of manufacturers. Patients were classified into bacteremia/sepsis and fever of unknown origin groups. Median of PCT and sIL-2R were considerably higher in bacteremia/sepsis group compared to fever of unknown origin group, whereas median of sHLA-G and presepsin levels between investigated groups did not differ sufficiently. PCT and sIL-2R determination might be used as an additional diagnostic tool for the detection of bacteremia/sepsis in childhood oncology patients with febrile neutropenia. Copyright © 2013 Elsevier Ltd. All rights reserved.

Universal antifungal therapy is not needed in persistent febrile neutropenia: a tailored diagnostic and therapeutic approach

PubMed Central

Aguilar-Guisado, Manuela; Martín-Peña, Almudena; Espigado, Ildefonso; Ruiz Pérez de Pipaon, Maite; Falantes, José; de la Cruz, Fátima; Cisneros, José M.

2012-01-01

Background Giving antifungal therapy exclusively to selected patients with persistent febrile neutropenia may avoid over-treatment without increasing mortality. The aim of this study was to validate an innovative diagnostic and therapeutic approach based on assessing patients’ risk profile and clinical criteria in order to select those patients requiring antifungal therapy. The efficacy of this approach was compared to that of universal empirical antifungal therapy. Design and Methods This was a prospective study which included all consecutive adult hematology patients with neutropenia and fever refractory to 5 days of empirical antibacterial therapy admitted to a teaching hospital in Spain over a 2-year period. A diagnostic and therapeutic approach based on clinical criteria and risk profile was applied in order to select patients for antifungal therapy. The sensitivity, specificity and negative predictive value of this approach and also the overall success rate, according to the same criteria of efficacy described in classical clinical trials, were analyzed. Results Eighty-five episodes were included, 35 of them (41.2%) in patients at high risk of invasive fungal infections. Antifungal therapy was not indicated in 33 episodes (38.8%). The overall incidence of proven and probable invasive fungal infections was 14.1%, all of which occurred in patients who had received empirical antifungal therapy. The 30-day crude mortality rate was 15.3% and the invasive fungal infection-related mortality rate was 2.8% (2/72). The overall success rate following the diagnostic and therapeutic approach was 36.5% compared with 33.9% and 33.7% obtained in the trial by Walsh et al. The sensitivity, specificity and negative predictive value of the study approach were 100%, 52.4% and 100%, respectively. Conclusions Based on the high negative predictive value of this diagnostic and therapeutic approach in persistent febrile neutropenia patients with hematologic malignancies or patients

Time to clinical response: an outcome of antibiotic therapy of febrile neutropenia with implications for quality and cost of care.

PubMed

Elting, L S; Rubenstein, E B; Rolston, K; Cantor, S B; Martin, C G; Kurtin, D; Rodriguez, S; Lam, T; Kanesan, K; Bodey, G

2000-11-01

To determine whether antibiotic regimens with similar rates of response differ significantly in the speed of response and to estimate the impact of this difference on the cost of febrile neutropenia. The time point of clinical response was defined by comparing the sensitivity, specificity, and predictive values of alternative objective and subjective definitions. Data from 488 episodes of febrile neutropenia, treated with either of two commonly used antibiotics (coded A or B) during six clinical trials, were pooled to compare the median time to clinical response, days of antibiotic therapy and hospitalization, and estimated costs. Response rates were similar; however, the median time to clinical response was significantly shorter with A-based regimens (5 days) compared with B-based regimens (7 days; P =.003). After 72 hours of therapy, 33% of patients who received A but only 18% of those who received B had responded (P =.01). These differences resulted in fewer days of antibiotic therapy and hospitalization with A-based regimens (7 and 9 days) compared with B-based regimens (9 and 12 days, respectively; P <.04) and in significantly lower estimated median costs ($8,491 v $11,133 per episode; P =.03). Early discharge at the time of clinical response should reduce the median cost from $10,752 to $8,162 (P <.001). Despite virtually identical rates of response, time to clinical response and estimated cost of care varied significantly among regimens. An early discharge strategy based on our definition of the time point of clinical response may further reduce the cost of treating non-low-risk patients with febrile neutropenia.

The diagnostic value of interleukin-6 and interleukin-8 for early prediction of bacteremia and sepsis in children with febrile neutropenia and cancer.

PubMed

Urbonas, Vincas; Eidukaitė, Audronė; Tamulienė, Indrė

2012-03-01

Early diagnosis of sepsis in children with febrile neutropenia and cancer still remains a challenge for modern medicine because of lack of specific laboratory markers and clinical signs especially at the beginning of the infection. The objective of this study was to evaluate the ability of interleukin-6 and interleukin-8 to predict bacteremia and sepsis during the first 2 days in oncohematologic patients with febrile neutropenia. A total of 61 febrile neutropenic episodes in 37 children were studied. Serum samples were collected on day 1 and day 2 from the onset of fever and analyzed using an automated random access analyzer. Neutropenic children with febrile episodes were classified into the following 2 groups: (1) fever of unknown origin group--patients with a negative blood culture--and (2) bacteremia/sepsis group--patients with a positive blood culture or clinical sepsis. High negative predictive values were found on day 1 for interleukin-6 and interleukin-8 (89% and 82%, respectively) for exclusion of bacteremia/sepsis. These interleukins could be used as a screening tool for the rejection of sepsis or bacteremia on the first day of fever in neutropenic children with cancer.

Pegfilgrastim for primary prophylaxis of febrile neutropenia in breast cancer patients undergoing TAC chemotherapy.

PubMed

Lee, Jihyoun; Lee, Jong Eun; Kim, Zisun; Han, Sun Wook; Hur, Sung Mo; Kim, Sung Yong; Lee, Min Hyuk; Lim, Cheol Wan

2018-05-01

Primary prophylaxis with granulocyte colony-stimulating factor can effectively prevent febrile neutropenia (FN) during breast cancer treatment. The aims of this study were to evaluate the incidence of FN and the ANC profile in patients undergoing chemotherapy and pegfilgrastim primary prophylaxis. Patients receiving 6 cycles of adjuvant docetaxel, doxorubicin, and cyclophosphamide (TAC) chemotherapy were included in this study. Pegfilgrastim was administered with analgesics 24 hours after treatment. Laboratory tests were performed on day 0 (before chemotherapy) and ANC was measured daily starting day 5 until it were restored to 1,000/mm 3 . Bone pain was checked via the numeral rating scale (NRS). A total of 61 patients and 366 cycles were evaluated. Mean age was 49.2 ± 7.1 years. FN was seen in 5 patients (16.4%) and 12 cycles (3.3%) with pegfilgrastim. Grades 3 and 4 neutropenia was seen in 91.5% of cycles with FN. The ANC nadir was most commonly seen at day 7 and the mean ANC nadir depth was 265.7/m 3 . Age was negatively correlated with nadir depth (r = -0.137, P = 0.009). Severe pain higher than NRS 7 occurred in less than 20% of patients after the administration of pegfilgrastim. Incidence of FN was low during the chemotherapy by primary prophylaxis with pegfilgrastim. The ANC nadir was seen on day 7 after chemotherapy. Bone pain with pegfilgrastim was well tolerated during TAC chemotherapy.

Outcomes of febrile children presumed to be immunocompetent who present with leukopenia or neutropenia to an ambulatory setting.

PubMed

Serwint, J R; Dias, M M; Chang, H; Sharkey, M; Walker, A R

2005-09-01

To determine significant medical outcomes in febrile children presenting to an ambulatory setting with neutropenia and/or leukopenia. Retrospective medical record review conducted on febrile patients who had a blood culture drawn, with white blood cell counts less than 5,000/mm3 and/or an absolute neutrophil count less than 1000/mm3. Ninety-one patients were identified; 5 with positive blood culture results, 13 with significant non-oncologic disease, and 3 patients with leukemia who had involvement of 2 or more cell lines. In the majority of patients, clinical judgment, physical findings, and review of all cell lines of the complete blood cell count identified those with significant disease.

Management of infection and febrile neutropenia in patients with solid cancer.

PubMed

Virizuela, J A; Carratalà, J; Aguado, J M; Vicente, D; Salavert, M; Ruiz, M; Ruiz, I; Marco, F; Lizasoain, M; Jiménez-Fonseca, P; Gudiol, C; Cassinello, J; Carmona-Bayonas, A; Aguilar, M; Cruz, J J

2016-06-01

An expert group from the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC, for its acronym in Spanish) and the Spanish Society of Medical Oncology (SEOM, for its acronym in Spanish) have reviewed the main aspects to be considered when evaluating patients with solid cancer and infectious complications contained in this article. Recommendations have, therefore, been put forth regarding the prophylaxis of the most prevalent infections in these patients, the use of vaccines, measures to control infection through vascular catheters, and preventing infection in light of certain surgical maneuvers. The following is a revision of the criteria for febrile neutropenia management and the use of colony-stimulating factors and closes with several guidelines for treating the cancer patient with serious infection. The document concludes with a series of measures to control hospital infection.

A comparison of ED and direct admission care of cancer patients with febrile neutropenia.

PubMed

Owolabi, Diwura K; Rowland, Richard; King, Lauren; Miller, Rick; Hegde, Gajanan G; Shang, Jennifer; Lister, John; Venkat, Arvind

2015-07-01

We compared the quality of care in admitted febrile neutropenic cancer patients presenting through the emergency department (ED) vs those directly admitted (DA) from the clinic or infusion center. We hypothesized that the quality of care would be comparable between these 2 pathways. We conducted a retrospective, observational cohort study of all adult cancer patients hospitalized with subjective or objective fever (≥100.4°F) and documented neutropenia (absolute neutrophil count ≤1000/mm(3)) from January 1, 2011 to June 30, 2013, at 2 hospitals. Two investigators retrieved data including patient age, sex, race, tumor type, blood culture growth, temperature (actual or reported), pathway to admission (ED or DA), time to antibiotic administration, length of stay, and the Multinational Association for Supportive Care in Cancer (MASCC) risk score. The primary outcome measures were time to antibiotic administration, appropriateness of antibiotic(s) administered based on published guidelines, length of stay, and MASCC score-based risk assessment. We used the t test for the difference between 2 means with unequal population variances to compare these outcome measures between ED and DA patients. One hundred twenty-seven visits met inclusion criteria (42 [33%] ED visits, 85 [67%] DA visits). Mean time to antibiotic administration, mean length of stay, appropriateness of antibiotics, and MASCC score-based risk assessment were comparable between ED and DA visits (P>.05 for all comparisons). The quality of care for febrile neutropenia in patients presenting through the ED was comparable to those directly admitted to the hospital in this 2-center study. Copyright © 2015 Elsevier Inc. All rights reserved.

Prediction of serious complications in patients with seemingly stable febrile neutropenia: validation of the Clinical Index of Stable Febrile Neutropenia in a prospective cohort of patients from the FINITE study.

PubMed

Carmona-Bayonas, Alberto; Jiménez-Fonseca, Paula; Virizuela Echaburu, Juan; Antonio, Maite; Font, Carme; Biosca, Mercè; Ramchandani, Avinash; Martínez, Jerónimo; Hernando Cubero, Jorge; Espinosa, Javier; Martínez de Castro, Eva; Ghanem, Ismael; Beato, Carmen; Blasco, Ana; Garrido, Marcelo; Bonilla, Yaiza; Mondéjar, Rebeca; Arcusa Lanza, María Ángeles; Aragón Manrique, Isabel; Manzano, Aránzazu; Sevillano, Elena; Castañón, Eduardo; Cardona, Mercé; Gallardo Martín, Elena; Pérez Armillas, Quionia; Sánchez Lasheras, Fernando; Ayala de la Peña, Francisco

2015-02-10

To validate a prognostic score predicting major complications in patients with solid tumors and seemingly stable episodes of febrile neutropenia (FN). The definition of clinical stability implies the absence of organ dysfunction, abnormalities in vital signs, and major infections. We developed the Clinical Index of Stable Febrile Neutropenia (CISNE), with six explanatory variables associated with serious complications: Eastern Cooperative Oncology Group performance status ≥ 2 (2 points), chronic obstructive pulmonary disease (1 point), chronic cardiovascular disease (1 point), mucositis of grade ≥ 2 (National Cancer Institute Common Toxicity Criteria; 1 point), monocytes < 200 per μL (1 point), and stress-induced hyperglycemia (2 points). We integrated these factors into a score ranging from 0 to 8, which classifies patients into three prognostic classes: low (0 points), intermediate (1 to 2 points), and high risk (≥ 3 points). We present a multicenter validation of CISNE. We prospectively recruited 1,133 patients with seemingly stable FN from 25 hospitals. Complication rates in the training and validation subsets, respectively, were 1.1% and 1.1% in low-, 6.1% and 6.2% in intermediate-, and 32.5% and 36% in high-risk patients; mortality rates within each class were 0% in low-, 1.6% and 0% in intermediate-, and 4.3% and 3.1% in high-risk patients. Areas under the receiver operating characteristic curves in the validation subset were 0.652 (95% CI, 0.598 to 0.703) for Talcott, 0.721 (95% CI, 0.669 to 0.768) for Multinational Association for Supportive Care in Cancer (MASCC), and 0.868 (95% CI, 0.827 to 0.903) for CISNE (P = .002 for comparison between CISNE and MASCC). CISNE is a valid model for accurately classifying patients with cancer with seemingly stable FN episodes. © 2015 by American Society of Clinical Oncology.

Urinary tract infections in pediatric oncology patients with fever and neutropenia.

PubMed

Sandoval, Claudio; Sinaki, Banafsheh; Weiss, Robert; Munoz, Jose; Ozkaynak, M Fevzi; Tugal, Oya; Jayabose, Somasundaram

2012-02-01

The relevancy of the urinary tract as a source of infection during febrile neutropenia is not known. The authors sought to determine the frequency of urinary tract infections (UTIs) in pediatric cancer patients with febrile neutropenia. Urine was collected from a mid-stream void before the administration of antibiotics. Demographic, clinical, and laboratory data were collected. The frequency of UTI and usefulness of urinalysis and localizing signs in predicting UTI in pediatric cancer patients with fever and neutropenia were determined. Forty-five patients had 58 febrile neutropenic episodes eligible for study participation. No patient presented with localizing signs. The urinalysis was negative in 53 episodes and positive in 5 episodes. Four patients had 5 UTIs. The frequency of UTI was 8.6% (5 of 58 febrile neutropenia episodes). Four patients had bacteremia, none of whom had a UTI. The sensitivity, specificity, and negative predictive value of urinalysis was 40%, 94%, and 94%, respectively, and for localizing signs was undefined, 100%, and 91%, respectively. UTI is as common as bacteremia in the current pediatric cancer patients with fever and neutropenia. Urinalysis and urine culture should be obtained routinely as part of the diagnostic evaluation of patients with fever and neutropenia.

Significance of interleukin-6 (IL-6) and C-reactive protein (CRP) in children and young adults with febrile neutropenia during chemotherapy for cancer: a prospective study.

PubMed

Chaudhary, Narendra; Kosaraju, Kranthi; Bhat, Kamalakshi; Bairy, Indira; Borker, Anupama

2012-11-01

We evaluated the usefulness of interleukin-6 (IL-6) and C-reactive protein (CRP) at the onset of febrile neutropenia and 72 hours later, in identifying risk groups and assessing response to antibiotic therapy. All episodes of febrile neutropenia were divided in 3 study groups-microbiologically documented infection (MDI), clinically documented infection (CDI), and fever of unknown origin (FUO). Three outcome groups were defined as those responding to first-line antibiotics (R1), those responding to second-line antibiotics (R2), and those requiring antifungal therapy (RAF). Median values of IL-6 and CRP were compared between the groups. There were 57 episodes of febrile neutropenia among 26 patients younger than 25 years during 1 year of study period. On day 1, median IL-6 level was significantly lower in FUO group compared with CDI+MDI groups combined (P < 0.001). Rise in CRP on day 3 was highly significant to differentiate MDI group from other 2 groups (P < 0.001). The CRP also increased significantly on day 3 in RAF (P < 0.001) and R2 (P = 0.002) groups than in R1 group. Low level of IL-6 may help differentiate patients with FUO from those with documented infections. A rising CRP is indicative of serious infection.

Independent Factors for Prediction of Poor Outcomes in Patients with Febrile Neutropenia

PubMed Central

Günalp, Müge; Koyunoğlu, Merve; Gürler, Serdar; Koca, Ayça; Yeşilkaya, İlker; Öner, Emre; Akkaş, Meltem; Aksu, Nalan Metin; Demirkan, Arda; Polat, Onur; Elhan, Atilla Halil

2014-01-01

Background Febrile neutropenia (FN) is a life-threatening condition that requires urgent management in the emergency department (ED). Recent progress in the treatment of neutropenic fever has underscored the importance of risk stratification. In this study, we aimed to determine independent factors for prediction of poor outcomes in patients with FN. Material/Methods We retrospectively evaluated 200 chemotherapy-induced febrile neutropenic patients who visited the ED. Upon arrival at the ED, clinical data, including sex, age, vital signs, underlying systemic diseases, laboratory test results, estimated GFR, blood cultures, CRP, radiologic examinations, and Multinational Association of Supportive Care in Cancer (MASCC) score of all febrile neutropenic patients were obtained. Outcomes were categorized as “poor” if serious complications during hospitalization, including death, occurred. Results The platelet count <50 000 cells/mm3 (OR 3.90, 95% CI 1.62–9.43), pulmonary infiltration (OR 3.45, 95% CI 1.48–8.07), hypoproteinemia <6 g/dl (OR 3.30, 95% CI 1.27–8.56), respiratory rate >24/min (OR 8.75, 95% CI 2.18–35.13), and MASCC score <21 (OR 9.20, 95% CI 3.98–21.26) were determined as independent risk factors for the prediction of death. The platelet count <50 000 cells/mm3 (OR 3.93, 95% CI 1.42–10.92), serum CRP >50 mg/dl (OR 3.80, 95% CI 1.68–8.61), hypoproteinemia (OR 7.81, 95% CI 3.43–17.78), eGFR ≤90 ML/min/1.73 m2 (OR 3.06, 95% CI 1.13–8.26), and MASCC score <21 (OR 3.45, 95% CI 1.53–7.79) were determined as independent risk factors for the prediction of poor clinical outcomes of FN patients. Platelet count, protein level, respiratory rate, pulmonary infiltration, CRP, MASCC score, and eGFR were shown to have a significant association with outcome. Conclusions The results of our study may help emergency medicine physicians to prevent serious complications with proper use of simple independent risk factors besides MASCC score. PMID

The time has come for new models in febrile neutropenia: a practical demonstration of the inadequacy of the MASCC score.

PubMed

Carmona-Bayonas, A; Jiménez-Fonseca, P; Virizuela Echaburu, J; Sánchez Cánovas, M; Ayala de la Peña, F

2017-09-01

Since its publication more than 15 years ago, the MASCC score has been internationally validated any number of times and recommended by most clinical practice guidelines for the management of febrile neutropenia (FN) around the world. We have used an empirical data-supported simulated scenario to demonstrate that, despite everything, the MASCC score is impractical as a basis for decision-making. A detailed analysis of reasons supporting the clinical irrelevance of this model is performed. First, seven of its eight variables are "innocent bystanders" that contribute little to selecting low-risk candidates for ambulatory management. Secondly, the training series was hardly representative of outpatients with solid tumors and low-risk FN. Finally, the simultaneous inclusion of key variables both in the model and in the outcome explains its successful validation in various series of patients. Alternative methods of prognostic classification, such as the Clinical Index of Stable Febrile Neutropenia, have been specifically validated for patients with solid tumors and should replace the MASCC model in situations of clinical uncertainty.

Discrete choice experiment produced estimates of acceptable risks of therapeutic options in cancer patients with febrile neutropenia.

PubMed

Sung, Lillian; Alibhai, Shabbir M; Ethier, Marie-Chantal; Teuffel, Oliver; Cheng, Sylvia; Fisman, David; Regier, Dean A

2012-06-01

To use a discrete choice experiment (DCE) to describe patient/proxy tolerance for the number of clinic visits, and chances of readmission, intensive care unit admission, and mortality to accept oral outpatient management of low-risk febrile neutropenia. Adults and children aged 12-18 years with cancer and parents of pediatric cancer patients were asked to choose between outpatient oral and inpatient intravenous management of low-risk febrile neutropenia. Using a DCE, we varied the attribute levels with the outpatient option and kept them constant for the inpatient option. Seventy-eight adults, 153 parents, and 43 children provided responses. All four attributes significantly affected choices. The mean tolerance (95% confidence interval) for the number of clinic visits per week was 3.6 (2.2-4.8), 2.1 (1.1-3.2), and 4.3 (2.5-6.0) to accept outpatient management among adults, parents, and children, respectively. With thrice weekly clinic visits and 7.5% chance of readmission, probabilities of accepting the outpatient strategy were 50% (44-54%) for adults, 43% (39-48%) for parents, and 53% (46-59%) for children. Using a DCE, we determined that a 7.5% chance of readmission and clinic visits more frequently than thrice weekly are unlikely to be acceptable. Copyright © 2012 Elsevier Inc. All rights reserved.

A new prognostic model for chemotherapy-induced febrile neutropenia.

PubMed

Ahn, Shin; Lee, Yoon-Seon; Lee, Jae-Lyun; Lim, Kyung Soo; Yoon, Sung-Cheol

2016-02-01

The objective of this study was to develop and validate a new prognostic model for febrile neutropenia (FN). This study comprised 1001 episodes of FN: 718 for the derivation set and 283 for the validation set. Multivariate logistic regression analysis was performed with unfavorable outcome as the primary endpoint and bacteremia as the secondary endpoint. In the derivation set, risk factors for adverse outcomes comprised age ≥ 60 years (2 points), procalcitonin ≥ 0.5 ng/mL (5 points), ECOG performance score ≥ 2 (2 points), oral mucositis grade ≥ 3 (3 points), systolic blood pressure <90 mmHg (3 points), and respiratory rate ≥ 24 breaths/min (3 points). The model stratified patients into three severity classes, with adverse event rates of 6.0 % in class I (score ≤ 2), 27.3 % in class II (score 3-8), and 67.9 % in class III (score ≥ 9). Bacteremia was present in 1.1, 11.5, and 29.8 % of patients in class I, II, and III, respectively. The outcomes of the validation set were similar in each risk class. When the derivation and validation sets were integrated, unfavorable outcomes occurred in 5.9 % of the low-risk group classified by the new prognostic model and in 12.2 % classified by the Multinational Association for Supportive Care in Cancer (MASCC) risk index. With the new prognostic model, we can classify patients with FN into three classes of increasing adverse outcomes and bacteremia. Early discharge would be possible for class I patients, short-term observation could safely manage class II patients, and inpatient admission is warranted for class III patients.

A clinical evaluation of efficacy and safety of cefepime monotherapy versus piperacillin-tazobactam in patients of paediatric age group with febrile neutropenia in a tertiary care centre of north India.

PubMed

Aamir, Mohammad; Abrol, Pankaj; Sharma, Deepak; Punia, Harish

2016-07-01

To evaluate clinically the efficacy and safety in northern India of cefepime monotherapy versus piperacillin-tazobactam in patients of paediatric age group with febrile neutropenia. Children aged ≤18 years admitted febrile with chemotherapy-induced neutropenia were randomised into two groups comprising 20 cases in each group viz. CEF (receiving cefepime only) and PIP-TAZO (receiving piperacillin-tazobactam). Based on clinical and laboratory tests, patients were classified into: microbiologically documented infections (MDI); clinically documented infections (CDI); and unexplained fever (UF). They were assessed for clinical signs and symptoms as well as laboratory parameters at the time of enrolment and subsequently on days 3 and 7. Incidence of MDI, CDI and UF were 22.5%, 47.5% and 30%, respectively. The mean duration of neutropenia (in days) was 5.45 ± 2.1 in the PIP-TAZO group and 5.5 ± 1.5 in the CEF group (P = 0.305). The success rate defined as clearing infection effectively and improvement of neutropenia was comparable (P = 0.705). There was a mortality rate of 20% in the PIP-TAZO group as compared to 10% in the CEF group. We conclude that cefepime monotherapy and piperacillin-tazobactam are equally efficacious and safe in treating patients with febrile neutropenia. Empirical monotherapy with cefepime would prevent an unnecessary extra economic burden as well as avoiding the serious adverse or toxic effects of multi-drug regimes, especially in low- and middle-income countries. © The Author(s) 2015.

The role of ¹⁸F-FDG PET/CT for the diagnosis of infections in patients with hematological malignancies and persistent febrile neutropenia.

PubMed

Gafter-Gvili, Anat; Paul, Mical; Bernstine, Hanna; Vidal, Liat; Ram, Ron; Raanani, Pia; Yeshurun, Moshe; Tadmor, Boaz; Leibovici, Leonard; Shpilberg, Ofer; Groshar, David

2013-09-01

We assessed the performance of PET/CT for diagnosis and management of infections in high-risk hematological cancer patients with persistent febrile neutropenia in a prospective study. (18)F-FDG PET/CT with contrast-enhanced CT was performed on day 5-7 of persistent fever. Between 2008 and 2011, 91 PET/CT examinations were performed for different episodes in 79 patients, resulting in 117 diagnoses. The sensitivity of the PET/CT was 79.8% (71/89) compared to 51.7% (46/89) with chest/sinus CT alone. Specificities were 32.14% (9/28) vs. 42.85% (12/28), respectively. PET/CT resulted in a change from the pre-test diagnosis in 63/91 (69%) of episodes and in modification of patients' management in 46/91 (55%). PET/CT was beneficial in diagnosing abdominal infections. PET/CT has a potential role in the diagnostic evaluation of patients with persistent febrile neutropenia. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Neoadjuvant chemotherapy using epirubicin, cyclophosphamide and fluorouracil: neutropenia and elevation of transaminase, and their management].

PubMed

Wang, Xinguang; Fan, Tie; Fan, Zhaoqing; Wang, Tianfeng; Xie, Yuntao; Li, Jinfeng; Ouyang, Tao

2015-03-01

To retrospectively investigate the incidence of severe neutropenia and elevation of transaminase during neoadjuvant chemotherapy using epirubicin, cyclophosphamide and fluorouracil in breast cancer patients. From January 2011 to December 2012, 303 consecutive breast cancer patients with complete treatment data treated in our department were included in this analysis. All patients received neoadjuvant chemotherapy with equal dose of EPI (100 mg/m(2)) administered every 3 weeks for 4 cycles before surgery. 200 patients (66.0%) experienced at least one episode of grade 3/4 neutropenia/leukopenia, among them 176 patients experienced their first episode after the first cycle. Febrile neutropenia (FN) occurred in 13 patients for 14 episodes. Elevation of transaminase occurred in a total of 46 patients (15.2%), among them, grade 2 or higher elevation occurred in 15 patients (5.0%). Three blood test plans were adopted to monitor the patients during chemotherapy: (1) Routine blood count repeated every week; (2) Routine blood count before and on day 10 of each chemotherapy episode; (3) Routine blood count before and on day 7, 10 and 14 of each chemotherapy episode. The number of patients whose chemotherapy was delayed due to 3/4 neutropenia/leucopenia in each blood test plan was 3 (5.0%), 7 (3.9%) and 2 (3.2%), respectively. The number of patients with febrile neutropenia (FN) in each blood test plan was 2 (3.3%), 8 (4.4%) and 3 (4.8%), respectively. No statistically significant difference in treatment delay or the incidence of FN was observed among different blood test plans. No statistically significant difference in the incidence of grade 3/4 neutropenia/leukopenia or grade 2 or higher transaminase elevation was observed among different 5-Fu regimens. During neoadjuvant chemotherapy using FE100 C, Fci E100 C or E100 C for breast cancer patients without routine prophylactic G-CSF, the incidence of grade 3/4 neutropenia/leukopenia is 66.0%. With the patient management plan

Management of Infection and Febrile Neutropenia in Patients with Solid Cancer.

PubMed

Aguado, José María; Cruz, Juan Jesús; Virizuela, Juan Antonio; Aguilar, Manuela; Carmona, Alberto; Cassinello, Javier; Gudiol, Carlota; Jiménez Fonseca, Paula; Lizasoain, Manuel; Marco, Francesc; Ruiz, Isabel; Ruiz, Maribel; Salavert, Miguel; Vicente, David; Carratalà, Jordi

A group of experts from the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) and the Spanish Society of Medical Oncology (SEOM) have reviewed in this paper the main aspects to be considered in the evaluation of patients with solid cancer and infectious diseases. They have established a series of recommendations on the prevention of the most prevalent infections in these patients, the use of vaccines, the control measures of vascular catheter infection and prevention of infections before certain surgical procedures. Also the criteria for management of febrile neutropenia and the use of colony-stimulating factors were revised. Finally they provide a series of recommendations for the treatment of cancer patients with severe infection. The document is completed with a series of measures for the control of hospital infection. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Comparison of cefepime versus ceftriaxone-amikacin as empirical regimens for the treatment of febrile neutropenia in acute leukemia patients.

PubMed

Borbolla, J R; López-Hernández, M A; González-Avante, M; DeDiego, J; Trueba, E; Alvarado, M L; Jiménez, R M

2001-01-01

High-intensity regimes of chemotherapy have led to longer and more severe episodes of neutropenia with a resulting increase in morbidity and mortality due to infections. Which empiric antibiotic regimen to use in these cases is still under debate. We performed a randomized comparative study to evaluate the efficacy of cefepime versus ceftriaxone plus amikacin as the initial treatment in an escalating, empirical, antibiotic therapy regimen in febrile neutropenic patients. Both adults and children were included. All patients had less than 500 neutrophils/microl at the time of infection. Patients were randomized to receive either cefepime or ceftriaxone plus amikacin. If infection continued 72 h later, patients in both groups received vancomycin, and if infection had not disappeared 7 days after starting antibiotics, amphotericin B was started. Twenty patients were included in each group. Both treatment and control groups were comparable for age and sex, among other factors. There were 18 cures in the cefepime group and 17 in the ceftriaxone plus amikacin group (p = 0.9). No patient discontinued therapy because of toxicity. Cefepime is a safe and very effective therapy for patients with acute leukemia and febrile neutropenia; in addition, it is a cheaper regimen in our country, and lacks the potential toxicity of the aminoglycosides. Copyright 2001 S. Karger AG, Basel

Cost-effectiveness evaluation of voriconazole versus liposomal amphotericin B as empirical therapy for febrile neutropenia in Australia.

PubMed

Al-Badriyeh, Daoud; Liew, Danny; Stewart, Kay; Kong, David C M

2009-01-01

A major randomized clinical trial, evaluating voriconazole versus liposomal amphotericin B (LAMB) as empirical therapy in febrile neutropenia, recommended voriconazole as a suitable alternative to LAMB. The current study sought to investigate the health economic impact of using voriconazole and LAMB for febrile neutropenia in Australia. A decision analytic model was constructed to capture downstream consequences of empirical antifungal therapy with each agent. The main outcomes were: success, breakthrough fungal infection, persistent baseline fungal infection, persistent fever, premature discontinuation and death. Underlying transition probabilities and treatment patterns were derived directly from trial data. Resource use was estimated using an expert panel. Cost inputs were obtained from the latest Australian representative published sources. The perspective adopted was that of the Australian hospital. Uncertainty and sensitivity analyses were undertaken via the Monte Carlo simulation. Compared with voriconazole, LAMB was associated with a net cost saving of AU$1422 (2.9%) per patient. A similar trend was observed with the cost per death prevented and successful treatment. LAMB dominated voriconazole as it resulted in higher efficacy and lower costs when compared with voriconazole. The results were most sensitive to the duration of therapy and the alternative therapy used post discontinuations. In uncertainty analysis, LAMB had 99.8% chance of costing less than voriconazole. In this study, which used the current standard five component endpoint to assess the impact of empirical antifungal therapy, LAMB was associated with cost savings relative to voriconazole.

Comparative levels of macrophage migration inhibitory factor, procalcitonin, osteoprotegerin, interleukin-8, hs-C reactive protein, D-dimer in febrile neutropenia, newly diagnosed cancer patients, and infectious fever.

PubMed

Bilgir, Oktay; Bilgir, Ferda; Kebapcilar, Levent; Bozkaya, Giray; Çalan, Mehmet; Kırbıyık, Halil; Avci, Meltem; Sari, İsmail; Yuksel, Arif; Isikyakar, Tolgay

2012-02-01

The purpose of this study is to determine the levels of procalcitonin (PCT), IL-8 (interleukin-8), MIF (macrophage migration inhibitory factor), osteoprotegerin (OPG), hs-CRP and D-dimer during fever above 38.3°C due to various causes. Blood samples taken from a total of consecutive 65 hospitalized patients during fever were prospectively tested for hsCRP, PCT, IL-8, OPG, MIF and D-dimer. Of these patients, there were 26 patients presenting with chemotherapy-induced neutropenia who had no infectious agents found; 23 patients, who had a malignancy with a febrile episode which was neither a microbiologically documented infection nor a chemotherapy-induced neutropenia, and 16 patients who did not have a malignancy and were considered to have a clinically and microbiologically documented infection. IL-8 and D-dimer levels were higher in patients with febrile neutropenia than in the other two groups. Although MIF and OPG were higher in patients with newly diagnosed cancers, there were no differences among the three groups regarding PCT and hs-CRP values. High serum IL-8 and D-dimer levels can be useful markers to identify hospitalized chemotherapy-induced neutropenia patients. MIF and OPG were found to be higher in patients with newly diagnosed cancer. Copyright © 2011 Elsevier Ltd. All rights reserved.

[Septic shock following platelet transfusion contaminated with Citrobacter koseri in a child with postchemotherapy febrile neutropenia].

PubMed

Tichit, R; Saumet, L; Marchandin, H; Haouy, S; Latry, P; Sirvent, N

2016-01-01

The bacterial transfusion risk is currently the greatest infectious risk of blood transfusion. We report the case of a child with postchemotherapy febrile neutropenia who presented septic shock following platelet transfusion contaminated with Citrobacter koseri. The life-threatening development could have been avoided by strict compliance with good clinical practice. The stability of mortality rates due to adverse effects of bacterial proliferation during platelet transfusions in France since 1994 calls for optimization of all preventive measures throughout the transfusion chain and perfect knowledge of transfusion rules by medical staff and care givers. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Bloodstream infections and inpatient length of stay among pediatric cancer patients with febrile neutropenia in Mexico City.

PubMed

Avilés-Robles, Martha; Ojha, Rohit P; González, Miriam; Ojeda-Diezbarroso, Karla; Dorantes-Acosta, Elisa; Jackson, Bradford E; Johnson, Kyle M; Caniza, Miguela A

2014-11-01

We assessed the association between bloodstream infections (BSIs) and inpatient length of stay among pediatric cancer patients with febrile neutropenia in Mexico City. The estimated length of stay for BSIs was 19 days, which corresponded with a 100% (95% confidence limits, 60%-160%) relative increase in the length of stay compared with patients for whom no pathogen was identified. Feasible options for reducing the length of stay should be considered to alleviate patient and resource burden. Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

[A general description of the clinical guideline for the management of febrile neutropenia].

PubMed

Takamatsu, Yasushi

2013-06-01

The most serious adverse event in cancer patients who receive anti-neoplastic agents is febrile neutropenia(FN). The clinical guideline for the use of antimicrobial agents in managing patients with FN was published by the Infectious Diseases Society of America. However, the dosage and administration of antimicrobial agents are not completely adapted for Japanese insurance coverage. The Japanese Society of Medical Oncology therefore decided to develop a clinical guideline for the management of FN in Japanese patients. In this study, we provide a general description of the guideline. According to the guideline, fever is defined as a single axillary temperature of B37. 5°C(or an oral temperature of B38°C)and neutropenia is defined as a neutrophil count of <500/mL or <1, 000/mL if the count is expected to decrease to <500/mL within the next 48 h. In patients who develop FN, empirical anti-pseudomonal b-lactam agent monotherapy should be administered promptly at the onset of fever. Antibiotic therapy should continue until patients become afebrile and their neutrophil counts recover to B500/mL. If fever persists for 4-7 days under antibiotic therapy in high-risk patients, empirical antifungal therapy should be considered. Granulocyte colony-stimulating factor prophylaxis should be considered for high-risk patients with an anticipated risk of FN of B20%.

Spectrum of systemic bacterial infections during febrile neutropenia in pediatric oncology patients in tertiary care pediatric center.

PubMed

Siddaiahgari, Sirisharani; Manikyam, A; Kumar, K Anand; Rauthan, A; Ayyar, R

2014-01-01

Outcome of pediatric cancers has significantly improved with modern chemotherapy and good supportive care. However, febrile neutropenia remains one of the important limiting factors in these patients especially with the emergence of resistant organisms. Choosing appropriate antimicrobials is possible only if we understand the local microbial spectrum and their sensitivity pattern. To study the likely etiologic agents and their antibiotic sensitivity pattern among systemic infections in children with cancer. This is a prospective study. The study was conducted at a tertiary care center for pediatrics, in which culture samples representing blood stream infections and others like urinary tract infections sent from the Oncology services of the Hospital during the year of 2013 were analyzed. The microbiological profile and antibiotic sensitivity pattern of these isolates were studied. There were 89 isolates that represented blood and urinary tract infections in neutropenic patients with cancer.Out of 89 positive cultures 76 were gram negative isolates. The most common gram negative bacterial isolates were Escherichia coli 33 (37%), followed by Pseudomonas 21 (23.5%). Acinetobacter grew in 2 patients (2.2%). Extended spectrum beta-lactamases (ESBL's), carbepenem resistant and pan-resistant organisms seen in 28 (31.4%), 5 (5.6%) and 2 cases (2.3%) respectively. Over all Gram-positive organisms were 13/89 (12.3%). Staphylococcus was the most common Gram-positive organism and methicillin resistant Staphylococcus aureus seen in 5 each. Gram-negative organism is a common isolate in cancer children with febrile neutropenia, which is resistant to first-line antibiotic cefepime. Meropenem is most sensitive antibiotic and ESBL's are sensitive to piperacillin-tazobactam.

Performance of the clinical index of stable febrile neutropenia (CISNE) in different types of infections and tumors.

PubMed

Carmona-Bayonas, A; Jiménez-Fonseca, P; Virizuela, J; Antonio, M; Font, C; Biosca, M; Ramchandani, A; Martinez-Garcia, J; Hernando, J; Espinosa, J; de Castro, E M; Ghanem, I; Beato, C; Blasco, A; Garrido, M; Mondéjar, R; Arcusa, M Á; Aragón, I; Manzano, A; Sevillano, E; Castañón, E; Ayala, F

2017-03-01

The clinical index of stable febrile neutropenia (CISNE) can contribute to patient safety without increasing the complexity of decision-making. However, febrile neutropenia (FN) is a diverse syndrome. The aim of this analysis is to assess the performance of CISNE according to the type of tumor and infection and to characterize these patients. We prospectively recruited 1383 FN episodes in situations of apparent clinical stability. Bonferroni-adjusted z tests of proportions were used to assess the association between the infections suspected at the time of onset and the type of tumor with the risk of serious complications and mortality. The performance of CISNE was appraised in each category using the Breslow-Day test for homogeneity of odds ratios and Forest Plots. 171 patients had a serious complication (12.3 %, 95 % confidence interval 10.7-14.2 %). The most common initial assumptive diagnoses were: fever without focus (34.5 %), upper respiratory infection (14.9 %), enteritis (12.7 %), stomatitis (11.8 %), and acute bronchitis (10.7 %). Lung and breast were the most common tumors, accounting for approximately 56 % of the series. The distribution of complications, mortality, and bacteremia varies for each of these categories. However, Breslow-Day tests indicate homogeneity of the odds ratio of the dichotomized CISNE score to predict complications in all infection and tumor subtypes. Despite FN's clinical and microbiological heterogeneity, the CISNE score was seen to be consistent and robust in spite of these variations. Hence, it appears to be a safe tool in seemingly stable FN.

Predictive factors for severe and febrile neutropenia during docetaxel chemotherapy for castration-resistant prostate cancer.

PubMed

Shigeta, Keisuke; Kosaka, Takeo; Yazawa, Satoshi; Yasumizu, Yota; Mizuno, Ryuichi; Nagata, Hirohiko; Shinoda, Kazunobu; Morita, Shinya; Miyajima, Akira; Kikuchi, Eiji; Nakagawa, Ken; Hasegawa, Shintaro; Oya, Mototsugu

2015-06-01

The aim of this study is to identify factors that increase the occurrence of severe neutropenia (SN) and febrile neutropenia (FN) during docetaxel treatment for castration-resistant prostate cancer (CRPC). We retrospectively reviewed 258 courses during the first three cycles among 95 patients. Docetaxel at a dose of 75 mg/m(2) was administered every 3 or 4 weeks. Patient background, laboratory data, and bone scan results were collected to assess predictive factors for SN and FN. We defined SN as an absolute neutrophil count (ANC) of <500/mm(3) and defined FN as an ANC of <1000/mm(3) with a body temperature of >38.3 °C. The mean age of the patients was 72.6 ± 6.4 years and the mean prostate-specific antigen was 135.4 ± 290.9 ng/ml. During the first three courses of treatment, SN occurred in 72.6% of patients and FN occurred in 9.5 % of patients. Univariate analysis demonstrated that age ≥ 75 years (p = 0.002), number of comorbidities ≥ 1.2 (p = 0.008 and p = 0.006) and previous external beam radiation therapy (EBRT) (p = 0.001) were predictive factors for the development of SN or FN. In multivariate analysis, significant predictors of SN or FN were age ≥ 75 years (hazard ratio [HR] 5.77; p = 0.004) and previous EBRT (HR 14.5; p = 0.012). According to the subgroup analysis dividing SN and FN separately, multivariate analysis also revealed that age ≥ 75 years and previous EBRT were also significant predictors for developing SN (HR 5.09; p = 0.023, HR 12.7; p = 0.020, respectively) and for developing FN (HR 5.45; p = 0.042, HR 7.72; p = 0.015, respectively). Patients aged ≥ 75 years and with a history of localized radiation therapy are at higher risk for significant neutropenic events and require closer surveillance.

Impact of chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN) on cancer treatment outcomes: An overview about well-established and recently emerging clinical data.

PubMed

Lalami, Yassine; Klastersky, Jean

2017-12-01

Despite the overwhelming evidence for the role of granulocyte colony stimulating factors (G-CSF) in managing febrile neutropenia (FN) risk, chemotherapy-induced neutropenia (CIN) and/or FN still remain the most common reasons for reducing relative dose intensity (RDI) and/or delaying chemotherapy schedule. The need to maintain RDI to ensure optimal clinical outcomes is one of the key rationales for utilizing G-CSF. There is a high incidence of reduced RDI in both curative and palliative settings, and this observation is especially evidenced in retrospective analyses. Reduced RDI leads to significantly decreased survival outcomes and quality of life in various malignancies at various clinical settings and stages. Beyond its role as a surrogate prognostic marker, high-grade CIN may have an unexpected predictive role in clinical practice, as illustrated by several data relating CIN occurrence with favorable survival outcomes; this may be due to the fact that body surface area (BSA) - based calculation of dose may not fully account for the pharmacokinetics (PK) of cytotoxic drugs and the fact that there may be variability in drug metabolism between patients treated with same chemotherapy regimens. Copyright © 2017 Elsevier B.V. All rights reserved.

Clinical practice in secondary prophylaxis and management of febrile neutropenia in Poland: results of the febrile neutropenia awareness project

PubMed Central

Chmielowska, Ewa; Filipczyk-Cisarż, Emilia; Krzemieniecki, Krzysztof; Leśniewski-Kmak, Krzysztof; Litwiniuk, Maria M.; Wieruszewska-Kowalczyk, Karolina; Kosno-Kruszewska, Elżbieta

2014-01-01

Aim of the study This paper presents the second part of the GoPractice project involving oncologists from seven Polish provinces. The aim of this part of the project was to assess the knowledge of oncologists on indications for granulocyte colony-stimulating factor (G-CSF) secondary prophylaxis (SP) of febrile neutropenia (FN) and FN management based on current therapeutic guidelines (Polish Society of Clinical Oncology [PTOK] and European Organisation for Research and Treatment of Cancer [EORTC]). Material and methods The project involved 169 oncologists from 7 regions working in large specialist oncological centers, university hospitals, regional and city hospitals, specialist outpatient clinics and oncological wards in small, local hospitals. The participants completed a questionnaire based on 7 prepared clinical cases of patients with different tumor types and patient characteristics, receiving chemotherapy (CT) with different levels of FN risk. Participants answered questions related to FN risk assessment and G-CSF use as secondary prophylaxis (SP) and for the management of FN. After completing the questionnaire, the participants proceeded to an educational module in which they were provided with an analysis of correct diagnostic and therapeutic procedures according to the PTOK and EORTC guidelines. Results and Conclusions Indications for G-CSF SP were generally well recognized: in nearly 90% of responses, oncologists assessed correctly indications/lack of indications for secondary prophylaxis, in accordance with guideline recommendations and Experts’ opinion. However, the use of daily G-CSFs was often recommended by the study participants for the management of FN. This clinical practice is contradictory to PTOK and EORTC recommendations and may unnecessarily increase treatment costs. Changing this clinical approach may be achieved through regular training to improve guideline adherence. PMID:25784842

Patterns of growth factor usage and febrile neutropenia among older patients with diffuse large B-cell non-Hodgkin lymphoma treated with CHOP or R-CHOP: the Intergroup experience (CALGB 9793; ECOG-SWOG 4494).

PubMed

Morrison, Vicki A; Weller, Edie A; Habermann, Thomas M; Li, Shuli; Fisher, Richard I; Cheson, Bruce D; Peterson, Bruce A

2017-08-01

Patterns of myeloid growth factor (GF) usage and febrile neutropenia (FN) were examined in patients >60 years of age with diffuse large B-cell non-Hodgkin lymphoma (DLBCL) enrolled on CALGB 9793/ECOG-SWOG 4494, receiving initial therapy with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or rituximab + CHOP (R-CHOP). Myeloid GFs were administered to 256/520 (49%) patients. Indications for use were: prevent dose reduction/dose delay (81%, 207/256); treat FN or non-febrile neutropenia (NFN) (19%, 48/256). One or more FN episodes occurred in 41% (212/520) of patients, with FN most often in cycle 1 (38% of episodes). In multivariate analysis, risk factors for FN included age >65 years (odds ratio (OR) = 2.6, 95% CI: [1.4, 4.9]) and anemia (hemoglobin <12 g/dl) (OR =2.2, 95% confidence intervals (CI): [1.4, 3.5]. Myeloid GF use was common in this older DLBCL population receiving CHOP-based therapy, as was FN, especially during cycle one. Risk factors predictive for FN should be used prospectively to identify patients for whom myeloid GFs are best utilized.

Low-dose computed tomography in assessment of pulmonary abnormalities in children with febrile neutropenia suffering from malignant diseases.

PubMed

Zaleska-Dorobisz, Urszula; Olchowy, Cyprian; Łasecki, Mateusz; Sokołowska-Dąbek, Dąbrówka; Pawluś, Aleksander; Frączkiewicz, Jowita; Gorczyńska, Ewa

2017-07-01

Management of febrile neutropenia in pediatric patients is challenging. Chest X-ray and CT scan help to identify infective foci; however, exposure to radiation is a risk factor for development of secondary cancer. For this reason, attention is paid to reducing radiation exposure. The aim of the study was to define the role of LDCT examination in the early detection of pulmonary lesions in children during oncology or autoimmune treatment complicated by neutropenia-related fever. Additionally, we focused on the possibility to optimize image quality in low-dose protocols. The study included 138 pediatric patients (mean age 8.08 years) with fever of 38.2°C or higher with an absolute neutrophil count of 10 mm with or without surrounding GGO or cavitations was sensitive at 77% and specific at 65% for fungal infection insert after neutrophil count: < 500/pL who underwent chest X-ray and LDCT in the maximal interval of 24 h. CT findings were compared with initial and final diagnosis as well as with clinical information. LDCT detected pulmonary abnormalities in 116 patients (84.06%) showing ground-glass opacities (GGO) (n = 79), nodules (n = 60) and air-space consolidations (n = 58). Radiologists correctly diagnosed infective lesions in 94 out of 116 patients (81.03%). The presence of random or pleural-based nodules. Diagnosis of pyogenic infection based on the presence of air-space consolidation, pleural effusion, GGO or centrilobular nodules showed a sensitivity of 78% and specificity of 67%, whereas patchy or diffuse GGO, interstitial thickening and/or air-space consolidation showed a high sensitivity of 81% and specificity of 68% for Pneumocystis jirovecii pneumonia. LDCT is an excellent modality in the diagnostic algorithm in patients with febrile neutropenia. It allows early detection and detailed characterization of pulmonary abnormalities. Using contrast, unenhanced CT examinations can further reduce radiation dose and diminish the number of complications without a

Oncology nurses' use of National Comprehensive Cancer Network clinical practice guidelines for chemotherapy-induced and febrile neutropenia.

PubMed

Nirenberg, Anita; Reame, Nancy K; Cato, Kenrick D; Larson, Elaine L

2010-11-01

To describe oncology nurses' use of National Comprehensive Cancer Network (NCCN) clinical practice guidelines for chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN). Cross-sectional survey design; descriptive, correlational analysis. E-mail invitation to Web-based survey. Random sample of 309 Oncology Nursing Society (ONS) members with e-mail addresses who provide care to adult patients receiving chemotherapy. The investigator-developed Neutropenia Oncology Nurses Survey was used. Descriptive tests compared respondents' personal and professional characteristics to those of general ONS members; nonparametric chi-square and Kruskal-Wallis tests were used to correlate respondents' survey subscale scores with demographic data. Significant associations were entered into multiple logistic regression models. The Neutropenia Oncology Nurses Survey's subscales measured subjective norm, attitude, perceived competence and confidence, perceived barriers, and use of NCCN clinical practice guidelines for CIN and FN. Response rate of nurses who opened the survey was 50%. Most practiced in community versus academic centers. Eighty percent reported using the NCCN clinical practice guidelines for CIN and FN. Respondents were more likely to use clinical practice guidelines when they were expected to by physician and nurse colleagues, they perceived fewer barriers, or they held advanced oncology certification. This study was the first to assess oncology nurses' reported use of NCCN clinical practice guidelines for CIN and FN. It also demonstrated the feasibility of partnering with ONS for Web-based survey research. The findings give insight into work-place barriers to evidence-based practice in various settings. Expanding dissemination and implementation of clinical practice guideline recommendations will support the development of oncology nursing standards for risk assessment, management, and patient and family education in CIN and FN.

Central line-associated bloodstream infections in adult hematology patients with febrile neutropenia: an evaluation of surveillance definitions using differential time to blood culture positivity.

PubMed

Freeman, Joshua T; Elinder-Camburn, Anna; McClymont, Catherine; Anderson, Deverick J; Bilkey, Mary; Williamson, Deborah A; Berkahn, Leanne; Roberts, Sally A

2013-01-01

We used differential time to positivity between central and peripheral blood cultures to evaluate the positive predictive value (PPV) of the National Healthcare Safety Network central line-associated bloodstream infection (CLABSI) surveillance definition among hematology patients with febrile neutropenia. The PPV was 27.7%, which suggests that, when the definition is applied to this population, CLABSI rates will be substantially overestimated.

A Patient Risk Model of Chemotherapy-Induced Febrile Neutropenia: Lessons Learned From the ANC Study Group.

PubMed

Lyman, Gary H; Poniewierski, Marek S

2017-12-01

Neutropenia and its complications, including febrile neutropenia (FN), represent major toxicities associated with cancer chemotherapy, resulting in considerable morbidity, mortality, and costs. The myeloid growth factors such as granulocyte colony-stimulating factor (G-CSF) have been shown to reduce the risk of neutropenia complications while enabling safe and effective chemotherapy dose intensity. Concerns about the high costs of these agents along with limited physician adherence to clinical practice guidelines, resulting in both overuse and underuse, has stimulated interest in models for individual patient risk assessment to guide appropriate use of G-CSF. In a model developed and validated by the ANC Study Group, half of patients were classified as high risk and half as low risk based on patient-, disease-, and treatment-related factors. This model has been further validated in an independent patient population. Physician-assessed risk of FN, as well as the decision to use prophylactic CSF, has been shown to correlate poorly with the FN risk estimated by the model. Additional modeling efforts in both adults and children receiving cancer treatment have been reported. Identification of patients at a high individual risk for FN and its consequences may offer the potential for optimal chemotherapy delivery and patient outcomes. Likewise, identification of patients at low risk for neutropenic events may reduce costs when such supportive care is not warranted. This article reviews and summarizes FN modeling studies and the opportunities for personalizing supportive care in patients receiving chemotherapy. Copyright © 2017 by the National Comprehensive Cancer Network.

How I diagnose and treat neutropenia.

PubMed

Dale, David C

2016-01-01

Neutropenia absolute neutrophil count (ANC) less than 1.5 × 10(9)/l is a common hematological finding, and severe neutropenia, that is, ANC less than 0.5 × 10(9)/l is a well known risk factor for susceptibility to bacterial infections. This review provides a succinct clinical approach to the diagnosis and treatment of neutropenia with specific recommendations on the treatment of severe chronic neutropenia with the myeloid growth factor, granulocyte colony-stimulating factor (G-CSF). Experts agree that patients with acute febrile neutropenia should be treated with antibiotics and that patients at high risk of severe neutropenia (>20% risk) after myelosuppressive chemotherapy should be treated prophylactically with a myeloid growth factor, usually G-CSF. The diversity of causes and consequences of chronic neutropenia make the diagnosis and management of these patients more complicated. The review provides a stepwise approach to neutropenia focusing first on reaching a provisional diagnosis and treatment plan then steps to a final diagnosis. It also provides specific recommendations on the treatment of severe chronic neutropenia with G-CSF.

Procalcitonin-guided protocol is not useful to manage antibiotic therapy in febrile neutropenia: a randomized controlled trial.

PubMed

Lima, Stella Sala Soares; Nobre, Vandack; de Castro Romanelli, Roberta Maia; Clemente, Wanessa Trindade; da Silva Bittencourt, Henrique Neves; Melo, Ana Catarina Mourão; Salomão, Luciana Caetano Botelho; Serufo, José Carlos

2016-06-01

Febrile neutropenia (FN) requires immediate use of antibiotics (ATB), and procalcitonin (PCT) is proven to be useful in guiding antibiotic therapy in different settings. This study investigated the use of PCT as a guide for the duration of ATB in FN. A randomized controlled trial was carried out from January-December 2010. A total of 62 hematological adult patients with FN were randomized, in 1:1 ratio, into two groups: (1) PCT group: length of ATB guided by institutional protocol plus PCT dynamics, and (2) control group: duration of ATB in accordance with institutional protocol. There was no difference between groups regarding the use of ATB for the first episode of fever (HR 1.14, 95 % CI 0.66-1.95, p = 0.641), with equivalent median duration of ATB therapy (PCT group 9.0 days and control group 8.0 days, p = 0.67), and median number of days without ATB (0 days, IQR 0-2 days for both groups, p = 0.96). We observed no difference in clinical cure rate (p = 0.68), infection relapse (p = 1.0), superinfection (p = 0.85), length of hospitalization (p = 0.64), and mortality at 28 days (p = 0.39) and at 90 days (p = 0.72). Considering the cut-off of 0.5 ng/ml, PCT was correlated with bacteremia (sensitivity of 51.9 % and specificity of 76.5 %). In this randomized controlled trial, adding a PCT-guided protocol to the standard recommendations did not reduce the use of antibiotics in febrile neutropenia, although no apparent harm was caused. PCT proved to be a marker of bacteremia in this setting.

Weak circadian rhythm increases neutropenia risk among breast cancer patients undergoing adjuvant chemotherapy.

PubMed

Li, Wentao; Kwok, Carol Chi-Hei; Chan, Dominic Chun-Wan; Wang, Feng; Tse, Lap Ah

2018-04-01

Severe neutropenia is a common dose-limiting side effect of adjuvant breast cancer chemotherapy. We aimed to test the hypothesis that weak circadian rhythm is associated with an increased risk of neutropenia using a cohort study. We consecutively recruited 193 breast cancer patients who received adjuvant chemotherapy (5-fluorouracil, epirubicin, and cyclophosphamide followed by docetaxel; doxorubicin and cyclophosphamide; docetaxel and cyclophosphamide). Participants wore a wrist actigraph continuously for 168 h at the beginning of chemotherapy. Values of percent rhythm and double amplitude below medians represented weak circadian rhythm. Mesor measured the mean activity level and acrophase symboled the peak time of the rhythm. We used Cox proportional hazard regression model to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of grade 4 neutropenia and febrile neutropenia in relation to actigraphy-derived parameters. Low levels of percent rhythm (HR:2.59, 95% CI 1.50-4.72), double amplitude (HR:2.70, 95% CI 1.51-4.85), and mesor (HR: 2.48, 95% CI 1.44-4.29) were positively associated with the risk of grade 4 neutropenia during chemotherapy. Low levels of percent rhythm (HR: 2.41, 95% CI 1.02-5.69) and double amplitude (HR:2.49, 95% CI 1.05-5.90) were also associated with increased risks of febrile neutropenia. The HRs for acrophase were not statistically significant. This study provides the first epidemiological evidence that increased risks of grade 4 neutropenia and febrile neutropenia are associated with weak circadian rhythm among adjuvant breast cancer patients. The results suggest that circadian rhythm might be one potential target for the prevention of chemotherapy-induced neutropenia among cancer patients.

Antimicrobial regimens prescribed by Canadian physicians for chemotherapy-induced febrile neutropenic episodes

PubMed Central

Laverdière, Michel; Bow, Eric J; Rotstein, Coleman; Ioannou, Stratis; Carr, Danielle; Moghaddam, Narguess

1999-01-01

OBJECTIVE: To study the antimicrobial management of cancer patients with chemotherapy-induced neutropenia by Canadian physicians. SETTING: A cohort of 274 cancer patients with severe neutropenia (ie, less than 0.5×109 neutrophils/L) who participated in a prospective double-blind, placebo controlled study on antifungal prophylaxis conducted in 14 Canadian university-affiliated centres. Antifungal prophylaxis (oral fluconazole 400 mg daily) was administered to 153 of 274 (56%) patients. RESULTS: Antibacterial prophylaxis with a quinolone was given to 87 patients (32%) at the onset of chemotherapy whereas trimethoprim/sulphamethoxazole was given to 56 (20%) patients. Fever (ie, 38°C or over) occurred in 216 (79%) patients after a median duration of neutropenia of four days (range one to 31 days). Empirical antibacterial antibiotics were administered in 214 febrile patients. In 164 (77%) patients antibiotics were started during the first 24 h of fever. Monotherapy with a third generation cephalosporin and duotherapy with a antipseudomonal beta-lactam and an aminoglycoside were prescribed in 69 (32%) and 61 (28%) of the febrile patients, respectively. Inclusion of vancomycin in the initial empirical regimen was noted in 32 (15%) patients. Modifications of the initial regimen occurred in 187 (87%) patients after a median of five days (range one to 28 days). Empirical systemic amphotericin B was added after a median duration of nine days (range one to 34 days) of the empirical antibacterial regimen. CONCLUSIONS: Overall, the antimicrobial management of cancer patients with chemotherapy-induced neutropenia by Canadian physicians follows the current guidelines promulgated by the Infectious Diseases Society of America. PMID:22346394

Prognostic evaluation of febrile neutropenia in apparently stable adult cancer patients

PubMed Central

Carmona-Bayonas, A; Gómez, J; González-Billalabeitia, E; Canteras, M; Navarrete, A; Gonzálvez, M L; Vicente, V; Ayala de la Peña, F

2011-01-01

Background: Predictive models to identify low-risk febrile neutropenia (FN) have been developed with heterogeneous samples, which included stable and unstable patients, solid tumours, acute leukaemia and bone marrow transplantation. These models fail to recognise 5–15% of cases with unexpected complications, and literature specifically addressing apparently stable patients (ASPs) is scarce. Methods: We reviewed 861 episodes of FN in outpatients with solid tumours, including 692 (80%) episodes with apparent clinical stability. We aimed to investigate the prognosis of this latter group and explore the possibility of stratifying it according to the presenting features. A case–control study was performed and the MASCC index was evaluated. Results: The rates of complications and bacteraemia in ASPs were 7.3% and 6.2%, respectively. The MASCC index yielded a low sensitivity to detect complications (36%). Prognostic factors were identified: ECOG performance status ⩾2, chronic bronchitis, chronic heart failure, stomatitis NCI grade ⩾2, monocytes <200 mm−3 and stress hyperglycaemia. Conclusion: A very simple assessment is useful to classify the patients with FN according to the risk of complications. A few additional variables may predict the clinical course of the patients. We additionally show that the MASCC index applied to this specific group has a low sensitivity to predict complications. PMID:21811253

Detection of bacteria and fungi in blood of patients with febrile neutropenia by real-time PCR with universal primers and probes.

PubMed

Teranishi, Hideto; Ohzono, Nanae; Inamura, Norikazu; Kato, Atsushi; Wakabayashi, Tokio; Akaike, Hiroto; Terada, Kihei; Ouchi, Kazunobu

2015-03-01

Febrile neutropenia is the main treatment-related cause of mortality in cancer patients. During June 2012 to April 2014, 97 blood culture samples were collected from patients receiving chemotherapy for hematological malignancy and cancer with febrile neutropenia episodes (FNEs). The samples were examined for the presence of bacteria and fungi using real-time PCR amplification and sequencing of 16S and 18S rRNA genes. Bacteria were identified in 20 of 97 samples (20.6%) by the real-time PCR assay and in 10 of 97 (10.3%) samples by blood culture. In 6 blood culture-positive samples, the real-time PCR assay detected the same type of bacteria. No fungi were detected by the real-time PCR assay or blood culture. During antibiotic therapy, all samples were negative by blood culture, but the real-time PCR assay yielded a positive result in 2 cases of 2 (100%). The bacterial DNA copy number was not well correlated with the serum C-reactive protein titer of patients with FNEs. We conclude that a real-time PCR assay could provide better detection of causative microbes' in a shorter time, and with a smaller blood sample than blood culture. Using a real-time PCR assay in combination with blood culture could improve microbiological documentation of FNEs. Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Economic burden of chemotherapy-induced febrile neutropenia in patients with lymphoma: a systematic review.

PubMed

Wang, Xiao Jun; Lopez, Shaun Eric; Chan, Alexandre

2015-05-01

The primary objective of this review was to identify the cost components that were most frequently associated with the economic burden of febrile neutropenia (FN) among patients with lymphoma. The secondary objective was to identify any parameter associated with higher FN cost. Ten cost of illness (COI) studies were identified. General characteristics on study design, country, perspective, and patient population were extracted and systematically reported. It was observed that majority (70%) of the studies employed the perspective of healthcare provider. 20% of the studies considered long-term costs. Estimated costs were adjusted to 2013 US dollars and ranged from US$5819 to US$34,756. The cost components that were most frequently associated with economic burden were ward and medication costs. Inpatient management, male gender, discharged dead, and comorbidity were positively associated with higher FN costs. Future COI studies on FN should focus on the accurate estimation on ward and medication costs. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Antibiotic susceptibility of Gram-negatives isolated from bacteremia in children with cancer. Implications for empirical therapy of febrile neutropenia.

PubMed

Castagnola, Elio; Caviglia, Ilaria; Pescetto, Luisa; Bagnasco, Francesca; Haupt, Riccardo; Bandettini, Roberto

2015-01-01

Monotherapy is recommended as the first choice for initial empirical therapy of febrile neutropenia, but local epidemiological and antibiotic susceptibility data are now considered pivotal to design a correct management strategy. To evaluate the proportion of Gram-negative rods isolated in bloodstream infections in children with cancer resistant to antibiotics recommended for this indication. The in vitro susceptibility to ceftazidime, piperacillin-tazobactam, meropenem and amikacin of Gram-negatives isolated in bacteremic episodes in children with cancer followed at the Istituto "Giannina Gaslini", Genoa, Italy in the period of 2001-2013 was retrospectively analyzed using the definitions recommended by EUCAST in 2014. Data were analyzed for any single drug and to the combination of amikacin with each β-lactam. The combination was considered effective in absence of concomitant resistance to both drugs, and not evaluated by means of in vitro analysis of antibiotic combinations (e.g., checkerboard). A total of 263 strains were evaluated: 27% were resistant to piperacillin-tazobactam, 23% to ceftazidime, 12% to meropenem and 13% to amikacin. Concomitant resistance to β-lactam and amikacin was detected in 6% of strains for piperacillin-tazobactam, 5% for ceftazidime and 5% for meropenem. During the study period there was a nonsignificant increase in the proportions of strains resistant to β-lactams indicated for monotherapy, and also increase in the resistance to combined therapies. in an era of increasing resistance to antibiotics guideline-recommended monotherapy could be not appropriate for initial empirical therapy of febrile neutropenia. Strict local survey on etiology and antibiotic susceptibility is mandatory for a correct management of this complication in cancer patients.

Outpatient management of febrile neutropenia associated with cancer chemotherapy: risk stratification and treatment review.

PubMed

Pherwani, Nisha; Ghayad, Joanna M; Holle, Lisa M; Karpiuk, Emilie L

2015-04-15

Strategies for the management of chemotherapy-induced febrile neutropenia (FN), including assessment tools for determining which patients are at low risk for FN complications and can be treated in the outpatient setting, are discussed. Due to the potential for life-threatening complications, the development of FN in patients receiving cancer chemotherapy traditionally prompted hospitalization and i.v. antimicrobial therapy, but there is convincing published evidence that an identifiable subset of patients can be safely treated as outpatients. Two validated assessment tools recommended for identifying patients at low risk for FN complications are the Talcott classification system and the Multinational Association for Supportive Care in Cancer (MASCC) risk index; the MASCC index is superior in terms of sensitivity and negative predictive value but has lower specificity. In low-risk FN cases, outpatient oral antimicrobial therapy has been shown to be a safe and effective alternative to i.v. therapy for both inpatients and outpatients; current practice guidelines recommend an oral fluoroquinolone (e.g., ciprofloxacin) in combination with oral amoxicillin-clavulanate. The guidelines emphasize that in certain cases of FN (e.g., those involving prolonged or pronounced neutropenia or serious comorbidities), inpatient i.v. therapy is required. Pharmacists can play an important role in the management of chemotherapy-associated FN through involvement in risk assessment to identify candidates for outpatient oral antimicrobial therapy, selection of appropriate pharmacotherapy, drug therapy monitoring, and development of institutional guidelines or pathways. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Efficacy and safety of biosimilar filgrastim in primary and secondary prevention of febrile neutropenia

PubMed Central

Kraj, Leszek; Krawczyk-Lipiec, Joanna; Górniewska, Joanna; Orlik, Grzegorz

2017-01-01

Neutropenia and febrile neutropenia (FN) are among the most common side effects/complications of chemotherapy. The aim of the present study was to evaluate the practice of the use of biosimilar filgrastim in the primary and secondary prevention of FN, and assess its efficacy and safety. A multi-center, non-interventional epidemiological study of 170 cancer patients aged 23–82 years was conducted. Data were collected via a questionnaire completed based on medical documentation and patient examination over five chemotherapy visits. The risk of FN related to the chemotherapy protocol used was in the range of 10–20% in >50% of the patients (53.5%) and a majority (74.7%) had additional FN risk factors. 60% of the patients received filgrastim as primary prevention of FN, and 40% received it as secondary prevention. In 40.6% of cases, six cycles of chemotherapy were used. More than 90% of patients continued chemotherapy according to the initial recommended dose. In majority of patients, no FN was observed following the final cycle of chemotherapy. Median neutrophil count at visit 1 was 2.2×103/µl and did not fall below that level. Majority of patients (>70%) performed self-injections of filgrastim, and 86.3% of patients were continuing therapy with this drug at the last visit. No treatment-related side effects were recorded. The use of biosimilar filgrastim in the primary and secondary prevention of FN allows to maintain initial chemotherapy dosage. Furthermore, the use of biosimilar filgrastim is safe and tolerable, and has a high acceptance by patients. PMID:28804626

Updated systematic review and meta-analysis of the performance of risk prediction rules in children and young people with febrile neutropenia.

PubMed

Phillips, Robert S; Lehrnbecher, Thomas; Alexander, Sarah; Sung, Lillian

2012-01-01

Febrile neutropenia is a common and potentially life-threatening complication of treatment for childhood cancer, which has increasingly been subject to targeted treatment based on clinical risk stratification. Our previous meta-analysis demonstrated 16 rules had been described and 2 of them subject to validation in more than one study. We aimed to advance our knowledge of evidence on the discriminatory ability and predictive accuracy of such risk stratification clinical decision rules (CDR) for children and young people with cancer by updating our systematic review. The review was conducted in accordance with Centre for Reviews and Dissemination methods, searching multiple electronic databases, using two independent reviewers, formal critical appraisal with QUADAS and meta-analysis with random effects models where appropriate. It was registered with PROSPERO: CRD42011001685. We found 9 new publications describing a further 7 new CDR, and validations of 7 rules. Six CDR have now been subject to testing across more than two data sets. Most validations demonstrated the rule to be less efficient than when initially proposed; geographical differences appeared to be one explanation for this. The use of clinical decision rules will require local validation before widespread use. Considerable uncertainty remains over the most effective rule to use in each population, and an ongoing individual-patient-data meta-analysis should develop and test a more reliable CDR to improve stratification and optimise therapy. Despite current challenges, we believe it will be possible to define an internationally effective CDR to harmonise the treatment of children with febrile neutropenia.

Updated Systematic Review and Meta-Analysis of the Performance of Risk Prediction Rules in Children and Young People with Febrile Neutropenia

PubMed Central

Phillips, Robert S.; Lehrnbecher, Thomas; Alexander, Sarah; Sung, Lillian

2012-01-01

Introduction Febrile neutropenia is a common and potentially life-threatening complication of treatment for childhood cancer, which has increasingly been subject to targeted treatment based on clinical risk stratification. Our previous meta-analysis demonstrated 16 rules had been described and 2 of them subject to validation in more than one study. We aimed to advance our knowledge of evidence on the discriminatory ability and predictive accuracy of such risk stratification clinical decision rules (CDR) for children and young people with cancer by updating our systematic review. Methods The review was conducted in accordance with Centre for Reviews and Dissemination methods, searching multiple electronic databases, using two independent reviewers, formal critical appraisal with QUADAS and meta-analysis with random effects models where appropriate. It was registered with PROSPERO: CRD42011001685. Results We found 9 new publications describing a further 7 new CDR, and validations of 7 rules. Six CDR have now been subject to testing across more than two data sets. Most validations demonstrated the rule to be less efficient than when initially proposed; geographical differences appeared to be one explanation for this. Conclusion The use of clinical decision rules will require local validation before widespread use. Considerable uncertainty remains over the most effective rule to use in each population, and an ongoing individual-patient-data meta-analysis should develop and test a more reliable CDR to improve stratification and optimise therapy. Despite current challenges, we believe it will be possible to define an internationally effective CDR to harmonise the treatment of children with febrile neutropenia. PMID:22693615

Treatment patterns and outcomes in the prophylaxis of chemotherapy-induced (febrile) neutropenia with biosimilar filgrastim (the MONITOR-GCSF study).

PubMed

Gascón, Pere; Aapro, Matti; Ludwig, Heinz; Bokemeyer, Carsten; Boccadoro, Mario; Turner, Matthew; Denhaerynck, Kris; MacDonald, Karen; Abraham, Ivo

2016-02-01

The purpose of this study is to examine the real-world treatment patterns and outcomes of chemotherapy-induced (febrile) neutropenia (chemotherapy-induced (CIN)/febrile neutropenia (FN)) prophylaxis with biosimilar filgrastim (Zarzio®). MONITOR-GCSF is an international (12 countries), multi-center (140), prospective (max. six cycles), observational, open-label, pharmaco-epidemiologic study of cancer patients (n = 1447) treated with myelosuppressive chemotherapy across a total of 6,213 cycles and receiving prophylaxis with Zarzio®. Data were analyzed using both the patient and cycle as unit of analysis. Most (72.3 %) received primary prophylaxis; dosed mainly (53.2 %) at 30 MIU but differentiated by weight, chemotoxicity, and tumor type; and mainly (53.2 %) initiated in the 24-72h post-chemotherapy window but differentiated by prophylaxis type, tumor type, and chemotoxicity and for modal/median duration of 5 days. Relative to European Organisation for Research and Treatment of Cancer (EORTC) guidelines, 56.6 % were correctly prophylacted, 17.4 % under-prophylacted, and 26.0 % over-prophylacted. The following incidence rates were recorded: CIN grade 4 13.2 % of patients and 3.9 % of cycles, FN 5.9 % of patients and 1.4 % of cycles, CIN/FN-related hospitalizations 6.1 % of patients and 1.5 % of cycles, CIN/FN-related chemotherapy disturbances 9.5 % of patients and 2.8 % of cycles, and composite outcomes index 22.3 % of patients and 6.7 % of cycles. Rates varied by type of prophylaxis and tumor, chemotoxicity, initiation day, and prophylaxis duration. There were 1834 musculoskeletal events with 24.7 % of patients reporting bone pain of any grade (mostly mild to moderate), and 148 adverse drug reactions, including 4 serious, were recorded in 76 patients. The clinical and safety outcomes are well within the range of historically reported data for originator filgrastim underscoring the clinical effectiveness and safety of biosimilar filgrastim in daily clinical

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

PubMed

Nahon, Sophie; Rastkhah, Mansour; Ben Abdelghani, Meher; Soumoudronga, Ravaka-Fatoma; Gasnereau, Isabelle; Labourey, Jean-Luc

2016-05-01

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. We conducted an observational, prospective, longitudinal, and multicentric study in France. The incidence of neutropenia was evaluated at each cycle of chemotherapy. 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. The results obtained in real-life conditions confirm that Zarzio(®) is efficient and well tolerated in cancer patients.

Comparative cost-efficiency across the European G5 countries of various regimens of filgrastim, biosimilar filgrastim, and pegfilgrastim to reduce the incidence of chemotherapy-induced febrile neutropenia.

PubMed

Aapro, Matti; Cornes, Paul; Abraham, Ivo

2012-06-01

This cost-efficiency analysis of the granulocyte colony-stimulating factors (G-CSF) filgrastim (originator Neupogen® and biosimilar Zarzio®) and pegfilgrastim (Neulasta®) examined against a time horizon of 1-14 days of treatment and across the European Union G5 countries (a) when, cost-wise, using Neulasta® 6 mg versus Neupogen® or Zarzio® 300 µg may be cost-saving in reducing the incidence of chemotherapy-induced febrile neutropenia; and (b) if cost-wise, treatment with Zarzio® 300 µg yields a savings advantage over Neupogen® 300 µg. Cost-efficiency analysis of the direct costs a buyer or payer would incur when purchasing or covering any of these agents for managing one patient during one cycle of chemotherapy under regimens of 1-14 days of standard filgrastim using the population-weighted average unit dose cost of each agent per their public pack cost across the European G5 countries. The cost of Neupogen® treatment ranged from €128.16 (1 day) to €1794.30 (14 days), compared to €95.46 and €1336.46 for Zarzio®, thus yielding potential cost savings from €32.70 to €457.84 for the latter. Neulasta® turns cost-saving at day 12 of Neupogen® treatment. At no point over a 14-day treatment period did Neulasta® yield a savings advantage over Zarzio®. Prophylaxis or treatment of febrile neutropenia with Zarzio® is cost-efficient under all possible treatment scenarios relative to Neupogen® and to Neulasta®. In the absence of convincing evidence that pegfilgrastim is pharmacotherapeutically superior to standard filgrastim, there is no cost-efficiency rationale to treat with Neulasta® over Zarzio®, though there may be a small window of approximately 3 days where Neulasta® is cost-efficient over Neupogen®. Regardless, our analysis shows Zarzio® to be the most cost-efficient approach to reducing the incidence of febrile neutropenia in chemotherapy-treated patients.

Results of a prospective dose intensity and neutropenia prophylaxis evaluation programme (DIEPP) in cancer patients at risk of febrile neutropenia due to myelosuppressive chemotherapy.

PubMed

Mądry, Radosław; Popławska, Lidia; Haslbauer, Ferdinand; Šafanda, Martin; Ghizdavescu, Doru; Benkovicova, Jana; Csőszi, Tibor; Mihaylov, Georgi; Niepel, Daniela; Jaeger, Christine; Frkanova, Iveta; Macovei, Alina; Staudigl, Christine

2016-04-01

To describe the incidence of febrile neutropenia (FN) and use of pegfilgrastim in cancer patients with high overall risk of FN and to investigate the relationship between granulocyte-colony stimulating factor (G-CSF) guideline adherence and chemotherapy delivery in Central and Eastern Europe (CEE) and Austria. Dose Intensity Evaluation Program and Prophylaxis (DIEPP) was a multicentre, prospective, and observational study of adult patients with breast cancer, lymphoma, lung cancer, gastric cancer, and ovarian cancer, who received chemotherapy with pegfilgrastim support and who had an overall risk of FN ≥ 20 %. Physicians assessed patient risk factors and reported their reasons for administering pegfilgrastim. Patients were enrolled from 113 centres in CEE and Austria between August 2010 and July 2013, and data were analysed from 1072 patients. The most common tumour types were breast cancer (50 %) and lymphoma (24 %). FN incidence was 5 % overall. FN occurred in 3 % of patients (28/875) who received pegfilgrastim as primary prophylaxis (PP) and 13 % of patients (19/142) who received it as secondary prophylaxis (SP); 79 % of FN events in SP patients occurred in the first cycle before pegfilgrastim was administered. The three most frequently chosen reasons for using pegfilgrastim were planned chemotherapy with high FN risk, female gender, and advanced disease. Overall, 40 % of patients received > 90 % of their planned chemotherapy dose within 3 days of the planned schedule. FN incidence was relatively low with pegfilgrastim PP in patients with a physician-assessed overall FN risk of ≥ 20 %. The most important reasons for pegfilgrastim use were consistent with the investigators' risk assessment and international guidelines.

Microbiology and mortality of pediatric febrile neutropenia in El Salvador.

PubMed

Gupta, Sumit; Bonilla, Miguel; Gamero, Mario; Fuentes, Soad L; Caniza, Miguela; Sung, Lillian

2011-05-01

Febrile neutropenia (FN) and infection-related mortality are major problems for children with cancer in low-income countries. Identifying predictors for adverse outcome of FN in low-income countries permits targeted interventions. We describe the nature and predictors of microbiologically documented infection (MDI) and mortality of FN in children with cancer in El Salvador. We examined Salvadoran pediatric oncology patients admitted with FN over a 1-year period. Data were collected prospectively. Demographic, treatment, and admission-related variables were examined as predictors of outcomes. Hundred six FN episodes among 85 patients were included. Twenty-three of 106 episodes (22%) were microbiologically documented; 13 of 106 episodes (12%) resulted in death. Gram-positive and gram-negative organisms were isolated in 14 of 23 and 11 of 23 specimens; polymicrobial infections were common (11 of 23 episodes of MDI). Older age decreased the MDI risk [odds ratio (OR) per year=0.87, 95% confidence interval (CI), 0.75-0.99; P=0.04] while increasing number of days since the last chemotherapy increased the risk (OR=1.03 per day, 95% CI, 1.01-1.04; P=0.002). Pneumonia diagnosed either clinically (OR=6.6, 95% CI, 1.8-30.0; P=0.005) or radiographically (OR=5.5, 95% CI, 1.7-18.1; P=0.005) was the only predictor of mortality. In El Salvador, polymicrobial infections were common. Pneumonia at admission identified children with FN at high risk of death; these children may benefit from targeted interventions.

Time-to-Antibiotic Administration as a Quality of Care Measure in Children with Febrile Neutropenia: A Survey of Pediatric Oncology Centers

PubMed Central

McCavit, Timothy L.; Winick, Naomi

2011-01-01

Time-to-antibiotic administration (TTA) has been suggested as a quality-of-care (QOC) measure for pediatric oncology patients with febrile neutropenia (FN). Unknown, however, is to what extent pediatric oncology centers utilize TTA. Therefore, we designed and administered an electronic survey (68% response rate) of programs in the Children's Oncology Group to assess TTA utilization. Nearly half of respondents track TTA. Most reported using a benchmark of less than 60 minutes from arrival. TTA is a commonly used QOC measure for pediatric FN despite an absence of studies establishing its validity and a lack of data supporting its impact on outcomes of FN. PMID:21509930

Primary prophylactic colony-stimulating factors for the prevention of chemotherapy-induced febrile neutropenia in breast cancer patients.

PubMed

Renner, Peter; Milazzo, Stefania; Liu, Jian Ping; Zwahlen, Marcel; Birkmann, Josef; Horneber, Markus

2012-10-17

High-dose or dose-intensive cytotoxic chemotherapy often causes myelosuppression and severe neutropenia among cancer patients. Severe neutropenia accompanied by fever, named febrile neutropenia (FN), is the most serious manifestation of neutropenia usually requiring hospitalization and intravenous antibiotics. FN and neutropenia can lead to chemotherapy treatment delays or dose reductions, which potentially compromises the effectiveness of cancer treatment and prospects for a cure. Granulocyte-macrophage (GM) and granulocyte colony-stimulating factors (G-CSFs) are administered during chemotherapy in order to prevent or reduce the incidence or the duration of FN and neutropenia. To assess the effect of prophylactic colony-stimulating factors (CSFs) in reducing the incidence and duration of FN, and all-cause and infection-related mortality during chemotherapy in patients with breast cancer. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, HEALTHSTAR, International Health Technology Assessment, SOMED, AMED and BIOSIS up to 8 August 2011. We also searched three Chinese databases (VIP, CNKI, CBM), the metaRegister of Controlled Trials, ClinicalTrials.gov, the World Health Organization's International Clinical Trials Registry Platform (WHO ICTRP) and OpenGrey.eu up to August 2011. Randomized controlled trials (RCTs) comparing CSFs (any dose) with placebo or no treatment in patients with breast cancer at any stage, at risk of developing FN while undergoing any type of chemotherapy. We used pooled risk ratios (RR) with 95% confidence intervals (CIs) for binary outcomes. At least two review authors independently extracted data and assessed the risk of bias of the included studies. Trial authors were contacted for further details when information was unclear. We included eight RCTs involving 2156 participants with different stages of breast cancer and chemotherapy regimens. The trials were carried out between 1995 and 2008 and judged

The Role of Multidetector Computed Tomography in the Early Diagnosis of Invasive Pulmonary Aspergillosis in Patients with Febrile Neutropenia Undergoing Hematopoietic Stem Cell Transplantation

PubMed Central

Çiledağ, Nazan; Arda, Kemal; Arıbaş, Bilgin Kadri; Tekgündüz, Ali Irfan Emre; Altuntaş, Fevzi

2012-01-01

Objective: To evaluate vessel involvement and the role of multidetector computed tomography (MDCT) in the earlydiagnosis of invasive pulmonary aspergillosis (IPA) in patients with febrile neutropenia and antibiotic-resistant feverundergoing autologous bone morrow transplantation. Material and Methods: In all, 74 pulmonary MDCT examinations in 37 consecutive hematopoietic stem celltransplantation patients with febrile neutropenia and clinically suspected IPA were retrospectively evaluated. Results: Diagnosis of IPA was based on Fungal Infections Cooperative Group, and National Institute of Allergy andInfectious Diseases Mycoses Study Consensus Group criteria. In all, 0, 14, and 11 patients were diagnosed as proven,probable, and possible IPA, respectively. Among the 25 patients accepted as probable and possible IPA, all had pulmonaryMDCT findings consistent with IPA. The remaining 12 patients were accepted as having fever of unknown origin (FUO)and had patent vessels based on MDCT findings.In the patients with probable and possible IPA, 72 focal pulmonary lesions were observed; in 41 of the 72 (57%) lesionsvascular occlusion was noted and the CT halo sign was observed in 25 of these 41 (61%) lesions. Resolution of feveroccurred following antifungal therapy in 19 (76%) of the 25 patients with probable and possible IPA. In all, 6 (25%)of the patients diagnosed as IPA died during follow-up. Transplant-related mortality 100 d post transplant in patientswith IPA and FUO was 24% and 0%, respectively. Conclusion: In conclusion, MDCT has a potential role in the early diagnosis of IPA via detection of vessel occlusion. PMID:24744620

Pharmacogenetic association between GSTP1 genetic polymorphism and febrile neutropenia in Japanese patients with early breast cancer.

PubMed

Sugishita, Mihoko; Imai, Tsuneo; Kikumori, Toyone; Mitsuma, Ayako; Shimokata, Tomoya; Shibata, Takashi; Morita, Sachi; Inada-Inoue, Megumi; Sawaki, Masataka; Hasegawa, Yoshinori; Ando, Yuichi

2016-03-01

Genetic risk factors for febrile neutropenia (FN), the major adverse event of perioperative chemotherapy for early breast cancer, remain unclear. This study retrospectively explored pharmacogenetic associations of single nucleotide polymorphisms (SNPs) of the uridine glucuronosyltransferase 2B7 (UGT2B7, rs7668258), glutathione-S-transferase pi 1 (GSTP1, rs1695), and microcephalin 1 (MCPH1, rs2916733) genes with chemotherapy-related adverse events in 102 Japanese women who received epirubicin and cyclophosphamide as perioperative chemotherapy for early breast cancer. The allele frequencies for all of the SNPs were in concordance with the Hap-Map data of Japanese individuals. Among the 24 patients who had FN at least once during all courses of chemotherapy, 23 had the A/A genotype, and 1 had the A/G genotype of the GSTP1 polymorphism (rs1695, P = 0.001); 23 of the 70 patients with the A/A genotype had FN, as compared with only 1 of the 32 patients with the A/G and G/G genotypes. The genotype distributions of the UGT2B7 and MCPH1 polymorphisms did not differ between the patients who had FN or grade 3/4 neutropenia and those who did not. Among Japanese women who received epirubicin and cyclophosphamide as perioperative chemotherapy for early breast cancer, those with the A/A genotype of the GSTP1 polymorphism (rs1695) were more likely to have FN.

Antibiotic Rotation for Febrile Neutropenic Patients with Hematological Malignancies: Clinical Significance of Antibiotic Heterogeneity

PubMed Central

Chong, Yong; Shimoda, Shinji; Yakushiji, Hiroko; Ito, Yoshikiyo; Miyamoto, Toshihiro; Kamimura, Tomohiko; Shimono, Nobuyuki; Akashi, Koichi

2013-01-01

Background Our unit adopted the single administration of cefepime as the initial treatment for febrile episodes in neutropenic patients with hematological malignancies. However, recently, cefepime-resistant gram-negative bacteremia, including those with extended-spectrum β-lactamase (ESBL)-producers, was frequently observed in these patients. Therefore, we instituted a rotation of primary antibiotics for febrile neutropenic patients in an attempt to control antibiotic resistance. Methods This prospective trial was performed from August 2008 through March 2011 at our unit. After a pre-intervention period, in which cefepime was used as the initial agent for febrile neutropenia, 4 primary antibiotics, namely, piperacillin-tazobactam, ciprofloxacin, meropenem, and cefepime, were rotated at 1-month intervals over 20 months. Blood and surveillance cultures were conducted for febrile episodes, in order to assess the etiology, the resistance pattern (particularly to cefepime), and the prognosis. Results In this trial, 219 patients were registered. A 65.9% reduction in the use of cefepime occurred after the antibiotic rotation. In the surveillance stool cultures, the detection rate of cefepime-resistant gram-negative isolates, of which ESBL-producers were predominant, declined significantly after the intervention (8.5 vs 0.9 episodes per 1000 patient days before and after intervention respectively, P<0.01). Interestingly, ESBL-related bacteremia was not detected after the initiation of the trial (1.7 vs 0.0 episodes per 1000 patient days before and after intervention respectively, P<0.01). Infection-related mortality was comparable between the 2 periods. Conclusions We implemented a monthly rotation of primary antibiotics for febrile neutropenic patients. An antibiotic heterogeneity strategy, mainly performed as a cycling regimen, would be useful for controlling antimicrobial resistance among patients treated for febrile neutropenia. PMID:23372683

Incidence of neutropenia and use of granulocyte colony-stimulating factors in multiple myeloma: is current clinical practice adequate?

PubMed

Leleu, Xavier; Gay, Francesca; Flament, Anne; Allcott, Kim; Delforge, Michel

2018-03-01

Although immunomodulatory drugs, alkylating agents, corticosteroids, protease inhibitors, and therapeutic monoclonal antibodies improve multiple myeloma outcomes, treatment burden is still an issue. Neutropenia is a known complication of cytotoxic cancer therapy and is often associated with infections; it is an important consideration in myeloma given the fact that patients often have a weakened immune system. The risk of febrile neutropenia increases with severe and persisting neutropenia. Recombinant granulocyte colony-stimulating factors (G-CSFs) are commonly used to reduce the incidence, duration, and severity of febrile neutropenia. Here, we review the risk and management of neutropenia associated with new and commonly used anti-myeloma agents. Few papers report the use of G-CSF in patients with multiple myeloma receiving anti-cancer treatments, and fewer describe whether G-CSF was beneficial. None of the identified studies reported G-CSF primary prophylaxis. Further studies are warranted to evaluate the need for G-CSF prophylaxis in multiple myeloma. Prophylaxis may be particularly useful in patients at high risk of prolonged severe neutropenia.

Evaluation of six risk factors for the development of bacteremia in children with cancer and febrile neutropenia

PubMed Central

Asturias, E.J.; Corral, J.E.; Quezada, J.

2010-01-01

Febrile neutropenia is a well-known entity in children with cancer, being responsible for the high risk for infection that characterizes this population. For this reason, cancer patients are hospitalized so that they can receive prophylactic care. Risk factors have been used to classify patients at a high risk for developing bacteremia. The present study evaluates whether those risk factors (C-reactive protein, hypotension, leukemia as the cancer type, thrombocytopenia, recent chemotherapy, and acute malnutrition) apply to patients at the Unidad Nacional de Oncología Pediátrica. We evaluated 102 episodes in 88 patients, in whom risk factors and blood cultures were tested. We observed no statistical relationship between the six risk factors and bacteremia. There was also no relationship between bacteremia and the simultaneous presence of two, three, or more risk factors. A significant relationship of C-reactive protein and platelet count with other outcome factors was observed. PMID:20404980

Randomized controlled trial comparing oral amoxicillin-clavulanate and ofloxacin with intravenous ceftriaxone and amikacin as outpatient therapy in pediatric low-risk febrile neutropenia.

PubMed

Gupta, Ajay; Swaroop, Chetanya; Agarwala, Sandeep; Pandey, Ravindra Mohan; Bakhshi, Sameer

2009-09-01

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.

Granulocyte colony-stimulating factors for febrile neutropenia prophylaxis following chemotherapy: systematic review and meta-analysis

PubMed Central

2011-01-01

Background Febrile neutropenia (FN) occurs following myelosuppressive chemotherapy and is associated with morbidity, mortality, costs, and chemotherapy reductions and delays. Granulocyte colony-stimulating factors (G-CSFs) stimulate neutrophil production and may reduce FN incidence when given prophylactically following chemotherapy. Methods A systematic review and meta-analysis assessed the effectiveness of G-CSFs (pegfilgrastim, filgrastim or lenograstim) in reducing FN incidence in adults undergoing chemotherapy for solid tumours or lymphoma. G-CSFs were compared with no primary G-CSF prophylaxis and with one another. Nine databases were searched in December 2009. Meta-analysis used a random effects model due to heterogeneity. Results Twenty studies compared primary G-CSF prophylaxis with no primary G-CSF prophylaxis: five studies of pegfilgrastim; ten of filgrastim; and five of lenograstim. All three G-CSFs significantly reduced FN incidence, with relative risks of 0.30 (95% CI: 0.14 to 0.65) for pegfilgrastim, 0.57 (95% CI: 0.48 to 0.69) for filgrastim, and 0.62 (95% CI: 0.44 to 0.88) for lenograstim. Overall, the relative risk of FN for any primary G-CSF prophylaxis versus no primary G-CSF prophylaxis was 0.51 (95% CI: 0.41 to 0.62). In terms of comparisons between different G-CSFs, five studies compared pegfilgrastim with filgrastim. FN incidence was significantly lower for pegfilgrastim than filgrastim, with a relative risk of 0.66 (95% CI: 0.44 to 0.98). Conclusions Primary prophylaxis with G-CSFs significantly reduces FN incidence in adults undergoing chemotherapy for solid tumours or lymphoma. Pegfilgrastim reduces FN incidence to a significantly greater extent than filgrastim. PMID:21943360

Safe fluoroquinolones prophylaxis in blood cancer patients with chemotherapy-induced neutropenia and Glucose-6-Phosphate-Dehydrogenase deficiency.

PubMed

Sanna, M; Caocci, G; Orrù, F; Ledda, A; Vacca, A; Piras, E; Fozza, C; Deias, P; Tidore, G; Dore, F; La Nasa, G

2017-12-01

Bacterial infections are the leading causes of morbidity and mortality in haematologic patients with chemotherapy-induced neutropenia. The only strategy shown to be effective in reducing febrile neutropenia incidence is fluoroquinolone prophylaxis, but the safety of this class of drugs in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD-), the most common human enzyme defect, is still controversial because of the claimed association with acute haemolytic anaemia. We retrospectively analysed 242 patients treated with 628 intensive chemotherapy courses. Of these, 59 patients were with G6PD-. All patients underwent fluoroquinolone prophylaxis and were transfused according to our single-unit transfusion policy. The principal endpoint was the incidence of acute haemolytic anaemia. Secondary endpoints included the incidence of febrile neutropenia, microbiologically and clinically documented infection (MDI and CDI) and the incidence of Gram-positive or Gram-negative infections. No episode of acute haemolytic anaemia was observed in the entire cohort. The incidence of MDI and CDI was similar, but the incidence of invasive fungal disease (IFD; P<.0001, HR 11.4, 95%CI 3.5-37.05) and Candida sepsis (P=.008, HR 37, 95%CI 2.01-680.9) was higher in patients with G6PD-. Interestingly, we observed a reduced incidence of febrile neutropenia in patients with G6PD- (P=.01, HR 0.46, 95%CI 0.25-0.8). Our data suggest that fluoroquinolone prophylaxis in patients with G6PD-, treated with intensive chemotherapy, is feasible and safe. Our findings on the incidence of IFD and febrile neutropenia suggest that G6PD may be important in susceptibility to opportunistic pathogens and host response in neutropenic patients. © 2017 John Wiley & Sons Ltd.

Third generation cephalosporin resistant Enterobacteriaceae and multidrug resistant gram-negative bacteria causing bacteremia in febrile neutropenia adult cancer patients in Lebanon, broad spectrum antibiotics use as a major risk factor, and correlation with poor prognosis.

PubMed

Moghnieh, Rima; Estaitieh, Nour; Mugharbil, Anas; Jisr, Tamima; Abdallah, Dania I; Ziade, Fouad; Sinno, Loubna; Ibrahim, Ahmad

2015-01-01

Bacteremia remains a major cause of life-threatening complications in patients receiving anticancer chemotherapy. The spectrum and susceptibility profiles of causative microorganisms differ with time and place. Data from Lebanon are scarce. We aim at evaluating the epidemiology of bacteremia in cancer patients in a university hospital in Lebanon, emphasizing antibiotic resistance and risk factors of multi-drug resistant organism (MDRO)-associated bacteremia. This is a retrospective study of 75 episodes of bacteremia occurring in febrile neutropenic patients admitted to the hematology-oncology unit at Makassed General Hospital, Lebanon, from October 2009-January 2012. It corresponds to epidemiological data on bacteremia episodes in febrile neutropenic cancer patients including antimicrobial resistance and identification of risk factors associated with third generation cephalosporin resistance (3GCR) and MDRO-associated bacteremia. Out of 75 bacteremias, 42.7% were gram-positive (GP), and 57.3% were gram-negative (GN). GP bacteremias were mostly due to methicillin-resistant coagulase negative staphylococci (28% of total bacteremias and 66% of GP bacteremias). Among the GN bacteremias, Escherichia coli (22.7% of total, 39.5% of GN organisms) and Klebsiella pneumoniae(13.3% of total, 23.3% of GN organisms) were the most important causative agents. GN bacteremia due to 3GC sensitive (3GCS) bacteria represented 28% of total bacteremias, while 29% were due to 3GCR bacteria and 9% were due to carbapenem-resistant organisms. There was a significant correlation between bacteremia with MDRO and subsequent intubation, sepsis and mortality. Among potential risk factors, only broad spectrum antibiotic intake >4 days before bacteremia was found to be statistically significant for acquisition of 3GCR bacteria. Using carbapenems or piperacillin/tazobactam>4 days before bacteremia was significantly associated with the emergence of MDRO (p < 0.05). Our findings have major

Mucosal barrier injury, fever and infection in neutropenic patients with cancer: introducing the paradigm febrile mucositis.

PubMed

van der Velden, Walter J F M; Herbers, Alexandra H E; Netea, Mihai G; Blijlevens, Nicole M A

2014-11-01

Infection remains one of the most prominent complications after cytotoxic treatment for cancer. The connection between neutropenia and both infections and fever has long been designated as 'febrile neutropenia', but treatment with antimicrobial agents and haematopoietic growth factors has failed to significantly reduce its incidence. Moreover, emerging antimicrobial resistance is becoming a concern that necessitates the judicious use of available antimicrobial agents. In addition to neutropenia, patients who receive cytotoxic therapy experience mucosal barrier injury (MBI) or 'mucositis'. MBI creates a port-de-entrée for resident micro-organisms to cause blood stream infections and contributes directly to the occurrence of fever by disrupting the highly regulated host-microbe interactions, which, even in the absence of an infection, can result in strong inflammatory reactions. Indeed, MBI has been shown to be a pivotal factor in the occurrence of inflammatory complications after cytotoxic therapy. Hence, the concept 'febrile neutropenia' alone may no longer suffice and a new concept 'febrile mucositis' should be recognized as the two are at least complementary. This review we summarizes the existing evidence for both paradigms and proposes new therapeutic approaches to tackle the perturbed host-microbe interactions arising from cytotoxic therapy-induced tissue damage in order to reduce fever in neutropenic patients with cancer. © 2014 John Wiley & Sons Ltd.

Burden of Chemotherapy-Induced Febrile Neutropenia Hospitalizations in US Clinical Practice, by Use and Patterns of Prophylaxis with Colony-Stimulating Factor.

PubMed

Weycker, Derek; Li, Xiaoyan; Tzivelekis, Spiros; Atwood, Mark; Garcia, Jacob; Li, Yanli; Reiner, Maureen; Lyman, Gary H

2017-02-01

Evidence suggests that many cancer chemotherapy patients who are candidates for colony-stimulating factor (CSF) prophylaxis do not receive it or receive it inconsistent with guidelines, and that such patients have a higher risk of febrile neutropenia hospitalization (FNH). Little is known about the number and consequences of FNH by use/patterns of CSF prophylaxis in US clinical practice. A retrospective cohort design and private healthcare claims data were employed. Study population comprised adults who received a chemotherapy course with a high-risk regimen, or an intermediate-risk regimen (if ≥1 FN risk factor present), for non-metastatic breast cancer or non-Hodgkin's lymphoma (NHL); each chemotherapy cycle within the course and each FNH episode within the cycles were identified. Consequences included mortality, inpatient days, and costs (US$2013) during FNH. Use (yes/no) and patterns (agent, administration day/duration) of CSF prophylaxis were evaluated within cycles in which FNH episodes occurred. Among all FNH episodes (n=6,355; 109 episodes per 1,000 patients), 41.3% (95% CI: 40.1-42.5) occurred among patients who did not receive CSF prophylaxis in that cycle, and 8.8% (8.1-9.5) occurred among those who received CSF prophylaxis on the same day as chemotherapy. Among FNH episodes occurring in patients who received daily CSF agents (2% of CSF use), 56.1% (44.1-68.0) received prophylaxis <7 days during the cycle. Results for FNH consequences were comparable. In this retrospective evaluation, one-half of FNH episodes, outcomes, and costs among cancer chemotherapy patients who were candidates for CSF prophylaxis occurred in those who either did not receive it or received it inconsistent with guidelines.

Pharmacokinetics, Safety, and Efficacy of Posaconazole in Patients with Persistent Febrile Neutropenia or Refractory Invasive Fungal Infection

PubMed Central

Ullmann, A. J.; Cornely, O. A.; Burchardt, A.; Hachem, R.; Kontoyiannis, D. P.; Töpelt, K.; Courtney, R.; Wexler, D.; Krishna, G.; Martinho, M.; Corcoran, G.; Raad, I.

2006-01-01

The pharmacokinetic profiles, safety, and efficacies of different dosing schedules of posaconazole oral suspension in patients with possible, probable, and proven refractory invasive fungal infection (rIFI) or febrile neutropenia (FN) were evaluated in a multicenter, open-label, parallel-group study. Sixty-six patients with FN and 32 patients with rIFI were randomly assigned to one of three posaconazole regimens: 200 mg four times a day (q.i.d.) for nine doses, followed by 400 mg twice a day (b.i.d.); 400 mg q.i.d. for nine doses, followed by 600 mg b.i.d.; or 800 mg b.i.d. for five doses, followed by 800 mg once a day (q.d.). Therapy was continued for up to 6 months in patients with rIFI or until neutrophil recovery occurred in patients with FN. The 400-mg-b.i.d. dose provided the highest overall mean exposure, with 135% (P = 0.0004) and 182% (P < 0.0001) greater exposure than the 600-mg-b.i.d. and 800-mg-q.d. doses, respectively. However, exposure in allogeneic bone marrow transplant (BMT) recipients (n = 12) was 52% lower than in non-BMT patients. Treatment-related adverse events (occurring in 24% of patients) were mostly gastrointestinal in nature. Twenty-four percent of patients had adverse events leading to premature discontinuation (none were treatment related). In efficacy-evaluable patients, successful clinical response was observed in 43% with rIFI (56% of patients receiving 400 mg b.i.d., 17% receiving 600 mg b.i.d., and 50% receiving 800 mg q.d.) and 77% with FN (74% receiving 400 mg b.i.d., 78% receiving 600 mg b.i.d., and 81% receiving 800 mg q.d.). Posaconazole is well tolerated and absorbed. Divided doses of 800 mg (400 mg b.i.d.) provide the greatest posaconazole exposure. PMID:16436724

Multisite external validation of a risk prediction model for the diagnosis of blood stream infections in febrile pediatric oncology patients without severe neutropenia.

PubMed

Esbenshade, Adam J; Zhao, Zhiguo; Aftandilian, Catherine; Saab, Raya; Wattier, Rachel L; Beauchemin, Melissa; Miller, Tamara P; Wilkes, Jennifer J; Kelly, Michael J; Fernbach, Alison; Jeng, Michael; Schwartz, Cindy L; Dvorak, Christopher C; Shyr, Yu; Moons, Karl G M; Sulis, Maria-Luisa; Friedman, Debra L

2017-10-01

Pediatric oncology patients are at an increased risk of invasive bacterial infection due to immunosuppression. The risk of such infection in the absence of severe neutropenia (absolute neutrophil count ≥ 500/μL) is not well established and a validated prediction model for blood stream infection (BSI) risk offers clinical usefulness. A 6-site retrospective external validation was conducted using a previously published risk prediction model for BSI in febrile pediatric oncology patients without severe neutropenia: the Esbenshade/Vanderbilt (EsVan) model. A reduced model (EsVan2) excluding 2 less clinically reliable variables also was created using the initial EsVan model derivative cohort, and was validated using all 5 external validation cohorts. One data set was used only in sensitivity analyses due to missing some variables. From the 5 primary data sets, there were a total of 1197 febrile episodes and 76 episodes of bacteremia. The overall C statistic for predicting bacteremia was 0.695, with a calibration slope of 0.50 for the original model and a calibration slope of 1.0 when recalibration was applied to the model. The model performed better in predicting high-risk bacteremia (gram-negative or Staphylococcus aureus infection) versus BSI alone, with a C statistic of 0.801 and a calibration slope of 0.65. The EsVan2 model outperformed the EsVan model across data sets with a C statistic of 0.733 for predicting BSI and a C statistic of 0.841 for high-risk BSI. The results of this external validation demonstrated that the EsVan and EsVan2 models are able to predict BSI across multiple performance sites and, once validated and implemented prospectively, could assist in decision making in clinical practice. Cancer 2017;123:3781-3790. © 2017 American Cancer Society. © 2017 American Cancer Society.

Clinical significance of repeat blood cultures during febrile neutropenia in adult acute myeloid leukaemia patients undergoing intensive chemotherapy.

PubMed

Kimura, Shun-Ichi; Gomyo, Ayumi; Hayakawa, Jin; Tamaki, Masaharu; Akahoshi, Yu; Harada, Naonori; Ugai, Tomotaka; Kusuda, Machiko; Kameda, Kazuaki; Wada, Hidenori; Ishihara, Yuko; Kawamura, Koji; Sakamoto, Kana; Sato, Miki; Terasako-Saito, Kiriko; Kikuchi, Misato; Nakasone, Hideki; Kako, Shinichi; Tanihara, Aki; Kanda, Yoshinobu

2017-10-01

We evaluated the clinical significance of repeat blood cultures in persistent and recurrent fever during neutropenia in adult acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) patients undergoing intensive chemotherapy. We retrospectively reviewed the chemotherapy cycles at our centre between January 2007 and December 2015. Blood cultures obtained within three days after initial febrile neutropenia (FN) were defined as initial blood cultures and those obtained on or after day 4 were defined as repeat blood cultures. Overall, 321 chemotherapy cycles in 89 patients were subjected to review. FN was identified in 276 (86.0%) chemotherapy cycles. In persistent FN (134 episodes), the causative pathogens were detected by repeat blood cultures in seven episodes (5.2%), including only three episodes (2.2%) of new infection. Shaking chills and high body temperature were identified as significant predictors for bloodstream infection (BSI). In recurrent FN (85 episodes), the causative pathogens were detected in seven episodes (8.2%), and all of these were new organisms. The frequency of detecting new pathogens by repeat blood cultures in recurrent FN (7/85) was higher than that in persistent FN (3/134) (p = .0491). A history of recent BSI was identified as a significant predictor for BSI in recurrent FN. The diagnostic yield of repeat blood cultures for persistent FN was low in intensive chemotherapy for AML and MDS. The frequency of repeat blood cultures for persistent FN could be reduced based on predictors. On the other hand, blood cultures were considered to be essential in cases with recurrent FN.

Identification of educational and infrastructural barriers to prompt antibiotic delivery in febrile neutropenia: a quality improvement initiative.

PubMed

Burry, Erica; Punnett, Angela; Mehta, Ashley; Thull-Freedman, Jennifer; Robinson, Lisa; Gupta, Sumit

2012-09-01

Antibiotic administration within 60 minutes of presentation for medical care may be used as a treatment target for febrile neutropenia (FN); however, anecdotal evidence suggests this target is often missed. Few studies have examined the prevalence or causes of delay. We describe the median time to antibiotic administration at our institution, predictors of delay, and barriers to prompt administration to inform quality improvement strategies. A random sample of 50 episodes of FN presenting to the emergency department (ED) between 2008 and 2009 were reviewed. Times between triage, MD assessment, lab results, and antibiotic administration were recorded. Patient and ED variables were examined as possible predictors of delay. In parallel, lean methodology was used to identify system inefficiencies. A trained moderator conducted group interviews with interdisciplinary representatives involved in the emergency care of neutropenic patients to identify process barriers to prompt antibiotics. The median time from triage to antibiotics was 216 minutes (interquartile range [IQR] = 151-274 minutes). The greatest delay occurred following the reporting of lab results (152 minutes, IQR = 84-210 minutes). Only fall season predicted a longer time to antibiotics (P = 0.03). The lean process identified unnecessary areas of delay between departments. Time to antibiotic administration exceeded 1 hour. The chart review and lean process suggested targets for educational and infrastructural interventions, including an ED pre-printed order sheet, targeted combined subspecialty education between emergency and hematology/oncology staff, and family education. A mixed methodology approach represents a model for improving process efficiency and meeting "best-practice" targets in medicine. Copyright © 2011 Wiley Periodicals, Inc.

Microbial translocation contribute to febrile episodes in adults with chemotherapy-induced neutropenia.

PubMed

Wong, Michelle; Barqasho, Babilonia; Ohrmalm, Lars; Tolfvenstam, Thomas; Nowak, Piotr

2013-01-01

In this study we sought to determine the contribution of microbial translocation to febrile episodes with no attributable microbiological cause (Fever of Unknown Origin, FUO) in an adult febrile neutropaenic cohort. Endotoxin concentrations were measured with the chromogenic Limulus Amoebocyte Assay and used as a direct measure of bacterial products whilst soluble CD14 (sCD14), measured with ELISA was selected as an indicator of the early host response to endotoxins. Endotoxin concentrations in this cohort were generally elevated but did not differ with the presentation of fever. Further stratification of the febrile episodes based on the microbiological findings revealed significantly (p = 0.0077) elevated endotoxin concentrations in FUO episodes compared with episodes with documented bacterial and viral findings. sCD14 concentrations were however, elevated in febrile episodes (p = 0.0066) and no association was observed between sCD14 concentration and microbiological findings. However, FUO episodes and episodes with Gram-negative bacteraemia were associated with higher median sCD14 concentrations than episodes with Gram-positive bacteraemia (p = 0.030). In conclusion, our findings suggest that in the absence of microbiological findings, microbial translocation could contribute to febrile episodes in an adult neutropaenic cohort. We further observed an association between prophylactic antibiotic use and increased plasma endotoxin concentrations (p = 0.0212).

Cost-effectiveness of outpatient management for febrile neutropenia in children with cancer.

PubMed

Teuffel, Oliver; Amir, Eitan; Alibhai, Shabbir M H; Beyene, Joseph; Sung, Lillian

2011-02-01

Inpatient management remains the standard of care for treatment of febrile neutropenia (FN) in children with cancer. Clinical data suggest, however, that outpatient management might be a safe and efficacious alternative for patients with low-risk FN episodes. A cost-utility model was created to compare 4 treatment strategies for low-risk FN. The base case considered pediatric cancer patients with low-risk FN. The model used a health care payer's perspective and a time horizon of 1 FN episode. Four treatment strategies were evaluated: (1) entire treatment in hospital with intravenous antibiotics (HospIV); (2) early discharge consisting of 48 hours of inpatient observation with intravenous antibiotics followed by oral outpatient treatment (EarlyDC); (3) entirely outpatient management with intravenous antibiotics (HomeIV); and (4) entirely outpatient management with oral antibiotics (HomePO). Outcome measures were quality-adjusted FN episodes (QAFNEs), costs (Canadian dollars), and incremental cost-effectiveness ratios. Parameter uncertainty was assessed with probabilistic sensitivity analyses. The most cost-effective strategy was HomeIV. It was cost-saving ($2732 vs $2757) and more effective (0.66 vs 0.55 QAFNE) as compared with HomePO. EarlyDC was slightly more effective (0.68 QAFNE) but significantly more expensive ($5579) than HomeIV, which resulted in an unacceptably high incremental cost-effectiveness ratio of more than $130 000 per QAFNE. HospIV was the least cost-effective strategy because it was more expensive ($14 493) and less effective (0.65 QAFNE) than EarlyDC. The findings of this decision-analytic model indicate that the substantially higher costs of inpatient management cannot be justified on the basis of safety and efficacy considerations or patient/parent preferences.

[Relation of MBL ExonI 54 and NFκB1-94ins/del ATTG Polymorphism with Fever during Neutropenia in Patients with Acute Leukaemia after Chemotherapy].

PubMed

Xu, Wen-Ning; Jiang, Zu-Jun; Li, Yong-Hua; Xiao, Hao-Wen; Gao, Yang; Pang, Yan; Ouyang, Lin; Liu, Zeng-Hui; Zhang, Le-Qing; Wang, Yang; Xiao, Yang

2015-10-01

To explore the correlation between MBL ExonI 54 and NFκB1-94ins/del ATTG polymorphism and fever during neutropenia in patients with acute leukaemia (AL) (except M3) after first chemotherapy in Chinese Han population. Blood samples obtained from 76 fever patients with AL during neutropenia episodes were detected to analyse single nucleotide polymorphism (SNP) in the MBL ExonI 54 and NFκB1-94ins/del ATTG gene, and analyse the correlation between above-mentioned 2 polymorphisms and fever during neutropenia of AL patients after chemotherapy. In 76 patients, no correlation were found between MBL ExonI 54 and NFκB1-94ins/del ATTG polymorphism and fever during neutropenia in patients with acute leukaemia after chemotherapy (P > 0.05). No significant relation were found in sex, age, underlying disease, disease status or degrees of neutropenia in febrile neutropenia between MBL ExonI 54 and NFκB1-94ins/del ATTG polymorphism (P > 0.05). However, patients with MBL ExonI 54 mutation presented longer febrile duration with a median of 5 days compared to 3 days of patients with wildtype MBL ExonI 54 genotype (P < 0.05). There is no clear correlation between MBL ExonI 54 and NFκB1-94ins/del ATTG polymorphism and fever during neutropenia in patients with acute leukaemia after chemotherapy. However, the patients with MBL ExonI 54 mutation have been observed to present a longer febrile duration.

Febrile seizures

MedlinePlus

... proper care. Occasionally, a provider will prescribe a medicine called diazepam to prevent or treat febrile seizures that occur more than once. However, no drug is completely effective in preventing febrile seizures. Alternative Names Seizure - fever induced; Febrile convulsions Patient Instructions ...

New developments in the treatment of chemotherapy-induced neutropenia: focus on balugrastim.

PubMed

Ghidini, Michele; Hahne, Jens Claus; Trevisani, Francesco; Panni, Stefano; Ratti, Margherita; Toppo, Laura; Tomasello, Gianluca

2016-01-01

Neutropenia and febrile neutropenia are two major complications of chemotherapy. Dose reductions, delays in treatment administration, and the use of granulocyte colony-stimulating factors are equally recommended options to preserve absolute neutrophil count in case of chemotherapy regimens bringing a risk of febrile neutropenia of 20% or higher. Recombinant granulocyte colony-stimulating factors, such as filgrastim and lenograstim, have a short elimination half-life (t1/2) and need to be used daily, while others, like pegfilgrastim and lipegfilgrastim, are characterized by a long t1/2 requiring only a single administration per cycle. Balugrastim is a novel long-acting recombinant granulocyte colony-stimulating factor obtained by means of a genetic fusion between recombinant human serum albumin and granulocyte colony-stimulating factor. Albumin binding increases the molecular weight and determines a high plasmatic stability leading to a t1/2 of ~19 days. Balugrastim's efficacy, safety, and tolerability have been assessed in four different clinical trials involving breast cancer patients treated with doxorubicin and docetaxel. Pegfilgrastim was chosen as a comparator. Balugrastim was noninferior to pegfilgrastim with regard to the reduction of mean duration of severe neutropenia during cycle 1. Moreover, both treatments were comparable in terms of efficacy and safety profile. Balugrastim was well tolerated, with the only related adverse event being mild to moderate bone pain. The aim of this review is to summarize the currently available literature data on balugrastim.

Clinical Significance of Non-neutropenic Fever in the Management of Diffuse Large B-Cell Lymphoma Patients Treated with Rituximab-CHOP: Comparison with Febrile Neutropenia and Risk Factor Analysis.

PubMed

Park, Silvia; Kang, Cheol-In; Chung, Doo Ryeon; Peck, Kyong Ran; Kim, Won Seog; Kim, Seok Jin

2015-07-01

Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the standard chemotherapy in diffuse large B-cell lymphoma (DLBCL) patients. Although febrile neutropenia (FN) is the major toxicity of this regimen, non-neutropenic fever (NNF) becomes an emerging issue. We analyzed clinical features and outcomes of febrile complications from 397 patients with newly diagnosed DLBCL who were registered in the prospective cohort study. They had completed R-CHOP between September 2008 and January 2013. Thirty-nine patients (9.8%) had NNF whereas 160 patients (40.3%) had FN. Among them, 24 patients (6.0%) had both during their treatment. Compared to frequent occurrence of initial FN after the first cycle (> 50% of total events), more than 80% of NNF cases occurred after the third cycle. Interstitial pneumonitis comprised the highest proportion of NNF cases (54.8%), although the causative organism was not identified in the majority of cases. Thus, pathogen was identified in a limited number of patients (n=9), and Pneumocystis jiroveci pneumonia (PJP) was the most common. Considering that interstitial pneumonitis without documented pathogen could be clinically diagnosed with PJP, the overall rate of PJP including probable cases was 4.5% (18 cases from 397 patients). The NNF-related mortality rate was 10.3% (four deaths from 39 patients with NNF) while the FN-related mortality rate was only 1.3%. NNF was observed with incidence of 10% during R-CHOP treatment, and showed different clinical manifestations with respect to the time of initial episode and causes.

Risk-adapted approach for fever and neutropenia in paediatric cancer patients--a national multicentre study.

PubMed

Miedema, Karin G E; Tissing, Wim J E; Abbink, Floor C H; Ball, Lynne M; Michiels, Erna M C; van Vliet, Michel J; de Vries, Wilma Y; Kamps, Willem A; Norbruis, Obbe F; Fiocco, Marta; de Groot-Kruseman, Hester A; van de Wetering, Marianne D; de Bont, Eveline S J M

2016-01-01

In this national multicentre study, we examined the safety of reducing antibiotics in selected paediatric cancer patients with febrile neutropenia. Patients with signs of a bacterial infection and/or abnormal vital signs indicating sepsis were considered high risk and received antibiotic therapy. Remaining patients were allocated to low- or medium risk, depending on their interleukin-8 level. Low-risk patients did not receive any antibiotics and were discharged from the hospital after having been afebrile for 12 h. Medium-risk patients were re-evaluated after 72 h of antibiotic treatment and, in selected patients, antibiotics were stopped. Two hundred thirty-three febrile neutropenic episodes in 141 paediatric cancer patients were included in the study. Sixty-four episodes were classified high risk (28%), 122 medium risk (52%), and 47 (20%) low risk. In the medium-risk group, antibiotics were stopped after 72 h in 50 in 122 episodes (41%). Median duration of antibiotic treatment and hospital admission was significantly lower in low- and medium-risk episodes with early discharge. No failures were observed in the medium-risk group with early discharge. In the low-risk group, six failures were observed (12.8%), due to coagulase-negative staphylococci-positive blood cultures and recurrent fever. We showed that it is safe to shorten antibiotic treatment to 72 h in selected medium-risk patients with febrile neutropenia, regardless of the neutrophil count. The safety of withholding antibiotics in selected low-risk paediatric cancer patients with febrile neutropenia requires further investigation, using more suitable definitions for safety. Reduction in hospital admissions allows children with cancer more time at home and consequently improves their quality of life. Copyright © 2015 Elsevier Ltd. All rights reserved.

A multicenter phase 2 study of empirical low-dose liposomal amphotericin B in patients with refractory febrile neutropenia.

PubMed

Miyao, Kotaro; Sawa, Masashi; Kurata, Mio; Suzuki, Ritsuro; Sakemura, Reona; Sakai, Toshiyasu; Kato, Tomonori; Sahashi, Satomi; Tsushita, Natsuko; Ozawa, Yukiyasu; Tsuzuki, Motohiro; Kohno, Akio; Adachi, Tatsuya; Watanabe, Keisuke; Ohbayashi, Kaneyuki; Inagaki, Yuichiro; Atsuta, Yoshiko; Emi, Nobuhiko

2017-01-01

Invasive fungal infection (IFI) is a major life-threatening problem encountered by patients with hematological malignancies receiving intensive chemotherapy. Empirical antifungal agents are therefore important. Despite the availability of antifungal agents for such situations, the optimal agents and administration methods remain unclear. We conducted a prospective phase 2 study of empirical 1 mg/kg/day liposomal amphotericin B (L-AMB) in 80 patients receiving intensive chemotherapy for hematological malignancies. All enrolled patients were high-risk and had recurrent prolonged febrile neutropenia despite having received broad-spectrum antibacterial therapy for at least 72 hours. Fifty-three patients (66.3 %) achieved the primary endpoint of successful treatment, thus exceeding the predefined threshold success rate. No patients developed IFI. The treatment completion rate was 73.8 %, and only two cases ceased treatment because of adverse events. The most frequent events were reversible electrolyte abnormalities. We consider low-dose L-AMB to provide comparable efficacy and improved safety and cost-effectiveness when compared with other empirical antifungal therapies. Additional large-scale randomized studies are needed to determine the clinical usefulness of L-AMB relative to other empirical antifungal therapies.

High pentraxin 3 level predicts septic shock and bacteremia at the onset of febrile neutropenia after intensive chemotherapy of hematologic patients

PubMed Central

Vänskä, Matti; Koivula, Irma; Hämäläinen, Sari; Pulkki, Kari; Nousiainen, Tapio; Jantunen, Esa; Juutilainen, Auni

2011-01-01

We evaluated pentraxin 3 as a marker for complications of neutropenic fever in 100 hematologic patients receiving intensive chemotherapy. Pentraxin 3 and C-reactive protein were measured at fever onset and then daily to day 3. Bacteremia was observed in 19 patients and septic shock in 5 patients (three deaths). In comparison to C-reactive protein, pentraxin 3 achieved its maximum more rapidly. Pentraxin 3 correlated not only with the same day C-reactive protein but also with the next day C-reactive protein. High pentraxin 3 on day 0 was associated with the development of septic shock (P=0.009) and bacteremia (P=0.046). The non-survivors had constantly high pentraxin 3 levels. To conclude, pentraxin 3 is an early predictor of complications in hematologic patients with neutropenic fever. High level of pentraxin 3 predicts septic shock and bacteremia already at the onset of febrile neutropenia. (ClinicalTrials.gov Identifier: NCT00781040.) PMID:21880642

Clinical efficacy of cycling empirical antibiotic therapy for febrile neutropenia in pediatric cancer patients.

PubMed

Teranishi, Hideto; Koga, Yuhki; Nishio, Hisanori; Kato, Wakako; Ono, Hiroaki; Kanno, Shunsuke; Nakashima, Kentaro; Takada, Hidetoshi

2017-07-01

Febrile neutropenia (FN) is the main treatment-related cause of mortality among children with cancer, as the prolonged use of broad-spectrum antibiotics can lead to antibiotic resistance in these patients. Antibiotic cycling has been reported to limit the emergence of antibiotic-resistant bacteria among adult patients. However, no studies have evaluated pediatric patients with FN. Between September 2011 and February 2014, 126 pediatric cancer patients were admitted to our center for chemotherapy and/or hematopoietic stem cell transplantation and were included in this study. Retrospective and prospective data collection were performed before and after antibiotic cycling, respectively. Between September 2011 and November 2012 (before antibiotic cycling was implemented), intravenous cefpirome was used as the empirical therapy for FN. Between December 2012 and February 2014 (after antibiotic cycling was implemented), the monthly antibiotic cycling involved intravenous piperacillin-tazobactam (PIPC/TAZ), intravenous meropenem or ciprofloxacin (CPFX), and intravenous cefepime in that order. For children aged ≥13 years, the monthly cycling involved intravenous PIPC/TAZ, and CPFX was administered. The detection rates for extended-spectrum β-lactamase producers in blood and stool culture samples decreased significantly after the implementation of antibiotic cycling (0.33/1000 patient-days vs 0/1000 patient-days, p = 0.03; 1.00/1000 patient-days vs 0/1000 patient-days, p < 0.01; respectively). Antibiotic cycling was associated with a decreased emergence of multidrug-resistant microbes. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Levofloxacin to prevent bacterial infection in patients with cancer and neutropenia.

PubMed

Bucaneve, Giampaolo; Micozzi, Alessandra; Menichetti, Francesco; Martino, Pietro; Dionisi, M Stella; Martinelli, Giovanni; Allione, Bernardino; D'Antonio, Domenico; Buelli, Maurizio; Nosari, A Maria; Cilloni, Daniela; Zuffa, Eliana; Cantaffa, Renato; Specchia, Giorgina; Amadori, Sergio; Fabbiano, Francesco; Deliliers, Giorgio Lambertenghi; Lauria, Francesco; Foà, Robin; Del Favero, Albano

2005-09-08

The prophylactic use of fluoroquinolones in patients with cancer and neutropenia is controversial and is not a recommended intervention. We randomly assigned 760 consecutive adult patients with cancer in whom chemotherapy-induced neutropenia (<1000 neutrophils per cubic millimeter) was expected to occur for more than seven days to receive either oral levofloxacin (500 mg daily) or placebo from the start of chemotherapy until the resolution of neutropenia. Patients were stratified according to their underlying disease (acute leukemia vs. solid tumor or lymphoma). An intention-to-treat analysis showed that fever was present for the duration of neutropenia in 65 percent of patients who received levofloxacin prophylaxis, as compared with 85 percent of those receiving placebo (243 of 375 vs. 308 of 363; relative risk, 0.76; absolute difference in risk, -20 percent; 95 percent confidence interval, -26 to -14 percent; P=0.001). The levofloxacin group had a lower rate of microbiologically documented infections (absolute difference in risk, -17 percent; 95 percent confidence interval, -24 to -10 percent; P<0.001), bacteremias (difference in risk, -16 percent; 95 percent confidence interval, -22 to -9 percent; P<0.001), and single-agent gram-negative bacteremias (difference in risk, -7 percent; 95 percent confidence interval, -10 to -2 percent; P<0.01) than did the placebo group. Mortality and tolerability were similar in the two groups. The effects of prophylaxis were also similar between patients with acute leukemia and those with solid tumors or lymphoma. Prophylactic treatment with levofloxacin is an effective and well-tolerated way of preventing febrile episodes and other relevant infection-related outcomes in patients with cancer and profound and protracted neutropenia. The long-term effect of this intervention on microbial resistance in the community is not known. Copyright 2005 Massachusetts Medical Society.

Risk of Febrile Neutropenia Associated With Select Myelosuppressive Chemotherapy Regimens in a Large Community-Based Oncology Practice.

PubMed

Li, Yanli; Family, Leila; Yang, Su-Jau; Klippel, Zandra; Page, John H; Chao, Chun

2017-09-01

Background: NCCN has classified commonly used chemotherapy regimens into high (>20%), intermediate (10%-20%), or low (<10%) febrile neutropenia (FN) risk categories based primarily on clinical trial evidence. Many chemotherapy regimens, however, remain unclassified by NCCN or lack FN incidence data in real-world clinical practice. Patients and Methods: We evaluated incidence proportions of FN and grade 4 and 3/4 neutropenia during the first chemotherapy course among patients from Kaiser Permanente Southern California who received selected chemotherapy regimens without well-established FN risk. Patients given granulocyte colony-stimulating factor (G-CSF) prophylaxis were excluded. Sensitivity analyses were performed to account for FN misclassification and censoring. Results: From 2008 to 2013, 1,312 patients with breast cancer who received docetaxel and cyclophosphamide (TC; n=853) or docetaxel, carboplatin, and trastuzumab (TCH; n=459); 1,321 patients with colorectal cancer who received capecitabine and oxaliplatin (XELOX; n=401) or leucovorin, 5-fluorouracil, and oxaliplatin (FOLFOX6; n=920); 307 patients with non-Hodgkin's lymphoma who received bendamustine with or without rituximab; and 181 patients with multiple myeloma who received lenalidomide with or without dexamethasone were included. Crude FN risk was >20% for both breast cancer regimens (TC and TCH). Crude FN risks for XELOX, FOLFOX6, bendamustine, and lenalidomide were <10%; however, when potential FN misclassification and censoring were considered, FN risks were >10%. Conclusions: Our results support published literature highlighting the real-world, "high" FN risk of the TC and TCH regimens for breast cancer. There is strong suggestive evidence that FN risks for XELOX, FOLFOX6, bendamustine, and lenalidomide are >10%. Calculation of chemotherapy course-level FN incidence without controlling for differential censoring for patients who discontinued regimens early, or possible FN misclassification, might

A case of feverish neutropenia

PubMed Central

Invernizzi, Rosangela; Ambaglio, Chiara; Quaglia, Federica

2014-01-01

Key Clinical Message A case of feverish benign neutropenia occurring in a diabetic patient receiving pregabalin for peripheral neuropathy is reported. Although pregabalin-induced neutropenia is very rare, it is important to keep in mind that this drug like other anticonvulsants used for neuropathic pain, can cause severe neutropenia. PMID:25548642

Costs of Home Versus Inpatient Treatment for Fever and Neutropenia: Analysis of a Multicenter Randomized Trial

PubMed Central

Hendricks, Ann M.; Loggers, Elizabeth Trice; Talcott, James A.

2011-01-01

Purpose For patients with cancer who have febrile neutropenia, relative costs of home versus hospital treatment, including unreimbursed costs borne by patients and families, are poorly characterized. We estimated costs from a randomized trial of patients with low-risk febrile neutropenia for whom outpatient care was feasible, comparing inpatient treatment with discharge to home care after inpatient observation. Methods We collected direct medical and self-reported indirect costs for 57 inpatient and 35 outpatient treatment episodes of patients enrolled in a randomized trial from 1996 through 2000. Charges from hospital bills were converted to costs using Medicare cost-to-charge ratios. Patients kept daily logs of out-of-pocket payments and time spent by informal caregivers providing care. Dollar amounts were standardized to June 2008. Results Mean total charges for the hospital arm were 49% higher than for the home treatment arm ($16,341 v $10,977; P < .01). Mean estimated total costs for the hospital arm were 30% higher ($10,143 v $7,830; P < .01). Inspection of sparse available data suggests that payments made were similar by treatment arm. Inpatients and their caregivers spent more out of pocket than their outpatient counterparts (mean, $201 v $74; P < .01). Informal caregivers for both treatment arms reported similar time caring and lost from work. Conclusion Home intravenous antibiotic treatment was less costly than continued inpatient care for carefully selected patients with cancer having febrile neutropenia without significantly increased indirect costs or caregiver burden. PMID:21931037

Protocol for a systematic review of reductions in therapy for children with low-risk febrile neutropenia

PubMed Central

2014-01-01

Background Febrile neutropenia is a common complication of therapy in children with cancer. Some patients are at low risk of complications, and research has considered reduction in therapy for these patients. A previous systematic review broadly considered whether outpatient treatment and oral antibiotics were safe in this context and concluded that this was likely to be the case. Since that review, there has been further research in this area. Therefore, we aim to provide a more robust answer to these questions and to additionally explore whether the exact timing of discharge, including entirely outpatient treatment, has an impact on outcomes. Methods/design The search will cover MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, CDSR, CENTRAL, LILACS, HTA and DARE. A full search strategy is provided. Key conference proceedings and reference lists of included papers will be hand searched. Prominent authors/clinicians in the field will be contacted. We will include randomised and quasi-randomised controlled trials along with prospective single-arm studies that examine the location of therapy and/or the route of administration of antibiotics in children or young adults (aged less than 18 years) who attend paediatric services with fever and neutropenia due to treatment for cancer and are assessed to be at low risk of medical complications. Studies will be screened and data extracted by one researcher and independently checked by a second. All studies will be critically appraised using tools appropriate to the study design. Data from randomised controlled trials (RCTs) will be combined to provide comparative estimates of treatment failure, safety and adequacy. Information from quasi-randomised trials and single-arm studies will provide further data on the safety and adequacy of regimes. Random effects meta-analysis will be used to combine studies. A detailed analysis plan, including assessment of heterogeneity and publication bias, is provided

Emergency Department Management of Patients With Febrile Neutropenia: Guideline Concordant or Overly Aggressive?

PubMed

Baugh, Christopher W; Wang, Thomas J; Caterino, Jeffrey M; Baker, Olesya N; Brooks, Gabriel A; Reust, Audrey C; Pallin, Daniel J

2017-01-01

The Infectious Diseases Society of America and the American Society of Clinical Oncology recommend risk stratification of patients with febrile neutropenia (FN) and discharge with oral antibiotics for low-risk patients. We studied guideline concordance and clinical outcomes of FN management in our emergency department (ED). Our urban, tertiary care teaching hospital provides all emergency and inpatient services to a large comprehensive cancer center. We performed a structured chart review of all FN patients seen in our ED from January 2010 to December 2014. Using electronic medical records, we identified all visits by patients with fever and an absolute neutrophil count of <1000 cells/mm 3 and then included only patients without a clear source of infection. Following national guidelines, we classified patients as low or high risk and assessed guideline concordance in disposition and parenteral versus oral antibiotic therapy by risk category as our main outcome measure. Of 173 qualifying visits, we classified 44 (25%) as low risk and 129 (75%) as high risk. Management was guideline concordant in 121 (70%, 95% confidence interval [CI] = 63% to 77%). Management was guideline discordant in 43 (98%, 95% CI = 88% to 100%) of low-risk patients versus 9 (7%, 95% CI = 3% to 13%) of high-risk patients (relative risk [RR] = 14, 95% CI = 7.5 to 26). Of 52 guideline-discordant cases, 36 (83%, 95% CI = 72% to 93%) involved low-risk cases with treatment that was more aggressive than recommended. Guideline concordance was low among low-risk patients, with management tending to be more aggressive than recommended. Unless data emerge that undermine the guidelines, we believe that many of these hospitalizations and parenteral antibiotic regimens can be avoided, decreasing the risks associated with hospitalization, while improving antibiotic stewardship and patient comfort. © 2016 by the Society for Academic Emergency Medicine.

Canadian supportive care recommendations for the management of neutropenia in patients with cancer.

PubMed

Kouroukis, C T; Chia, S; Verma, S; Robson, D; Desbiens, C; Cripps, C; Mikhael, J

2008-01-01

Hematologic toxicities of cancer chemotherapy are common and often limit the ability to provide treatment in a timely and dose-intensive manner. These limitations may be of utmost importance in the adjuvant and curative intent settings. Hematologic toxicities may result in febrile neutropenia, infections, fatigue, and bleeding, all of which may lead to additional complications and prolonged hospitalization. The older cancer patient and patients with significant comorbidities may be at highest risk of neutropenic complications. Colony-stimulating factors (csfs) such as filgrastim and pegfilgrastim can effectively attenuate most of the neutropenic consequences of chemotherapy, improve the ability to continue chemotherapy on the planned schedule, and minimize the risk of febrile neutropenia and infectious morbidity and mortality. The present consensus statement reviews the use of csfs in the management of neutropenia in patients with cancer and sets out specific recommendations based on published international guidelines tailored to the specifics of the Canadian practice landscape. We review existing international guidelines, the indications for primary and secondary prophylaxis, the importance of maintaining dose intensity, and the use of csfs in leukemia, stem-cell transplantation, and radiotherapy. Specific disease-related recommendations are provided related to breast cancer, non-Hodgkin lymphoma, lung cancer, and gastrointestinal cancer. Finally, csf dosing and schedules, duration of therapy, and associated acute and potential chronic toxicities are examined.

A nomogram for predicting complications in patients with solid tumours and seemingly stable febrile neutropenia.

PubMed

Fonseca, Paula Jiménez; Carmona-Bayonas, Alberto; García, Ignacio Matos; Marcos, Rosana; Castañón, Eduardo; Antonio, Maite; Font, Carme; Biosca, Mercè; Blasco, Ana; Lozano, Rebeca; Ramchandani, Avinash; Beato, Carmen; de Castro, Eva Martínez; Espinosa, Javier; Martínez-García, Jerónimo; Ghanem, Ismael; Cubero, Jorge Hernando; Manrique, Isabel Aragón; Navalón, Francisco García; Sevillano, Elena; Manzano, Aránzazu; Virizuela, Juan; Garrido, Marcelo; Mondéjar, Rebeca; Arcusa, María Ángeles; Bonilla, Yaiza; Pérez, Quionia; Gallardo, Elena; Del Carmen Soriano, Maria; Cardona, Mercè; Lasheras, Fernando Sánchez; Cruz, Juan Jesús; Ayala, Francisco

2016-05-24

We sought to develop and externally validate a nomogram and web-based calculator to individually predict the development of serious complications in seemingly stable adult patients with solid tumours and episodes of febrile neutropenia (FN). The data from the FINITE study (n=1133) and University of Salamanca Hospital (USH) FN registry (n=296) were used to develop and validate this tool. The main eligibility criterion was the presence of apparent clinical stability, defined as events without acute organ dysfunction, abnormal vital signs, or major infections. Discriminatory ability was measured as the concordance index and stratification into risk groups. The rate of infection-related complications in the FINITE and USH series was 13.4% and 18.6%, respectively. The nomogram used the following covariates: Eastern Cooperative Group (ECOG) Performance Status ⩾2, chronic obstructive pulmonary disease, chronic cardiovascular disease, mucositis of grade ⩾2 (National Cancer Institute Common Toxicity Criteria), monocytes <200/mm(3), and stress-induced hyperglycaemia. The nomogram predictions appeared to be well calibrated in both data sets (Hosmer-Lemeshow test, P>0.1). The concordance index was 0.855 and 0.831 in each series. Risk group stratification revealed a significant distinction in the proportion of complications. With a ⩾116-point cutoff, the nomogram yielded the following prognostic indices in the USH registry validation series: 66% sensitivity, 83% specificity, 3.88 positive likelihood ratio, 48% positive predictive value, and 91% negative predictive value. We have developed and externally validated a nomogram and web calculator to predict serious complications that can potentially impact decision-making in patients with seemingly stable FN.

Response of first-line antibiotic therapy in patients with febrile neutropenia during treatment of hematological disorders.

PubMed

Taj, M; Qureshi, R N; Farzana, T; Shamsi, T S; Ahmed, S S

2015-06-01

Patients with hematological disorders develop febrile neutropenia (FN); most of these events remain undetermined in origin. We performed a prospective study to determine the microbiological characteristics of infections and their response to the first-line antibiotic therapy in FN. The study was conducted at National Institute of Blood Disease and Bone Marrow Transplant. Two-hundred episodes of FN were assessed for the bacterial growth, antimicrobial susceptibility pattern and response to the first-line treatment of FN. All patients were given Ceftazidime and Amikacin Bosch Pharmaceutical (Pvt. Ltd), as first-line antibiotic in FN. Out of 200 episodes we had 108 clinically and microbiologically documented infections. The isolated frequencies for gram negative and gram positive organisms were n = 52 and 49 (48 and 45 %) respectively. Among gram negative micro-organisms, Escherichia coli (E. coli) was isolated in 15 (28.8 %), Klebsiella pneumonae in 4 (7.6 %) and Pseudomonas aeruginosa in 10 (19.2 %) were in highest frequencies. Methicillin sensitive staphylococci emerged as the frequently isolated gram-positive bacteria. Eight-one episodes (45.3 %) responded to the first-line treatment and death reported in 20 cases (10 %). Our study showed almost equal trend of gram positive and gram negative bacteria isolated from patients suffering from neutropenic fever. Empirical use of Ceftazidime and Amikacin as first-line antibiotics was able to cover the infection only in 45.3 % of episodes suffering from FN.

Outpatient management of febrile neutropenia in children with cancer

PubMed Central

Ziino, Ottavio; Tucci, Fabio; Rossi, Mario Renato

2011-01-01

Optimizing the therapeutic strategies based on the results of randomized studies comparing different regimens led to a better prognosis of nearly all pediatric malignancies during the past four decades. Fever and neutropenia (FN) is a common complication in patients undergoing chemotherapy to treat cancer. There is no consensus on when standard therapy can be safely reduced; this lack of consensus leads to important variations in management of FN between different institutions, usually conducted according to local attitudes. To address this issue, the Infection working group of the Italian association for pediatric hematology oncology (AIEOP) organized a consensus meeting. This paper reports the agreement derived from this meeting. PMID:21647281

Severe neutropenia in infectious mononucleosis.

PubMed

Hammond, W P; Harlan, J M; Steinberg, S E

1979-08-01

Mild neutropenia is a well-known concomitant of infectious mononucleosis caused by the Epstein-Barr virus (EBV) occurring in the first weeks of illness. However, severe neutropenia (less than 200 polymorphonuclear leukocytes per mul) is not generally regarded as a complication of infectious mononucleosis. Three patients were seen with severe neutropenia and EBV infection, and an additional eight cases were found in the literature. In two of the latter cases the neutropenia was fatal. In the 11 cases the severe neutropenia began 14 to 40 days after illness and usually lasted for three to seven days. At the time of severe neutropenia, studies of marrow specimens showed increased proportions of promyelocytes and myelocytes. Our data suggest that EBV infection is the proximate cause of the severe neutropenia in some patients with infectious mononucleosis and that in such cases close observation and early treatment of suspected superinfections is necessary.

Severe Neutropenia in Infectious Mononucleosis

PubMed Central

Hammond, William P.; Harlan, John M.; Steinberg, Stephen E.

1979-01-01

Mild neutropenia is a well-known concomitant of infectious mononucleosis caused by the Epstein-Barr virus (EBV) occurring in the first weeks of illness. However, severe neutropenia (less than 200 polymorphonuclear leukocytes per μl) is not generally regarded as a complication of infectious mononucleosis. Three patients were seen with severe neutropenia and EBV infection, and an additional eight cases were found in the literature. In two of the latter cases the neutropenia was fatal. In the 11 cases the severe neutropenia began 14 to 40 days after illness and usually lasted for three to seven days. At the time of severe neutropenia, studies of marrow specimens showed increased proportions of promyelocytes and myelocytes. Our data suggest that EBV infection is the proximate cause of the severe neutropenia in some patients with infectious mononucleosis and that in such cases close observation and early treatment of suspected superinfections is necessary. PMID:229647

Gene Expression Analysis of Circulating Hormone Refractory Prostate Cancer Micrometastases

DTIC Science & Technology

2008-01-01

Toxicity Grade 3 or 4 neutropenia occurred in 54% and 63% of patients treated with second-line ixabepilone and MP, respectively (Table 3). Febrile ... Neutropenia 22 (54) 10 (33) 26 (63) 10 (63) Febrile neutropenia 2 (5)* 2 (7) 4 (10) — Thrombocytopenia 3 (7) 3 (10) 1 (2) 1 (6) * 1 patient died of...independently predicted improved survival. The most common grade 3/4 toxicity associated with second-line treatment was neutropenia (54% of ixabe- pilone

A nomogram for predicting complications in patients with solid tumours and seemingly stable febrile neutropenia

PubMed Central

Fonseca, Paula Jiménez; Carmona-Bayonas, Alberto; García, Ignacio Matos; Marcos, Rosana; Castañón, Eduardo; Antonio, Maite; Font, Carme; Biosca, Mercè; Blasco, Ana; Lozano, Rebeca; Ramchandani, Avinash; Beato, Carmen; de Castro, Eva Martínez; Espinosa, Javier; Martínez-García, Jerónimo; Ghanem, Ismael; Cubero, Jorge Hernando; Manrique, Isabel Aragón; Navalón, Francisco García; Sevillano, Elena; Manzano, Aránzazu; Virizuela, Juan; Garrido, Marcelo; Mondéjar, Rebeca; Arcusa, María Ángeles; Bonilla, Yaiza; Pérez, Quionia; Gallardo, Elena; del Carmen Soriano, Maria; Cardona, Mercè; Lasheras, Fernando Sánchez; Cruz, Juan Jesús; Ayala, Francisco

2016-01-01

Background: We sought to develop and externally validate a nomogram and web-based calculator to individually predict the development of serious complications in seemingly stable adult patients with solid tumours and episodes of febrile neutropenia (FN). Patients and methods: The data from the FINITE study (n=1133) and University of Salamanca Hospital (USH) FN registry (n=296) were used to develop and validate this tool. The main eligibility criterion was the presence of apparent clinical stability, defined as events without acute organ dysfunction, abnormal vital signs, or major infections. Discriminatory ability was measured as the concordance index and stratification into risk groups. Results: The rate of infection-related complications in the FINITE and USH series was 13.4% and 18.6%, respectively. The nomogram used the following covariates: Eastern Cooperative Group (ECOG) Performance Status ⩾2, chronic obstructive pulmonary disease, chronic cardiovascular disease, mucositis of grade ⩾2 (National Cancer Institute Common Toxicity Criteria), monocytes <200/mm3, and stress-induced hyperglycaemia. The nomogram predictions appeared to be well calibrated in both data sets (Hosmer–Lemeshow test, P>0.1). The concordance index was 0.855 and 0.831 in each series. Risk group stratification revealed a significant distinction in the proportion of complications. With a ⩾116-point cutoff, the nomogram yielded the following prognostic indices in the USH registry validation series: 66% sensitivity, 83% specificity, 3.88 positive likelihood ratio, 48% positive predictive value, and 91% negative predictive value. Conclusions: We have developed and externally validated a nomogram and web calculator to predict serious complications that can potentially impact decision-making in patients with seemingly stable FN. PMID:27187687

Protocol for Reducing Time to Antibiotics in Pediatric Patients Presenting to an Emergency Department With Fever and Neutropenia: Efficacy and Barriers.

PubMed

Cohen, Clay; King, Amber; Lin, Chee Paul; Friedman, Gregory K; Monroe, Kathy; Kutny, Matthew

2016-11-01

Patients with febrile neutropenia are at high risk of morbidity and mortality from infectious causes. Decreasing time to antibiotic (TTA) administration is associated with improved patient outcomes. We sought to reduce TTA for children presenting to the emergency department with fever and neutropenia. In a prospective cohort study with historical comparison, TTA administration was evaluated in patients with neutropenia presenting to the Children's of Alabama Emergency Department. A protocol was established to reduce delays in antibiotic administration and increase the percentage of patients who receive treatment within 60 minutes of presentation. One hundred pre-protocol patient visits between August 2010 and December 2011 were evaluated and 153 post-protocol visits were evaluated between August 2012 and September 2013. We reviewed individual cases to determine barriers to rapid antibiotic administration. Antibiotics were administered in 96.9 ± 57.8 minutes in the pre-protocol patient group, and only 35% of patients received antibiotics within 60 minutes of presentation and 70% received antibiotics within 120 minutes. After implementation of the protocol, TTA for neutropenic patients was decreased to 64.3 ± 28.4 minutes (P < 0.0001) with 51.4% receiving antibiotics within 60 minutes and 93.2% within 120 minutes. Implementing a standard approach to patients at risk for neutropenia decreased TTA. There are numerous challenges in providing timely antibiotics to children with febrile neutropenia. Identified delays included venous access (time to effect of topical anesthetics, and difficulty obtaining access), physicians waiting on laboratory results, and antibiotic availability.

Comparison of filgrastim and pegfilgrastim to prevent neutropenia and maintain dose intensity of adjuvant chemotherapy in patients with breast cancer.

PubMed

Kourlaba, Georgia; Dimopoulos, Meletios A; Pectasides, Dimitrios; Skarlos, Dimosthenis V; Gogas, Helen; Pentheroudakis, George; Koutras, Angelos; Fountzilas, George; Maniadakis, Nikos

2015-07-01

The aim of this study was to compare the effectiveness of prophylactic single fixed dose of pegfilgrastim and daily administration of filgrastim on febrile neutropenia (FN), severe neutropenia, treatment delay, and dose reduction in patients with breast cancer receiving dose-dense adjuvant chemotherapy. A retrospective cohort study with 1058 breast cancer patients matched by age and chemotherapy was conducted. The primary endpoints were FN, severe (grade 3, 4) neutropenia, dose reduction (>10 % reduction of the dose planned), and treatment delay (dose given more than 2 days later). Eighteen episodes of FN (3.4%) in the filgrastim group and 23 (4.3%) in the pegfilgrastim group (p = 0.500) were recorded. More than half of the total episodes (27/41) occurred during the first 4 cycles of treatment. Patients who received filgrastim were almost three times more likely to experience a severe neutropenia episode and were significantly more likely to experience a dose reduction (18.5%) compared to those who received pegfilgrastim (10.8%) (p < 0.001). The percentage of patients, who received their planned dose on time, was significantly lower in patients receiving filgrastim (58%) compared to those receiving pegfilgrastim (72.4%, p < 0.001). No significant difference was detected on FN rate between daily administration of filgrastim and single administration of pegfilgrastim. However, patients receiving pegfilgrastim had a significantly lower rate of severe neutropenia, as well as dose reduction and treatment delay, thus, achieving a higher dose density.

Validation of risk stratification for children with febrile neutropenia in a pediatric oncology unit in India.

PubMed

Das, Anirban; Trehan, Amita; Oberoi, Sapna; Bansal, Deepak

2017-06-01

The study aims to validate a score predicting risk of complications in pediatric patients with chemotherapy-related febrile neutropenia (FN) and evaluate the performance of previously published models for risk stratification. Children diagnosed with cancer and presenting with FN were evaluated in a prospective single-center study. A score predicting the risk of complications, previously derived in the unit, was validated on a prospective cohort. Performance of six predictive models published from geographically distinct settings was assessed on the same cohort. Complications were observed in 109 (26.3%) of 414 episodes of FN over 15 months. A risk score based on undernutrition (two points), time from last chemotherapy (<7 days = two points), presence of a nonupper respiratory focus of infection (two points), C-reactive protein (>60 mg/l = five points), and absolute neutrophil count (<100 per μl = two points) was used to stratify patients into "low risk" (score <7, n = 208) and assessed using the following parameters: overall performance (Nagelkerke R 2 = 34.4%), calibration (calibration slope = 0.39; P = 0.25 in Hosmer-Lemeshow test), discrimination (c-statistic = 0.81), overall sensitivity (86%), negative predictive value (93%), and clinical net benefit (0.43). Six previously published rules demonstrated inferior performance in this cohort. An indigenous decision rule using five simple predefined variables was successful in identifying children at risk for complications. Prediction models derived in developed nations may not be appropriate for low-middle-income settings and need to be validated before use. © 2016 Wiley Periodicals, Inc.

Antineutrophil Cytoplasmic Antibodies, Autoimmune Neutropenia, and Vasculitis

PubMed Central

Grayson, Peter C.; Sloan, J. Mark; Niles, John L.; Monach, Paul A.; Merkel, Peter A.

2011-01-01

Objectives Reports of an association between antineutrophil cytoplasmic antibodies (ANCA) and autoimmune neutropenia have rarely included cases of proven vasculitis. A case of ANCA-associated vasculitis (AAV) with recurrent neutropenia is described and relevant literature on the association between ANCA, neutropenia, and vasculitis is reviewed. Methods Longitudinal clinical assessments and laboratory findings are described in a patient with AAV and recurrent episodes of profound neutropenia from December 2008 – October 2010. A PubMed database search of the medical literature was performed for papers published from 1960 through October 2010 to identify all reported cases of ANCA and neutropenia. Results A 49 year-old man developed recurrent neutropenia, periodic fevers, arthritis, biopsy-proven cutaneous vasculitis, sensorineural hearing loss, epididymitis, and positive tests for ANCA with specificity for antibodies to both proteinase 3 and myeloperoxidase. Antineutrophil membrane antibodies were detected during an acute neutropenic phase and were not detectable in a post-recovery sample, whereas ANCA titers did not seem to correlate with neutropenia. An association between ANCA and neutropenia has been reported in 74 cases from 24 studies in the context of drug/toxin exposure, underlying autoimmune disease, or chronic neutropenia without underlying autoimmune disease. In these cases, the presence of atypical ANCA patterns and other antibodies were common; however, vasculitis was uncommon and when it occurred was usually limited to the skin and in cases of underlying toxin exposure. Conclusions ANCA is associated with autoimmune neutropenia, but systemic vasculitis rarely occurs in association with ANCA and neutropenia. The interaction between neutrophils and ANCA may provide insight into understanding both autoimmune neutropenia and AAV. PMID:21507463

Predicting neutropenia risk in patients with cancer using electronic data.

PubMed

Pawloski, Pamala A; Thomas, Avis J; Kane, Sheryl; Vazquez-Benitez, Gabriela; Shapiro, Gary R; Lyman, Gary H

2017-04-01

Clinical guidelines recommending the use of myeloid growth factors are largely based on the prescribed chemotherapy regimen. The guidelines suggest that oncologists consider patient-specific characteristics when prescribing granulocyte-colony stimulating factor (G-CSF) prophylaxis; however, a mechanism to quantify individual patient risk is lacking. Readily available electronic health record (EHR) data can provide patient-specific information needed for individualized neutropenia risk estimation. An evidence-based, individualized neutropenia risk estimation algorithm has been developed. This study evaluated the automated extraction of EHR chemotherapy treatment data and externally validated the neutropenia risk prediction model. A retrospective cohort of adult patients with newly diagnosed breast, colorectal, lung, lymphoid, or ovarian cancer who received the first cycle of a cytotoxic chemotherapy regimen from 2008 to 2013 were recruited from a single cancer clinic. Electronically extracted EHR chemotherapy treatment data were validated by chart review. Neutropenia risk stratification was conducted and risk model performance was assessed using calibration and discrimination. Chemotherapy treatment data electronically extracted from the EHR were verified by chart review. The neutropenia risk prediction tool classified 126 patients (57%) as being low risk for febrile neutropenia, 44 (20%) as intermediate risk, and 51 (23%) as high risk. The model was well calibrated (Hosmer-Lemeshow goodness-of-fit test = 0.24). Discrimination was adequate and slightly less than in the original internal validation (c-statistic 0.75 vs 0.81). Chemotherapy treatment data were electronically extracted from the EHR successfully. The individualized neutropenia risk prediction model performed well in our retrospective external cohort. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions

Pattern of infection, therapy, outcome and risk stratification of patients with febrile neutropenia in a tertiary care oncology hospital in India.

PubMed

Noronha, V; Joshi, A; Patil, V M; Bhosale, B; Muddu, V K; Banavali, S; Kelkar, R; Prabhash, K

2014-01-01

Indian febrile neutropenia (FN) data are limited, especially in adult solid tumor patients. The aim was to study patterns of presentation, source of infection, management and outcome and to evaluate the factors which may correlate with outcome. A retrospective analysis of prospective data of FN patients at a tertiary care oncology teaching hospital in India between 2007 and 2012. A standardized form was filled for each patient. Patient management was at the discretion of the treating physician. Multinational Association for Supportive Care in Cancer (MASCC) score was retrospectively calculated. Failure of therapy was defined as death, organ failure, shifting from outpatient to inpatient or requirement of intensive care support. SPSS version 16 was used for analysis. A total of 388 FN episodes were included: 256 in hematolymphoid and 132 in solid tumor patients. 156 episodes were high-risk by MASCC score. Focus of infection was clinical in 45% and radiologic in 16%. Blood cultures were positive in 18% cases, most commonly Gram-negative organisms (72%). 93% patients were treated with an antibiotic combination of third-generation cephalosporin/beta-lactamase inhibitor, with aminoglycoside or fluoroquinolone. Antibiotic sensitivity to ceftriaxone was low at 38% while sensitivity to cefoperazone/sulbactam and piperacillin/tazobactam ranged between 50% and 55% and for carbapenems 75%. Failure of therapy occurred in 156 episodes, most commonly due to the need for second line antibiotics. Mortality was 5.5%. On univariate analysis, MASCC score, age, type of malignancy, prophylactic growth factors, presence of focus of infection, hemoglobin and nadir platelet count correlated with FN complications. Gram-negative bacteremia continues to be the predominant cause of FN in our setup.

Prophylactic and therapeutic strategies in chemotherapy-induced neutropenia.

PubMed

Saloustros, Emmanouil; Tryfonidis, Kostas; Georgoulias, Vassilis

2011-04-01

Neutropenia poses a serious threat to patients on chemotherapy. It exposes them to the risk of infection--including potentially fatal infections--and also leads to delays in treatment and reductions in dose intensity, which can compromise the possibility of a favorable outcome. The use of granulocyte colony-stimulating factors (G-CSF) and antibiotics to prevent febrile neutropenia (FN) and to ameliorate cancer chemotherapy-induced myelosuppression is discussed, based on a systematic search of Pubmed for clinical trials, reviews and meta-analysis published in the last 20 years. We consider that the treatment of FN, with the emphasis on careful attention to the patient, prompts antibiotic therapy and good hospital care. We would argue that antibiotic prophylaxis should be offered routinely to patients receiving cytotoxic chemotherapy for acute leukemia and for patients with solid tumors and lymphoma receiving high-dose chemotherapy. In patients undergoing cyclical standard-dose myelosuppressive chemotherapy, we believe that prophylaxis is indicated during the first cycle of chemotherapy in which there is an expectation of grade 4 neutropenia (< 500 neutrophils). However, although the use of antibiotics and haematopoietic growth factors may improve quality of life by reducing the risk and consequences of FN, further study of the magnitude of their effects is needed.

Pharmacokinetic/pharmacodynamic modeling and simulation of neutropenia during phase I development of liposome-entrapped paclitaxel.

PubMed

Fetterly, Gerald J; Grasela, Thaddeus H; Sherman, Jeffrey W; Dul, Jeanne L; Grahn, Amy; Lecomte, Diane; Fiedler-Kelly, Jill; Damjanov, Nevena; Fishman, Mayer; Kane, Michael P; Rubin, Eric H; Tan, Antoinette R

2008-09-15

To evaluate the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), and pharmacokinetics of liposome-entrapped paclitaxel easy-to-use (LEP-ETU) and to characterize the relationship between LEP-ETU concentrations and the time course of neutropenia in cancer patients. LEP-ETU was administered to 88 patients and 63 were evaluable for pharmacokinetic/pharmacodynamic (PK/PD) analysis following 1.5- and 3-h infusions every 3 weeks (q3w; dose range, 135-375 mg/m(2)). MTD was identified using a 3 + 3, up-and-down dose-finding algorithm. PK/PD modeling was done to describe the temporal relationship between paclitaxel concentrations and neutrophil count. Simulations assessed the influence of dose and schedule on neutropenia severity to help guide dose selection. The MTD of LEP-ETU was identified as 325 mg/m(2). DLTs occurring at 375 mg/m(2) consisted of febrile neutropenia and neuropathy. The C(max) and area under the plasma concentration-time curve of LEP-ETU were less than proportional with increasing dose. The PK/PD model showed that LEP-ETU inhibition of neutrophil proliferation was 9.1% per 10 mug/mL of total paclitaxel concentration. The incidence of grade 4 neutropenia increased from 33% to 42% across the dose range of 275 to 325 mg/m(2) q3w. For a dose of 110 mg/m(2) given weekly, grade 4 neutropenia was estimated to be 16% compared with 42% for the same total dose administered q3w. LEP-ETU can be administered safely at higher doses than Taxol. Modeling and simulation studies predict that 325 mg/m(2) LEP-ETU q3w provides acceptable neutropenic events relative to those observed at 175 mg/m(2) Taxol q3w. A 275 mg/m(2) dose may offer an improved therapeutic index.

Periodic neutropenia and monocytopenia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adams, W.H.; Liu, Y.K.

A patient with periodic neutropenia exhibited simultaneous monocytopenia, and epinephrine infusion revealed no monocytes in the marginating pool during neutropenia. Lymphocytes, eosinophils, and platelets also fluctuated periodically, but serial bone marrow studies and epinephrine infusion data indicate these fluctuations could have represented epiphenomena rather than a more global form of periodic hematopoiesis. Bone marrow descriptions of most cases of periodic neutropenia have indicated a ''maturation arrest'' at the promyelocyte or myelocyte stage prior to development of neutropenia; peripheral blood monocytes are usually normal or fluctuate out of phase with neutrophils. In the present case, ''maturation arrest'' occurred at the myeloblastmore » stage, and neutrophils and monocytes cycled together. Morphologically normal eosinophilopoiesis with a mean eosinophil to erythroid ratio in the marrow of 0.27 +/- 0.10 (SD) persisted despite a sustained disappearance of promyelocytes.« less

Effect of outpatient treatment of febrile neutropenia on the risk threshold for the use of CSF in patients with cancer treated with chemotherapy.

PubMed

Cosler, Leon E; Sivasubramaniam, Visaharan; Agboola, Olayemi; Crawford, Jeffrey; Dale, David; Lyman, Gary H

2005-01-01

Febrile neutropenia (FN) in patients with cancer treated with chemotherapy has traditionally been managed with inpatient broad-spectrum antibiotics until the infection and neutropenia have resolved. A newer strategy is outpatient oral or intravenous antibiotics in selected patients after an initial hospitalization. We sought to determine these costs, both overall and relative to those of traditional management, and the optimal role of prophylactic colony-stimulating factor (CSF) in patients at greatest risk for FN. Existing economic decision models were modified by incorporating a treatment strategy for FN in which patients are classified as high- and low-risk according to criteria described by Talcott. Low-risk patients were assumed to be treated as outpatients. Overall costs with the revised economic model were assessed and sensitivity analyses were performed. The costs of an episode of FN were estimated as 1) no CSF: dollar 13,355; 2) CSF with hospitalization for FN: dollar 8677; and 3) CSF with risk stratification and outpatient management in low-risk patients: dollar 8188. The risk threshold for the cost-effective use of CSF was only slightly lower with outpatient treatment. When all patients with FN are treated as inpatients and the cost of hospitalization is dollar 1750/day the risk threshold for FN at which prophylactic CSF becomes cost-effective is 16%. It is 15% when low-risk patients are treated as outpatients. Outpatient treatment slightly decreases the risk threshold for FN at which prophylactic CSF becomes cost-effective. The limited economic effect of this strategy may be because the patients who were at greatest risk of complications had significantly longer lengths of stay and accounted for most of the hospitalization costs.

Clinical Predictive Models for Chemotherapy-Induced Febrile Neutropenia in Breast Cancer Patients: A Validation Study

PubMed Central

Zhu, Liling; Su, Fengxi; Jia, Weijuan; Deng, Xiaogeng

2014-01-01

Background Predictive models for febrile neutropenia (FN) would be informative for physicians in clinical decision making. This study aims to validate a predictive model (Jenkin’s model) that comprises pretreatment hematological parameters in early-stage breast cancer patients. Patients and Methods A total of 428 breast cancer patients who received neoadjuvant/adjuvant chemotherapy without any prophylactic use of colony-stimulating factor were included. Pretreatment absolute neutrophil counts (ANC) and absolute lymphocyte counts (ALC) were used by the Jenkin’s model to assess the risk of FN. In addition, we modified the threshold of Jenkin’s model and generated Model-A and B. We also developed Model-C by incorporating the absolute monocyte count (AMC) as a predictor into Model-A. The rates of FN in the 1st chemotherapy cycle were calculated. A valid model should be able to significantly identify high-risk subgroup of patients with FN rate >20%. Results Jenkin’s model (Predicted as high-risk when ANC≦3.1*10∧9/L;ALC≦1.5*10∧9/L) did not identify any subgroups with significantly high risk (>20%) of FN in our population, even if we used different thresholds in Model-A(ANC≦4.4*10∧9/L;ALC≦2.1*10∧9/L) or B(ANC≦3.8*10∧9/L;ALC≦1.8*10∧9/L). However, with AMC added as an additional predictor, Model-C(ANC≦4.4*10∧9/L;ALC≦2.1*10∧9/L; AMC≦0.28*10∧9/L) identified a subgroup of patients with a significantly high risk of FN (23.1%). Conclusions In our population, Jenkin’s model, cannot accurately identify patients with a significant risk of FN. The threshold should be changed and the AMC should be incorporated as a predictor, to have excellent predictive ability. PMID:24945817

C-reactive protein in critically ill cancer patients with sepsis: influence of neutropenia

PubMed Central

2011-01-01

Introduction Several biomarkers have been studied in febrile neutropenia. Our aim was to assess C-reactive protein (CRP) concentration in septic critically ill cancer patients and to compare those with and without neutropenia. Methods A secondary analysis of a matched case-control study conducted at an oncologic medical-surgical intensive care unit (ICU) was performed, segregating patients with severe sepsis/septic shock. The impact of neutropenia on CRP concentrations at admission and during the first week of ICU stay was assessed. Results A total of 154 critically ill septic cancer patients, 86 with neutropenia and 68 without, were included in the present study. At ICU admission, the CRP concentration of neutropenic patients was significantly higher than in non-neutropenic patients, 25.9 ± 11.2 mg/dL vs. 19.7 ± 11.4 mg/dL (P = 0.009). Among neutropenic patients, CRP concentrations at ICU admission were not influenced by the severity of neutropenia (< 100/mm3 vs. ≥ 100/mm3 neutrophils), 25.1 ± 11.6 mg/dL vs. 26.9 ± 10.9 mg/dL (P = 0.527). Time dependent analysis of CRP from Day 1 to Day 7 of antibiotic therapy showed an almost parallel decrease in both groups (P = 0.335), though CRP of neutropenic patients was, on average, always higher in comparison to that of non-neutropenic patients. Conclusions In septic critically ill cancer patients CRP concentrations are more elevated in those with neutropenia. However, the CRP course seems to be independent from the presence or absence of neutropenia. PMID:21595932

Prediction of Febrile Neutropenia after Chemotherapy Based on Pretreatment Risk Factors among Cancer Patients

PubMed Central

Aagaard, Theis; Roen, Ashley; Daugaard, Gedske; Brown, Peter; Sengeløv, Henrik; Mocroft, Amanda; Lundgren, Jens; Helleberg, Marie

2017-01-01

Abstract Background Febrile neutropenia (FN) is a common complication to chemotherapy associated with a high burden of morbidity and mortality. Reliable prediction of individual risk based on pretreatment risk factors allows for stratification of preventive interventions. We aimed to develop such a risk stratification model to predict FN in the 30 days after initiation of chemotherapy. Methods We included consecutive treatment-naïve patients with solid cancers and diffuse large B-cell lymphomas at Copenhagen University Hospital, 2010–2015. Data were obtained from the PERSIMUNE repository of electronic health records. FN was defined as neutrophils ≤0.5 × 10E9/L ​at the time of either a blood culture sample or death. Time from initiation of chemotherapy to FN was analyzed using Fine-Gray models with death as a competing event. Risk factors investigated were: age, sex, body surface area, haemoglobin, albumin, neutrophil-to-lymphocyte ratio, Charlson Comorbidity Index (CCI) and chemotherapy drugs. Parameter estimates were scaled and summed to create the risk score. The scores were grouped into four: low, intermediate, high and very high risk. Results Among 8,585 patients, 467 experienced FN, incidence rate/30 person-days 0.05 (95% CI, 0.05–0.06). Age (1 point if > 65 years), albumin (1 point if < 39 g/L), CCI (1 point if > 2) and chemotherapy (range -5 to 6 points/drug) predicted FN. Median score at inclusion was 2 points (range –5 to 9). The cumulative incidence and the incidence rates and hazard ratios of FN are shown in Figure 1 and Table 1, respectively. Conclusion We developed a risk score to predict FN the first month after initiation of chemotherapy. The score is easy to use and provides good differentiation of risk groups; the score needs independent validation before routine use. Disclosures All authors: No reported disclosures.

Gene polymorphisms and febrile neutropenia in acute leukemia--no association with IL-4, CCR-5, IL-1RA, but the MBL-2, ACE, and TLR-4 are associated with the disease in Turkish patients: a preliminary study.

PubMed

Pehlivan, Mustafa; Sahin, Handan Haydaroğlu; Ozdilli, Kurşat; Onay, Hüseyin; Ozcan, Ali; Ozkinay, Ferda; Pehlivan, Sacide

2014-07-01

The aim of this study was to investigate the mannose-binding lectin 2 (MBL-2), interleukin (IL)-4, Toll-like receptor 4 (TLR-4), angiotensin converting enzyme (ACE), chemokine receptor 5 (CCR-5), and IL-1 receptor antagonist (RA) gene polymorphisms (GPs) in acute leukemias (ALs) and to evaluate their roles in febrile neutropenia (FN) resulting from chemotherapy. The study included 60 AL patients hospitalized between the period of July 2001 and August 2006. Polymorphisms for the genes ACE(I/D), CCR-5, IL-1RA, MBL-2, TLR-4, and IL-4 were typed by polymerase chain reaction (PCR) and/or PCR-restriction fragment length polymerase. Genotype frequencies for these genes were compared in the patient and control groups. The relationships between the genotypes and the body distribution of infections, pathogens, the duration of neutropenia, and febrile episodes in AL patients were evaluated. No significant differences in either the genotype distribution or the allelic frequencies of TLR-4, IL-4, CCR-5, IL-1RN GPs were observed between patients and healthy controls. The AB/BB genotype (53.3%) in the MBL-2 gene was found to be significantly higher in the AL patients compared with control groups. There were correlations between the presence of MBL-2, TLR-4, and ACE polymorphisms and clinical parameters due to FN. Overall, bacteremia was more common in MBL BB and ACE DD. Gram-positive bacteremia was more common in ACE for ID versus DD genotype. Gram-negative bacteremia was more common for both the MBL-2 AB/BB genotype and TLR-4 AG genotype. Median durations of febrile episodes were significantly shorter in ACE DD and MBL AB/BB. Although TLR-4, ACE, and MBL-2 GPs have been extensively investigated in different clinical pictures, this is the first study to evaluate the role of these polymorphisms in the genetic etiopathogenesis of FN in patients with ALs. As a conclusion, TLR-4, ACE, and MBL-2 genes might play roles in the genetic etiopathogenesis of FN in patients with ALs.

Cost effectiveness of primary pegfilgrastim prophylaxis in patients with breast cancer at risk of febrile neutropenia.

PubMed

Aarts, Maureen J; Grutters, Janneke P; Peters, Frank P; Mandigers, Caroline M; Dercksen, M Wouter; Stouthard, Jacqueline M; Nortier, Hans J; van Laarhoven, Hanneke W; van Warmerdam, Laurence J; van de Wouw, Agnes J; Jacobs, Esther M; Mattijssen, Vera; van der Rijt, Carin C; Smilde, Tineke J; van der Velden, Annette W; Temizkan, Mehmet; Batman, Erdogan; Muller, Erik W; van Gastel, Saskia M; Joore, Manuela A; Borm, George F; Tjan-Heijnen, Vivianne C

2013-12-01

Guidelines advise primary granulocyte colony-stimulating factor (G-CSF) prophylaxis during chemotherapy if risk of febrile neutropenia (FN) is more than 20%, but this comes with considerable costs. We investigated the incremental costs and effects between two treatment strategies of primary pegfilgrastim prophylaxis. Our economic evaluation used a health care perspective and was based on a randomized study in patients with breast cancer with increased risk of FN, comparing primary G-CSF prophylaxis throughout all chemotherapy cycles (G-CSF 1-6 cycles) with prophylaxis during the first two cycles only (G-CSF 1-2 cycles). Primary outcome was cost effectiveness expressed as costs per patient with episodes of FN prevented. The incidence of FN increased from 10% in the G-CSF 1 to 6 cycles study arm (eight of 84 patients) to 36% in the G-CSF 1 to 2 cycles study arm (30 of 83 patients), whereas the mean total costs decreased from € 20,658 (95% CI, € 20,049 to € 21,247) to € 17,168 (95% CI € 16,239 to € 18,029) per patient, respectively. Chemotherapy and G-CSF determined 80% of the total costs. As expected, FN-related costs were higher in the G-CSF 1 to 2 cycles arm. The incremental cost effectiveness ratio for the G-CSF 1 to 6 cycles arm compared with the G-CSF 1 to 2 cycles arm was € 13,112 per patient with episodes of FN prevented. We conclude that G-CSF prophylaxis throughout all chemotherapy cycles is more effective, but more costly, compared with prophylaxis limited to the first two cycles. Whether G-CSF prophylaxis throughout all chemotherapy cycles is considered cost effective depends on the willingness to pay per patient with episodes of FN prevented.

Risk of chemotherapy-induced febrile neutropenia with early discontinuation of pegfilgrastim prophylaxis in US clinical practice.

PubMed

Weycker, Derek; Li, Xiaoyan; Barron, Rich; Li, Yanli; Reiner, Maureen; Kartashov, Alex; Figueredo, Jacqueline; Tzivelekis, Spiros; Garcia, Jacob

2016-06-01

Accumulating evidence suggests that not all cancer chemotherapy patients who receive first-cycle pegfilgrastim prophylaxis continue to receive it in subsequent cycles and that these patients may be subsequently at higher risk of febrile neutropenia (FN). Additional evidence from US clinical practice is warranted. Data from two US private healthcare claims repositories were employed. The source population comprised adults who received "intermediate-risk" or "high-risk" chemotherapy regimens for solid cancers or non-Hodgkin's lymphoma and first-cycle pegfilgrastim prophylaxis. From the source population, all patients who did not receive second-cycle pegfilgrastim prophylaxis ("comparison patients") were matched (1:1) to those who received it ("pegfilgrastim patients") based on cancer, regimen, and propensity score. Odds ratios (OR) for FN-broad and narrow definitions-during the second chemotherapy cycle were estimated for comparison patients versus pegfilgrastim patients using generalized estimating equations. A total of 2245 comparison patients (5.3 % of source population) were matched to pegfilgrastim patients; cohorts were well-balanced on baseline characteristics. Second-cycle FN incidence proportions for comparison and pegfilgrastim patients were 3.8 versus 2.2 % based on broad definition and 2.6 versus 0.8 % based on narrow definition; corresponding OR were 1.7 (95 % CI 1.2-2.5, p = 0.002) and 3.5 (95 % CI 2.0-6.0, p < 0.001). Results were similar within cancer/regimen-subgroups and were robust when using alternative methods for confounding adjustment. In this retrospective evaluation of cancer chemotherapy patients who received first-cycle pegfilgrastim prophylaxis in US clinical practice, a clinically relevant minority did not receive second-cycle prophylaxis. Second-cycle FN odds among this subset were significantly higher than they were among those who continued prophylaxis.

An infant with chronic severe neutropenia

PubMed Central

Bhat, Ramesh Y; Varma, Chaitanya P V; Bhatt, Sonia

2014-01-01

Neutropenia in infancy and childhood poses a diagnostic challenge as the aetiology ranges from acute life-threatening conditions to chronic benign diseases. Chronic benign neutropenia of infancy is a rare disorder occurring in 1:100 000. The neutrophil count continues to be low for a prolonged period until spontaneous resolution by the age of 3–4 years. Such infants are having higher incidences of minor infections requiring treatment with antibiotics and rare incidences of meningitis and sepsis. The authors describe an infant presenting with fever and cervical lymphadenitis, who was found to have isolated severe neutropenia and its persistence posing a diagnostic challenge. The prolonged course with minor infections and absence of serious underlying conditions finally confirmed chronic benign neutropenia of infancy. PMID:24711472

Chemotherapy-induced (febrile) neutropenia prophylaxis with biosimilar filgrastim in elderly versus non-elderly cancer patients: Patterns, outcomes, and determinants (MONITOR-GCSF study).

PubMed

Aapro, Matti; Bokemeyer, Carsten; Ludwig, Heinz; Gascón, Pere; Boccadoro, Mario; Denhaerynck, Kris; Gorray, Michael; Krendyukov, Andriy; MacDonald, Karen; Abraham, Ivo

2017-03-01

Myelotoxic chemotherapy is associated with chemotherapy-induced (febrile) neutropenia (CIN/FN). The MONITOR-GCSF study evaluated biosimilar filgrastim (Zarzio®) prophylaxis patterns, associated outcomes, and determinants. We performed stratified analyses comparing elderly and non-elderly patients. Comparative (elderly/non-elderly) analysis of demographics and clinical status, prophylaxis, associated CIN/FN outcomes (CIN grade 4 [CIN4], FN, CIN/FN-related hospitalizations and chemodisturbances, composite), and, per hierarchical modeling, determinants thereof evaluated at the patient- and cycle-level. There were no significant differences between both cohorts in prophylaxis initiation/duration and associated outcomes, but proportionately more elderly patients were correctly-prophylacted and fewer over-prophylacted. Common determinants of poor CIN/FN outcomes included concomitant antibiotic prophylaxis, impaired performance status, and any grade CIN in a previous cycle, whereas common determinants of good outcomes included over-prophylaxis and prophylaxis initiation within 24-72h. In the elderly, female gender, liver/renal/cardiovascular disease, secondary prophylaxis, and under-prophylaxis were associated with poorer outcomes. In the non-elderly, CIN4 at baseline or in a prior cycle was associated with poorer CIN/FN outcomes, and higher biosimilar filgrastim dose and, perhaps counter-intuitively, under-prophylaxis with better outcomes. Adequate GCSF support is essential for all patients, but especially for elderly patients with serious chronic disease, certainly, if concomitant antibiotic prophylaxis is indicated and if a CIN4 episode occurred in a prior cycle. The potential impact of impaired performance status, especially ECOG≥2 at chemotherapy start or a worsening to such during chemotherapy; under-prophylaxis, including inadequate secondary prophylaxis, should be considered in elderly patients. Timely GCSF initiation and over-prophylaxis is associated with

Risk predictors for adverse outcome in pediatric febrile neutropenia: Single center experience from a low and middle-income country.

PubMed

Prasad, M; Chinnaswamy, G; Arora, B; Vora, T; Hawaldar, R; Banavali, S

2014-01-01

Risk stratification of patients with febrile neutropenia (FN) into those at "High Risk" and "Low Risk" of developing complications helps in making decisions regarding optimal treatment, such as whether to treat with oral or intravenous antibiotics, whether to treat as inpatient or outpatient and how long to treat. Risk predictors obtained from Western studies on pediatric FN are unlikely to be relevant to low middle-income country (LMICs). Our study aimed to identify clinical and laboratory parameters predictive of poor outcomes in children with chemotherapy-induced FN in a LMIC. Two hundred and fifty consecutive episodes of chemotherapy-induced FN in pediatric (<15 years) patients were analyzed prospectively. Adverse outcomes were defined as per SPOG 2003 FN study as serious medical complications (SMC) due to infection, microbiologically defined infection, and radiologically defined pneumonia (RDP). Variables found to be significant for adverse outcome (P < 0.05) on univariate analysis were selected for multivariate analysis. Five factors that were found to independently predict adverse outcome were (a) previously documented infection in the past 6 months, (b) presence of significant focus of infection, (c) absolute phagocyte count <100/mm3, (d) peak temperature more than 39°C in this episode of FN, and (e) fever lasting more than 5 days during this episode of FN. Identifying the risk factors for adverse outcome in pediatric FN, which are objective and applicable across LMICs would contribute in developing guidelines for the management of FN in a resource-limited setting.

Mannose-binding lectin (MBL) and the risk for febrile neutropenia and infection in pediatric oncology patients with chemotherapy.

PubMed

Frakking, F N J; Israëls, J; Kremer, L C M; Kuijpers, T W; Caron, H N; van de Wetering, M D

2011-07-15

We determined whether mannose-binding lectin (MBL) deficiency is associated with an increased risk of febrile neutropenia (FN) and/or infection in pediatric oncology patients. We systematically searched and reviewed all the literature on MBL and infections in children with cancer, identified from a literature search of Medline, Embase, and Central (1966-April 2010). We extracted information on the type of study, patient characteristics, definition of MBL deficiency, definition of infection and method of detection, follow-up period and the results of the outcome in different groups. The validity of each study was assessed. Six cohort studies were retrieved, consisting of 581 children with leukemia (n = 2) or varying types of cancer (n = 4). Many different outcome definitions were used. In only one out of three genotype studies, variant MBL2 genotypes, as well as MBL levels < 1,000 µg/L, were associated with an increased duration of FN. In one additional MBL level study the number of FN episodes, bacteremia and severe bacterial infection were increased in patients with MBL levels < 100 µg/L as compared to those with MBL levels of 100-999 µg/L. Sepsis, pneumonia, viral infection, and fungal infection were not associated with either MBL levels or genotypes in any of the studies. MBL deficiency could not be identified as an independent risk factor for FN or infection in pediatric oncology patients. A multicenter study of children with comparable chemotherapy regimens, relevant and equal outcome definitions and measuring both MBL levels and genotypes, will be required to avoid clinical and methodological inconsistencies. Copyright © 2010 Wiley-Liss, Inc.

Comparing the Incidence of Febrile Neutropenia Resulting in Hospital Admission Between the Branded Docetaxel and the Generic Formulations.

PubMed

Faqeer, Nour Al; Mashni, Ola; Dawoud, Rawan; Rumman, Asma; Hanoun, Esraa; Nazer, Lama

2017-02-01

Studies have raised concern about the safety of generic compared with branded drugs. Febrile neutropenia (FN) resulting in hospital admission was compared between the branded docetaxel (Taxotere®, Sanofi) and 2 generic formulations (docetaxel Ebewe and docetaxel Hospira) in patients with breast cancer. This was a retrospective study that included patients with breast cancer who received docetaxel between January 2012 and December 2014. Patients who had an admission diagnosis of FN and had received docetaxel within 14 days prior to admission were evaluated. The docetaxel brand and dose, patient characteristics, hospital length of stay, admission to the intensive care unit (ICU), and mortality were recorded. During the study period, 2904 cycles of docetaxel were given for 876 patients (1519 cycles of docetaxel Sanofi, 811 cycles of docetaxel Hospira, and 574 cycles of docetaxel Ebewe). Among the cycles given, 130 cycles were associated with FN that required hospital admission. The overall incidence of FN resulting in hospital admission was significantly higher in patients who had received docetaxel Hospira, compared with patients who had received docetaxel Sanofi (47[5.8%] cycles vs 53 [3.5%] cycles, P = .009), but there was no significant difference between docetaxel Ebewe and docetaxel Sanofi (30[5.2%] cycles vs 53 [3.5%] cycles, P = .069). All cases of FN resolved except for 1 patient who died in the ICU after receiving docetaxel Ebewe. There was a significant difference in the incidence of FN between docetaxel Sanofi and docetaxel Hospira, but all cases in both groups resolved completely. © 2016, The American College of Clinical Pharmacology.

Distribution of pathogens in central line-associated bloodstream infections among patients with and without neutropenia following chemotherapy: evidence for a proposed modification to the current surveillance definition.

PubMed

Steinberg, James P; Robichaux, Chad; Tejedor, Sheri Chernetsky; Reyes, Mary Dent; Jacob, Jesse T

2013-02-01

Many bloodstream infections (BSIs) occurring in patients with febrile neutropenia following cytotoxic chemotherapy are due to translocation of intestinal microbiota. However, these infections meet the National Healthcare Safety Network (NHSN) definition of central line-associated BSIs (CLABSIs). We sought to determine the differences in the microbiology of NHSN-defined CLABSIs in patients with and without neutropenia and, using these data, to propose a modification of the CLABSI definition. Retrospective review. Two large university hospitals over 18 months. All hospital-acquired BSIs occurring in patients with central venous catheters in place were classified using the NHSN CLABSI definition. Patients with postchemotherapy neutropenia (500 neutrophils/mm(3) or lower) at the time of blood culture were considered neutropenic. Pathogens overrepresented in the neutropenic group were identified to inform development of a modified CLABSI definition. Organisms that were more commonly observed in the neutropenic group compared with the nonneutropenic group included Escherichia coli (22.7% vs 2.5%; P < .001) but not other Enterobacteriaceae, Enterococcus faecium (18.2% vs 6.1%; P = .002), and streptococci (18.2% vs 0%; P < .001). Application of a modified CLABSI definition (removing BSI with enterococci, streptococci, or E. coli) excluded 33 of 66 neutropenic CLABSIs and decreased the CLABSI rate in one study hospital with large transplant and oncology populations from 2.12 to 1.79 cases per 1,000 line-days. Common gastrointestinal organisms were more common in the neutropenia group, suggesting that many BSIs meeting the NHSN criteria for CLABSI in the setting of neutropenia may represent translocation of gut organisms. These findings support modification of the NHSN CLABSI definition.

Microorganisms isolated from cultures and infection focus and antibiotic treatments in febrile neutropenic children from Şanlıurfa, Turkey.

PubMed

Özdemir, Z Canan; Koç, Ahmet; Ayçiçek, Ali

2016-01-01

Chemotherapy induced febrile neutropenia predisposes patients to life threatening infections. We aimed to determine the causative microorganisms, infection focus and antibiotic treatment success in febrile neutropenic children with leukemia. A total of 136 febrile neutropenic episodes in 48 leukemic children were reviewed retrospectively from records. Among 136 febrile neutropenic episodes, 68 (50%) episodes were microbiologically documented. Methicillin sensitive coagulase (-) Staphylococcus aureus were the most common isolates from hemoculture (20.5%). The most frequently documented infection focus was mucositis (31.9%). Ceftazidime plus amikacin was the most commonly used antimicrobial treatment for the empirical therapy (52.9%). The overall response rates were 70.5%, 86.9%, and 66.6% of first line, second line and third line therapies, respectively. The spectrum of isolates among febrile neutropenic children in our hematology clinic appears to be gram positive pathogens which are the most common agents. Therefore the, documentation of the flora in each unit could help to decide appropriate empirical therapy which is life saving.

Granulocyte-Colony Stimulating Factor (G-CSF) Administration for Chemotherapy-Induced Neutropenia.

PubMed

Yalçin, Ş; Güler, N; Kansu, E; Ertenli, I; Güllü, I; Barişta, I; Çelik, I; Kars, A; Tekuzman, G; Baltali, E; Firat, D

1996-01-01

This study was aimed to evaluate the efficacy of G-CSF (Granulocyte colony stimulating factor) administration to 37 patients with neutropenia following intensive combination chemotherapy. The patients were divided into two subgroups including solid tumors given ifosfamide and etoposide combination chemotherapy (IMET subgroup) and acute myeloid leukemia (AML) patients treated with mitoxantrone and cytarabine. Control group consisted of 31 acute myeloid leukemia patients. G-CSF was started on the first day of absolute neutropenia until the absolute neutrophil count was above 1000/mm(3) for two consecutive days. G-CSF was found to be effective for early recovery of neutrophil count. Expected response was achieved within 14 days in 91.5% of the courses with a median of fifth day of G-CSF treatment. In conclusion, this study showed the efficacy of G-CSF in early recovery of neutrophil count without any reduction in the incidence of febrile episodes and documented rates of bacterial and fungal infections in patients with acute myeloid leukemia.

Etiology and Clinical Course of Febrile Neutropenia in Children with Cancer

PubMed Central

Hakim, Hana; Flynn, Patricia M.; Knapp, Katherine M.; Srivastava, Deo Kumar; Gaur, Aditya

2009-01-01

Background The etiology, clinical course and outcome of fever and neutropenia (FN) in children with cancer using the current FN guidelines and diagnostic resources in the United States have not been well described. Patients and Methods Medical records of one randomly selected FN episode per patient during 2004–2005 at a pediatric oncology center were reviewed. Patients were managed as per institutional FN guidelines and blood cultures collected in continuously-read BACTEC™ bottles. Results Of 337 FN episodes, infection was proven in 86 (25%) and probable in 75 (22%). 177 episodes (53%) were judged fever of unknown origin (FUO). Bacteremia accounted for most (41) of the proven bacterial episodes, with viridans streptococci (13), Pseudomonas spp (6) and E. coli (6) the most frequently isolated organisms. The median time to positivity of blood cultures was 12 hrs (range 5.4 – 143.7) with 93% positive within 24 hours of incubation. Viral pathogens were identified in 29 (34%) episodes. Compared to other patients, those with FUO had shorter median duration of fever (0.5 vs. 2.0 days; p<0.0001) and hospitalization (3 vs. 6 days; p<0.0001), longer median duration since last chemotherapy (6.0 vs. 4.0 days; p=0.01) and were less likely to have a diagnosis of acute myelogenous leukemia (AML) (11% vs 22%; p=0.009) or develop a clinical complication (5.1% vs 24.4%; p<0.0001). Conclusion Despite currently available diagnostic resources, the majority of patients with FN have FUO marked by a low rate of clinical complications and no infection-related mortality. Emergence of viridans streptococci as the most common blood isolate has affected FN treatment recommendations. Study findings will help further development of strategies for risk stratified management of fever with neutropenia in pediatric patients. PMID:19644403

Over- and under-prophylaxis for chemotherapy-induced (febrile) neutropenia relative to evidence-based guidelines is associated with differences in outcomes: findings from the MONITOR-GCSF study.

PubMed

Bokemeyer, Carsten; Gascón, Pere; Aapro, Matti; Ludwig, Heinz; Boccadoro, Mario; Denhaerynck, Kris; Gorray, Michael; Krendyukov, Andriy; Abraham, Ivo; MacDonald, Karen

2017-06-01

In the MONITOR-GCSF study of chemotherapy-induced (febrile) neutropenia with biosimilar filgrastim, 56.6% of patients were prophylacted according to amended EORTC guidelines, but 17.4% were prophylacted below and 26.0% above guideline recommendations. MONITOR-GCSF is a prospective, observational study of 1447 evaluable patients from 140 cancers centers in 12 European countries treated with myelosuppressive chemotherapy for up to 6 cycles receiving biosimilar GCSF prophylaxis. Patients were classified as under-, correctly-, or over-prophylacted with GCSF relative to guideline recommendations based on their chemotherapy risk, individual risk factors, and type of GCSF prophylaxis (primary versus secondary). Differences between under- (17.4%), correctly- (56.6%), or over-prophylacted (26.0%) groups were found in terms of patient risk factors (age, performance status, history of FN, comorbid conditions) as well as prophylaxis patterns (type of prophylaxis, day of GCSF initiation, and GCSF duration). Rates of chemotherapy-induced neutropenia (CIN) (all grades), FN, and CIN-related hospitalizations were consistently lower in over-prophylacted patients relative to under- and correctly-prophylacted patients. No differences were observed between under- and correctly-prophylacted patients except for CIN/FN-related chemotherapy disturbances. No GCSF safety differences were found between groups (except for headaches). The real-world evidence provided by the MONITOR-GCSF study indicates that providing GCSF support may yield better CIN, FN, and CIN/FN-related hospitalization outcomes if patients are prophylacted at levels above guideline recommendations. Patients who are under-prophylacted are at higher risk for disturbances to their chemotherapy regimens. Our findings support the guideline recommendation that CIN/FN risk be assessed at the beginning of each chemotherapy cycle.

Mold colonization of fiberglass insulation of the air distribution system: effects on patients with hematological malignancies.

PubMed

Takuma, Takahiro; Okada, Kaoru; Yamagata, Akihiro; Shimono, Nobuyuki; Niki, Yoshihito

2011-02-01

We investigated mold colonization of air handling units (AHUs) of heating, ventilating, and air conditioning (HVAC) systems and its effects, including invasive pulmonary mycoses and febrile neutropenia, in patients with hematological malignancies. Sample collection with transparent adhesive tape and culture swabs revealed that AHUs were heavily colonized with molds, including thermotolerant, variously distributed Penicillium spp. Cases of nosocomial invasive pulmonary mycosis were not clustered in specific patient rooms but did occur frequently when the HVAC systems were not in use, prior to intervention (i.e., sealing and disuse of AHUs in private room), and during construction of a new hospital building. Multivariate logistic regression analysis of initial episodes of febrile neutropenia showed that the rate of febrile neutropenia was significantly associated with the duration of neutropenia (odds ratio [OR]: 1.16; 95% confidence interval [CI]: 1.07-1.27) and with sex (OR: 0.469; CI: 0.239-0.902). An evaluation of private rooms showed that female patients also had a lower rate of fever after intervention (OR: 0.0016; 95% CI: 0.000-0.209). The reduced rate of febrile neutropenia after intervention suggests that mold colonization of AHUs had adverse effects on patients with hematological malignancies.

Risk of chemotherapy-induced febrile neutropenia in cancer patients receiving pegfilgrastim prophylaxis: does timing of administration matter?

PubMed

Weycker, Derek; Li, Xiaoyan; Figueredo, Jacqueline; Barron, Rich; Tzivelekis, Spiros; Hagiwara, May

2016-05-01

Contrary to the approved indication for pegfilgrastim prophylaxis, some patients receive it on the same day as the last administration of chemotherapy in clinical practice, which could adversely impact risk of febrile neutropenia (FN). An evaluation of the timing of pegfilgrastim prophylaxis and FN risk was undertaken. A retrospective cohort design and data from two US private health care claims repositories were employed. Study population comprised adults who received intermediate/high-risk chemotherapy regimens for solid tumors or non-Hodgkin's lymphoma (NHL) and received pegfilgrastim prophylaxis in ≥1 cycle; all cycles with pegfilgrastim were pooled for analyses. Odds ratios (OR) for FN during the cycle were estimated for patients who received pegfilgrastim on the same day (day 1) as the last administration of chemotherapy versus days 2-4 from chemotherapy completion. The study population included 45,592 patients who received pegfilgrastim in 179,152 cycles (n = 37,095 in cycle 1); in 12 % of cycles, patients received pegfilgrastim on the same day as chemotherapy. Odds of FN were higher for patients receiving pegfilgrastim prophylaxis on the same day as chemotherapy versus days 2-4 from chemotherapy in cycle 1 (OR = 1.6, 95 % CI = 1.3-1.9, p < 0.001) and all cycles (OR = 1.5, 95 % CI = 1.3-1.6, p < 0.001). In this large-scale evaluation of adults who received intermediate/high-risk regimens for solid tumors or NHL in US clinical practice, FN incidence was found to be significantly higher among those who received pegfilgrastim prophylaxis on the same day as chemotherapy completion versus days 2-4 from chemotherapy completion, underscoring the importance of adhering to the indicated administration schedule.

Optimal primary febrile neutropenia prophylaxis for patients receiving docetaxel-cyclophosphamide chemotherapy for breast cancer: a systematic review.

PubMed

Fernandes, Ricardo; Mazzarello, Sasha; Stober, Carol; Vandermeer, Lisa; Dudani, Shaan; Ibrahim, Mohamed F K; Majeed, Habeeb; Perdrizet, Kirstin; Shorr, Risa; Hutton, Brian; Fergusson, Dean; Clemons, Mark

2017-01-01

Due to the high rate of febrile neutropenia (FN) with docetaxel-cyclophosphamide (DC) chemotherapy, primary FN prophylaxis is recommended. However, the optimal choice of prophylaxis [i.e., granulocyte-colony stimulating factors (G-CSF) or antibiotics] is unknown. A systematic review was performed to address this knowledge gap. Embase, Ovid Medline, Pubmed, the Cochrane database of systematic reviews, and Cochrane register of controlled trials were searched from 1946 to April 2016 for studies evaluating primary prophylactic FN treatments in breast cancer patients receiving DC chemotherapy. Outcome measures evaluated included: incidence of FN and treatment-related hospitalizations, chemotherapy dose reduction/delays/discontinuations, and adverse events. Screening and data collection were performed by two independent reviewers. Of 2105 identified records, 7 studies (n = 2535) met the pre-specified eligibility criteria. Seven additional studies (n = 621) were identified from prior systematic reviews. There were 3 randomized controlled trials (RCTs) (n = 2256) and 11 retrospective studies (n = 900). Study sample sizes ranged from 30 to 982 patients (median 99.5), evaluating pegfilgrastim (n = 1274), filgrastim (n = 1758), and oral ciprofloxacin (n = 108). Given the heterogeneity of patients and study design, a narrative synthesis of results was performed. Median FN rates with and without primary prophylaxis were 6.6 % (IQR 3.9-10.6 %) and 31.3 % (IQR 25-33 %), respectively. No FN-related deaths were reported. No RCT directly compared G-CSF with antibiotic interventions. Primary FN prophylaxis reduces the incidence of FN. Despite considerable cost and toxicity differences between G-CSF and antibiotics, there is insufficient data to make a recommendation of one strategy over another.

Is febrile neutropenia prophylaxis with granulocyte-colony stimulating factors economically justified for adjuvant TC chemotherapy in breast cancer?

PubMed

Skedgel, Chris; Rayson, Daniel; Younis, Tallal

2016-01-01

Febrile neutropenia (FN) during adjuvant chemotherapy is associated with morbidity, mortality risk, and substantial cost, and subsequent chemotherapy dose reductions may result in poorer outcomes. Patients at high risk of, or who develop FN, often receive prophylaxis with granulocyte colony-stimulating factors (G-CSF). We investigated whether different prophylaxis strategies with G-CSF offered favorable value-for-money. We developed a decision model to estimate the short- and long-term costs and outcomes of a hypothetical cohort of women with breast cancer receiving adjuvant taxotere + cyclophosphamide (TC) chemotherapy. The short-term phase estimated upfront costs and FN risks with adjuvant TC chemotherapy without G-CSF prophylaxis (i.e., chemotherapy dose reductions) as well as with secondary and primary G-CSF prophylaxis strategies. The long-term phase estimated the expected costs and quality-adjusted life years (QALYs) for patients who completed adjuvant TC chemotherapy with or without one or more episodes of FN. Secondary G-CSF was associated with lower costs and greater QALY gains than a no G-CSF strategy. Primary G-CSF appears likely to be cost-effective relative to secondary G-CSF at FN rates greater than 28%, assuming some loss of chemotherapy efficacy at lower dose intensities. The cost-effectiveness of primary vs. secondary G-CSF was sensitive to FN risk and mortality, and loss of chemotherapy efficacy following FN. Secondary G-CSF is more effective and less costly than a no G-CSF strategy. Primary G-CSF may be justified at higher willingness-to-pay thresholds and/or higher FN risks, but this threshold FN risk appears to be higher than the 20% rate recommended by current clinical guidelines.

[Use of procalcitonin and C-reactive protein as infection markers in febrile neutropenic patients undergoing haematopoietic stem cell transplant].

PubMed

Sánchez-Yepes, Marina; Aznar-Oroval, Eduardo; Lorente-Alegre, Pablo; García-Lozano, Tomás; Picón-Roig, Isabel; Pérez-Ballestero, Pilar; Ortiz-Muñoz, Blanca

2014-01-01

Neutropenia is a frequent sign in patients who are going to have a haematopoietic stem cell transplant (HSCT). Infection is an important complication in these patients, which is favoured by immunosuppression and the degree of neutropenia. This study aims to evaluate the diagnostic usefulness of procalcitonin (PCT) and C-reactive protein (CRP) in onco-haematological patients undergoing chemotherapy and HSCT to determine the origin of the fever. PCT and CRP values were measured in 30 episodes of febrile neutropenia: before starting chemotherapy, appearance of neutropenia, onset of fever, days 1, 2, 3 and 6 after the onset of fever, and when the febrile episode ended. The episodes were classified as 5 bacteraemia, 3 microbiologically documented infections, 10 clinical infections, and 12 fevers of unknown origin. The highest PCT mean values corresponded to the group of patients with bacteraemia. Statistically significant differences (P=.04) were found on the second day after the onset of fever. The cut-off point of 0.5ng/ml showed a sensitivity of 66% and a specificity of 75%. PCR results showed statistically significant differences on days 1, 2 and 3 after the onset of fever (P=.01, P=.003, and P=.002, respectively). The cut-off point of 7.5mg/L had a sensitivity of 88% and a specificity of 58%. The combination of PCT and CRP is an insufficient method to detect bacterial infections and may not replace the proper clinical and microbiological diagnosis. Copyright © 2013 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Novel ELANE Gene Mutation in a Korean Girl with Severe Congenital Neutropenia

PubMed Central

Shim, Ye Jee; Kim, Hee-Jin; Suh, Jang Soo

2011-01-01

Severe congenital neutropenia is a heterozygous group of bone marrow failure syndromes that cause lifelong infections. Mutation of the ELANE gene encoding human neutrophil elastase is the most common genetic alteration. A Korean female pediatric patient was admitted because of recurrent cervical lymphadenitis without abscess formation. She had a past history of omphalitis and isolated neutropenia at birth. The peripheral blood showed a markedly decreased absolute neutrophil count, and the bone marrow findings revealed maturation arrest of myeloid precursors at the promyelocyte to myelocyte stage. Her direct DNA sequencing analysis demonstrated an ELANE gene mutation (c.607G > C; p.Gly203Arg), but her parents were negative for it. She showed only transient response after subcutaneous 15 µg/kg/day of granulocyte colony stimulating factor administration for six consecutive days. During the follow-up observation period, she suffered from subsequent seven febrile illnesses including urinary tract infection, septicemia, and cellulitis. PMID:22148006

Análisis de Costo Efectividad de Estrategias de Tratamiento Antimicótico en Pacientes con Neutropenia Febril Persistente y Tratamiento Antibiótico de Amplio Espectro.

PubMed

Gamboa Garay, Oscar Andrés; Fuentes Pachón, Juan Camilo; Cuervo Maldonado, Sonia Isabel; Gómez Rincón, Julio Cesar; Castillo Londoño, Juan Sebastian

2012-12-01

To assess cost-effectiveness of antifungal treatment on patients with persistent fever neutropenia: empiric antifungal therapy (EAT) vs. anticipated antifungal therapy (AAT). A decision model was performed to evaluate the cost-effectiveness of antifungal treatment strategies in patients with febrile neutropenia not responding to a broad spectrum antibiotic treatment. The strategies included were: 1) EAT with amphotericin B deoxycholate; 2) EAT with liposomal amphotericin B; 3) EAT with caspofungin; and 4) AAT with voriconazole and amphotericin B deoxycholate or liposomal amphotericin B or caspofungin in patients who initiate treatment despite having negative CT scan and galactomannan or fail to voriconazole. Effectiveness was measured as the number of deaths averted. Cost-effectiveness and incremental cost-effectiveness ratios were calculated. Deterministic and probabilistic sensitivity analyzes were performed. EAT with Amphotericin B deoxycholate was the least expensive and least effective strategy. The EAT with caspofungin was the most effective. The cost per death averted for caspofungin when compared with amphotericin B deoxycholate was $17,011,073.83, which would indicate that this strategy would be cost-effective for the country if the willingness to pay per death averted is equal to or greater than this value. EAT with liposomal amphotericin B and AAT with voriconazole were dominated by AET with caspofungin, which is less costly and more effective. EAT with caspofungin would be cost-effective for Colombia if the threshold per death averted is greater to $18.000.000. If the threshold is lesser the EAT with amphotericin B deoxycholate would be the election. Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Methodology for clinical trials involving patients with cancer who have febrile neutropenia: updated guidelines of the Immunocompromised Host Society/Multinational Association for Supportive Care in Cancer, with emphasis on outpatient studies.

PubMed

Feld, Ronald; Paesmans, Marianne; Freifeld, Alison G; Klastersky, Jean; Pizzo, Philip A; Rolston, Kenneth V I; Rubenstein, Edward; Talcott, James A; Walsh, Thomas J

2002-12-15

Two multinational organizations, the Immunocompromised Host Society and the Multinational Association for Supportive Care in Cancer, have produced for investigators and regulatory bodies a set of guidelines on methodology for clinical trials involving patients with febrile neutropenia. The guidelines suggest that response (i.e., success of initial empirical antibiotic therapy without any modification) be determined at 72 h and again on day 5, and the reasons for modification should be stated. Blinding and stratification are to be encouraged, as should statistical consideration of trials specifically designed for showing equivalence. Patients enrolled in outpatient studies should be selected by use of a validated risk model, and patients should be carefully monitored after discharge from the hospital. Response and safety parameters should be recorded along with readmission rates. If studies use these guidelines, comparisons between studies will be simpler and will lead to further improvements in patient therapy.

Transplantation of allogenic bone marrow in canine cyclic neutropenia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dale, D.C.; Graw, R.G. Jr.

Transplantation of normal bone marrow cells to a gray collie dog with cyclic neutropenia resulted in normal granulocytopoiesis. The finding suggests that cyclic neutropenia occurs because the hematopoietic stem cells are defective. Because of the similarity of human and canine cyclic neutropenia, it also suggests that the human disease may be curable by marrow transplantation. One day before transplantation, the recipient received 1000 rads gamma irradiation from opposing /sup 60/Co sources at 9 rad/min. (CH)

Neutropenia during HIV Infection: Adverse Consequences and Remedies

PubMed Central

Shi, Xin; Sims, Matthew D; Hanna, Michel M; Xie, Ming; Gulick, Peter G; Zheng, Yong-Hui; Basson, Marc D; Zhang, Ping

2016-01-01

Neutropenia frequently occurs in patients with Human immunodeficiency virus (HIV) infection. Causes for neutropenia during HIV infection are multifactoral, including the viral toxicity to hematopoietic tissue, the use of myelotoxic agents for treatment, complication with secondary infections and malignancies, as well as the patient’s association with confounding factors which impair myelopoiesis. An increased prevalence and severity of neutropenia is commonly seen in advanced stages of HIV disease. Decline of neutrophil phagocytic defense in combination with the failure of adaptive immunity renders the host highly susceptible to developing fatal secondary infections. Neutropenia and myelosuppression also restrict the use of many antimicrobial agents for treatment of infections caused by HIV and opportunistic pathogens. In recent years, HIV infection has increasingly become a chronic disease because of progress in antiretroviral therapy (ART). Prevention and treatment of severe neutropenia becomes critical for improving the survival of HIV-infected patients. PMID:24654626

Evaluation and Management of Patients with Isolated Neutropenia

PubMed Central

Newburger, Peter E.; Dale, David C.

2013-01-01

Neutropenia, defined as an absolute neutrophil count below 1.5 × 109/L, encompasses a wide range of diagnoses, from normal variants to life-threatening acquired and congenital disorders. This review addresses the diagnosis and management of isolated neutropenia, not multiple cytopenias due to splenomegaly, bone marrow replacement, or myelosuppression by chemotherapy or radiation. Laboratory evaluation generally includes repeat complete blood counts with differentials and bone marrow examination with cytogenetics. Neutrophil antibody testing may be useful, but only in the context of clinical and bone marrow findings. The discovery of genes responsible for congenital neutropenias now permits genetic diagnosis in many cases. Management of severe chronic neutropenia includes common-sense precautions to avoid infection; aggressive treatment of bacterial or fungal infections; and administration of granulocyte colony-stimulating factor (G-CSF). Patients with severe congenital neutropenia, particularly those who respond poorly to G-CSF, have a risk of eventually developing myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) and require monitoring for this complication, which can also occur without G-CSF therapy. Patients with cyclic, idiopathic and autoimmune neutropenia have virtually no risk of evolving to MDS or AML. Hematopoietic stem cell transplantation is a curative therapy for congenital neutropenia with MDS/AML or with cytogenetic abnormalities indicating impending conversion. PMID:23953336

Severe Neutropenia in Dengue Patients: Prevalence and Significance

PubMed Central

Thein, Tun-Linn; Lye, David C.; Leo, Yee-Sin; Wong, Joshua G. X.; Hao, Ying; Wilder-Smith, Annelies

2014-01-01

Studies on severe neutropenia in dengue are scarce, and its clinical significance is uncertain. We analyzed a cohort of 1,921 reverse transcription polymerase chain reaction-confirmed adult dengue patients admitted to the Communicable Disease Center in Singapore between 2005 and 2008. Time trend analyses for daily absolute neutrophil counts (ANCs) were done using Bayesian hierarchical and Markov models. We found that severe neutropenia, defined as ANC ≤ 0.5 × 109/L, was found in 11.8% with a median duration of 1 day. ANC nadir occurred on illness day 5. Severe neutropenia was not predictive of more severe disease and not associated with secondary bacterial infections, prolonged hospital stay, prolonged fever, or fatal outcome. We concluded that prophylactic antibiotics are not indicated in patients with severe neutropenia without indication for bacterial infection. PMID:24732460

[Invasive fungal infections in children with cancer, neutropenia and fever, in Chile].

PubMed

Lucero, Yalda; Brücher, Roberto; Alvarez, Ana María; Becker, Ana; Cofré, José; Enríquez, Nancy; Payá, Ernesto; Salgado, Carmen; Santolaya, María Elena; Tordecilla, Juan; Varas, Mónica; Villarroel, Milena; Viviani, Tamara; Zubieta, Marcela; O'Ryan, Miguel

2002-10-01

Invasive fungal infections (IFI) cause prolonged hospitalizations and increase the possibility of death among patients with cancer and febrile neutropenia (FN). Up to 10% of febrile neutropenic episodes may be caused by IFI. To estimate the incidence of IFI among a large group of Chilean children with cancer and FN. Clinical and laboratory information was collected from a data base provided by the "Programa Infantil Nacional de Drogas Antineoplásicas" (PINDA) that included 445 FN episodes occurring in five hospitals in Santiago, Chile. This information was used to identify children that presented with signs and symptoms compatible with an IFI. According to predefined criteria based on a literature review, IFI episodes were categorized as "proven", "probable" or "possible". A total of 41/445 episodes (9.2%) were compatible with an IFI of which 4 (0.9%) were proven, 23 (5.2%) probable, and 14 (3.1%) possible. Hospitalization was longer (27 vs 8 days, p < .01), new infectious foci appeared with higher frequency (71 vs 38%, p < .01), and mortality was higher (10 vs 1.6%, p < .001) in children with IFI compatible episodes, when compared to children who did not have an IFI. The estimated incidence of IFI in Chilean children with cancer and FN ranged between 6-9% depending on the stringency of criteria selection used for classification. This estimate is similar to that reported by other studies. The low detection yield of clinically compatible IFI underscores the need of improved diagnosis of fungal infections in this population.

Indomethacin-associated neutropenia with subsequent Gram-negative sepsis in a preterm infant. Cause or coincidence?

PubMed

Bengtsson, B-O S; Milstein, J M; Sherman, M P

2006-06-01

A preterm male infant with a patent ductus arteriosus developed neutropenia during treatment with indomethacin. Afterward, the mother described her own history of indomethacin-associated neutropenia. During the recovery from the neutropenia, the infant became septic with bacteremia caused by Enterobacter cloacae. Although indomethacin-related neutropenia has been described in adults, no case in a neonate has been reported. If neutropenia occurs after indomethacin therapy in a neonate, a familial history of indomethacin-associated neutropenia should be sought and the increased risk of infection should be considered.

Alloimmune neonatal neutropenia due to anti-HNA-2a alloimmunization with severe and prolonged neutropenia but mild clinical course: two case reports.

PubMed

Tomicic, Maja; Starcevic, Mirta; Zach, Vanja; Hundric-Haspl, Zeljka

2007-10-01

Alloimmunization to granulocyte-specific antigens can occur during pregnancy. Maternal IgG can cross the placenta and result in neonatal neutropenia. The clinical course of alloimmune neonatal neutropenia is usually self-limiting with only mild infection. However, in severe cases complicated with bacterial sepsis it is a potentially life-threatening disorder. The effect of intravenous (IV) immunoglobulin, prophylactic antibiotic therapy, and recombinant human granulocyte-colony stimulating factor is variable and may prove useful in some cases. Two cases of alloimmune neonatal neutropenia due to anti HNA-2a alloimmunization in two siblings are reported. The first neonate was administered IV gammaglobulins to increase the blood neutrophil count, at a standard dosage (0.4 g/kg body weight) for 5 days without response. The second neonate did not receive specific therapy for blood neutrophil count increase. Neutropenia persisted for 2 and 6 months, respectively. The choice and efficacy of specific therapy for neutrophil count increase in the management of alloimmune neonatal neutropenia have not yet been fully defined and require additional evaluation in the majority of cases.

Neutropenia in primary immunodeficiency

PubMed Central

Sokolic, Robert

2016-01-01

Purpose of review Neutropenia is a feature of several primary immunodeficiency diseases (PIDDs). Because of the diverse pathophysiologies of the PIDDs and the rarity of each disorder, data are often lacking, leading to the necessity of empiric treatment. Recent developments in the understanding of neutropenia in several of the PIDDs make a review of the data timely. Recent findings The category of severe congenital neutropenia continues to expand. Mutations in G6PC3 have been identified as the cause of neutropenia in a minority of previously molecularly undefined cases. Recent advances have broadened our understanding of the pathophysiology and the clinical expression of this disorder. A possible function of the C16orf57 gene has been hypothesized that may explain the clinical overlap between Clerucuzio-type poikiloderma with neutropenia and other marrow diseases. Plerixafor has been shown to be a potentially useful treatment in the warts, hypogammaglobulinemia, infection, and myelokathexis syndrome. Investigations of patients with adenosine deaminase deficient severe combined immunodeficiency have identified neutropenia, and particularly susceptibility to myelotoxins, as a feature of this disorder. Granulocyte-colony stimulating factor is the treatment of choice for neutropenia in PIDD, whereas hematopoietic cell transplantation is the only curative option. Summary The number of PIDDs associated with neutropenia has increased, as has our understanding of the range of phenotypes. Additional data and hypotheses have been generated helping to explain the diversity of presentations of neutropenia in PIDDs. PMID:23196894

Assessment of Fever Advisory Cards (FACs) as an Initiative to Improve Febrile Neutropenia Management in a Regional Cancer Center Emergency Department.

PubMed

Kapil, Priyanka; MacMillan, Meghan; Carvalho, Maritza; Lymburner, Patricia; Fung, Ron; Almeida, Bernadette; Van Dorn, Laurie; Enright, Katherine

2016-09-01

We aimed to improve the time to antibiotics (TTA) for patients treated with chemotherapy who present to the emergency department (ED) with febrile neutropenia (FN) by using standardized fever advisory cards (FACs). Patients treated with chemotherapy who visited the ED at the Peel Regional Cancer Center in Ontario, Canada, with suspected FN were identified, before (April 2012 to March 2013) and after (October 2013 to March 2014) FAC implementation. The primary outcome of interest was TTA. Additional process measures included Canadian Triage and Acuity Scale score, time to physician assessment, and FAC compliance. Outcomes were analyzed with descriptive statistics and control charts to determine whether the change in primary measures were within statistical control over time. Between the pre-FAC cohort (n = 239) and post-FAC cohort (n = 69), TTA did not change significantly post-FACs (195 v 244 min, P = .09), with monthly averages demonstrating normal variation by statistical process control methodology. The introduction of FACs increased the percentage of patients with correctly assigned Canadian Triage and Acuity Scale scores (87% v 100%) but did not affect time to physician assessment. Compliance with FACs among patients was not ideal, with only 62.5% using them as intended. The distribution of FACs was associated with an improved incidence of correct FN triaging but did not demonstrate a meaningful improvement in the quality of FN management. This may be explained by FAC use among patients not being ideal. Next steps in the continued effort toward high-quality FN care include redesign of FACs, reinforcement of provider and patient education, and ED outreach. Copyright © 2016 by American Society of Clinical Oncology.

Costs associated with febrile neutropenia in Japanese patients with primary breast cancer: post-hoc analysis of a randomized clinical trial.

PubMed

Miyake, Osamu; Murata, Kyoko; Tanaka, Shiro; Ishiguro, Hiroshi; Toi, Masakazu; Tamura, Kazuo; Kawakami, Koji

2018-05-01

Febrile neutropenia (FN), a decrease in blood neutrophils accompanied by fever, is a major adverse event (AE) associated with cancer chemotherapy. We aimed to estimate the direct medical costs associated with FN management in breast cancer patients within a clinical trial with pegfilgrastim, a pegylated form of recombinant granulocyte colony-stimulating factor (G-CSF). We obtained data from 346 Japanese breast cancer patients in a randomized, placebo-controlled clinical trial comparing FN incidence due to TC adjuvant chemotherapy (docetaxel 75 mg/m2, cyclophosphamide 600 mg/m2) between pegfilgrastim-treated and placebo groups. We estimated mean costs for chemotherapy drugs, drugs for all AEs and FN, and hospitalization for all AEs and FN. We also calculated mean costs associated with drugs and hospitalization for FN specifically for patients who developed FN in the placebo group. For the pegfilgrastim and placebo groups, the total cost during the first cycle of chemotherapy was ¥189 135 and ¥98 106. This difference is associated with prophylactic use of pegfilgrastim. Our analysis clarified in the placebo group that FN incidents of 119/173 (68.6%), the mean drug cost related to all AEs and hospitalization caused by the first cycle of chemotherapy were ¥14 411and ¥11 180, respectively. The cost of each for FN treatment was ¥16 429 for the placebo group. The mean treatment cost for patients who developed FN in placebo group, was ¥11 145 for drugs and ¥28 420 for drugs and hospitalization. Pegfilgrastim reduced the costs incurred for both drugs and hospitalization for AEs as well as FN, although the total medical cost during the chemotherapy increased. Our study constitutes baseline data for further health economic evaluations of pegfilgrastim.

A phase III, randomized, non-inferiority study comparing the efficacy and safety of biosimilar filgrastim versus originator filgrastim for chemotherapy-induced neutropenia in breast cancer patients

PubMed Central

Hegg, Roberto; Mattar, André; de Matos, João Nunes; Pedrini, José Luiz; Aleixo, Sabina Bandeira; Rocha, Roberto Odebrecht; Cramer, Renato Peixoto; van-Eyll-Rocha, Sylvie

2016-01-01

OBJECTIVES: To compare the efficacy and safety of two filgrastim formulations for controlling chemotherapy-induced neutropenia and to evaluate the non-inferiority of the test drug relative to the originator. METHODS: This phase III non-inferiority study had a randomized, multicenter, and open-label design. The patients were randomized at a ratio of 1:1 with a follow-up period of 6 weeks for each patient. In both study arms, filgrastim was administered subcutaneously at a daily dose of 5 mg/kg body weight. The primary endpoint was the rate of grade 4 neutropenia in the first treatment cycle. The secondary endpoints were the duration of grade 4 neutropenia, the generation of anti-filgrastim antibodies, and the rates of adverse events, laboratory abnormalities, febrile neutropenia, and neutropenia of any grade. RESULTS: The primary efficacy analysis demonstrated the non-inferiority of the test drug compared with the originator drug; the upper limit of the 90% confidence interval (CI) for the rate of neutropenia between the two groups (12.61%) was lower than the established margin of non-inferiority. The two treatments were similar with respect to the secondary endpoints and safety. CONCLUSION: The efficacy and safety profile of the test drug were similar to those of the originator product based on the rate of grade 4 neutropenia in the first treatment cycle. This study supports Anvisa's approval of the first biosimilar drug manufactured by the Brazilian industry (Fiprima®). PMID:27759847

History of chronic comorbidity and risk of chemotherapy-induced febrile neutropenia in cancer patients not receiving G-CSF prophylaxis.

PubMed

Chao, C; Page, J H; Yang, S-J; Rodriguez, R; Huynh, J; Chia, V M

2014-09-01

Chemotherapy-induced febrile neutropenia (FN) is a clinically important complication that affects patient outcome by delaying chemotherapy doses or reducing dose intensity. Risk of FN depends on chemotherapy- and patient-level factors. We sought to determine the effects of chronic comorbidities on risk of FN. We conducted a cohort study to examine the association between a variety of chronic comorbidities and risk of FN in patients diagnosed with six types of cancer (non-Hodgkin lymphoma and breast, colorectal, lung, ovary, and gastric cancer) from 2000 to 2009 who were treated with chemotherapy at Kaiser Permanente Southern California, a large managed care organization. We excluded those patients who received primary prophylactic granulocyte colony-stimulating factor. History of comorbidities and FN events were identified using electronic medical records. Cox models adjusting for propensity score, stratified by cancer type, were used to determine the association between comorbid conditions and FN. Models that additionally adjusted for cancer stage, baseline neutrophil count, chemotherapy regimen, and dose reduction were also evaluated. A total of 19 160 patients with mean age of 60 years were included; 963 (5.0%) developed FN in the first chemotherapy cycle. Chronic obstructive pulmonary disease [hazard ratio (HR) = 1.30 (1.07-1.57)], congestive heart failure [HR = 1.43 (1.00-1.98)], HIV infection [HR = 3.40 (1.90-5.63)], autoimmune disease [HR = 2.01 (1.10-3.33)], peptic ulcer disease [HR = 1.57 (1.05-2.26)], renal disease [HR = 1.60 (1.21-2.09)], and thyroid disorder [HR = 1.32 (1.06-1.64)] were all associated with a significantly increased FN risk. These results provide evidence that history of several chronic comorbidities increases risk of FN, which should be considered when managing patients during chemotherapy. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For

A novel homozygous mutation in G6PC3 presenting as cyclic neutropenia and severe congenital neutropenia in the same family.

PubMed

Alangari, Abdullah A; Alsultan, Abdulrahman; Osman, Mohamed Elfaki; Anazi, Shamsa; Alkuraya, Fowzan S

2013-11-01

Patients with autosomal recessive cyclic neutropenia have no known causative genetic defect yet. Autozygosity mapping on two branches of an extended multiplex consanguineous family presenting with cyclic neutropenia or severe congenital neutropenia to look for candidate gene, followed by candidate gene selection and sequencing. A single autozygous interval on Chr17:33,901,938-45,675,414 that is exclusively shared by the affected members was identified. This interval spans 11.8 Mb and contains 30 genes. Review of these genes highlighted G6PC3 as the most likely candidate given its known role in neutrophil biology. Direct sequencing revealed a novel homozygous mutation (NM_138387.3, c.974T > G, p.Leu325Arg). Two of our patients had associated congenital defects that are known to occur in patients with G6PC3 mutations, including congenital heart disease and intermittent thrombocytopenia. Biallelic G6PC3 defects should be considered in patients with autosomal recessive cyclic neutropenia, especially those with typical associated congenital defects.

Antimicrobial prophylaxis and outpatient management of fever and neutropenia in adults treated for malignancy: American Society of Clinical Oncology clinical practice guideline.

PubMed

Flowers, Christopher R; Seidenfeld, Jerome; Bow, Eric J; Karten, Clare; Gleason, Charise; Hawley, Douglas K; Kuderer, Nicole M; Langston, Amelia A; Marr, Kieren A; Rolston, Kenneth V I; Ramsey, Scott D

2013-02-20

To provide guidelines on antimicrobial prophylaxis for adult neutropenic oncology outpatients and on selection and treatment as outpatients of those with fever and neutropenia. A literature search identified relevant studies published in English. Primary outcomes included: development of fever and/or infections in afebrile neutropenic outpatients and recovery without complications and overall mortality in febrile neutropenic outpatients. Secondary outcomes included: in afebrile neutropenic outpatients, infection-related mortality; in outpatients with fever and neutropenia, defervescence without regimen change, time to defervescence, infectious complications, and recurrent fever; and in both groups, hospital admissions, duration, and adverse effects of antimicrobials. An Expert Panel developed guidelines based on extracted data and informal consensus. Forty-seven articles from 43 studies met selection criteria. Antibacterial and antifungal prophylaxis are only recommended for patients expected to have < 100 neutrophils/μL for > 7 days, unless other factors increase risks for complications or mortality to similar levels. Inpatient treatment is standard to manage febrile neutropenic episodes, although carefully selected patients may be managed as outpatients after systematic assessment beginning with a validated risk index (eg, Multinational Association for Supportive Care in Cancer [MASCC] score or Talcott's rules). Patients with MASCC scores ≥ 21 or in Talcott group 4, and without other risk factors, can be managed safely as outpatients. Febrile neutropenic patients should receive initial doses of empirical antibacterial therapy within an hour of triage and should either be monitored for at least 4 hours to determine suitability for outpatient management or be admitted to the hospital. An oral fluoroquinolone plus amoxicillin/clavulanate (or plus clindamycin if penicillin allergic) is recommended as empiric therapy, unless fluoroquinolone prophylaxis was used

Cost-effectiveness of febrile neutropenia prevention with primary versus secondary G-CSF prophylaxis for adjuvant chemotherapy in breast cancer: a systematic review.

PubMed

Younis, T; Rayson, D; Jovanovic, S; Skedgel, C

2016-10-01

The adoption of primary (PP) versus secondary prophylaxis (SP) of febrile neutropenia (FN), with granulocyte colony-stimulating factors (G-CSF), for adjuvant chemotherapy (AC) regimens in breast cancer (BC) could be affected by its "value for money". This systematic review examined (i) cost-effectiveness of PP versus SP, (ii) FN threshold at which PP is cost-effective including the guidelines 20 % threshold and (iii) potential impact of G-CSF efficacy assumptions on outcomes. The systematic review identified all cost-effectiveness/cost-utility analyses (CEA/CUA) involving PP versus SP G-CSF for AC in BC that met predefined inclusion/exclusion criteria. Five relevant CEA/CUA were identified. These CEA/CUA examined different AC regimens (TAC = 2; FEC-D = 1; TC = 2) and G-CSF formulations (filgrastim "F" = 4; pegfilgrastim "P" = 4) with varying baseline FN-risk (range 22-32 %), mortality (range 1.4-6.0 %) and utility (range 0.33-0.47). The potential G-CSF benefit, including FN risk reduction with P versus F, varied among models. Overall, relative to SP, PP was not associated with good value for money, as per commonly utilized CE thresholds, at the baseline FN rates examined, including the consensus 20 % FN threshold, in most of these studies. The value for money associated with PP versus SP was primarily dependent on G-CSF benefit assumptions including reduced FN mortality and improved BC survival. PP G-CSF for FN prevention in BC patients undergoing AC may not be a cost-effective strategy at the guidelines 20 % FN threshold.

Comparison of effectiveness of biosimilar filgrastim (Nivestim™), reference Amgen filgrastim and pegfilgrastim in febrile neutropenia primary prevention in breast cancer patients treated with neo(adjuvant) TAC: a non-interventional cohort study.

PubMed

Brito, M; Esteves, S; André, R; Isidoro, M; Moreira, A

2016-02-01

Biosimilars are supported by limited clinical data at the time of approval. Recently, Nivestim™, a biosimilar of reference of filgrastim, was approved for prevention of chemotherapy-related febrile neutropenia (FN). To add clinical experience to this new biosimilar, we performed a study to compare the effectiveness of Nivestim™ with reference filgrastim and pegfilgrastim in FN prevention in patients receiving high-risk FN chemotherapy. This is a comparative cohort study, with retrospective data collection. Three cohorts were identified according to the type of primary prophylaxis employed over different time periods: reference filgrastim (2004-2006), pegfilgrastim (2007-2008) and biosimilar filgrastim (2011-2012). The study included female patients with early breast cancer that received FN primary prophylaxis during (neo)adjuvant docetaxel/doxorubicin/cyclophosphamide (TAC). Reference filgrastim cohort included 147 patients and pegfilgrastim and biosimilar filgrastim cohorts 139 and 134 patients, respectively. FN rates per patient/cycle were 16 % (95 % confidence interval (CI) 10.2-22.5 %)/3 % (95 % CI 2.1-4.7 %) in the reference filgrastim group, 9 % (95 % CI 4.5-14.6 %)/2 % (95 % CI 1.3-3.6 %) in the pegfilgrastim group and 16 % (95 % CI 10.0-22.9 %)/4 % (95 % CI 2.5-5.3 %) in the biosimilar filgrastim cohort. The median absolute neutrophil count (ANC) at FN presentation was lower in the biosimilar group in comparison with reference filgrastim. FN episodes with ANC < 100 cells/μL were more frequent in the biosimilar group (50 %) when compared with reference filgrastim (4 %) and pegfilgrastim (6 %). No differences concerning FN complications were seen, with the exception of more chemotherapy delays in the biosimilar group when compared with pegfilgrastim. No differences in biosimilar effectiveness were detected. The clinical relevance of the profound neutropenia found in the biosimilar cohort needs further attention.

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.

PubMed

Ahn, Shin; Rice, Terry W; Yeung, Sai-Ching J; Cooksley, Tim

2018-05-01

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. 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. 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). 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.

Genetics Home Reference: cyclic neutropenia

MedlinePlus

... Facebook Twitter Home Health Conditions Cyclic neutropenia Cyclic neutropenia Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Cyclic neutropenia is a disorder that causes frequent infections and ...

Therapeutic Use of Filgrastim for Established Febrile Neutropenia Is Cost Effective Among Patients With Solid Tumors and Lymphomas.

PubMed

Wang, Xiao Jun; Tong, Wei Xiang; Chan, Alexandre

2017-06-01

With the emergence of biosimilar filgrastim to the market, there is a gradual decrease in the listed price of the originator product of filgrastim over the years, and this could have an impact on the cost-effectiveness of filgrastim in the treatment of febrile neutropenia (FN). A cost-effectiveness analysis would allow clinicians to make informed decision when considering the therapeutic filgrastim among low-risk FN patients. This study aims to evaluate the cost-effectiveness of adding therapeutic filgrastim to antibiotics in the treatment of established FN among patients with solid tumors and lymphomas. A decision tree model was created to compare two treatment options for established FN as follows: (1) antibiotics alone (standard care) and (2) antibiotics with therapeutic filgrastim (comparator). The target population was a hypothetical cohort of adult cancer patients with solid tumors or lymphomas hospitalized with FN in Singapore. The analysis was performed from a hospital's perspective over a 21-day time horizon. The main outcome measures included costs, quality-adjusted life year (QALY) and incremental cost-effectiveness ratio (ICER). One-way sensitivity analysis and probabilistic sensitivity analysis were conducted to evaluate the robustness of the results. Compared with antibiotics alone, the treatment strategy of antibiotics with therapeutic filgrastim was a dominant choice, incurring a cost saving of US$125 per patient (comparator versus standard care: US$9110 versus US$9235) and additional health benefit of 0.0007 QALY gained per patient (comparator versus standard care: 0.0450 versus 0.0443). Model results were robust against the parameter variations in the one-way sensitivity analyses, but increasing the cost of filgrastim beyond US$87 per injection would increase the ICER to >US$50,000/QALY. Furthermore, the strategy of antibiotics with therapeutic filgrastim was the preferred choice (dominant or cost-effective) in 83.7% of the model iterations at a

[Prophylactic antibiotic treatment of neutropenic patients].

PubMed

Telekes, András; Hegedüs, Márta

2004-07-11

There is no special signs of neutropenia therefore it is usually diagnosed due to an acute infection or laboratory control. Infections acquired during chemotherapy induced myelosuppression may further deteriorate the neutropenia in cancer patients. There are many possible cause of fever in cancer patients but in case of neutropenia infection is the most likely reason. If febrile neutropenia occurs immediately broad spectrum intravenous antibiotic treatment should be initiated. Recently introduced aggressive chemotherapy protocols further increased the number of neutropenic patients. Therefore it would be important to prevent febrile neutropenia. Unfortunately the available data still insufficient to make any conclusions regarding the efficacy of short or long term prophylactic treatment. While there are generally accepted recommendations of empiric antibiotic therapy no such options are available regarding prophylactic treatments. The decision regarding prophylactic treatment (similarly to empiric therapy) should be based on the resistance of the dominant pathogens in a therapeutic unit. Several study had been conducted regarding prophylactic administration of antibiotics the results however contradictory. Considering the advantages and disadvantages, the prophylactic antibiotic treatment of neutropenic patients could be suggested only in certain cases.

The Characterization and Treatment of Aggressive Breast Cancer

DTIC Science & Technology

2007-05-01

of febrile neutropenia , G- CSF should be given with the next cycle. For an episode of febrile neutropenia despite dose reduction and G-CSF, protocol...permitted, and should be documented. 5.2.3 The use of granulocyte colony stimulating agents should only be used if there is persistent neutropenia ... neutropenia , leukopenia, more pronounced in patients with compromised renal function Gastrointestinal: nausea and vomiting, treatable with moderate doses

Prolonged or Standard Infusion of Cefepime Hydrochloride in Treating Patients With Febrile Neutropenia

ClinicalTrials.gov

2017-05-25

Adult Acute Lymphoblastic Leukemia; Adult Acute Myeloid Leukemia; Adult Burkitt Lymphoma; Adult Diffuse Large Cell Lymphoma; Adult Diffuse Mixed Cell Lymphoma; Adult Diffuse Small Cleaved Cell Lymphoma; Adult Hodgkin Lymphoma; Adult Immunoblastic Large Cell Lymphoma; Adult Lymphoblastic Lymphoma; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Breast Cancer; Chronic Eosinophilic Leukemia; Chronic Lymphocytic Leukemia; Chronic Myelogenous Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Cutaneous T-cell Non-Hodgkin Lymphoma; Disseminated Neuroblastoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Grade 3 Follicular Lymphoma; Malignant Testicular Germ Cell Tumor; Mantle Cell Lymphoma; Marginal Zone Lymphoma; Multiple Myeloma; Mycosis Fungoides/Sezary Syndrome; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Neutropenia; Nodal Marginal Zone B-cell Lymphoma; Ovarian Epithelial Cancer; Ovarian Germ Cell Tumor; Plasma Cell Neoplasm; Poor Prognosis Metastatic Gestational Trophoblastic Tumor; Primary Myelofibrosis; Prolymphocytic Leukemia; Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma

Neutropenia in the Newborn

PubMed Central

Maheshwari, Akhil

2013-01-01

PURPOSE OF REVIEW Review normal blood neutrophil concentrations and the clinical approach to neutropenia in the neonatal period. A literature search on neonatal neutropenia was performed using the databases PubMed, EMBASE, and Scopus and the electronic archive of abstracts presented at the annual meetings of the Pediatric Academic Societies. RECENT FINDINGS This review summarizes current knowledge on the causes of neutropenia in premature and critically-ill neonates, focusing on common causes such as maternal hypertension, neonatal sepsis, twin-twin transfusion, alloimmunization, and hemolytic disease. The article provides a rational approach to diagnosis and treatment of neonatal neutropenia, including current evidence on the role of recombinant hematopoietic growth factors. SUMMARY Neutrophil counts should be carefully evaluated in premature and critically-ill neonates. Although neutropenia is usually benign and runs a self-limited course in most neonates, it can be prolonged and constitute a serious deficiency in antimicrobial defense in some infants. PMID:24322487

European guidelines for empirical antibacterial therapy for febrile neutropenic patients in the era of growing resistance: summary of the 2011 4th European Conference on Infections in Leukemia

PubMed Central

Averbuch, Diana; Orasch, Christina; Cordonnier, Catherine; Livermore, David M.; Mikulska, Małgorzata; Viscoli, Claudio; Gyssens, Inge C.; Kern, Winfried V.; Klyasova, Galina; Marchetti, Oscar; Engelhard, Dan; Akova, Murat

2013-01-01

Owing to increasing resistance and the limited arsenal of new antibiotics, especially against Gram-negative pathogens, carefully designed antibiotic regimens are obligatory for febrile neutropenic patients, along with effective infection control. The Expert Group of the 4th European Conference on Infections in Leukemia has developed guidelines for initial empirical therapy in febrile neutropenic patients, based on: i) the local resistance epidemiology; and ii) the patient’s risk factors for resistant bacteria and for a complicated clinical course. An ‘escalation’ approach, avoiding empirical carbapenems and combinations, should be employed in patients without particular risk factors. A ‘de-escalation’ approach, with initial broad-spectrum antibiotics or combinations, should be used only in those patients with: i) known prior colonization or infection with resistant pathogens; or ii) complicated presentation; or iii) in centers where resistant pathogens are prevalent at the onset of febrile neutropenia. In the latter case, infection control and antibiotic stewardship also need urgent review. Modification of the initial regimen at 72–96 h should be based on the patient’s clinical course and the microbiological results. Discontinuation of antibiotics after 72 h or later should be considered in neutropenic patients with fever of unknown origin who are hemodynamically stable since presentation and afebrile for at least 48 h, irrespective of neutrophil count and expected duration of neutropenia. This strategy aims to minimize the collateral damage associated with antibiotic overuse, and the further selection of resistance. PMID:24323983

The Usefulness of Procalcitonin and C-Reactive Protein as Early Diagnostic Markers of Bacteremia in Cancer Patients with Febrile Neutropenia

PubMed Central

Kim, Dae Yong; Ahn, Shin; Chun, Yeon Hee; Lim, Kyung Soo

2011-01-01

Purpose Procalcitonin (PCT) and C-reactive protein (CRP) are well known inflammatory markers. This study was designed to determine whether PCT and CRP are useful as early diagnostic markers for bacteremia in cancer patients with febrile neutropenia (FN) in the emergency department (ED). Materials and Methods In this retrospective study, 286 episodes of FN in the ED were consecutively included between June 2009 and August 2010. From medical records, clinical characteristics including PCT and CRP were extracted and analyzed. Results Bacteremia was identified in 38 (13.3%) of the 286 episodes. The median values of PCT (2.8 ng/mL vs. 0.0 ng/mL, p=0.000) and CRP (15.9 mg/dL vs. 5.6 mg/dL, p=0.002) were significantly higher in the group with bacteremia compared to the group without bacteremia. In univariate analysis, elevated PCT (>0.5 ng/mL) and CRP (>10 mg/dL) as well as older age, hypotension, tachycardia, tachypnea, and high body temperature were significantly associated with bacteremia. On multivariate analysis, elevated PCT (>0.5 ng/mL) (odds ratio [OR], 3.6; 95% confidence interval [CI], 1.4 to 9.2; p<0.01) and tachypnea (OR, 3.4; 95% CI, 1.4 to 8.5; p<0.01) were independent early diagnostic markers for bacteremia in FN patients. The area under the curve of PCT was 74.8% (95% CI, 65.1 to 84.6%) and that of CRP was 65.5% (95% CI, 54.8 to 76.1%). With a PCT cut-off value of 0.5 ng/mL, sensitivity and specificity were 60.5% and 82.3%, respectively, while the sensitivity and specificity were 57.6% and 67.3%, respectively, with a CRP cutoff of 10 mg/dL. Conclusion These findings suggest that PCT is a useful early diagnostic marker for the detection of bacteremia in FN at the ED and has better diagnostic value than CRP. PMID:22022295

Radioimmunotherapy (RIT) Dose-Escalation Studies in Prostate Cancer Using Anti-PSMA Antibody 177Lu-J591: RIT Alone and RIT in Combination with Docetaxel

DTIC Science & Technology

2008-10-01

for > 3 platelet transfusion in 30 days • Gr 4 neutropenia • Febrile neutropenia • Attributable Gr > 3 non-hematologic toxicity (excluding infusion...0% No febrile neutropenia (no growth factor use) • Transaminitis (n=12 evaluable) Transient Gr 1 17% (no Gr > 1) Figure-1...therapies and 36% progressed on 1-4 lines of chemotherapy including docetaxel. No DLT’s have been seen. 2 pts experienced reversible Gr 3 neutropenia

[Advances in research on childhood neutropenia].

PubMed

Feng, Jian-Hua; Qian, Yan

2017-04-01

Neutrophils, an important type of human immune cells, are involved in host defense against infections. Neutropenia refers to a group of diseases manifesting as a reduction in the absolute value of mature neutrophils and is often accompanied by an increased risk of bacterial infection. According to etiology and pathogenesis, neutropenia is classified into congenital and acquired neutropenia. This article reviews the current research status and advances in the etiology of neutropenia in children. A deep understanding of the etiology of neutropenia helps to improve the diagnosis and treatment of this disease.

Octreotide-Associated Neutropenia.

PubMed

Tse, Stacy S; Kish, Troy

2017-06-01

Drug-induced neutropenia and agranulocytosis are rare adverse events but can be fatal. Neutropenia can be induced by a myriad of drugs from almost every pharmacologic class. Octreotide is a somatostatin analog that has been used to treat variceal bleeding, acromegaly, and severe diarrhea associated with metastatic tumors, and to reduce symptoms in the setting of malignant bowel obstruction and pseudoobstruction. The most common adverse effects associated with octreotide include pain at the injection site and gastrointestinal effects such as loose stools, cramping, and nausea; neutropenia is not currently listed as an adverse effect of the drug. We describe the case of an 87-year-old man who developed neutropenia immediately after administration of three doses of subcutaneous octreotide. He presented to the hospital with a history of constipation and straining for 3 days. He was admitted, and laxatives, suppositories, and enemas were administered over the next 3 days to induce a bowel movement; however, they were ineffective. Bowel obstruction secondary to a mass was confirmed by computed tomography; the mass was eventually diagnosed as colon cancer. Octreotide 100 µg subcutaneously every 8 hours was started for the obstruction on the evening of hospital day 4. After the patient had received 3 doses of octreotide, his white blood cell count (WBC) had decreased from 4.1 × 10 3 /mm 3 (neutrophils 75.4%, absolute neutrophil count [ANC] 3.1 × 10 3 /mm 3 ) on admission to 1.6 × 10 3 /mm 3 (neutrophils 62%, ANC 0.99 × 10 3 /mm 3 ) on day 5. Given the temporal relationship of octreotide and neutropenia as well as the lack of a reasonable alternative cause, it was suspected that octreotide was the most likely culprit of the patient's neutropenia. Octreotide was subsequently discontinued, and his WBC increased to 4.9 × 10 3 /mm 3 (neutrophils 66.3%, ANC 3.2 × 10 3 /mm 3 ) the next day. The remainder of the patient's hospitalization was not significant

Outcome of severe infections in afebrile neutropenic cancer patients

PubMed Central

Mahkovic-Hergouth, Ksenija; Novakovic, Barbara Jezersek; Seruga, Bostjan

2016-01-01

Abstract Background In some neutropenic cancer patients fever may be absent despite microbiologically and/or clinically confirmed infection. We hypothesized that afebrile neutropenic cancer patients with severe infections have worse outcome as compared to cancer patients with febrile neutropenia. Patients and methods We retrospectively analyzed all adult cancer patients with chemotherapy-induced neutropenia and severe infection, who were admitted to the Intensive Care Unit at our cancer center between 2000 and 2011. The outcome of interest was 30-day in-hospital mortality rate. Association between the febrile status and in-hospital mortality rate was evaluated by the Fisher’s exact test. Results We identified 69 episodes of severe neutropenic infections in 65 cancer patients. Among these, 9 (13%) episodes were afebrile. Patients with afebrile neutropenic infection presented with hypotension, severe fatigue with inappetence, shaking chills, altered mental state or cough and all of them eventually deteriorated to severe sepsis or septic shock. Overall 30-day in-hospital mortality rate was 55.1%. Patients with afebrile neutropenic infection had a trend for a higher 30-day in-hospital mortality rate as compared to patients with febrile neutropenic infection (78% vs. 52%, p = 0.17). Conclusions Afebrile cancer patients with chemotherapy-induced neutropenia and severe infections might have worse outcome as compared to cancer patients with febrile neutropenia. Patients should be informed that severe neutropenic infection without fever can occasionally occur during cancer treatment with chemotherapy. PMID:27904453

How I manage children with neutropenia.

PubMed

Dale, David C

2017-08-01

Neutropenia, usually defined as a blood neutrophil count <1·5 × 10 9 /l, is a common medical problem for children and adults. There are many causes for neutropenia, and at each stage in life the clinical pattern of causes and consequences differs significantly. I recommend utilizing the age of the child and clinical observations for the preliminary diagnosis and primary management. In premature infants, neutropenia is quite common and contributes to the risk of sepsis with necrotizing enterocolitis. At birth and for the first few months of life, neutropenia is often attributable to isoimmune or alloimmune mechanisms and predisposes to the risk of severe bacterial infections. Thereafter when a child is discovered to have neutropenia, often associated with relatively minor symptoms, it is usually attributed to autoimmune disorder or viral infection. The congenital neutropenia syndromes are usually recognized when there are recurrent infections, the neutropenia is severe and there are congenital anomalies suggesting a genetic disorder. This review focuses on the key clinical finding and laboratory tests for diagnosis with commentaries on treatment, particularly the use of granulocyte colony-stimulating factor to treat childhood neutropenia. © 2017 John Wiley & Sons Ltd.

U.S. Army Medical Department Journal (April-June 2006)

DTIC Science & Technology

2006-06-01

sensitive groupings, gastrointestinal, respiratory, febrile , dermatological, psychological, and cause- stratified traumatic injuries. It should be...suffering from (an) obscure febrile disease” which “defied definite identification.”1 Invariably, each of these Soldiers had been training at nearby... neutropenia occurring on or about the second or third day of symptoms. The total white blood cell count frequently dropped to about 3,000/µl and

The VCS parameters: Potential hematological indicators for predicting antituberculosis drug-induced neutropenia.

PubMed

Shen, Tian; Gu, Delin; Zhu, Yihua; Shi, Junwei; Xu, Dongsheng; Cao, Xingjian

2016-08-01

The morphological changes in activated neutrophils associated with antituberculosis drugs can be measured by volume, conductivity, and scatter (VCS) technology on the Coulter LH750 hematology analyzer. We conducted the current study to further validate the clinical usefulness of the neutrophil VCS parameters in predicting drug-induced neutropenia. Peripheral blood samples were collected from 52 patients with drug-induced neutropenia, 309 patients without any abnormal CBC, and 237 healthy controls. The mean neutrophil volume (MNV) with its distribution width (NDW) and the mean neutrophil scatter (MNS) were studied. We observed a significant increase in the MNV and NDW as well as a significant decrease in the MNS in neutropenia patients approximately one week prior to development of neutropenia compared to healthy controls as well as to case controls. In addition, the delta MNV and delta MNS were respectively correlated well with delta absolute neutrophil counts when neutropenia occurred. The ROC curve analyses showed that the MNV、NDW and MNS had larger areas under curves compared to conventional parameters. With a cutoff of 150.15 for the MNV, a sensitivity of 84.4% and specificity of 75.7% were achieved prior to neutropenia. The neutrophil VCS parameters may be clinically useful as potential hematological indicators for predicting antituberculosis drug-induced neutropenia. Copyright © 2016 Elsevier B.V. All rights reserved.

Neutropenia induced by high-dose intravenous benzylpenicillin in treating neurosyphilis: Does it really matter?

PubMed Central

Zhao, Wei; Qi, Tengfei; Shi, Mei; Guan, Zhifang; Lu, Haikong; Long, Fuquan; Gao, Zixiao; Zhang, Sufang; Zhou, Pingyu

2017-01-01

Background Prompt therapy with high-dose intravenous benzylpenicillin for a prolonged period is critical for neurosyphilis patients to avoid irreversible sequelae. However, life-threatening neutropenia has been reported as a complication of prolonged therapy with high doses of benzylpenicillin when treating other diseases. This study aimed to investigate the incidence, presentation, management and prognosis of benzylpenicillin-induced neutropenia in treating neurosyphilis based on a large sample of syphilis patients in Shanghai. Methodology/Principal findings Between 1st January 2013 and 31st December 2015, 1367 patients with neurosyphilis were treated with benzylpenicillin, 578 of whom were eligible for recruitment to this study. Among patients without medical co-morbidities, the total incidence of benzylpenicillin-induced neutropenia and severe neutropenia was 2.42% (95% CI: 1.38–4.13%) and 0.35% (95% CI: 0.06–1.39%), respectively. The treatment duration before onset of neutropenia ranged from 10 to 14 days, with a total cumulative dose of between 240 and 324 megaunits of benzylpenicillin. Neutropenia was accompanied by symptoms of chills and fever (5 patients), fatigue (2 patients), cough (1 patient), sore throat (1 patient), diarrhea (1 patient) and erythematous rash (1 patient). The severity of neutropenia was not associated with age, gender or type of neurosyphilis (p>0.05). Neutropenia, even when severe, was often tolerated and normalized within one week. A more serious neutropenia did not occur when reinstituting benzylpenicillin in patients with mild or moderate neutropenia nor when ceftriaxone was used three months after patients had previously experienced severe neutropenia. Conclusions/Significance Benzylpenicillin-induced neutropenia was uncommon in our cohort of patients. Continuation of therapy was possible with intensive surveillance for those with mild or moderate neutropenia. For severe neutropenia, it is not essential to aggressively use

Neutropenia induced by high-dose intravenous benzylpenicillin in treating neurosyphilis: Does it really matter?

PubMed

Peng, Rui-Rui; Wu, Juan; Zhao, Wei; Qi, Tengfei; Shi, Mei; Guan, Zhifang; Lu, Haikong; Long, Fuquan; Gao, Zixiao; Zhang, Sufang; Zhou, Pingyu

2017-03-01

Prompt therapy with high-dose intravenous benzylpenicillin for a prolonged period is critical for neurosyphilis patients to avoid irreversible sequelae. However, life-threatening neutropenia has been reported as a complication of prolonged therapy with high doses of benzylpenicillin when treating other diseases. This study aimed to investigate the incidence, presentation, management and prognosis of benzylpenicillin-induced neutropenia in treating neurosyphilis based on a large sample of syphilis patients in Shanghai. Between 1st January 2013 and 31st December 2015, 1367 patients with neurosyphilis were treated with benzylpenicillin, 578 of whom were eligible for recruitment to this study. Among patients without medical co-morbidities, the total incidence of benzylpenicillin-induced neutropenia and severe neutropenia was 2.42% (95% CI: 1.38-4.13%) and 0.35% (95% CI: 0.06-1.39%), respectively. The treatment duration before onset of neutropenia ranged from 10 to 14 days, with a total cumulative dose of between 240 and 324 megaunits of benzylpenicillin. Neutropenia was accompanied by symptoms of chills and fever (5 patients), fatigue (2 patients), cough (1 patient), sore throat (1 patient), diarrhea (1 patient) and erythematous rash (1 patient). The severity of neutropenia was not associated with age, gender or type of neurosyphilis (p>0.05). Neutropenia, even when severe, was often tolerated and normalized within one week. A more serious neutropenia did not occur when reinstituting benzylpenicillin in patients with mild or moderate neutropenia nor when ceftriaxone was used three months after patients had previously experienced severe neutropenia. Benzylpenicillin-induced neutropenia was uncommon in our cohort of patients. Continuation of therapy was possible with intensive surveillance for those with mild or moderate neutropenia. For severe neutropenia, it is not essential to aggressively use hematopoietic growth factors or broad-spectrum antibiotics for patients in

Radioimmunotherapy (RIT) Dose-Escalation Studies in Prostate Cancer Using Anti-PSMA Antibody 177Lu-J591: RIT Alone and RIT in Combination with Docetaxel

DTIC Science & Technology

2010-10-01

count < 15,000 > 7 days or need for > 3 plt transfusions in 30 days • Gr 4 neutropenia > 7 days • Febrile neutropenia • Attributable Gr > 3...11% No febrile neutropenia (no growth factor use) • Transaminitis Transient Gr 1 AST 29% (1 Gr 2) Need for transfusions 6 pts...No pts had significant bleeding; 2 received plt transfusions (cohort 6) • Neutropenia Gr 0 = 40%; Gr 1-2 = 32%; Gr 3 = 29%; Gr 4

Interpreting febrile neutropenia rates from randomized, controlled trials for consideration of primary prophylaxis in the real world: a systematic review and meta-analysis.

PubMed

Truong, J; Lee, E K; Trudeau, M E; Chan, K K W

2016-04-01

Guidelines recommend primary prophylaxis (PP) with granulocyte-colony-stimulating factors (G-CSF) for patients above a febrile neutropenia (FN) risk threshold of 20%. Practitioners often use FN rates of regimens based on data from randomized, controlled trials (RCTs), which are often comprised of highly selected patients. Patients in the community setting may be at higher risk of FN. A systematic literature search was conducted for full-length articles reporting FN rates for breast cancer-related chemotherapies between January 1996 and February 2014. A regimen was included if there was at least one RCT and one observational study. Meta-regression was used to model the odds of FN. 130 studies involving 29 regimens and 50 069 patients were identified. Sixty-five observational study (n = 7812) and 110 RCT (n = 42 257) cohorts were included. The unadjusted FN rate was 11.7% in observational and 7.9% in RCT cohorts. The univariable odds ratio (OR) for FN in the observational study compared with RCT cohorts was 1.58 [95% confidence interval (CI) 1.09-2.28; P = 0.017]. The FN rates remained significantly higher in the observational study compared with RCT cohorts (OR = 1.74; 95% CI 1.15-2.62; P = 0.012) after adjusting for age, chemotherapy intent, and regimen; this meant that a 13% (95% CI 8.7% to 17.9%) FN rate in RCT would translate into 20% FN rate in observational study. FN rates in the observational studies are significantly higher than suggested by RCTs. Guidelines should clarify how FN rates from RCTs should be applied in clinical practice. Large population-based studies are needed to confirm FN rates in the real world. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Cost-effectiveness of granulocyte colony-stimulating factor prophylaxis in chemotherapy-induced febrile neutropenia among breast cancer and Non-Hodgkin's lymphoma patients under Taiwan's national health insurance system.

PubMed

Wen, Tsun-Jen; Wen, Yu-Wen; Chien, Chun-Ru; Chiang, Shao-Chin; Hsu, William Wei-Yuan; Shen, Li-Jiuan; Hsiao, Fei-Yuan

2017-04-01

The beneficial effects of granulocyte colony-stimulating factor (G-CSF) prophylaxis on reducing the risk of chemotherapy-induced febrile neutropenia (CIFN) were well documented throughout the literature. However, existing data regarding its cost-effectiveness were conflicting. We estimated the cost-effectiveness of G-CSF prophylaxis in CIFN under Taiwan's National Health Insurance (NHI) system. Data on clinical outcomes and direct medical costs were derived for 5179 newly diagnosed breast cancer and 629 non-Hodgkin's lymphoma (NHL) patients from the NHI claims database. Patients were further categorized into three subgroups as "primary-", "secondary-" and "no -" prophylaxis based on their patterns of G-CSF use. Generalized estimating equations were applied to estimate the impact of G-CSF use on the incidence of CIFN. The incremental cost-effectiveness ratios of primary and secondary prophylactic G-CSF use were calculated and sensitivity analyses were performed. Primary prophylaxis of G-CSF decreased the incidence of CIFN by 27% and 83%, while secondary prophylaxis by 34% and 22% in breast cancer and NHL patients, respectively. Compared with those with no prophylaxis, the incremental cost per CIFN reduced in primary prophylaxis is $931 and $52 among patients with breast cancer and NHL, respectively. In contrast, secondary prophylaxis is dominated by no prophylaxis and primary prophylaxis in both cancer patients. Primary but not secondary prophylactic use of G-CSF was cost-effective in CIFN in breast cancer and NHL patients under Taiwan's NHI system. © 2016 John Wiley & Sons, Ltd.

Variation in Management of Fever and Neutropenia Among Pediatric Patients with Cancer: A Survey of Providers in Michigan

PubMed Central

Mueller, Emily L.; Walkovich, Kelly J.; Yanik, Gregory A.; Clark, Sarah J.

2016-01-01

Considerable variation in the management of fever and neutropenia (FN) exists, with factors associated with treatment variation not well described. An on-line survey of 90 pediatric cancer providers in Michigan was performed in Spring 2014. The survey frame was pediatric patients with cancer receiving treatment, with a Port-a-cath, who were clinically stable. Criteria for “Decreased” and “Increased” risk groups were defined by respondents. Survey questions addressed FN definitions, risk groups conceptualization, routine clinical practice, and management guidelines, in the context of risk groups and distance to treating institution. Fifty providers responded (56%), the majority defined a febrile event as temperature >38.3°C and/or two events > 38.0°C within a 24-hour period. Neutropenia was defined as current or anticipated absolute neutrophil count (ANC) <500/μL. Majority of respondents recommended “Decreased” and “Increased” patients present to a local emergency department (ED) if they live >2 hours away. Respondents were significantly more likely to have a “Decreased Risk” patient travel over 2 hours if they rated the local ED as “Poor to Fair” on ability to access Port-a-caths (p 0.048). Most respondents would discharge patients who are afebrile for 24 hours, blood cultures negative for 48 hours, and neutrophil count of greater than 200/μL. 40% preferred discharge on oral antibiotics when the ANC<500/μL. Triaging for febrile pediatric patients with cancer is significantly influenced by the providers’ perceptions of local EDs. Future investigation of local hospitals’ ability to provide urgent evaluation, combined with parental perspectives could lead to improvements in timely and effective management. PMID:26086779

Variation in Management of Fever and Neutropenia Among Pediatric Patients With Cancer: A Survey of Providers in Michigan.

PubMed

Mueller, Emily L; Walkovich, Kelly J; Yanik, Gregory A; Clark, Sarah J

2015-01-01

Considerable variation in the management of fever and neutropenia (FN) exists, with factors associated with treatment variation not well described. An online survey of 90 pediatric cancer providers in Michigan was performed in Spring 2014. The survey frame was pediatric patients with cancer receiving treatment, with a Port-a-cath, who were clinically stable. Criteria for "Decreased" and "Increased" risk groups were defined by respondents. Survey questions addressed FN definitions, risk groups conceptualization, routine clinical practice, and management guidelines, in the context of risk groups and distance to treating institution. Fifty providers responded (56%); the majority defined a febrile event as temperature >38.3°C and/or 2 events >38.0°C within a 24-hour period. Neutropenia was defined as current or anticipated absolute neutrophil count (ANC) <500/μL. Majority of respondents recommended "Decreased" and "Increased" patients present to a local emergency department (ED) if they live >2 hours away. Respondents were significantly more likely to have a "Decreased Risk" patient travel over 2 hours if they rated the local ED as "Poor to Fair" on ability to access Port-a-caths (P = .048). Most respondents would discharge patients who are afebrile for 24 hours, blood cultures negative for 48 hours, and neutrophil count of greater than 200/μL; 40% preferred discharge on oral antibiotics when the ANC <500/μL. Triaging for febrile pediatric patients with cancer is significantly influenced by the providers' perceptions of local EDs. Future investigation of local hospitals' ability to provide urgent evaluation, combined with parental perspectives, could lead to improvements in timely and effective management.

Filgrastim as a Rescue Therapy for Persistent Neutropenia in a Case of Dengue Hemorrhagic Fever with Acute Respiratory Distress Syndrome and Myocarditis

PubMed Central

Deepak, Desh; Garg, Rakesh; Pawar, Mridula; Banerjee, Neerja; Solanki, Rakesh; Maurya, Indubala

2011-01-01

Pathogenesis of dengue involves suppression of immune system leading to development of characteristic presentation of haematological picture of thrombocytopenia and leucopenia. Sometimes, this suppression in immune response is responsible for deterioration in clinical status of the patient in spite of all specific and supportive therapy. Certain drugs like steroids are used for rescue therapy in conditions like sepsis. We present a novel use of filgrastim as a rescue therapy in a patient with dengue hemorrhagic fever (DHF) with acute respiratory distress syndrome (ARDS), myocarditis, and febrile neutropenia and not responding to standard management. PMID:22606398

Use of computed tomography abdomen and pelvis for investigation of febrile neutropenia in adult haematology patients.

PubMed

Lim, H Y; Ashby, M; Williams, B; Grigg, A

2016-11-01

We retrospectively evaluated the use of computed tomography abdomen and pelvis (CTAP) in febrile neutropenic autologous stem cell transplant (ASCT) and acute myeloid leukaemia (AML) patients. CTAP was more common in ASCT patients (59%) compared with AML (31%; P  < 0.001). Although abnormal findings were reported in 51%, only 10% resulted in therapy change (addition of anaerobic antibiotic/bowel rest), which would have otherwise been instituted based on clinical grounds. CTAP in these patients rarely provide useful information unsuspected clinically. © 2016 Royal Australasian College of Physicians.

Prostate Cancer Clinical Trials Group: The University of Michigan Site

DTIC Science & Technology

2011-04-01

monotherapy, 10% of the 41 patients on the mitoxantrone/prednisone second-line arm experienced febrile neutropenia , and 9% of the 56 patients on this...study of the combination (with pegfilgrastim support) experi- enced febrile neutropenia . It is important to note, however, that this margin of safety can...15.9). Thirty-two percent of patients experienced grade 3 of 4 neutropenia , and 11% experienced grade 3 or higher neutropenic infections, including 1

Adherence to granulocyte-colony stimulating factor (G-CSF) guidelines to reduce the incidence of febrile neutropenia after chemotherapy--a representative sample survey in Germany.

PubMed

Link, Hartmut; Nietsch, J; Kerkmann, M; Ortner, P

2016-01-01

Febrile neutropenia (FN) after chemotherapy increases complications, morbidity, risk of death, reduction of dose delivery and impairs quality of life. Primary granulocyte-colony stimulating factor (G-CSF) prophylaxis after chemotherapy is recommended in the guideline (GL) if the risk of FN is high (≥20%) or intermediate (≥10-20%) with additional risk factors. This study evaluated the implementation of G-CSF GL. Sample size of the survey was calculated at 2% of the incidences of malignant lymphoma, breast cancer, and lung cancer in Germany in 2006. Patients were documented retrospectively over three to nine cycles of chemotherapy and FN risk ≥10%. Professional physician profiles were analyzed by classification and regression tree analysis (CART). One hundred ninety-five hematologists-oncologists and pulmonologists and gynecologists specialized in oncology documented data of 666 lung cancer patients, 286 malignant lymphoma patients, and 976 breast cancer patients, with 7805 chemotherapy cycles; 85.1% of physicians claimed adhering to G-CSF GL. Adherence to GL in all high-FN-risk chemotherapy cycles was 15.4% in lung cancer, 84.5% in malignant lymphoma, and 85.6% in breast cancer, and in all intermediate-FN-risk chemotherapy cycles, lung cancer it was 38.8%, malignant lymphoma it was 59.4%, and breast cancer it was 49.3%. G-CSF was overused without additional patient risk factors in 7.2% lung cancer cycles, 16.8% malignant lymphoma cycles, and 17.6% breast cancer cycles. The CART analysis split pulmonologists and other specialists, with the latter adhering more to GL. Pulmonologists, trained less than 22.5 years, adhered better to GL, as did also gynecologists or hematologists-oncologists with professional experience less than 8.1 years. Acceptance of and adherence to G-CSF GL differed between lung cancer, lymphoma, and breast cancer. Physicians overestimate their adherence to the GL. Physicians adhering to the GL can be characterized.

Effects of neutropenia and histological responses in esophageal squamous cell carcinoma with neo-adjuvant chemotherapy.

PubMed

Konishi, Hirotaka; Fujiwara, Hitoshi; Shiozaki, Atsushi; Hiramoto, Hidekazu; Kosuga, Toshiyuki; Komatsu, Shuhei; Ichikawa, Daisuke; Okamoto, Kazuma; Otsuji, Eigo

2016-02-01

Neo-adjuvant chemotherapy (NAC) followed by radical esophagectomy has been shown to prolong survival in patients with locally advanced esophageal squamous cell carcinoma (ESCC). However, neutropenia, one of the major adverse events due to NAC, influences the therapeutic course. The aim of this study is to clarify the relationship between neutropenia and therapeutic response in ESCC with NAC. A total of 117 patients with clinical stage II/III ESCC who had undergone NAC followed by radical esophagectomy were retrospectively analyzed in terms of the relationship between neutropenia and clinicopathological features or outcomes. Neutropenia was the major adverse event observed in 56 % (66/117) and grade 3/4 neutropenia occurred in 29 % of patients. Grade 3/4 neutropenia correlated with a high histological response (Grade 1b-3) (p < 0.01). Correlative analysis identified grade 3/4 neutropenia and poor differentiation as independent predictors of a high histological response (odds ratio 5.13 and 3.25, p < 0.01 and p = 0.01, respectively). Survival analysis showed that patients with a high histological response had significantly longer survival than those with a low histological response (Grade 0-1a) (p = 0.03), whereas no significant differences were found for survival according to the grade of neutropenia (p = 0.45). In a subgroup analysis according to histological response, grade 3/4 neutropenia correlated with worse survival in patients with a low histological response (p = 0.05). Severe neutropenia due to NAC correlates with a high histological response in ESCC. However, severe neutropenia may also result in a worse prognosis for patients with a low histological response.

Accelerate Genomic Aging in Congenital Neutropenia

DTIC Science & Technology

2017-10-01

syndrome (MDS) or acute myeloid leukemia (AML) in patients with congenital neutropenia. We hypothesize that replicative stress and/or changes in the...neutropenia; Shwachman Diamond syndrome ; Cyclic neutropenia; Hematopoietic stem cells; Granulocyte colony-stimulating factor; Acute myeloid leukemia... syndrome (MDS) or acute myeloid leukemia (AML). The cumulative incidence of MDS/AML in patients with SCN treated with G-CSF is 22%. Likewise, the

Primary granulocyte colony-stimulating factor prophylaxis during the first two cycles only or throughout all chemotherapy cycles in patients with breast cancer at risk for febrile neutropenia.

PubMed

Aarts, Maureen J; Peters, Frank P; Mandigers, Caroline M; Dercksen, M Wouter; Stouthard, Jacqueline M; Nortier, Hans J; van Laarhoven, Hanneke W; van Warmerdam, Laurence J; van de Wouw, Agnes J; Jacobs, Esther M; Mattijssen, Vera; van der Rijt, Carin C; Smilde, Tineke J; van der Velden, Annette W; Temizkan, Mehmet; Batman, Erdogan; Muller, Erik W; van Gastel, Saskia M; Borm, George F; Tjan-Heijnen, Vivianne C G

2013-12-01

Early breast cancer is commonly treated with anthracyclines and taxanes. However, combining these drugs increases the risk of myelotoxicity and may require granulocyte colony-stimulating factor (G-CSF) support. The highest incidence of febrile neutropenia (FN) and largest benefit of G-CSF during the first cycles of chemotherapy lead to questions about the effectiveness of continued use of G-CSF throughout later cycles of chemotherapy. In a multicenter study, patients with breast cancer who were considered fit enough to receive 3-weekly polychemotherapy, but also had > 20% risk for FN, were randomly assigned to primary G-CSF prophylaxis during the first two chemotherapy cycles only (experimental arm) or to primary G-CSF prophylaxis throughout all chemotherapy cycles (standard arm). The noninferiority hypothesis was that the incidence of FN would be maximally 7.5% higher in the experimental compared with the standard arm. After inclusion of 167 eligible patients, the independent data monitoring committee advised premature study closure. Of 84 patients randomly assigned to G-CSF throughout all chemotherapy cycles, eight (10%) experienced an episode of FN. In contrast, of 83 patients randomly assigned to G-CSF during the first two cycles only, 30 (36%) had an FN episode (95% CI, 0.13 to 0.54), with a peak incidence of 24% in the third cycle (ie, first cycle without G-CSF prophylaxis). In patients with early breast cancer at high risk for FN, continued use of primary G-CSF prophylaxis during all chemotherapy cycles is of clinical relevance and thus cannot be abandoned.

Presumed primary immune-mediated neutropenia in 35 dogs: a retrospective study.

PubMed

Devine, L; Armstrong, P J; Whittemore, J C; Sharkey, L; Bailiff, N; Huang, A; Rishniw, M

2017-06-01

To describe, in a cohort of dogs with presumed primary immune-mediated neutropenia, the presenting clinical characteristics, haematology results, bone marrow characteristics, therapies used (drugs and doses), clinical response to treatment, relapse and outcome at six months and one year. Multi-institutional recruited retrospective descriptive case series with voluntary submissions. Presumed immune-mediated neutropenia was diagnosed based on a neutrophil concentration <1·5×10 9 cells/L on a minimum of two complete blood counts, exclusion of other causes of neutropenia based on a diagnostic bone marrow aspirate or biopsy, and exclusion of secondary immune-mediated neutropenia. Dogs meeting these diagnostic criteria between 2006 and 2013, and that had a haematocrit of ≥29% and minimum of two complete blood clounts performed after initiation of therapy, were included. Information on 35 dogs was included. Neutropenia was less than 0·5×10 9 cells/L in most cases (21 dogs), 0·5 to ·99×10 9 cells/L in 11, and 1.0 to 1·49×10 9 cells/L in three. Eight dogs had thrombocytopenia, which was severe (<49·9×10 9 cells/L) in three. [Correction added on 23 May 2017, after first online publication: the cell numbers were incorrect due to errors in the conversion of cell measurements to international units. The numbers have been corrected throughout the article and Table 2.] Twenty-three dogs had myeloid hyperplasia, 10 dogs had myeloid hypoplasia and two dogs had normal myelopoiesis. Neutropenia resolved in 32 of 33 dogs within two weeks of starting corticosteroid therapy and in all dogs within one month. Relapse of neutropenia occurred in 12 cases within one year. Initial response of presumed primary immune-mediated neutropenia cases to corticosteroid therapy can be excellent. Long-term monitoring for relapse is warranted because 34% of cases relapsed during or after taper of immunosuppressive medications. © 2017 British Small Animal Veterinary Association.

Approach to the patient with neutropenia in childhood

PubMed Central

Celkan, Tiraje; Koç, Begüm Şirin

2015-01-01

Neutrophils have an important role in host defense and acute inflammation. It is well known that susceptibility to infection increases when the neutrophil count is low. Neutropenia were classified as mild, moderate and severe according to the neutrophil counts, or acute and chronic depending on the duration of neutropenia, or congenital and acquired according to the mechanism. The patients with neutropenia are clinically different due to underlying mechanism, they have life- threatening infections or no infection may be observed. The most common cause of acquired neutropenia is viral infection, followed by drugs and autoimmune neutropenia. Congenital neutropenia are usually diagnosed by acute and life- threatening invasive bacterial and fungal infections. Immune system disorders and other systemic abnormalities may be accompanied or not. Recent years, novel single gen defects causing congenital neutropenia were defined through advanced genetic techniques. Molecular diagnosis is useful for risk stratification, choice of therapy and prognosis on follow- up. This review was prepared for pediatricians as a guide focused on approach neutropenia, which tests should be performed and when should be referred to a specialist. PMID:26568688

Congenital neutropenia: diagnosis, molecular bases and patient management.

PubMed

Donadieu, Jean; Fenneteau, Odile; Beaupain, Blandine; Mahlaoui, Nizar; Chantelot, Christine Bellanné

2011-05-19

The term congenital neutropenia encompasses a family of neutropenic disorders, both permanent and intermittent, severe (<0.5 G/l) or mild (between 0.5-1.5 G/l), which may also affect other organ systems such as the pancreas, central nervous system, heart, muscle and skin. Neutropenia can lead to life-threatening pyogenic infections, acute gingivostomatitis and chronic parodontal disease, and each successive infection may leave permanent sequelae. The risk of infection is roughly inversely proportional to the circulating polymorphonuclear neutrophil count and is particularly high at counts below 0.2 G/l.When neutropenia is detected, an attempt should be made to establish the etiology, distinguishing between acquired forms (the most frequent, including post viral neutropenia and auto immune neutropenia) and congenital forms that may either be isolated or part of a complex genetic disease.Except for ethnic neutropenia, which is a frequent but mild congenital form, probably with polygenic inheritance, all other forms of congenital neutropenia are extremely rare and have monogenic inheritance, which may be X-linked or autosomal, recessive or dominant.About half the forms of congenital neutropenia with no extra-hematopoietic manifestations and normal adaptive immunity are due to neutrophil elastase (ELANE) mutations. Some patients have severe permanent neutropenia and frequent infections early in life, while others have mild intermittent neutropenia.Congenital neutropenia may also be associated with a wide range of organ dysfunctions, as for example in Shwachman-Diamond syndrome (associated with pancreatic insufficiency) and glycogen storage disease type Ib (associated with a glycogen storage syndrome). So far, the molecular bases of 12 neutropenic disorders have been identified.Treatment of severe chronic neutropenia should focus on prevention of infections. It includes antimicrobial prophylaxis, generally with trimethoprim-sulfamethoxazole, and also granulocyte

Congenital neutropenia: diagnosis, molecular bases and patient management

PubMed Central

2011-01-01

The term congenital neutropenia encompasses a family of neutropenic disorders, both permanent and intermittent, severe (<0.5 G/l) or mild (between 0.5-1.5 G/l), which may also affect other organ systems such as the pancreas, central nervous system, heart, muscle and skin. Neutropenia can lead to life-threatening pyogenic infections, acute gingivostomatitis and chronic parodontal disease, and each successive infection may leave permanent sequelae. The risk of infection is roughly inversely proportional to the circulating polymorphonuclear neutrophil count and is particularly high at counts below 0.2 G/l. When neutropenia is detected, an attempt should be made to establish the etiology, distinguishing between acquired forms (the most frequent, including post viral neutropenia and auto immune neutropenia) and congenital forms that may either be isolated or part of a complex genetic disease. Except for ethnic neutropenia, which is a frequent but mild congenital form, probably with polygenic inheritance, all other forms of congenital neutropenia are extremely rare and have monogenic inheritance, which may be X-linked or autosomal, recessive or dominant. About half the forms of congenital neutropenia with no extra-hematopoetic manifestations and normal adaptive immunity are due to neutrophil elastase (ELANE) mutations. Some patients have severe permanent neutropenia and frequent infections early in life, while others have mild intermittent neutropenia. Congenital neutropenia may also be associated with a wide range of organ dysfunctions, as for example in Shwachman-Diamond syndrome (associated with pancreatic insufficiency) and glycogen storage disease type Ib (associated with a glycogen storage syndrome). So far, the molecular bases of 12 neutropenic disorders have been identified. Treatment of severe chronic neutropenia should focus on prevention of infections. It includes antimicrobial prophylaxis, generally with trimethoprim-sulfamethoxazole, and also granulocyte

Understanding chronic neutropenia: life is short.

PubMed

Bartels, Marije; Murphy, Kate; Rieter, Ester; Bruin, Marrie

2016-01-01

The pathophysiological mechanisms underlying chronic neutropenia are extensive, varying from haematopoietic stem cell disorders resulting in defective neutrophil production, to accelerated apoptosis of neutrophil progenitors or circulating mature neutrophils. While the knowledge concerning genetic defects associated with congenital neutropenia or bone marrow failure is increasing rapidly, the functional role and consequences of these genetic alterations is often not well understood. In addition, there is a large group of diseases, including primary immunodeficiencies and metabolic diseases, in which chronic neutropenia is one of the symptoms, while there is no clear bone marrow pathology or haematopoietic stem cell dysfunction. Altogether, these disease entities illustrate the complexity of normal neutrophil development, the functional role of the (bone marrow) microenvironment and the increased propensity to undergo apoptosis, which is typical for neutrophils. The large variety of disorders associated with chronic neutropenia makes classification almost impossible and possibly not desirable, based on the clinical phenotypes. However, a better understanding of the regulation of normal myeloid differentiation and neutrophil development is of great importance in the diagnostic evaluation of unexplained chronic neutropenia. In this review we propose insights in the pathophysiology of chronic neutropenia in the context of the functional role of key players during normal neutrophil development, neutrophil release and neutrophil survival. © 2015 John Wiley & Sons Ltd.

Family caring strategies in neutropenia.

PubMed

Eggenberger, Sandra K; Krumwiede, Norma; Meiers, Sonja J; Bliesmer, Mary; Earle, Patricia

2004-12-01

Aggressive chemotherapy protocols result in neutropenia in approximately half of all patients receiving chemotherapy. Thus, neutropenia continues to be a significant and potentially life-threatening side effect of treatment, even with use of colony-stimulating factors. Families of patients with neutropenia often provide the primary healing environment because most chemotherapy protocols are managed on an outpatient basis. To learn about the family's experience of managing chemotherapy-induced neutropenia (CIN), a grounded-theory methodology was used to analyze data from seven families. The central theme revealed by these families was "turbulent waiting with intensified connections." This meant that when families had a sense of greater vulnerability in response to the waiting after diagnosis of CIN, they connected intensely with each other and healthcare providers. Families reported that connections with nurses became more significant when neutropenia interrupted chemotherapy. Families also developed family caring strategies to manage this period of waiting for the chemotherapy to resume. These strategies included family inquiry, family vigilance, and family balancing. Nurses need to be aware of approaches to support the family's ability to manage CIN. Interventions and approaches constructed from the perspective of a family-professional partnership will enhance the family cancer experience as well as ongoing family growth and function.

Meta-Analysis and Cost Comparison of Empirical versus Pre-Emptive Antifungal Strategies in Hematologic Malignancy Patients with High-Risk Febrile Neutropenia.

PubMed

Fung, Monica; Kim, Jane; Marty, Francisco M; Schwarzinger, Michaël; Koo, Sophia

2015-01-01

Invasive fungal disease (IFD) causes significant morbidity and mortality in hematologic malignancy patients with high-risk febrile neutropenia (FN). These patients therefore often receive empirical antifungal therapy. Diagnostic test-guided pre-emptive antifungal therapy has been evaluated as an alternative treatment strategy in these patients. We conducted an electronic search for literature comparing empirical versus pre-emptive antifungal strategies in FN among adult hematologic malignancy patients. We systematically reviewed 9 studies, including randomized-controlled trials, cohort studies, and feasibility studies. Random and fixed-effect models were used to generate pooled relative risk estimates of IFD detection, IFD-related mortality, overall mortality, and rates and duration of antifungal therapy. Heterogeneity was measured via Cochran's Q test, I2 statistic, and between study τ2. Incorporating these parameters and direct costs of drugs and diagnostic testing, we constructed a comparative costing model for the two strategies. We conducted probabilistic sensitivity analysis on pooled estimates and one-way sensitivity analyses on other key parameters with uncertain estimates. Nine published studies met inclusion criteria. Compared to empirical antifungal therapy, pre-emptive strategies were associated with significantly lower antifungal exposure (RR 0.48, 95% CI 0.27-0.85) and duration without an increase in IFD-related mortality (RR 0.82, 95% CI 0.36-1.87) or overall mortality (RR 0.95, 95% CI 0.46-1.99). The pre-emptive strategy cost $324 less (95% credible interval -$291.88 to $418.65 pre-emptive compared to empirical) than the empirical approach per FN episode. However, the cost difference was influenced by relatively small changes in costs of antifungal therapy and diagnostic testing. Compared to empirical antifungal therapy, pre-emptive antifungal therapy in patients with high-risk FN may decrease antifungal use without increasing mortality. We

Time trends in utilization of G-CSF prophylaxis and risk of febrile neutropenia in a Medicare population receiving adjuvant chemotherapy for early-stage breast cancer.

PubMed

Goyal, Ravi K; Tzivelekis, Spiros; Rothman, Kenneth J; Candrilli, Sean D; Kaye, James A

2018-02-01

The purpose of this study is to assess temporal trends in the use of granulocyte colony-stimulating factor (G-CSF) prophylaxis and risk of febrile neutropenia (FN) among older women receiving adjuvant chemotherapy for early-stage breast cancer. Women aged ≥ 66 years with diagnosis of early-stage breast cancer who initiated selected adjuvant chemotherapy regimens were identified using the SEER-Medicare data from 2002 to 2012. Adjusted, calendar-year-specific proportions were estimated for use of G-CSF primary prophylaxis (PP) and secondary prophylaxis and FN risk in the first and the second/subsequent cycles during the first course of chemotherapy, using logistic regression models. calendar-year-specific mean probabilities were estimated with covariates set to modal values. Among 11,107 eligible patients (mean age 71.7 years), 74% received G-CSF in the first course of chemotherapy. Of all patients, 5819 (52%) received G-CSF PP, and among those not receiving G-CSF PP, only 5% received G-CSF secondary prophylaxis. The adjusted proportion using G-CSF PP increased from 6% in 2002 to 71% in 2012. During the same period, the adjusted risk of FN in the first cycle increased from 2% to 3%; the adjusted risk increased from 1.5% to 2.9% among those receiving G-CSF PP and from 2.3% to 3.5% among those not receiving G-CSF PP. The use of G-CSF PP increased substantially during the study period. Although channeling of higher-risk patients to treatment with G-CSF PP is expected, the adjusted risk of FN among patients treated with G-CSF PP tended to be lower than among those not receiving G-CSF PP.

The Characterization and Treatment of Aggressive Breast Cancer

DTIC Science & Technology

2005-05-01

of a cycle for over 7 days, the carboplatin dose will be decreased by 25% for subsequent cycles. For a second episode of febrile neutropenia , G-CSF...should be given with the next cycle. For an episode of febrile neutropenia despite dose reduction and G-CSF, protocol treatment should be discontinued... neutropenia despite a dose reduction in the previous course. G-CSF may also be used as clinically indicated for neutropenic infection. 4.2.4 The use of

Neutrophil kinetics of recombinant human granulocyte colony-stimulating factor-induced neutropenia in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Okada, Yuji; Kawagishi, Mayumi; Kusaka, Masaru

Single injection of recombinant human granulocyte colony-stimulating factor (rhG-CSF) immediately induced a decrease in the number of circulating neutrophils in rats. This neutropenia occurred 10 minutes after the injection but disappeared 40 minutes after injection. This transient neutropenia was dose-dependently induced by rhG-CSF and also induced by repeated injections. We studied the kinetics of circulating neutrophils in transient neutropenia. rhG-CSF markedly decreased the number of {sup 3}H-diisopropylfluorophosphate ({sup 3}H-DFP) labeled neutrophils in the circulation 10 minutes after injection but the labeled neutrophils recovered to near the control level 40 minutes after the injection. These results indicate that the neutrophil marginationmore » accounts for the neutrophenia and the marginated neutrophils return to the circulation.« less

Severe congenital cyclic neutropenia: A case report

PubMed Central

Patil, Vidyavathi H; Hugar, Shivayogi M; Balikai, Girish; Patil, Sudha

2016-01-01

Congenital cyclic neutropenia syndrome is a constitutional genetic disorder which is characterized by very low number of neutrophils (neutropenia). Patients suffering from this disorder clinically present with neutropenia at early age, history of recurrent fever, ulcerations in the oral cavity, gingivitis, and other recurrent infections. This paper describes a case report of a child with recurrent mouth ulcers, fever, and later diagnosed with severe congenital cyclic neutropenia. This also emphasizes the importance of identification of rare causes of immunosuppressive conditions in children presenting with recurrent oral ulcers and poor dental hygiene, to prevent long-term complications of oral cavity and also morbidity and mortality secondary to neutropenic sepsis. PMID:27857902

Clozapine Rechallenge After Neutropenia or Leucopenia.

PubMed

Prokopez, Cintia R; Armesto, Arnaldo R; Gil Aguer, María F; Balda, María V; Papale, Rosa M; Bignone, Inés M; Daray, Federico M

2016-08-01

To rechallenge with clozapine for a patient who previously has experienced neutropenia or leucopenia or during clozapine treatment is a difficult clinical decision. Herein, we analyzed the results of such a rechallenge in 19 patients. We analyzed all the reports, from the database of the pharmacovigilance department of the Argentine National Administration of Drugs, Foods, and Medical Devices, of patients who were rechallenged with clozapine after a leucopenia or a neutropenia. Nineteen cases of rechallenge after leucopenia or neutropenia were reported between 1996 and 2014. One third of the patients re-exposed to clozapine developed a new hematologic adverse reaction. The second blood dyscrasia was less severe in 83% of the cases and had a shorter median latency as compared with the first (8 weeks vs 182 weeks, P = 0.0045). There were no significant differences for demographic and clinical characteristics of patients who developed a second dyscrasia as compared with those who did not. The present study shows that almost 70% of the patients rechallenged with clozapine after a leucopenia or a neutropenia did not develop a new hematological adverse effect, whereas the remaining 30% had a faster but less serious neutropenia.

[Neutropenia in dogs: etiology and prognostic factors].

PubMed

Cook, Andrea M; Bauer, Natali; Neiger, Reto; Peppler, Christine; Moritz, Andreas

2016-10-12

The aim of this retrospective study was to evaluate frequency, prognostic factors, and differences for various etiologies of neutropenia in dogs. A total of 391 dogs with neutrophil counts < 2.78 x 10 9 /l (January 2008 to December 2012) were included and, depending on the etiology of neutropenia, assigned to seven diagnostic groups: nonbacterial infectious disease, increased demand due to marked inflammation, drug-associated, bone-marrow diseases, immune-mediated, physiologic, miscellaneous. Absolute neutrophil counts, evidence of neutrophil toxicity or left shift, case history, rectal temperature, hospitalization, and survival were compared among groups. Increased demand due to marked inflammation (90/391, 23%) and nonbacterial infectious disease (70/391, 18%) were the most common causes for neutropenia, followed by drug-associated neutropenia (43/391, 11%) and bone-marrow disease (32/391, 8%). Immune-mediated and physiologic neutropenia (both 16/391, 4%) were uncommon. Almost one third (124/391, 32%) of dogs were assigned to the miscellaneous group. Absolute neutrophil counts were significantly higher (p < 0.01) in dogs of the physiologic and miscellaneous groups than in the other groups. Dogs with immune-mediated neutropenia or nonbacterial infectious disease displayed significantly lower absolute neutrophil counts than dogs with neutropenia due to an increased demand (p < 0.001) and were most commonly referred with a history of fever (11/16, 69%) or gastrointestinal signs (52/70, 74%), respectively. Neutrophil toxicity and left shift were most commonly associated with an increased demand due to marked inflammation (60/90 and 25/90, 67% and 28%, respectively) and the mortality rate was highest in this group (32/90, 36%). Neutrophil toxicity and left shift are associated with an increased demand due to marked inflammation and may indicate a poor prognosis. The lower the absolute neutrophil count, the greater the probability of an immune

Neutropenia Associated with Long-Term Ceftaroline Use.

PubMed

LaVie, Katherine W; Anderson, Scott W; O'Neal, Hollis R; Rice, Todd W; Saavedra, Tatiana C; O'Neal, Catherine S

2016-01-01

Ceftaroline is a fifth-generation cephalosporin with potent antimicrobial activity against Gram-positive and Gram-negative pathogens. Neutropenia is a rare serious adverse event for the class of cephalosporins; however, we observed several cases of severe neutropenia in our outpatient infectious disease practice believed to be associated with ceftaroline use. The aim of this study was to determine the incidence of neutropenia among patients receiving ceftaroline therapy for more than 7 days. We conducted a retrospective cohort analysis of patients admitted to an 800-bed regional medical center between June 2012 and December 2014 who received ceftaroline for more than 7 days to assess the incidence of developing clinically significant neutropenia. Demographic and patient care data points as well as underlying admitting and chronic diagnoses were retrospectively collected from the medical record. Clinically significant neutropenia was defined as an absolute neutrophil count (ANC) less than 1,500 cells/mm(3). Analysis was performed to determine the incidence, severity, and outcome of neutropenia following ceftaroline administration. A total of 39 patients were included in the cohort. The median duration of therapy was 27 days. Seven patients (18%) developed neutropenia while on ceftaroline therapy. Four (10%) of the neutropenic patients had an ANC of <500 cells/mm(3). The median first neutropenic day was day 17, with the median ANC nadir of 432 cells/mm(3) on day 24. We determined that extended ceftaroline infusion is associated with the development of neutropenia. We recommend obtaining a complete blood count (CBC) with differential at the onset of therapy and weekly thereafter. Should the ANC fall below 2,500 cells/mm(3), then twice-weekly CBCs should be monitored for the duration of ceftaroline therapy, and therapy should be discontinued if the ANC falls to 1,500 cells/mm(3) or less. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Weekly Carboplatin Reduces Toxicity During Synchronous Chemoradiotherapy for Merkel Cell Carcinoma of Skin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Poulsen, Michael; Walpole, Euan; Harvey, Jennifer

Purpose: The toxicity of radiotherapy (RT) combined with weekly carboplatin and adjuvant carboplatin and etoposide was prospectively assessed in a group of patients with high-risk Stage I and II Merkel cell carcinoma of the skin. This regimen was compared with the Trans-Tasman Radiation Oncology Group 96:07 study, which used identical eligibility criteria but carboplatin and etoposide every 3 weeks during RT. Patients and Methods: Patients were eligible if they had disease localized to the primary site and lymph nodes, with high-risk features. RT was delivered to the primary site and lymph nodes to a dose of 50 Gy and weeklymore » carboplatin (area under the curve of 2) was given during RT. This was followed by three cycles of carboplatin and etoposide. A total of 18 patients were entered into the study, and their data were compared with the data from 53 patients entered into the Trans-Tasman Radiation Oncology Group 96:07 study. Results: Involved lymph nodes (Stage II) were present in 14 patients (77%). Treatment was completed as planned in 16 patients. The weekly carboplatin dose was delivered in 17 patients, and 15 were able to complete all three cycles of adjuvant carboplatin and etoposide. Grade 3 and 4 neutrophil toxicity occurred in 7 patients, but no cases of febrile neutropenia developed. Compared with the Trans-Tasman Radiation Oncology Group 96:07 protocol (19 of 53 cases of febrile neutropenia), the reduction in the febrile neutropenia rate (p = 0.003) and decrease in Grade 3 skin toxicity (p = 0.006) were highly statistically significant. Conclusion: The results of our study have shown that weekly carboplatin at this dosage is a safe way to deliver synchronous chemotherapy during RT for MCC and results in a marked reduction of febrile neutropenia and Grade 3 skin toxicity compared with the three weekly regimen.« less

Atypical febrile seizures, mesial temporal lobe epilepsy, and dual pathology.

PubMed

Sanon, Nathalie T; Desgent, Sébastien; Carmant, Lionel

2012-01-01

Febrile seizures occurring in the neonatal period, especially when prolonged, are thought to be involved in the later development of mesial temporal lobe epilepsy (mTLE) in children. The presence of an often undetected, underlying cortical malformation has also been reported to be implicated in the epileptogenesis process following febrile seizures. This paper highlights some of the various animal models of febrile seizures and of cortical malformation and portrays a two-hit model that efficiently mimics these two insults and leads to spontaneous recurrent seizures in adult rats. Potential mechanisms are further proposed to explain how these two insults may each, or together, contribute to network hyperexcitability and epileptogenesis. Finally the clinical relevance of the two-hit model is briefly discussed in light of a therapeutic and preventive approach to mTLE.

Atypical Febrile Seizures, Mesial Temporal Lobe Epilepsy, and Dual Pathology

PubMed Central

Sanon, Nathalie T.; Desgent, Sébastien; Carmant, Lionel

2012-01-01

Febrile seizures occurring in the neonatal period, especially when prolonged, are thought to be involved in the later development of mesial temporal lobe epilepsy (mTLE) in children. The presence of an often undetected, underlying cortical malformation has also been reported to be implicated in the epileptogenesis process following febrile seizures. This paper highlights some of the various animal models of febrile seizures and of cortical malformation and portrays a two-hit model that efficiently mimics these two insults and leads to spontaneous recurrent seizures in adult rats. Potential mechanisms are further proposed to explain how these two insults may each, or together, contribute to network hyperexcitability and epileptogenesis. Finally the clinical relevance of the two-hit model is briefly discussed in light of a therapeutic and preventive approach to mTLE. PMID:22957226

2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours.

PubMed

Aapro, M S; Bohlius, J; Cameron, D A; Dal Lago, Lissandra; Donnelly, J Peter; Kearney, N; Lyman, G H; Pettengell, R; Tjan-Heijnen, V C; Walewski, J; Weber, Damien C; Zielinski, C

2011-01-01

Chemotherapy-induced neutropenia is a major risk factor for infection-related morbidity and mortality and also a significant dose-limiting toxicity in cancer treatment. Patients developing severe (grade 3/4) or febrile neutropenia (FN) during chemotherapy frequently receive dose reductions and/or delays to their chemotherapy. This may impact the success of treatment, particularly when treatment intent is either curative or to prolong survival. In Europe, prophylactic treatment with granulocyte-colony stimulating factors (G-CSFs), such as filgrastim (including approved biosimilars), lenograstim or pegfilgrastim is available to reduce the risk of chemotherapy-induced neutropenia. However, the use of G-CSF prophylactic treatment varies widely in clinical practice, both in the timing of therapy and in the patients to whom it is offered. The need for generally applicable, European-focused guidelines led to the formation of a European Guidelines Working Party by the European Organisation for Research and Treatment of Cancer (EORTC) and the publication in 2006 of guidelines for the use of G-CSF in adult cancer patients at risk of chemotherapy-induced FN. A new systematic literature review has been undertaken to ensure that recommendations are current and provide guidance on clinical practice in Europe. We recommend that patient-related adverse risk factors, such as elderly age (≥65 years) and neutrophil count be evaluated in the overall assessment of FN risk before administering each cycle of chemotherapy. It is important that after a previous episode of FN, patients receive prophylactic administration of G-CSF in subsequent cycles. We provide an expanded list of common chemotherapy regimens considered to have a high (≥20%) or intermediate (10-20%) risk of FN. Prophylactic G-CSF continues to be recommended in patients receiving a chemotherapy regimen with high risk of FN. When using a chemotherapy regimen associated with FN in 10-20% of patients, particular attention

Etirinotecan pegol administration is associated with lower incidences of neutropenia compared to irinotecan administration.

PubMed

Sy, S Kenneth; Sweeney, Theresa D; Ji, Chunmei; Hoch, Ute; Eldon, Michael A

2017-01-01

The relationship between incidences of neutropenia and 10-hydroxy-7-ethyl camptothecin (SN38) exposure was explored using SN38 pharmacokinetic and neutrophil count data from toxicology studies of etirinotecan pegol (EP) and irinotecan in beagle dogs. Dogs received four weekly intravenous infusions of either vehicle control (n = 22), EP (6, 15, 20, 25, 40/25 mg/kg; n = 3-9 dogs/dose group/sex; n = 48), or irinotecan (20 or 25 mg/kg n = 3-4 dogs/dose group/sex; n = 14). Blood samples were collected up to 50 days post-dose for characterization of SN38 pharmacokinetics. Two separate models were created describing SN38 concentration time profiles after either irinotecan or EP administrations to project the AUC 0-168h after Day 1 and Day 22 doses. The relationship between incidence of neutropenia and SN38 exposure was explored using logistic regression. The incidence of neutropenia in dogs receiving weekly doses of irinotecan or EP was strongly correlated with maximum plasma SN38 concentration (C max ), but not SN38 area under the concentration-time curve (AUC). Neutropenia occurred in approximately 80% of dogs receiving irinotecan (mean SN38 C max of 13.5 and 26.3 ng/mL for 20 and 25 mg/kg, respectively). No neutropenia occurred in dogs receiving EP at doses up to and including 25 mg/kg (mean SN38 C max of 3.4 and 4.9 ng/mL for 20 and 25 mg/kg, respectively), despite 2.5-3.6 times greater SN38 AUC after EP compared to irinotecan at equivalent doses. EP administration avoids both high SN38 C max values and development of dose-limiting neutropenia observed after irinotecan, while maintaining greater and sustained SN38 exposure between doses.

How to differentiate congenital from noncongenital chronic neutropenia at the first medical examination? Proposal of score: A pilot study from the French Severe Chronic Neutropenia registry.

PubMed

Bejjani, Naim; Beaupain, Blandine; Bertrand, Yves; Bellanne-Chantelot, Christine; Donadieu, Jean

2017-12-01

We developed a diagnostic score to differentiate congenital from noncongenital neutropenia at the time of diagnosis using reliable data collected at the first visit of a patients with neutropenia. In a pilot retrospective study, we included 120 patients diagnosed with chronic neutropenia; 61 had congenital and 59 had noncongenital neutropenia. We reviewed patient medical charts and collected the initial complete blood count (CBC) and other reliable data. We used logistic regression to determine the probability that the neutropenia was congenital. On the initial CBC, the degree of neutropenia had no predictive value; only monocytosis >1.5 × 10 9 /l, hemoglobin <90 g/l, or mild thrombocytopenia <150 × 10 9 /l suggested congenital neutropenia. The most predictive factors for congenital neutropenia were a medical history (consanguinity and patient history of neutropenia), severe infections, and oral stomatitis or gingivitis at the time of diagnosis. The age at diagnosis had limited predictive value. A diagnosis of congenital neutropenia may be reliably suspected based only on information from the CBC, some basic information from patient and parent interviews, and a clinical examination. A pilot score with six factors that could be readily, reliably collected, should facilitate the diagnosis of congenital neutropenia. © 2017 Wiley Periodicals, Inc.

[Guidelines for standardizedmanagement of neutropenia induced by chemotherapy and radiotherapy].

PubMed

2017-11-23

Neutropenia is the most common hematologic toxicity of myelosuppressive chemotherapy and radiotherapy. The degree and duration of neutropenia are directly related to the risk of infection and even death, which can also affect the relative dose intensity of chemotherapy and the prognosis of patients. At present, clinicians tend to underestimate the harm of neutropenia, and are in lack of knowledge on granulocyte colony-stimulating factor(G-CSF), especially on prevention and treatment of neutropenia. Based on clinical evidence, the Chinese Society of Clinical Oncology (CSCO) develops guidelines on the assessment, prevention and treatment of neutropenia and the application of G-CSF. It suggests a hierarchical management concept for neutropenia and establishes a clinical path of prevention and treatment, in order to provide guidance for standardized management of neutropenia and the rational use of G-CSF.

Four novel ELANE mutations in patients with congenital neutropenia.

PubMed

Kurnikova, Maria; Maschan, Michael; Dinova, Evgeniya; Shagina, Irina; Finogenova, Natalia; Mamedova, Elena; Polovtseva, Tatyana; Shagin, Dmitry; Shcherbina, Anna

2011-08-01

Congenital neutropenia is a heterogeneous bone marrow failure syndrome characterized by a maturation arrest of myelopoesis at the promyelocyte/myelocyte stage. Cyclic neutropenia (CyN) and severe congenital neutropenia (SCN) are two main forms of congenital neutropenia. Genetic analysis has shown that heterozygous mutations in the ELANE gene encoding the neutrophil elastase are the major cause of these disorders. We investigated the prevalence of ELANE mutations in a group of 16 patients from 14 families with congenital neutropenia. Five patients had typical manifestations of CyN, and 11 patients had SCN. Seven different heterozygous ELANE mutations were found, including four novel mutations. Copyright © 2011 Wiley-Liss, Inc.

Severe infections in children with acute leukemia undergoing intensive chemotherapy can successfully be prevented by ciprofloxacin, voriconazole, or micafungin prophylaxis.

PubMed

Yeh, Ting-Chi; Liu, Hsi-Che; Hou, Jen-Yin; Chen, Kuan-Hao; Huang, Ting-Huan; Chang, Ching-Yi; Liang, Der-Cherng

2014-04-15

The purpose of the current study was to prevent bloodstream infection and invasive fungal infection (IFI) by administering prophylactic antibiotic and antifungal agents during intensive chemotherapy in patients being treated for acute leukemia. Prophylaxis treatment was administered during intensive chemotherapy in children with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) from January 1, 2010 to December 31, 2012. Oral ciprofloxacin (at a dose of 300 mg/m(2) /12 hours) was administered after chemotherapy when a patient with AML or ALL became neutropenic and > 7 days of neutropenia was expected. Voriconazole (at a dose of 4 mg/kg/12 hours) was initiated at the onset of neutropenia in patients with AML and after 7 days of neutropenia in patients with ALL. Micafungin (at a dose of 2 mg/kg/day) was substituted for voriconazole when patients with ALL received vincristine. Prophylaxis treatment was discontinued when the absolute neutrophil count recovered to > 100/μL. All episodes of bloodstream infection, IFI, febrile neutropenia, and intensive care unit stays related to severe infection occurring between January 1, 2005 and December 31, 2012 were recorded. During the preprophylaxis period, 62 children with ALL and 24 children with AML experienced a total of 44 episodes of bloodstream infection and 22 episodes of IFI. Seven patients died of severe infection. In contrast, in the prophylaxis period, 10 episodes of bloodstream infection occurred and no IFIs were reported to occur in 51 patients with ALL and 14 patients with AML. Moreover, no patient died of severe infection. Episodes of febrile neutropenia and intensive care unit stay were significantly reduced during the prophylaxis period. Prophylaxis with ciprofloxacin and voriconazole or micafungin was found to reduce the rates of bloodstream infection and IFI in children with acute leukemia undergoing intensive chemotherapy. © 2013 American Cancer Society.

Clopidogrel-Induced Neutropenia after Coronary Stenting: Is Cilostazol a Good Alternative?

PubMed Central

Montalto, Massimo; Porto, Italo; Gallo, Antonella; Camaioni, Claudia; Della Bona, Roberta; Grieco, Antonio; Crea, Filippo; Landolfi, Raffaele

2011-01-01

Dual antiplatelet therapy with aspirin plus thienopyridines has become the standard treatment of patients undergoing coronary stenting. Clopidogrel has mostly replaced the use of ticlopidine due to its more favourable adverse event profile. However, also the use of clopidogrel is not without side effects. Clopidogrel major adverse events are represented by marrow suppression, manifesting with aplastic anaemia, thrombocytopenia and neutropenia. When clopidogrel toxicity occurs, there are few and unsubstantiated alternative treatments and thus, in these cases, medical decisions may be very difficult. We report a case of clopidogrel-induced bone marrow toxicity manifesting with severe neutropenia in a patient treated with multiple coronary stents and provide suggestions for an alternative treatment. PMID:21860799

Recombinant granulocyte colony-stimulating factor (rG-CSF) in the management of neutropenia induced by anthracyclines and ifosfamide in patients with soft tissue sarcomas (NEUSAR).

PubMed

Bongiovanni, Alberto; Monti, Manuela; Foca, Flavia; Recine, Federica; Riva, Nada; Di Iorio, Valentina; Liverani, Chiara; De Vita, Alessandro; Miserocchi, Giacomo; Mercatali, Laura; Amadori, Dino; Ibrahim, Toni

2017-01-01

Anthracycline and ifosfamide-based chemotherapy represents a widely used regimen both in early and advanced settings in soft tissue sarcoma (STS). Prophylaxis with granulocyte colony-stimulating factor (G-CSF) reduces the severity of chemotherapy-induced neutropenia. The aim of this study was to assess the efficacy and safety of biosimilar G-CSF in these patients. Between 2003 and 2013, 67 patients with soft tissue tumors under epirubicin and ifosfamide (EI) treatment receiving biosimilar filgrastim (Zarzio®), originator filgrastim (Granulokine®, Neupogen®), and lenograstim (only originator Myelostim®) as primary prophylaxis for a total of 260 cycles of therapy were retrospectively analyzed. Baseline patient characteristics were summarized in a propensity score (PS). The incidence of febrile neutropenia (FN) was 44.0 % in biosimilar filgrastim, 40.0 % in originator filgrastim, and 45.5 % in the lenograstim groups (p = 0.935). All grade and G4 neutropenia were similar in the three groups with the same safety profile. The use of biosimilar filgrastim achieved cost savings of €225.25 over originator filgrastim and €262.00 over lenograstim. Biosimilar G-CSF was effective in preventing FN and in reducing the need for hospitalization in STS patients undergoing EI treatment. It also proved comparable to its reference products from both a clinical and cost-effective standpoint.

Effect of an education program on knowledge, self-care behavior and handwashing competence on prevention of febrile neutropenia among breast cancer patients receiving Doxorubicin and Cyclophosphamide in Chemotherapy Day Centre

PubMed Central

Mak, Wai Chi; Yin Ching, Shirley Siu

2015-01-01

Objective: To evaluate the efficacy of an education program on the prevention of febrile neutropenia (FN) among breast cancer patients receiving AC regimen. Methods: Randomized controlled trial with the repeated-measures design was conducted in a Chemotherapy Day Centre of an acute hospital in Hong Kong. Twenty-five subjects in the intervention group received an individual education session followed by three follow-up sessions and routine care. Twenty-four subjects in the control group received routine care. Primary outcomes included the incidence of admission due to FN, the self-care behavior adherence, the knowledge level on prevention of FN and the self-efficacy in self-management, handwashing competence were assessed by self-designed questionnaires, Chinese version of patient activation measure, and handwashing competence checklist. Results: No statistically significant difference between the intervention group and the control group on the incidence of admission due to FN, the self-efficacy in self-management, and the knowledge on prevention of FN. The self-care behavior adherence was significant at cycle 4 of AC regimen in favor of the intervention group (P = 0.036). Handwashing competence improved more significantly among subjects in the intervention group than the control group (P = 0.009). Conclusions: The education program on the prevention of FN had significantly favorable effects on self-care behavior adherence and handwashing competence across time. However, the intervention did not lead to statistically significant improvement on the incidence of admission due to FN, the self-efficacy in self-management and the knowledge level on prevention of FN. PMID:27981125

Correlation Between Body Weight and Mitoxantrone-Associated Neutropenia in Dogs.

PubMed

Richardson, Danielle; Poirier, Valerie J; Matsuyama, Arata; Calvalido, Jerome

Thirty-seven dogs with histologically or cytologically confirmed malignant tumors treated with single-agent mitoxantrone at 5 mg/m 2 were evaluated in a retrospective study assessing the correlation between body weight and neutropenia associated with a single dose of mitoxantrone in dogs. Overall, eight dogs (21%) experienced grade 3 neutropenia and five dogs (14%) experienced grade 4 neutropenia on day 7 following mitoxantrone chemotherapy. Dogs ≤10 kg body weight were significantly more likely to develop grade 3 or 4 neutropenia (5.8 relative risk; 95% confidence interval, 2.6-12.9; P < .0001) than dogs >10 kg. Dogs ≤15 kg body weight were significantly more likely to develop grade 3 or 4 neutropenia (8.1 relative risk; 95% confidence interval, 2.1-31.3; P < .0001) than dogs >15 kg. Of the 13 patients who developed grade 3 or 4 neutropenia, 6 (46%) were hospitalized for clinical signs related to neutropenia. Based on the severity of neutropenia and the resulting hospitalization seen in dogs ≤10 kg, a dose reduction could be considered for the initial dose of mitoxantrone, and clinicians should be aware of the increased risk of neutropenia in patients 10.1 to ≤15 kg.

Neutrophil elastase in cyclic and severe congenital neutropenia

PubMed Central

Duan, Zhijun; Korkmaz, Brice; Lee, Hu-Hui; Mealiffe, Matthew E.; Salipante, Stephen J.

2007-01-01

Mutations in ELA2 encoding the neutrophil granule protease, neutrophil elastase (NE), are the major cause of the 2 main forms of hereditary neutropenia, cyclic neutropenia and severe congenital neutropenia (SCN). Genetic evaluation of other forms of neutropenia in humans and model organisms has helped to illuminate the role of NE. A canine form of cyclic neutropenia corresponds to human Hermansky-Pudlak syndrome type 2 (HPS2) and results from mutations in AP3B1 encoding a subunit of a complex involved in the subcellular trafficking of vesicular cargo proteins (among which NE appears to be one). Rare cases of SCN are attributable to mutations in the transcriptional repressor Gfi1 (among whose regulatory targets also include ELA2). The ultimate biochemical consequences of the mutations are not yet known, however. Gene targeting of ELA2 has thus far failed to recapitulate neutropenia in mice. The cycling phenomenon and origins of leukemic transformation in SCN remain puzzling. Nevertheless, mutations in all 3 genes are capable of causing the mislocalization of NE and may also induce the unfolded protein response, suggesting that there might a convergent pathogenic mechanism focusing on NE. PMID:17053055

Pharmacokinetics and pharmacogenomics of β-lactam-induced neutropenia

PubMed Central

Hahn, Andrea; Fukuda, Tsuyoshi; Hahn, David; Mizuno, Tomoyuki; Frenck, Robert W; Vinks, Alexander A

2016-01-01

Aim: Determine if individuals with β-lactam induced neutropenia have polymorphisms that impair function of MRP4 or OAT1/OAT3. Methods: Subjects with β-lactam induced neutropenia were compared to controls for the presence of MRP4 and OAT1/OAT3 polymorphisms, estimated plasma trough concentrations and area under the curve. Results: Subjects with a homozygous polymorphism at MRP4 3348 A to G were 5.3 times more likely to develop neutropenia (p = 0.171). No statistical differences were noted in pharmacokinetic parameters. Contingency analysis of children greater than 5 years of age showed neutropenia in subjects who were homozygous wild type at MRP4 3348 A to G was significantly associated with standard or high dosing (p = 0.03). Conclusion: MRP4 3348 A to G should be further studied for potential contribution to the development of β-lactam induced neutropenia. PMID:27045542

Cost of Cancer-Related Neutropenia or Fever Hospitalizations, United States, 2012.

PubMed

Tai, Eric; Guy, Gery P; Dunbar, Angela; Richardson, Lisa C

2017-06-01

Neutropenia and subsequent infections are life-threatening treatment-related toxicities of chemotherapy. Among patients with cancer, hospitalizations related to neutropenic complications result in substantial medical costs, morbidity, and mortality. Previous estimates for the cost of cancer-related neutropenia hospitalizations are based on older and limited data. This study provides nationally representative estimates of the cost of cancer-related neutropenia hospitalizations. We examined data from the 2012 National Inpatient Sample and Kids' Inpatient Database. Hospitalizations for cancer-related neutropenia were defined as those with a primary or secondary diagnosis of cancer and a diagnosis of neutropenia or a fever of unknown origin. We examined characteristics of cancer-related neutropenia hospitalizations among children (age < 18 years) and adults (age ≥ 18 years). Adjusted predicted margins were used to estimate length of stay and cost per stay. There were 91,560 and 16,859 cancer-related neutropenia hospitalizations among adults and children, respectively. Total cost of cancer-related neutropenia hospitalizations was $2.3 billion for adults and $439 million for children. Cancer-related neutropenia hospitalizations accounted for 5.2% of all cancer-related hospitalizations and 8.3% of all cancer-related hospitalization costs. For adults, the mean length of stay for cancer-related neutropenia hospitalizations was 9.6 days, with a mean hospital cost of $24,770 per stay. For children, the mean length of stay for cancer-related neutropenia hospitalizations was 8.5 days, with a mean hospital cost of $26,000 per stay. We found the costs of cancer-related neutropenia hospitalizations to be substantially high. Efforts to prevent and minimize neutropenia-related complications among patients with cancer may decrease hospitalizations and associated costs.

Cost of Cancer-Related Neutropenia or Fever Hospitalizations, United States, 2012

PubMed Central

Guy, Gery P.; Dunbar, Angela; Richardson, Lisa C.

2017-01-01

Purpose: Neutropenia and subsequent infections are life-threatening treatment-related toxicities of chemotherapy. Among patients with cancer, hospitalizations related to neutropenic complications result in substantial medical costs, morbidity, and mortality. Previous estimates for the cost of cancer-related neutropenia hospitalizations are based on older and limited data. This study provides nationally representative estimates of the cost of cancer-related neutropenia hospitalizations. Methods: We examined data from the 2012 National Inpatient Sample and Kids’ Inpatient Database. Hospitalizations for cancer-related neutropenia were defined as those with a primary or secondary diagnosis of cancer and a diagnosis of neutropenia or a fever of unknown origin. We examined characteristics of cancer-related neutropenia hospitalizations among children (age < 18 years) and adults (age ≥ 18 years). Adjusted predicted margins were used to estimate length of stay and cost per stay. Results: There were 91,560 and 16,859 cancer-related neutropenia hospitalizations among adults and children, respectively. Total cost of cancer-related neutropenia hospitalizations was $2.3 billion for adults and $439 million for children. Cancer-related neutropenia hospitalizations accounted for 5.2% of all cancer-related hospitalizations and 8.3% of all cancer-related hospitalization costs. For adults, the mean length of stay for cancer-related neutropenia hospitalizations was 9.6 days, with a mean hospital cost of $24,770 per stay. For children, the mean length of stay for cancer-related neutropenia hospitalizations was 8.5 days, with a mean hospital cost of $26,000 per stay. Conclusion: We found the costs of cancer-related neutropenia hospitalizations to be substantially high. Efforts to prevent and minimize neutropenia-related complications among patients with cancer may decrease hospitalizations and associated costs. PMID:28437150

Evidence on the use of paracetamol in febrile children.

PubMed Central

Russell, Fiona M.; Shann, Frank; Curtis, Nigel; Mulholland, Kim

2003-01-01

Antipyretics, including acetaminophen (paracetamol), are prescribed commonly in children with pyrexia, despite minimal evidence of a clinical benefit. A literature review was performed by searching Medline and the Cochrane databases for research papers on the efficacy of paracetamol in febrile illnesses in children and adverse outcomes related to the use of paracetamol. No studies showed any clear benefit for the use of paracetamol in therapeutic doses in febrile children with viral or bacterial infections or with malaria. Some studies suggested that fever may have a beneficial role in infection, although no definitive prospective studies in children have been done to prove this. The use of paracetamol in therapeutic doses generally is safe, although hepatotoxicity has occurred with recommended dosages in children. In developing countries where malnutrition is common, data on the safety of paracetamol are lacking. The cost of paracetamol for poor families is substantial. No evidence shows that it is beneficial to treat febrile children with paracetamol. Treatment should be given only to children who are in obvious discomfort and those with conditions known to be painful. The role of paracetamol in children with severe malaria or sepsis and in malnourished, febrile children needs to be clarified. PMID:12856055

[Examination of UGT1A1 polymorphisms and irinotecan-induced neutropenia in patients with Colorectal cancer].

PubMed

Teruya, Tsuyoshi; Nakachi, Atsushi; Shimabukuro, Nobuhiro; Toritsuka, Daisuke; Azuma, Yasuharu; Hanashiro, Kiyotoshi; Nishiki, Takehiro; Ota, Morihito; Shimabuku, Masamori; Shiroma, Hiroshi

2015-05-01

Irinotecan is an effective drug in the treatment of colorectal cancer. However, there are reports of an association between certain UGT1A1 genetic polymorphisms and the development of adverse reactions(such as neutropenia)related to irinotecan metabolism. We retrospectively investigated UGT1A1 genetic polymorphisms and the occurrences of irinotecan-induced neutropenia in 25 patients of colorectal cancer at our hospital. Analysis of UGT1A1 genetic polymorphisms in these patients yielded the following classifications: a wild-type group( *1/*1)comprising 13 patients(52%), a heterozygous group(*1/ *28, *1/*6)of 10 patients(40%), and a homozygous group(*28/*28, *6/*6)of 2 patients(8%). The frequency of neutropenia was 15.4%(2/13)in the wild-type group, 30%(3/10)in the heterozygous group, and 100%(2/2)in the homozygous group. Grade 4 neutropenia only occurred in the homozygous group. These results suggest that a dose reduction of irinotecan should be considered for patients who fall into the homozygous group upon analysis of their UGT1A1 genetic polymorphisms, as such patients might be susceptible to grade 4 neutropenia.

Characteristics and Outcomes of Neutropenia after Orthotopic Liver Transplantation

PubMed Central

Alraddadi, B; Nierenberg, NE; Price, LL; Chow, JKL; Poutsiaka, DD; Rohrer, RJ; Cooper, JT; Freeman, RB; Snydman, DR

2015-01-01

Neutropenia after orthotopic liver transplantation (LT) is relatively common but the factors associated with its development remain elusive. We assessed possible predictors of neutropenia (absolute neutrophil count [ANC] less than or equal to 1000/mm3) within the first year of LT in a cohort of 304 patients at a tertiary medical center between 1999 and 2009 using time-dependent survival analysis to identify risk factors for neutropenia. In addition, we analyzed neutropenia as a predictor of the clinical outcomes of death, blood stream infection (BSI), invasive fungal infection (IFI), Cytomegalovirus (CMV) disease and graft rejection within the first year of LT. Of the 304 LT recipients, 73 (24%) developed neutropenia, 5 (7%) of whom had grade 4 neutropenia (ANC less than 500/mm3). The following were independent predictors for neutropenia: Child-Turcotte-Pugh score (HR 1.15; 95% CI 1.02, 1.28; p=0.02), BSI (HR 2.89; 95% CI 1.64, 5.11; p=<0.001), CMV disease (HR 4.28; 95% CI 1.55, 11.8; p=0.005), baseline tacrolimus trough level (HR 1.02; 95% CI 1.01, 1.03; p=0.007) and later era LT (2004–2009 versus 1999–2003) (HR 2.28; 95% CI 1.43, 3.65; p=<0.001). Moreover, neutropenia was found to be an independent predictor for mortality within the first year of LT (HR 3.76; 95% CI 1.84, 7.68; p= <0.001). Conclusion Our data suggest that neutropenia within a year after LT is not unusual and is an important predictor of mortality. PMID:26336061

Clinical Impact of Fluoroquinolone-Resistant Escherichia coli in the Fecal Flora of Hematological Patients with Neutropenia and Levofloxacin Prophylaxis

PubMed Central

Chong, Yong; Shimoda, Shinji; Yakushiji, Hiroko; Ito, Yoshikiyo; Aoki, Takatoshi; Miyamoto, Toshihiro; Kamimura, Tomohiko; Shimono, Nobuyuki; Akashi, Koichi

2014-01-01

Background Fluoroquinolone prophylaxis in patients with neutropenia and hematological malignancies is said to be effective on febrile netropenia (FN)-related infection and mortality; however, the emergence of antibiotic resistance has become a concern. Ciprofloxacin and levofloxacin prophylaxis are most commonly recommended. A significant increase in the rate of quinolone-resistant Escherichia coli in fecal flora has been reported following ciprofloxacin prophylaxis. The acquisition of quinolone-resistant E. coli after levofloxacin use has not been evaluated. Methods We prospectively examined the incidence of quinolone-resistant E. coli isolates recovered from stool cultures before and after levofloxacin prophylaxis in patients with neutropenia from August 2011 to May 2013. Some patients received chemotherapy multiple times. Results In this trial, 68 patients were registered. Levofloxacin-resistant E. coli isolates were detected from 11 and 13 of all patients before and after the prophylaxis, respectively. However, this was not statistically significant (P = 0.65). Multiple prophylaxis for sequential chemotherapy did not induce additional quinolone resistance among E. coli isolates. Interestingly, quinolone-resistant E. coli, most of which were extended-spectrum β-lactamase (ESBL) producers, were already detected in approximately 20% of all patients before the initiation of prophylaxis. FN-related bacteremia developed in 2 patients, accompanied by a good prognosis. Conclusions Levofloxacin prophylaxis for neutropenia did not result in a significant acquisition of quinolone-resistant E. coli. However, we detected previous colonization of quinolone-resistant E. coli before prophylaxis, which possibly reflects the spread of ESBL. The epidemic spread of resistant E. coli as a local factor may influence strategies toward the use of quinolone prophylaxis. PMID:24465506

Neutropenia during High Dose Intravenous Oxacillin Therapy

PubMed Central

Ahern, Mary Jean; Hicks, Jeanne E.; Andriole, Vincent T.

1976-01-01

Five patients who developed neutropenia following intravenous administration of high dose oxacillin for serious Staphylococcus aureus infection are described. Neutropenia was reversible with cessation of intravenous oxacillin therapy. Two patients were continued on oral oxacillin without untoward effects. PMID:997595

Cardiomyopathy in a male patient with neutropenia and growth delay.

PubMed

Folsi, Veronica; Miglietti, Nunzia; Lombardi, Annamaria; Boccacci, Sara; Utyatnikova, Tatiana; Donati, Chiara; Squassabia, Livia; Gazzola, Laura; Bosio, Ilaria; Borghi, Adele; Grassi, Veronica; Notarangelo, Lucia D; Plebani, Alessandro

2014-05-12

Neutropenia encompasses a family of neutropenic disorders, both permanent and intermittent, ranging from severe (<500 neutrophils/mm(3)) to mild (500-1500 neutrophils/mm(3)), which may also affect other organ systems such as the pancreas, central nervous system, heart, muscle and skin. Neutropenia can lead to life-threatening pyogenic infections whose severity is roughly inversely proportional to the circulating neutrophil counts.When neutropenia is detected, an attempt should be made to establish the etiology, and to distinguish acquired forms (the most frequent, including post viral neutropenia and autoimmune neutropenia) and congenital forms (rare disorders) that may be either isolated or part of a complex rare genetic disease. We report on a male patient initially diagnosed with isolated neutropenia who later turned out to be affected with Barth syndrome, a rare complex inherited disorder.

Monitoring Procalcitonin in Febrile Neutropenia: What Is Its Utility for Initial Diagnosis of Infection and Reassessment in Persistent Fever?

PubMed Central

Bally, Frank; Knaup, Marlies; Calandra, Thierry; Marchetti, Oscar

2011-01-01

Background Management of febrile neutropenic episodes (FE) is challenged by lacking microbiological and clinical documentation of infection. We aimed at evaluating the utility of monitoring blood procalcitonin (PCT) in FE for initial diagnosis of infection and reassessment in persistent fever. Methods PCT kinetics was prospectively monitored in 194 consecutive FE (1771 blood samples): 65 microbiologically documented infections (MDI, 33.5%; 49 due to non-coagulase-negative staphylococci, non-CNS), 68 clinically documented infections (CDI, 35%; 39 deep-seated), and 61 fever of unexplained origin (FUO, 31.5%). Results At fever onset median PCT was 190 pg/mL (range 30–26'800), without significant difference among MDI, CDI and FUO. PCT peak occurred on day 2 after onset of fever: non-CNS-MDI/deep-seated-CDI (656, 80–86350) vs. FUO (205, 33–771; p<0.001). PCT >500 pg/mL distinguished non-CNS-MDI/deep-seated-CDI from FUO with 56% sensitivity and 90% specificity. PCT was >500 pg/ml in only 10% of FUO (688, 570–771). A PCT peak >500 pg/mL (1196, 524–11950) occurred beyond 3 days of persistent fever in 17/21 (81%) invasive fungal diseases (IFD). This late PCT peak identified IFD with 81% sensitivity and 57% specificity and preceded diagnosis according to EORTC-MSG criteria in 41% of cases. In IFD responding to therapy, median days to PCT <500 pg/mL and defervescence were 5 (1–23) vs. 10 (3–22; p = 0.026), respectively. Conclusion While procalcitonin is not useful for diagnosis of infection at onset of neutropenic fever, it may help to distinguish a minority of potentially severe infections among FUOs on day 2 after onset of fever. In persistent fever monitoring procalcitonin contributes to early diagnosis and follow-up of invasive mycoses. PMID:21541027

Monitoring procalcitonin in febrile neutropenia: what is its utility for initial diagnosis of infection and reassessment in persistent fever?

PubMed

Robinson, James Owen; Lamoth, Frédéric; Bally, Frank; Knaup, Marlies; Calandra, Thierry; Marchetti, Oscar

2011-04-25

Management of febrile neutropenic episodes (FE) is challenged by lacking microbiological and clinical documentation of infection. We aimed at evaluating the utility of monitoring blood procalcitonin (PCT) in FE for initial diagnosis of infection and reassessment in persistent fever. PCT kinetics was prospectively monitored in 194 consecutive FE (1771 blood samples): 65 microbiologically documented infections (MDI, 33.5%; 49 due to non-coagulase-negative staphylococci, non-CNS), 68 clinically documented infections (CDI, 35%; 39 deep-seated), and 61 fever of unexplained origin (FUO, 31.5%). At fever onset median PCT was 190 pg/mL (range 30-26'800), without significant difference among MDI, CDI and FUO. PCT peak occurred on day 2 after onset of fever: non-CNS-MDI/deep-seated-CDI (656, 80-86350) vs. FUO (205, 33-771; p<0.001). PCT >500 pg/mL distinguished non-CNS-MDI/deep-seated-CDI from FUO with 56% sensitivity and 90% specificity. PCT was >500 pg/ml in only 10% of FUO (688, 570-771). A PCT peak >500 pg/mL (1196, 524-11950) occurred beyond 3 days of persistent fever in 17/21 (81%) invasive fungal diseases (IFD). This late PCT peak identified IFD with 81% sensitivity and 57% specificity and preceded diagnosis according to EORTC-MSG criteria in 41% of cases. In IFD responding to therapy, median days to PCT <500 pg/mL and defervescence were 5 (1-23) vs. 10 (3-22; p = 0.026), respectively. While procalcitonin is not useful for diagnosis of infection at onset of neutropenic fever, it may help to distinguish a minority of potentially severe infections among FUOs on day 2 after onset of fever. In persistent fever monitoring procalcitonin contributes to early diagnosis and follow-up of invasive mycoses.

[Mortality of hematology-oncology patients with neutropenia in intensivecare].

PubMed

Suárez, I; Böll, B; Shimabukuro-Vornhagen, A; Michels, G; von Bergwelt-Baildon, M; Kochanek, M

2016-03-01

Febrile neutropenia remains one of the most common reasons for hospital admission of patients with underlying oncologic disease. These patients have an up to 10-fold increased risk of developing sepsis, which often leads to these patients being transferred to the intensive care unit (ICU). The survival of neutropenic patients with sepsis in particular has improved in recent years, due to advanced therapy in intensive care (surviving sepsis campaign); however few large international studies of neutropenic cancer patients in the ICU are available. In a retrospective study, 59 episodes of neutropenic cancer patients in the internal medicine ICU at the University Hospital of Cologne over a period of 2 years were analyzed. Pneumonia with or without sepsis are the main admission diagnoses of neutropenic cancer patients in the ICU. The mortality rate of these patients is very high (50.8 %). Pneumonia and sepsis, stem cell transplantation, mechanical ventilation, and acute renal failure with or without dialysis are correlated with mortality. Cancer patients should be admitted immediately to the ICU if they have signs of sepsis for early monitoring and treatment. Neutropenic patients have an increased risk for infectious complications and a risk for sepsis with higher mortality rates.

Cardiomyopathy in a male patient with neutropenia and growth delay

PubMed Central

2014-01-01

Neutropenia encompasses a family of neutropenic disorders, both permanent and intermittent, ranging from severe (<500 neutrophils/mm3) to mild (500–1500 neutrophils/mm3), which may also affect other organ systems such as the pancreas, central nervous system, heart, muscle and skin. Neutropenia can lead to life-threatening pyogenic infections whose severity is roughly inversely proportional to the circulating neutrophil counts. When neutropenia is detected, an attempt should be made to establish the etiology, and to distinguish acquired forms (the most frequent, including post viral neutropenia and autoimmune neutropenia) and congenital forms (rare disorders) that may be either isolated or part of a complex rare genetic disease. We report on a male patient initially diagnosed with isolated neutropenia who later turned out to be affected with Barth syndrome, a rare complex inherited disorder. PMID:24887148

A Randomized Multicenter Phase III Study of Single Administration of Mecapegfilgrastim (HHPG-19K), a Pegfilgrastim Biosimilar, for Prophylaxis of Chemotherapy-Induced Neutropenia in Patients With Advanced Non-Small-Cell Lung Cancer (NSCLC).

PubMed

Zhou, Caicun; Huang, Yunchao; Wang, Donglin; An, Changshan; Zhou, Fuxiang; Li, Yali; Chen, Gongyan; Wu, Changping; He, Jianxing; Wu, Gang; Song, Xia; Gao, Jianfei; Liu, Wei; Li, Baolan; Shi, Jianhua; Huang, Cheng; Yu, Jingrui; Feng, Jueping; Yue, Hongmei; Shi, Meiqi; Xia, Jielai

2016-03-01

Mecapegfilgrastim (code name HHPG-19K) is a biosimilar to pegylated recombinant human granulocyte-colony stimulating factor (PEG-rhG-CSF). The efficacy and safety of mecapegfilgrastim, using a regimen of once-per-cycle injection of 100-μg/kg or a fixed 6-mg dose, were evaluated for the prophylactic therapy for neutropenia in patients with advanced non-small-cell lung cancer (NSCLC) who were treated with myelosuppressive chemotherapy. Patients were randomized (1:1:1) blindly to 3 treatment arms to receive a single injection of mecapegfilgrastim 100 μg/kg, a 6-mg fixed dose of mecapegfilgrastim, or saline (control) in cycle 1. In cycles 2 to 4 following unblinding at the end of cycle 1, patients in the control arm received daily injections of short-acting rhG-CSF at a dose of 5 μg/kg, whereas patients in the 2 mecapegfilgrastim arms continued the same treatment as in cycle 1. All patients received 4 chemotherapy cycles of docetaxel combined with cisplatin or carboplatin every 21 days. The primary endpoint was the incidence of grade ≥ 3 neutropenia in cycle 1. A single dose of 100 μg/kg or a fixed 6-mg dose of mecapegfilgrastim per cycle effectively reduced chemotherapy-induced neutropenia and was comparable to daily rhG-CSF with regard to all efficacy endpoints, including incidence of grade ≥ 3 neutropenia, incidence of febrile neutropenia, duration of grade ≥ 3 neutropenia, and time to neutrophil recovery. No difference in efficacy parameters was observed between the 2-dose regimens of mecapegfilgrastim across all cycles. Mecapegfilgrastim was well-tolerated and was as safe as daily rhG-CSF. Once-per-cycle injection of mecapegfilgrastim is as effective and safe as daily rhG-CSF for prophylaxis of chemotherapy-induced neutropenia in patients with NSCLC. Mecapegfilgrastim (fixed 6-mg dose) is recommended in clinical practice for its convenient dose management. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Transient neutropenia: Neutrophil distribution and replacement

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thakur, M.L.; Li, Jinghua; Binoy, Li

Radiolabeled polymorphonuclear (PMN) receptor-specific proteins or peptides lead the list of agents being evaluated for imaging inflammatory foci. Some of these agents induce transient neutropenia. This study was designed to quantify the degree of dose dependency of neutropenia, determine the duration of neutropenia, identify the organs in which these PMNs sequester and ascertain if these PMNs return to the circulation. Rodent anti-PMN (Gr-1) MAb RB6-8C5 (lgG-2A) and Balb/c mice served as the model, and PMN nonspecific ME 31.3 (lgG-2A) as a control. Circulating PMN number was determined several times, 30 min prior to and between 1 min and 120 hrmore » after MAb administration. Iodine-125-MAbs provided quantification of circulating activity and tissue distribution as a function of time. Data showed the severity of neutropenia increased with the amount of MAb administered (>95% PMNs lost after 150 {mu}g versus <85% after 10 {mu}g). Moreover, the recovery time for PMN counts to reach the pretreatment level also increased in a dose-dependent manner (96 hr at 150 {mu}g versus 4 hr at 10 {mu}g and 2 hr at 2 {mu}g). The blood activity, however, which declined quickly with the neutropenia, never rose again with PMN recovery. As a function of time, radioactivity in the study group decreased from all organs except from the liver and spleen, whereas in the control group; and spleen, 15.5% decrease versus 63.6% decrease in control group. The degree and duration of neutropenia is dose-dependent. PMNs, lost from the circulation, sequester in the reticuloendothelial system, and do not return to circulation. Therefore, they are not available to image inflammatory foci. The PMN concentration is restored to a pretreatment level in a dose-dependent fashion, presumably by freshly released PMNs from bone marrow. 32 refs., 5 figs.« less

Neutropenia in childhood: a 5-year experience at a tertiary center.

PubMed

Lindqvist, Henric; Carlsson, Göran; Moell, Jacob; Winiarski, Jacek; Sundin, Mikael

2015-06-01

Clinical characteristics corroborated by laboratory investigations are essential to determine the etiology in cases of childhood neutropenia and the level of future health-care needs. Here the presentation, findings, and need of interventions in different types of neutropenia in children followed at our center from 2007 to 2012 were investigated retrospectively. Children with congenital and autoimmune neutropenia presented at a significantly younger age and with lower absolute neutrophil granulocyte counts than those with other types of neutropenia (p < 0.01-0.05). The duration of neutropenia, in case of remission, was shorter in post-infection and drug-induced cases compared to autoimmune and chronic idiopathic neutropenias (p = 0.001). Least affected from infections were children with ethnic and post-infection neutropenias compared to the others (p = 0.01-0.05). With the exception of congenital and autoimmune neutropenias, neutropenic children had few clinical infections and few hospital admissions even though the outpatient visit frequency was similar among the groups. A vast majority of the patients received no antibiotic prophylaxis. The majority of patients with pediatric neutropenia, apart from congenital types, display a benign clinical course. Our data suggest that most neutropenic children need neither antibiotic prophylaxis nor extensive medical attention.

Febrile Urinary Tract Infection after Radical Cystectomy and Ileal Neobladder in Patients with Bladder Cancer.

PubMed

Kim, Kwang Hyun; Yoon, Hyun Suk; Yoon, Hana; Chung, Woo Sik; Sim, Bong Suk; Lee, Dong Hyeon

2016-07-01

Urinary tract infection (UTI) is one of the most common complications after radical cystectomy and orthotopic neobladder reconstruction. This study investigated the incidence and implicated pathogen of febrile UTI after ileal neobladder reconstruction and identify clinical and urodynamic parameters associated with febrile UTI. From January 2001 to May 2015, 236 patients who underwent radical cystectomy and ileal neobladder were included in this study. Fifty-five episodes of febrile UTI were identified in 46 patients (19.4%). The probability of febrile UTI was 17.6% and 19.8% at 6 months and 24 months after surgery, respectively. While, Escherichia coli was the most common implicated pathogen (22/55, 40.0%), Enterococcus spp. were the most common pathogen during the first month after surgery (18/33, 54.5%). In multivariate logistic regression analysis, ureteral stricture was an independent risk factor associated with febrile UTI (OR 5.93, P = 0.023). However, ureteral stricture accounted for only 6 episodes (10.9%, 6/55) of febrile UTI. Most episodes of febrile UTI occurred within 6 months after surgery. Thus, to identify risk factors associated with febrile UTI in the initial postoperative period, we assessed videourodynamics within 6 months after surgery in 38 patients. On videourodyamic examination, vesicoureteral reflux (VUR) was identified in 16 patients (42.1%). The rate of VUR presence in patients who had febrile UTI was not significantly different from those in patients without febrile UTI (50% vs. 39.3%, P = 0.556). Patients with febrile UTI had significantly larger residual urine volume (212.0 ± 193.7 vs. 90.5 ± 148.2, P = 0.048) than those without. E. coli and Enterococcus spp. are common pathogens and ureteral stricture and residual urine are risk factors for UTI after ileal neobladder reconstruction.

Defining the impact of the use of granulocyte colony stimulating factors on the incidence of chemotherapy-induced neutropenia in patients with gynecologic malignancies.

PubMed

Julius, Justin M; Hammerstrom, Aimee; Wei, Caimiao; Rajesh, Raeshmma; Bodurka, Diane C; Kurian, Shiney; Smith, Judith A

2017-03-01

Purpose The objectives of this study were to characterize the incidence of chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN) with specific chemotherapy agents commonly used in the treatment of gynecologic malignancies, as well as defining the impact of granulocyte colony stimulating factors (G-CSF) on the prevention of CIN and FN in this patient population. Methods This retrospective analysis was conducted from a database of 635 gynecologic cancer patients who received chemotherapy between 1 September 2007 and 31 August 2008. A logistic regression analysis was conducted to determine the impact of potential covariates on the overall incidence of CIN. Results Overall, 28.3% of patients experienced CIN with one or more cycles chemotherapy, and 13.1% had treatment delays or dose reduction associated with CIN. The use of G-CSF prior to administration of chemotherapy resulted in a decrease in the incidence of CIN from 29.8% to 19.6% compared to no G-CSF use. No difference was observed in number of treatment delays or dose reductions in the 46 (7.2%) of gynecologic cancer patients that received G-CSF prophylaxis. Multivariate analysis found that both age and the number of current cycles jointly may predict risk of CIN. Conclusions Patients with gynecologic malignancies appear to be at a higher risk of development of neutropenia when treated with chemotherapy. The proactive use of G-CSF did decrease the risk of CIN by over 30%. Prospective study is warranted to determine the impact of G-CSF to reduce CIN in patients with gynecologic malignancies receiving chemotherapy.

Dose Schedule Optimization and the Pharmacokinetic Driver of Neutropenia

PubMed Central

Patel, Mayankbhai; Palani, Santhosh; Chakravarty, Arijit; Yang, Johnny; Shyu, Wen Chyi; Mettetal, Jerome T.

2014-01-01

Toxicity often limits the utility of oncology drugs, and optimization of dose schedule represents one option for mitigation of this toxicity. Here we explore the schedule-dependency of neutropenia, a common dose-limiting toxicity. To this end, we analyze previously published mathematical models of neutropenia to identify a pharmacokinetic (PK) predictor of the neutrophil nadir, and confirm this PK predictor in an in vivo experimental system. Specifically, we find total AUC and Cmax are poor predictors of the neutrophil nadir, while a PK measure based on the moving average of the drug concentration correlates highly with neutropenia. Further, we confirm this PK parameter for its ability to predict neutropenia in vivo following treatment with different doses and schedules. This work represents an attempt at mechanistically deriving a fundamental understanding of the underlying pharmacokinetic drivers of neutropenia, and provides insights that can be leveraged in a translational setting during schedule selection. PMID:25360756

Comparison of two oral regimens for the outpatient treatment of low-risk cancer patients with chemotherapy-induced neutropenia and fever: ciprofloxacin plus cefuroxime axetil versus ciprofloxacin plus amoxicillin/clavulanate.

PubMed

Sipsas, Nikolaos V; Kosmas, Christos; Ziakas, Panayiotis D; Karabelis, Athanasios; Vadiaka, Maria; Skopelitis, Elias; Kordossis, Theodore; Tsavaris, Nikolaos

2007-01-01

The objective of this investigation was to assess retrospectively the safety and the efficacy of oral ciprofloxacin plus cefuroxime axetil compared to the combination of oral ciprofloxacin plus amoxicillin/clavulanate, as initial outpatient treatment, in low-risk cancer patients with fever and neutropenia. We analysed retrospectively 120 episodes of febrile neutropenia, treated on an outpatient basis at 2 different oncology units; 63 episodes were treated with the oral regimen of ciprofloxacin plus amoxicillin/clavulanate and 57 were treated with the combination of oral ciprofloxacin plus cefuroxime. 20 treatment failures were recorded-2 of them among patients receiving ciprofloxacin plus amoxicillin/clavulanate and 18 in the ciprofloxacin plus cefuroxime group. Univariate analysis showed that the administration of ciprofloxacin plus cefuroxime was associated with a worse outcome compared to the regimen ciprofloxacin plus amoxicillin/clavulanate (OR 11, CI 2.42-49.9, p =0.002). In the multivariate model, after adjusting for the absolute number of neutrophils and the duration of neutropenia, the effect of the antibiotic regimen on the outcome disappeared, and no significant differences between the 2 regimens were noted, although the regimen of ciprofloxacin plus cefuroxime was associated with a trend to a worse outcome (OR 4.74, CI 0.72-31.1, p =0.10). In conclusion, the 2 regimens appeared equally safe and effective but prospective studies are needed to confirm these results.

Clinical characteristics of children with fever and transient neutropenia who experience serious bacterial infections.

PubMed

Bonadio, W A; Stremski, E; Shallow, K

1989-09-01

A review of consecutive previously healthy children with fever and newly discovered neutropenia without underlying malignancy, evaluated during a three-year period, was performed. A total of 68 episodes occurred in 68 patients; blood culture was performed on each. Of 17 patients who appeared compromised (ill, irritable, toxic) on presentation, five (30%) had either bacteremia or bacterial meningitis. All five patients had clinical evidence of a fulminant disease process on examination. By contrast, all 51 patients who appeared to be well on presentation were culture-negative. Fever and new-onset neutropenia in children is a heterogeneous disorder with several outcomes. Any child with fever and newly discovered neutropenia who appears ill should be presumed to be at high risk for systemic bacterial infection and receive hospitalization for parenteral antibiotic therapy. By contrast, the previously healthy child older than two months of age with fever and new-onset neutropenia who appears to be well, and whose clinical evaluation does not indicate a serious underlying disease process, is at low risk for accompanying systemic bacterial infection; hospitalization with empiric antibiotic therapy pending culture results is not warranted for the majority of such children. Close outpatient monitoring with serial evaluation of the peripheral blood absolute neutrophil count to document bone marrow recovery is recommended for such cases.

Febrile neutropaenia in cancer patients.

PubMed

Walwyn, M; Nicholson, A; Lee, M G; Wharfe, G; Frankson, M A

2010-03-01

Febrile neutropaenia is a common complication of chemotherapy in cancer patients. Empirical antibiotic regimes are based on the epidemiological characteristics of bacterial isolates globally and locally. This study retrospectively reviewed all cases of febrile neutropaenia in patients with confirmed cancer admitted at the University Hospital of the West Indies in the four-year period between, January 1, 2003 and December 31, 2006 and who received chemotherapy. Cases were identified from blood culture records and hospital charts which were reviewed to determine the aetiological agents causing bacteraemia, their antimicrobial susceptibilities and clinicalfeatures. These cases were compared with non-neutropaenic cancer patients admitted with fever. A total of 197 febrile episodes in cancer patients were reviewed. Thirty-seven per cent had febrile neutropaenia while 62% were non-neutropaenic. Acute myeloid leukaemia was the most common haematological malignancy and the most common solid tumour was breast cancer. Twenty-six per cent of patients had a positive blood culture. In febrile neutropaenic patients, Escherichia coli was the most common organism isolated followed by coagulase-negative staphylococci while in non-neutropaenic patients, coagulase-negative staphylococci was most common. Acinetobacter infections was prominent in non-neutropaenic patients but absent in neutropaenic patients. More than one organism was cultured in 9 neutropaenic and 18 non-neutropaenic patients. Mortality was 10.8% in neutropaenic and 24.4% in non-neutropaenic patients. Gram-negative organisms are the predominant isolates in febrile neutropaenic episodes in this cohort of patients. Non-neutropaenic patients had an increased mortality with an increase in Acinetobacter infections and multiple isolates.

[Benign ethnic neutropenia; an unrecognised cause of leukopenia in negroid patients].

PubMed

van Rooijen, Cleo R; Slieker, Walentina A T; Simsek, Suat

2012-01-01

Leukopenia has a high incidence and is usually a reason for additional testing. Benign ethnic neutropenia is a relatively common cause of neutropenia in the negroid population. It can be the cause of aberrant laboratory results in negroid patients. A 55-year-old woman from Ghana was referred to the outpatient clinic because of malaise, leukopenia and neutropenia. Viral infection, haematological malignancy, auto-immune disease and vitamin deficiency were considered, but could not be confirmed by additional testing. Upon further investigation, the neutropenia in this patient was found to have existed for years. Moreover, our patient's son also had asymptomatic leukopenia. Therefore, benign ethnic neutropenia was considered the most likely diagnosis. Serological analysis of the patient's erythrocytes revealed the absence of Duffy (Fy) blood group antigens Fy(a) and Fy(b), which is associated with benign ethnic neutropenia.

A case of severe Pembrolizumab-induced neutropenia.

PubMed

Ariane, Barbacki; Maliha, Peter G; Hudson, Marie; Small, David

2018-06-08

Immune checkpoint inhibitors have revolutionized cancer therapy. Given their mechanism of action, immune-related adverse events have been associated with their use. We present the first documented case of pembrolizumab-induced grade IV neutropenia. A 73-year-old women known for myositis, Crohn's disease, and hypothyroidism and diagnosed with PD-L1 positive stage IV pulmonary adenocarcinoma is treated with Pembrolizumab. She develops grade IV neutropenia 2 weeks after her second infusion. She is therefore hospitalized and treated initially with corticosteroids, granulocyte colony-stimulating factor, and intravenous immunoglobulins. Given the persistent neutropenia, cyclosporine was added, but quickly stopped owing to fever. The patient recovered her neutrophils 6.5 weeks after her initial Pembrolizumab infusion and 12 days after admission. She has been subsequently successfully tapered off steroids with no recurrence after 3 months of follow-up. This is the first case of grade IV neutropenia secondary to Pembrolizumab. This case is of particular interest given the patient's pre-existing autoimmune history. Treatment of severe neutropenia due to other PD1 inhibitors has generally consisted of steroids, granulocyte colony-stimulating factor, intravenous immunoglobulins, mycophenolate mofetil, cyclosporine A, and anti-thymocyte globulins - though the benefits of immunosuppression are not clear and may be harmful given the infectious risks. Large studies are required to clarify the spectrum and optimal management of immune-related adverse events and overall risk/benefits of immune checkpoint inhibitors in patients with pre-existing autoimmunity.

Bloodstream and central line isolates from hematopoietic stem cell transplant recipients: data from a developing country.

PubMed

Ali, N; Adil, S N; Shaikh, M U

2014-02-01

Bloodstream infections (BSIs) and central line infections remain among the major causes of morbidity and mortality in transplant recipients because of prolonged neutropenia and mucosal damage. The objective of this study was to determine the frequency and outcome of bacterial and fungal isolates from patients undergoing allogeneic hematopoietic stem cell transplant. This study was conducted at the Aga Khan University and Hospital's bone marrow transplant unit. All patients who underwent an allogeneic stem cell transplant with matched sibling/parent donor were included. The study period ranged from April 2004 to December 2012. Transplantation was performed according to institutional protocols. All patients were admitted in single rooms with positive pressure and high-efficiency particulate air filters. Ciprofloxacin, fluconazole, and valaciclovir were used for standard prophylaxis, which was started at the time of conditioning. All blood cultures were obtained at clinical suspicion of systemic infection, mainly documented as fever (temperature of >38.5°C). BSIs and line infections were defined as isolation of bacterial or fungal pathogen from at least one blood/central line culture. In total, 101 of 108 patients developed febrile neutropenia. In the 101 patients, 245 documented febrile episodes occurred. There were 40 culture-positive episodes and 205 culture-negative episodes. Of these 40 culture-positive episodes, 22 patients had bloodstream isolates and 18 had central line isolates. The median ± standard deviation time of febrile neutropenia was day 7 ± 2 days (range: day -3 to day +13). The most common bloodstream isolate was Escherichia coli (n = 9) followed by Staphylococcus epidermidis (n = 5). One patient developed Fusarium infection. In central line infections, S. epidermidis was the most common organism (n = 8). In 2 patients with central venous catheters, Candida albicans was the isolate. Transplant-related mortality from sepsis occurred in 9.2%. E

Leukopenia and neutropenia induced by quetiapine.

PubMed

Cowan, Colin; Oakley, Clare

2007-01-30

Leukopenia and neutropenia are recognised as side effects of antipsychotic medication, notably clozapine. A case is presented in which a female Caucasian patient who had previously developed these side effects with clozapine also developed them with quetiapine in conjunction with semisodium valproate. There was no such reaction to zuclopenthixol, sulpiride, olanzapine and aripiprazole. It is concluded that caution should be exercised when treating with quetiapine especially where there has been neutropenia with a previous antipsychotic agent.

Properdin Levels in Individuals with Chemotherapy-Induced Neutropenia.

PubMed

Tsyrkunou, Artsiom; Agarwal, Sarika; Koirala, Bibek; Finberg, Robert W; Nath, Rajneesh; Barton, Bruce; Levitz, Stuart M; Wang, Jennifer P; Ram, Sanjay

2017-01-01

Neutrophils produce and carry key components of the alternative pathway (AP) of complement, including properdin (P). The effect of chemotherapy-induced absolute neutropenia on circulating P levels and AP function has not been previously established. We prospectively measured free P levels in serum from 27 individuals expected to develop neutropenia after administration of chemotherapy for hematological malignancies in preparation for hematopoietic stem cell transplantation and here describe the relationship between serum P levels and the neutrophil count over time. When the absolute neutrophil count (ANC) was >500 cells/mm 3 pre-chemotherapy, P levels were significantly higher than P levels associated with an ANC ≤500 cells/mm 3 (median values 8392 ng/mL and 6355 ng/mL, respectively; P = .001). Pairwise comparison between pre-chemotherapy P levels and P levels at initial or last documented neutropenia before recovery showed a significant decline ( P < .0001). No correlation was observed between P levels during neutropenia and after recovery of neutropenia in 20 subjects for which postneutropenia samples were obtained. A small but significant ( P = .02) decrease in AP hemolytic activity was noted between baseline (preneutropenia) and samples obtained at the onset of neutropenia, but only with low (6.25%) and not higher (12.5 or 25%) serum concentrations. A decline in P levels and AP activity could contribute to the increased risk of infection in neutropenic patients and warrants further study. © The Author 2016. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

Chest CT scans are frequently abnormal in asymptomatic patients with newly diagnosed acute myeloid leukemia.

PubMed

Vallipuram, Janaki; Dhalla, Sidika; Bell, Chaim M; Dresser, Linda; Han, Heekyung; Husain, Shahid; Minden, Mark D; Paul, Narinder S; So, Miranda; Steinberg, Marilyn; Vallipuram, Mayuran; Wong, Gary; Morris, Andrew M

2017-04-01

Chest computed tomography (CT) findings of nodules, ground glass opacities, and consolidations are often interpreted as representing invasive fungal infection in individuals with febrile neutropenia. We assessed whether these CT findings were present in asymptomatic individuals with acute myeloid leukemia (AML) at low risk of invasive fungal disease. A retrospective study of consecutive asymptomatic adult patients with newly diagnosed AML over a 2-year period was performed at a tertiary care oncology center. Radiology reports of baseline chest CTs were reviewed. Of 145 CT scans, the majority (88%) had pulmonary abnormalities. Many (70%) had one or both of unspecified opacities (52%) and nodules (49%). Ground glass opacities (18%) and consolidations (12%) occurred less frequently. Radiologists suggested pneumonia as a possible diagnosis in 32% (n = 47) of scans. Chest CT may result in over-diagnosis of invasive fungal disease in individuals with febrile neutropenia if interpreted without correlation to the patients' clinical status.

Cost-efficiency analyses for the US of biosimilar filgrastim-sndz, reference filgrastim, pegfilgrastim, and pegfilgrastim with on-body injector in the prophylaxis of chemotherapy-induced (febrile) neutropenia.

PubMed

McBride, Ali; Campbell, Kim; Bikkina, Mohan; MacDonald, Karen; Abraham, Ivo; Balu, Sanjeev

2017-10-01

Guidelines recommend prophylaxis with granulocyte colony-stimulating factor for chemotherapy-induced (febrile) neutropenia (CIN/FN) based on regimen myelotoxicity and patient-related risk factors. The aim was to conduct a cost-efficiency analysis for the US of the direct acquisition and administration costs of the recently approved biosimilar filgrastim-sndz (Zarxio EP2006) with reference to filgrastim (Neupogen), pegfilgrastim (Neulasta), and a pegfilgrastim injection device (Neulasta Onpro; hereafter pegfilgrastim-injector) for CIN/FN prophylaxis. A cost-efficiency analysis of the prophylaxis of one patient during one chemotherapy cycle under 1-14 days' time horizon was conducted using the unit dose average selling price (ASP) and Current Procedural Terminology (CPT) codes for subcutaneous prophylactic injection under four scenarios: cost of medication only (COSTMED), patient self-administration (SELFADMIN), healthcare provider (HCP) initiating administration followed by self-administration (HCPSTART), and HCP providing full administration (HCPALL). Two case studies were created to illustrate real-world clinical implications. The analyses were replicated using wholesale acquisition cost (WAC). Using ASP + CPT, cost savings achieved with filgrastim-sndz relative to reference filgrastim ranged from $65 (1 day) to $916 (14 days) across all scenarios. Relative to pegfilgrastim, savings with filgrastim-sndz ranged from $834 (14 days) up to $3,666 (1 day) under the COSTMED, SELFADMIN, and HPOSTART scenarios; and from $284 (14 days) up to $3,666 (1 day) under the HPOALL scenario. Similar to the cost-savings compared to pegfilgrastim, filgrastim-sndz achieved savings relative to pegfilgrastim-injector: from $834 (14 days) to $3,666 (1 day) under the COSTMED scenario, from $859 (14 days) to $3,692 (1 day) under SELFADMIN, from $817 (14 days) to $3,649 (1 day) under HPOSTART, and from $267 (14 days) to $3,649 (1 day) under HPOALL. Cost savings of

Neutropenia as an Adverse Event following Vaccination: Results from Randomized Clinical Trials in Healthy Adults and Systematic Review

PubMed Central

Muturi-Kioi, Vincent; Lewis, David; Launay, Odile; Leroux-Roels, Geert; Anemona, Alessandra; Loulergue, Pierre; Bodinham, Caroline L.; Aerssens, Annelies; Groth, Nicola; Saul, Allan; Podda, Audino

2016-01-01

Background In the context of early vaccine trials aimed at evaluating the safety profile of novel vaccines, abnormal haematological values, such as neutropenia, are often reported. It is therefore important to evaluate how these trials should be planned not to miss potentially important safety signals, but also to understand the implications and the clinical relevance. Methodology We report and discuss the results from five clinical trials (two with a new Shigella vaccine in the early stage of clinical development and three with licensed vaccines) where the absolute neutrophil counts (ANC) were evaluated before and after vaccination. Additionally, we have performed a systematic review of the literature on cases of neutropenia reported during vaccine trials to discuss our results in a more general context. Principal Findings Both in our clinical trials and in the literature review, several cases of neutropenia have been reported, in the first two weeks after vaccination. However, neutropenia was generally transient and had a benign clinical outcome, after vaccination with either multiple novel candidates or well-known licensed vaccines. Additionally, the vaccine recipients with neutropenia frequently had lower baseline ANC than non-neutropenic vaccinees. In many instances neutropenia occurred in subjects of African descent, known to have lower ANC compared to western populations. Conclusions It is important to include ANC and other haematological tests in early vaccine trials to identify potential safety signals. Post-vaccination neutropenia is not uncommon, generally transient and clinically benign, but many vaccine trials do not have a sampling schedule that allows its detection. Given ethnic variability in the level of circulating neutrophils, normal ranges taking into account ethnicity should be used for determination of trial inclusion/exclusion criteria and classification of neutropenia related adverse events. Trial registration ClinicalTrials.gov NCT02017899

Primary immune-mediated neutropenia in a cat

PubMed Central

Waugh, Carly E.; Scott, Katherine D.; Bryan, Laura K.

2014-01-01

An 18-month-old male castrated indoor Himalayan cat was presented for recurrent fever, lethargy, and uveitis. Persistent neutropenia was identified and tests for infectious disease and bone marrow cytology were performed. Primary immune-mediated neutropenia was diagnosed and successfully treated. At the time of writing this report, 24 mo after the initial diagnosis. the patient was clinically normal and not receiving therapy. PMID:25392551

[Clozapine rechallenge after neutropenia in resistant schizophrenia: A review].

PubMed

Simon, L; Cazard, F

2016-08-01

clozapine despite lower blood counts. Then, rechallenge choice has to be done on a case-by-case basis and only after considering the benefits and risks of such a treatment. Most of the time, clinical advice of rechallenge arises from the inefficiency of other antipsychotics and even sismotherapy failure. Patients and sometimes families have to be informed and give their consent. Preventive measures have been found such as taking a hematologic recommendation and doing twice-a-week blood sample monitoring. With regards lithium and G-CSF, some efficient doses are assumed (lithium: 0,4-1,1 mEq/L and G-CSF>0,3 mg/week). Lithium as G-CSF may have other adverse effects which need to be considered. There is no successful rechallenge reported after agranulocytosis. Some publications highlight that if neutropenia occurs on rechallenge, it will do so more quickly and more severe than at the time of initial trial of clozapine. There is emerging evidence of successful clozapine rechallenging. However, further investigations are required as randomized controlled trials to reassess guidelines and establish the safety and effectiveness of the different procedures. Because of the practical and ethical difficulties of designing such studies, referral hospitals could be elected, and common background writing proposed in order to ease data comparison. Copyright © 2016 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

Levetiracetam-induced neutropenia following traumatic brain injury.

PubMed

Bunnell, Kristen; Pucci, Francesco

2015-01-01

Levetiracetam is being increasingly utilized for post-traumatic brain injury seizure prophylaxis, in part because of its more favourable adverse effect profile compared to other anti-epileptics. This report highlights an unusual, clinically significant adverse drug reaction attributed to levetiracetam use in a patient with blunt traumatic brain injury. This study describes a case of isolated neutropenia associated with levetiracetam in a 52-year-old man with traumatic brain injury. The patient developed neutropenia on day 3 of therapy with levetiracetam, with an absolute neutrophil count nadir of 200. There were no other medications that may have been implicated in the development of this haematological toxicity. Neutropenia rapidly resolved upon cessation of levetiracetam therapy. Clinicians should be aware of potentially serious adverse reactions associated with levetiracetam in patients with neurological injury.

An update on the diagnosis and treatment of chronic idiopathic neutropenia.

PubMed

Dale, David C; Bolyard, Audrey A

2017-01-01

Neutropenia lasting for at least for 3 months and not attributable to drugs or a specific genetic, infectious, inflammatory, autoimmune or malignant cause is called chronic idiopathic neutropenia (CIN). CIN and autoimmune neutropenia (AIN) are very similar and overlapping conditions. The clinical consequences depend upon the severity of neutropenia, but it is not considered a premalignant condition. Long-term observational studies in children indicate that the disease often lasts for 3-5 years in children, then spontaneously remits, but it rarely remits in adult cases. The value of antineutrophil antibody testing in both children and adults is uncertain. Most recent data suggest that CIN and AIN are immune-mediated diseases, but there are no new clinical or genetic tests to aid in diagnosis. Treatment with granulocyte colony stimulating factor (G-CSF) is effective to increase blood neutrophils in almost all cases; this treatment is reserved, however, for patients with both neutropenia and evidence of recurrent fevers, inflammatory symptoms and infections. There is little or no evidence to indicate that G-CSF treatment predisposes to myeloid malignancies in this population. It is important to recognize CIN and AIN, the most common causes of chronic neutropenia in both children and adults. If the neutropenia is not severe, that is more than 0.5 × 10/l, most patients can be observed and not treated prophylactically with antibiotics or a growth factor. When neutropenia is severe, treatment with G-CSF is often beneficial.

Factors associated with ambulance requests for febrile seizures.

PubMed

Sakai, Rie; Marui, Eiji

2008-08-01

The objective of this study was to determine factors associated with ambulance requests for febrile seizures. This study retrospectively investigated medical records of patients who visited the Emergency Care Unit at Tokyo Metropolitan Toshima Hospital in the 5-year period after April 2001. Subjects' basic characteristics (e.g., age and sex), medical history of febrile seizures, sibling and parental medical history of febrile seizures, and distance from hospital were investigated. In total, 310 subjects used ambulances, and 106 came to the hospital without requesting ambulances. The results of binomial logistic analysis indicated that factors associated with ambulance requests included patient's and parents' medical history of febrile seizures. Increasing awareness of febrile seizures and provision of a general public educational campaign are possible strategies to help decrease unnecessary ambulance requests. However, a medical history of febrile seizures among siblings revealed no association, indicating the need to conduct repeated early-stage interventions.

Febrile seizures: a population-based study.

PubMed

Dalbem, Juliane S; Siqueira, Heloise H; Espinosa, Mariano M; Alvarenga, Regina P

2015-01-01

To determine the prevalence of benign febrile seizures of childhood and describe the clinical and epidemiological profile of this population. This was a population-based, cross-sectional study, carried out in the city of Barra do Bugres, MT, Brazil, from August 2012 to August 2013. Data were collected in two phases. In the first phase, a questionnaire that was previously validated in another Brazilian study was used to identify suspected cases of seizures. In the second phase, a neurological evaluation was performed to confirm diagnosis. The prevalence was 6.4/1000 inhabitants (95% CI: 3.8-10.1). There was no difference between genders. Simple febrile seizures were found in 88.8% of cases. A family history of febrile seizures in first-degree relatives and history of epilepsy was present in 33.3% and 11.1% of patients, respectively. The prevalence of febrile seizures in Midwestern Brazil was lower than that found in other Brazilian regions, probably due to the inclusion only of febrile seizures with motor manifestations and differences in socioeconomic factors among the evaluated areas. Copyright © 2015 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Medical Management of Radiological Casualties, Second Edition, Handbook

DTIC Science & Technology

2003-04-01

neutropenia and fever) in irradiated persons is similar to that used for other febrile neutropenic patients, such as solid tumor patients receiving...of cytokines xii for patients expected to experience severe neutropenia . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 Table 3...toms of tissue injuries can mimic and obscure those caused by acute radiation effects. Conventional Therapy for Neutropenia and Infection The

Inheritance of Febrile Seizures in Sudden Unexplained Death in Toddlers

PubMed Central

Holm, Ingrid A.; Poduri, Annapurna; Crandall, Laura; Haas, Elisabeth; Grafe, Marjorie R.; Kinney, Hannah C.; Krous, Henry F.

2014-01-01

Sudden unexplained death in toddlers has been associated with febrile seizures, family history of febrile seizures, and hippocampal anomalies. We investigated the mode of inheritance for febrile seizures in these families. A three-generation pedigree was obtained from families enrolled in the San Diego Sudden Unexplained Death in Childhood Research Project, involving toddlers with sudden unexplained death, febrile seizures, and family history of febrile seizures. In our six cases, death was unwitnessed and related to sleep. The interval from last witnessed febrile seizure to death ranged from 3 weeks to 6 months. Hippocampal abnormalities were identified in one of three cases with available autopsy sections. Autosomal dominant inheritance of febrile seizures was observed in three families. A fourth demonstrated autosomal dominant inheritance with incomplete penetrance or variable expressivity. In two families, the maternal and paternal sides manifested febrile seizures. In this series, the major pattern of inheritance in toddlers with sudden unexplained death and febrile seizures was autosomal dominant. Future studies should develop markers (including genetic) to identify which patients with febrile seizures are at risk for sudden unexplained death in childhood, and to provide guidance for families and physicians. PMID:22490769

An update on the diagnosis and treatment of chronic idiopathic neutropenia

PubMed Central

Dale, David C.; Bolyard, Audrey Anna

2017-01-01

Purpose of Review Neutropenia lasting for at least for 3 months and not attributable to drugs or a specific genetic, infectious, inflammatory, autoimmune or malignant cause is called chronic idiopathic neutropenia. (CIN) CIN and autoimmune neutropenia (AIN) are very similar and overlapping conditions. The clinical consequences depend upon the severity of neutropenia, but it is not considered a premalignant condition. Recent findings Long-term observational studies in children indicate that the disease often lasts for 3 to 5 years in children, then spontaneously remits, but it rarely remits in adult cases. The value of anti-neutrophil antibody testing in both children and adults is uncertain. Most recent data suggest that CIN and AIN are immune mediated diseases, but there are no new clinical or genetic tests to aid in diagnosis. Treatment with granulocyte colony stimulating factor (G-CSF) is effective to increase blood neutrophils in almost all cases; this treatment is reserved, however for patients with both neutropenia and evidence of recurrent fevers, inflammatory symptoms and infections. There is little or no evidence to indicate that G-CSF treatment predisposes to myeloid malignancies in this population. Summary It is important to recognize CIN and AIN, the most common causes of chronic neutropenia in both children and adults. If the neutropenia is not severe, i.e. > 0.5 × 109/L, most patients can be observed and not treated prophylactically with antibiotics or a growth factor. When neutropenia is severe treatment with G-CSF is often beneficial. PMID:27841775

Prevention and treatment of chemotherapy-induced neutropenia with the biosimilar filgrastim: a non-interventional observational study of clinical practice patterns.

PubMed

Tesch, Hans; Ulshöfer, Thomas; Vehling-Kaiser, Ursula; Ottillinger, Bertram; Bulenda, Dietmar; Turner, Matthew

2015-01-01

Biosimilars are similar but non-identical versions of existing biological drugs. The HEXAFIL study was an observational study that assessed the clinical usage, safety and efficacy of the biosimilar filgrastim in routine clinical practice in Germany. A total of 1,337 cancer patients received the biosimilar filgrastim for primary prophylaxis (PP), secondary prophylaxis (SP) or interventional treatment (TX) plus chemotherapy. Data including neutropenic complications and adverse events (AEs) were documented for up to 3 consecutive cycles. In cycle 1, 44.9% of the patients received the biosimilar filgrastim as PP, 31.0% as SP, and 23.6% as TX. Approximately 90% of the patients required no modifications to their chemotherapy regimen, with lower rates among the PP/SP versus the TX patients. Neutropenic complications occurred in 7.9%, 6.9%, and 3.9% of the patients (cycles 1, 2, and 3, respectively). Only 1.8% of the patients experienced febrile neutropenia during cycle 1. Earlier and longer filgrastim treatment reduced grade 3/4 leukopenia and neutropenic complications. The observed safety/tolerability profile was as expected; the most common AE (4.3%) was musculoskeletal back/bone pain. In this observational real-life study of clinical practice, the biosimilar filgrastim was effective and well tolerated, with results consistent with those reported in phase II and phase III trials. © 2015 S. Karger GmbH, Freiburg.

Feasibility, efficacy, and adverse effects of outpatient antibacterial prophylaxis in children with acute myeloid leukemia

PubMed Central

Inaba, Hiroto; Gaur, Aditya H; Cao, Xueyuan; Flynn, Patricia M; Pounds, Stanley B; Avutu, Viswatej; Marszal, Lindsay N; Howard, Scott C; Pui, Ching-Hon; Ribeiro, Raul C; Hayden, Randall T; Rubnitz, Jeffrey E

2014-01-01

BACKGROUND Intensive chemotherapy for pediatric acute myeloid leukemia (AML) incurs the risk of infectious complications, but the benefits of antibiotic prophylaxis remain unclear. METHODS In 103 children treated on the AML02 protocol between October 2002 and October 2008 at St. Jude Children’s Research Hospital, we retrospectively assessed the effect of antibiotic prophylaxis on the frequency of febrile neutropenia, clinically or microbiologically confirmed infections (including bacteremia), and antibiotic resistance, and on the results of nasal and rectal surveillance cultures. Initially, patients received no prophylaxis or oral cephalosporin (Group A). Then the protocol was amended to give intravenous cefepime alone or intravenous vancomycin plus either oral cephalosporin, oral ciprofloxacin, or intravenous cefepime (Group B). RESULTS There were 334 infectious episodes. Group A had a significantly greater frequency of documented infections and bacteremia (both P < .0001) (including gram-positive and gram-negative bacteremia, P = .0003 and .001, respectively) than Group B, especially viridans streptococcal bacteremia (P = .001). The incidence of febrile neutropenia without documented infection was not different between the two groups. Five cases of bacteremia with vancomycin-resistant enterococci (VRE) occurred in group B (vs. none in Group A), without related mortality. Two of these cases were preceded by positive VRE rectal surveillance cultures. CONCLUSIONS Outpatient intravenous antibiotic prophylaxis is feasible in children with AML and reduces the frequency of documented infection but not of febrile neutropenia. Despite emergence of VRE bacteremia, the benefits favor antibiotic prophylaxis. Creative approaches to shorten the duration of prophylaxis and thereby minimize resistance should be explored. PMID:24677028

Pegfilgrastim in primary prophylaxis of febrile neutropenia following frontline bendamustine plus rituximab treatment in patients with indolent non-Hodgkin lymphoma: a single center, real-life experience.

PubMed

Cerchione, Claudio; De Renzo, Amalia; Di Perna, Maria; Della Pepa, Roberta; Pugliese, Novella; Catalano, Lucio; Pane, Fabrizio; Picardi, Marco

2017-03-01

In this prospective study, the impact of granulocyte colony-stimulating factors (G-2 CSF) administered during induction treatment with bendamustine plus rituximab for indolent non- Hodgkin Llymphoma (NHL) was evaluated by comparing patients who received secondary prophylaxis with filgrastim (control group) versus. patients who received pegfilgrastim as primary prophylaxis (peg-group). The primary endpoint was the incidence rate of febrile neutropenia (FN)- related chemotherapy disruptions (regarding dose-dense and/or dose-intensity of schedule). The Ssecondary endpoint included days of hospitalization due to FN, and G-CSF-related side effects (grade ≥3 WHO toxicity criteria) in each group. One hundred twenty-two: 122 consecutive patients, with untreated indolent NHL, were referred to our outpatient unit for remission induction immuno-chemotherapy with bendamustine-rituximab. During the first period, 61 patients received secondary prophylaxis with filgrastim, given "on demand" if ANC was <1000/mm3. During the second period, 61 patients received primary prophylaxis with pegfilgrastim in a single administration. Pegfilgrastim was significantly associated with fewer incidence rate of FN-related chemotherapy disruptions (11.4% in the control group vs. 1.6% in the peg-group, p = 0.04) and fewer days of hospitalization due to FN (median number 18 days in the control group vs. 6 in the peg-group, p = 0.04). In terms of G-CSF-related extra-hematological grade III side effects, no significant difference has been found in the two groups (9.8% in the control group vs. 11.5% in the peg-group, p = 0.77). Only one patient stopped the treatment in the peg-group due to intolerance. In patients with indolent NHL, in front-line treatment with bendamustine plus rituximab, primary prophylaxis with pegfilgrastim seems to reduce the incidence of chemotherapy disruptions due to FN, and the days of hospitalization. Moreover, it is well- tolerated and may increase the opportunity to

Adjusted neutropenia is associated with early serious infection in systemic lupus erythematosus.

PubMed

Lee, Sang-Won; Park, Min-Chan; Lee, Soo-Kon; Park, Yong-Beom

2013-05-01

The susceptibility to infection increases in systemic lupus erythematosus (SLE) patients with neutropenia, but the link between infection risk and the cutoff neutrophil count still remains controversial. In this study, we investigated a valuable parameter associated with early serious infection in SLE patients during the first follow-up year. We reviewed the medical records of 160 patients with SLE. The initial levels were defined as the mean of the results of the first two consecutive tests. The adjusted levels were defined as the results of the accumulated area under the curve divided by interval follow-up days. Patients were divided into two groups according to early serious infection and initial and adjusted neutropenia and were then compared. Immunosuppressive-naïve SLE patients with early serious infection more frequently had initial, latest, and adjusted leukopenia and neutropenia (<2,500/mm(3)) and hypocomplementemia than those without. Adjusted neutropenia was the only independent predictive value for early serious infection [odds ratio (OR 11.366)]. Initial neutropenia was the independent predictive value for adjusted neutropenia (OR 6.504). We suggest that adjusted neutropenia is useful for predicting early serious infection in SLE patients during the first follow-up year.

Periodontal disease in three siblings with familial neutropenia.

PubMed

Kirstilä, V; Sewón, L; Laine, J

1993-06-01

The periodontal status and treatment of three teenagers in a Finnish family with familial neutropenia is described. The mother was also diagnosed with neutropenia. At initial examination, the 15-year-old male and the 10-year-old female had severe periodontitis, whereas the 13-year-old male had oral ulcerations but no significant periodontal disease. The two siblings with periodontitis were treated and followed approximately 5 years. It was concluded that periodontal therapy including scaling, surgery, and use of antimicrobial agents can be successful in patients with familial neutropenia, and that such patients are not necessarily candidates for full mouth extraction. The role of granulocyte colony-stimulating factor in which was used in the treatment of these patients remains to be established.

ABCB1 polymorphism as a predictive biomarker for amrubicin-induced neutropenia.

PubMed

Takakuwa, Osamu; Oguri, Tetsuya; Uemura, Takehiro; Kunii, Eiji; Nakao, Makoto; Hijikata, Hisatoshi; Kawaguchi, Yuko; Ohkubo, Hirotsugu; Takemura, Masaya; Maeno, Ken; Niimi, Akio

2014-07-01

Amrubicin is a promising therapy for lung cancer, but is associated with a high incidence of severe neutropenia. The present study assessed the utility of ABCB1 and NAD(P)H quinone oxidoreductase 1 (NQO1) polymorphism as a predictor of amrubicin-induced neutropenia. Fifty-four Japanese lung cancer patients who received amrubicin chemotherapy were consecutively recruited and toxicities and SNPs (MDR1; C1236T, C3435T and G2677T/A, NQO1; C609T) were evaluated. The incidence of neutropenia was higher in patients treated with 40 mg/m2 of amrubicin (n=32) compared to patients treated with 35 mg/m2 of amrubicin (n=22) (53.1% vs. 22.7%). Patients who were homogenous for the wild-type allele of C3435T were at significantly higher risk of neutropenia compared to patients with other genotypes. By contrast, the C609T genotype of NQO1 was not related to neutropenia. C3435T polymorphisms of ABCB1 might be able to predict severe amrubicin-induced neutropenia. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Risk Factors for Neutropenia in Clozapine-Treated Children and Adolescents with Childhood-Onset Schizophrenia

PubMed Central

Maher, Kristin N.; Tan, Marcus; Tossell, Julia W.; Weisinger, Brian; Gochman, Peter; Miller, Rachel; Greenstein, Deanna; Overman, Gerald P.; Rapoport, Judith L.

2013-01-01

Abstract Objective The purpose of this study was to retrospectively analyze rates of neutropenia and risk factors for neutropenia in hospitalized children and adolescents treated with clozapine. Methods A retrospective chart review was conducted for all patients who received clozapine at any time during a hospitalization at the National Institute of Mental Health (NIMH) between 1990 and 2011. All patients satisfied screening criteria for the NIMH childhood-onset schizophrenia study, including onset of psychosis before the age of 13 years. Absolute neutrophil count (ANC) values recorded during inpatient hospitalization were extracted for 87 eligible patients with a mean age of 13.35±2.46 years at hospitalization and a mean length of stay of 117±43 days. Results Mild neutropenia only (lowest ANC<2000/mm3 but>1500/mm3) was observed in 27 (31%) patients and moderate neutropenia (any ANC<1500/mm3) was observed in 17 (20%) patients. There were no cases of agranulocytosis or severe infection. Significant risk factors for mild neutropenia compared with no hematologic adverse effects (HAEs) were male gender (p=0.012) and younger age (p<0.001). Male gender was also a significant risk factor for moderate neutropenia compared with no HAEs (p=0.003). If a child of African American ethnicity developed neutropenia during hospitalization at all that child was significantly more likely to develop moderate neutropenia than mild neutropenia only (p=0.017). African American boys had the highest rate of moderate neutropenia at 47%. Sixteen of the 17 patients exhibiting moderate neutropenia were successfully treated with clozapine by the time of discharge; 8 of these 16 required adjunctive lithium carbonate administration to maintain ANC>2000/mm3. Conclusions Our study shows that the rates of neutropenia in clozapine-treated children and adolescents are considerably higher than in the adult population. Younger age, African American ethnicity, and male gender were significant risk

High frequency of GATA2 mutations in patients with mild chronic neutropenia evolving to MonoMac syndrome, myelodysplasia, and acute myeloid leukemia.

PubMed

Pasquet, Marlène; Bellanné-Chantelot, Christine; Tavitian, Suzanne; Prade, Naïs; Beaupain, Blandine; Larochelle, Olivier; Petit, Arnaud; Rohrlich, Pierre; Ferrand, Christophe; Van Den Neste, Eric; Poirel, Hélène A; Lamy, Thierry; Ouachée-Chardin, Marie; Mansat-De Mas, Véronique; Corre, Jill; Récher, Christian; Plat, Geneviève; Bachelerie, Françoise; Donadieu, Jean; Delabesse, Eric

2013-01-31

Congenital neutropenia is a group of genetic disorders that involve chronic neutropenia and susceptibility to infections. These neutropenias may be isolated or associated with immunologic defects or extra-hematopoietic manifestations. Complications may occur as infectious diseases, but also less frequently as myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Recently, the transcription factor GATA2 has been identified as a new predisposing gene for familial AML/MDS. In the present study, we describe the initial identification by exome sequencing of a GATA2 R396Q mutation in a family with a history of chronic mild neutropenia evolving to AML and/or MDS. The subsequent analysis of the French Severe Chronic Neutropenia Registry allowed the identification of 6 additional pedigrees and 10 patients with 6 different and not previously reportedGATA2 mutations (R204X, E224X, R330X, A372T, M388V, and a complete deletion of the GATA2 locus). The frequent evolution to MDS and AML in these patients reveals the importance of screening GATA2 in chronic neutropenia associated with monocytopenia because of the frequent hematopoietic transformation, variable clinical expression at onset, and the need for aggressive therapy in patients with poor clinical outcome. Mutations of key transcription factor in myeloid malignancies.

High frequency of GATA2 mutations in patients with mild chronic neutropenia evolving to MonoMac syndrome, myelodysplasia, and acute myeloid leukemia

PubMed Central

Pasquet, Marlène; Bellanné-Chantelot, Christine; Tavitian, Suzanne; Prade, Naïs; Beaupain, Blandine; LaRochelle, Olivier; Petit, Arnaud; Rohrlich, Pierre; Ferrand, Christophe; Van Den Neste, Eric; Poirel, Hélène A.; Lamy, Thierry; Ouachée-Chardin, Marie; Mansat-De Mas, Véronique; Corre, Jill; Récher, Christian; Plat, Geneviève; Bachelerie, Françoise; Donadieu, Jean

2013-01-01

Congenital neutropenia is a group of genetic disorders that involve chronic neutropenia and susceptibility to infections. These neutropenias may be isolated or associated with immunologic defects or extra-hematopoietic manifestations. Complications may occur as infectious diseases, but also less frequently as myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Recently, the transcription factor GATA2 has been identified as a new predisposing gene for familial AML/MDS. In the present study, we describe the initial identification by exome sequencing of a GATA2 R396Q mutation in a family with a history of chronic mild neutropenia evolving to AML and/or MDS. The subsequent analysis of the French Severe Chronic Neutropenia Registry allowed the identification of 6 additional pedigrees and 10 patients with 6 different and not previously reported GATA2 mutations (R204X, E224X, R330X, A372T, M388V, and a complete deletion of the GATA2 locus). The frequent evolution to MDS and AML in these patients reveals the importance of screening GATA2 in chronic neutropenia associated with monocytopenia because of the frequent hematopoietic transformation, variable clinical expression at onset, and the need for aggressive therapy in patients with poor clinical outcome. PMID:23223431

Parvovirus B19 reactivation presenting as neutropenia after rituximab treatment.

PubMed

Klepfish, A; Rachmilevitch, E; Schattner, A

2006-11-01

A patient with primary biliary cirrhosis and associated refractory immune thrombocytopenic purpura was treated with 4 weekly courses of rituximab, a monoclonal antibody targeting B-cell surface antigen CD20. Her thrombocyte count and even cholestatic liver function tests improved. However, 17 weeks after rituximab treatment, she developed severe neutropenia (absolute neutrophil count 0.23x10(3)/mul) and recurrent thrombocytopenia with abnormal bone marrow of all three lineages. Although delayed-onset neutropenia has been reported after rituximab, reactivated viral infections have also been encountered. Parvovirus B19 was suspected and confirmed as the cause of neutropenia in our patient. The patient was supported by GCSF treatment and recovered uneventfully after several weeks. Neutropenia after rituximab can also be the predominant manifestation of reactivated parvovirus B19 infection and have a favorable prognosis.

Chemotherapy-induced neutropenia is associated with prolonged remission duration and survival time in canine lymphoma.

PubMed

Wang, S L; Lee, J J; Liao, A T

2015-07-01

Myelosuppression is one of the most common side effects of chemotherapy. The aim of this study was to determine whether chemotherapy-induced neutropenia is a positive prognostic indicator for remission and survival time in dogs with lymphoma. Fifty dogs with multicentric lymphoma received CHOP-based (C-cyclophosphamide; H-hydroxydaunorubicin; O-vincristine; P-prednisolone) chemotherapy using conventional dosages. Complete blood counts were recorded to determine the presence or absence of neutropenia after treatment. Toxicity, remission, and survival times were recorded and analysed. Thirteen dogs had chemotherapy-induced neutropenia and 37 had no neutropenia during the study period. No statistical difference was found between the groups for signalment or the presence of historical negative prognostic factors, except for bodyweight (P = 0.02). The median first remission times in the neutropenia and no neutropenia groups were 812 and 219 days, respectively (P <0.01). The median survival times of dogs in the neutropenia and no neutropenia groups were 952 and 282 days, respectively (P <0.01). Dogs with lymphoma that had chemotherapy-induced neutropenia exhibited significantly increased remission and survival times compared with dogs without neutropenia. Chemotherapeutic dosages may be adjusted individually to induce neutropenia without severe adverse effects in order to achieve longer remission and survival times. Copyright © 2015 Elsevier Ltd. All rights reserved.

Febrile seizures - what to ask your doctor

MedlinePlus

... I do? When should I call the doctor? Alternative Names What to ask your doctor about febrile ... Philadelphia, PA: Elsevier; 2016:chap 593. Read More Epilepsy - overview Febrile seizures Fever Seizures Patient Instructions Epilepsy ...

Phase I dose-escalation study of afatinib, an ErbB family blocker, plus docetaxel in patients with advanced cancer.

PubMed

Marshall, John; Shapiro, Geoffrey I; Uttenreuther-Fischer, Martina; Ould-Kaci, Mahmoud; Stopfer, Peter; Gordon, Michael S

2013-02-01

To determine the maximum tolerated dose (MTD), safety and anti-tumor activity of afatinib combined with docetaxel in advanced cancer. The MTD was determined from dose-limiting toxicities in the first cycle. Thirty-one patients received 10, 20 and 30 mg oral afatinib, plus 60 and 75 mg/m(2) intravenous docetaxel (six cohorts; 3-week cycles). The MTD of afatinib was 20 mg/day (days 2-21) with 75 mg/m(2) docetaxel (day 1). Dose-limiting toxicities were grade 3/4 diarrhea (n = 3) and febrile neutropenia (n = 6). Most frequently occurring adverse events were diarrhea, neutropenia and rash. Disease stabilization occurred in 14 patients. Afatinib 20 mg/day plus docetaxel was suboptimal and the study could not yield Phase II dose recommendations. The combination resulted in a manageable safety profile.

Outcome and management of pregnancies in severe chronic neutropenia patients by the European Branch of the Severe Chronic Neutropenia International Registry.

PubMed

Zeidler, Cornelia; Grote, Ulrike A H; Nickel, Anna; Brand, Beate; Carlsson, Göran; Cortesão, Emília; Dufour, Carlo; Duhem, Caroline; Notheis, Gundula; Papadaki, Helen A; Tamary, Hannah; Tjønnfjord, Geir E; Tucci, Fabio; Van Droogenbroeck, Jan; Vermylen, Christiane; Voglova, Jaroslava; Xicoy, Blanca; Welte, Karl

2014-08-01

Long-term granulocyte-colony stimulating factor treatment has been shown to be safe and effective in severe chronic neutropenia patients. However, data on its use during pregnancy are limited. To address this issue, we analyzed all pregnancies reported to the European branch of the Severe Chronic Neutropenia International Registry since 1994. A total of 38 pregnancies in 21 women with chronic neutropenia (16 pregnancies in 10 women with congenital, 10 in 6 women with cyclic, 12 in 5 women with idiopathic neutropenia) were reported. Granulocyte-colony stimulating factor was administered throughout pregnancy in 16 women and for at least one trimester in a further 5 women. No major differences were seen between treated and untreated women with respect to pregnancy outcome, newborn complications and infections. In addition, we evaluated the genetic transmission of known or suspected genetic defects in 16 mothers having 22 newborns as well as in 8 men fathering 15 children. As a proof of inheritance, neutropenia was passed on to the newborn in 58% from female and in 62% from male patients with ELANE mutations, but also to some newborns from parents with unknown gene mutation. Based on our results, granulocyte-colony stimulating factor therapy has been shown to be safe for mothers throughout pregnancies and for newborns without any signs of teratogenicity. With an increasing number of adult patients, genetic counseling prior to conception and supportive care of mothers during pregnancy are crucial. The acceptance of having affected children may reflect the high quality of life obtained due to this treatment. Copyright© Ferrata Storti Foundation.

Outcome and management of pregnancies in severe chronic neutropenia patients by the European Branch of the Severe Chronic Neutropenia International Registry

PubMed Central

Zeidler, Cornelia; Grote, Ulrike A.H.; Nickel, Anna; Brand, Beate; Carlsson, Göran; Cortesão, Emília; Dufour, Carlo; Duhem, Caroline; Notheis, Gundula; Papadaki, Helen A.; Tamary, Hannah; Tjønnfjord, Geir E.; Tucci, Fabio; Van Droogenbroeck, Jan; Vermylen, Christiane; Voglova, Jaroslava; Xicoy, Blanca; Welte, Karl

2014-01-01

Long-term granulocyte-colony stimulating factor treatment has been shown to be safe and effective in severe chronic neutropenia patients. However, data on its use during pregnancy are limited. To address this issue, we analyzed all pregnancies reported to the European branch of the Severe Chronic Neutropenia International Registry since 1994. A total of 38 pregnancies in 21 women with chronic neutropenia (16 pregnancies in 10 women with congenital, 10 in 6 women with cyclic, 12 in 5 women with idiopathic neutropenia) were reported. Granulocyte-colony stimulating factor was administered throughout pregnancy in 16 women and for at least one trimester in a further 5 women. No major differences were seen between treated and untreated women with respect to pregnancy outcome, newborn complications and infections. In addition, we evaluated the genetic transmission of known or suspected genetic defects in 16 mothers having 22 newborns as well as in 8 men fathering 15 children. As a proof of inheritance, neutropenia was passed on to the newborn in 58% from female and in 62% from male patients with ELANE mutations, but also to some newborns from parents with unknown gene mutation. Based on our results, granulocyte-colony stimulating factor therapy has been shown to be safe for mothers throughout pregnancies and for newborns without any signs of teratogenicity. With an increasing number of adult patients, genetic counseling prior to conception and supportive care of mothers during pregnancy are crucial. The acceptance of having affected children may reflect the high quality of life obtained due to this treatment. PMID:24997149

Psychometric Properties of the Functional Assessment of Cancer Therapy-Neutropenia in Asian Cancer Patients With Chemotherapy-Induced Neutropenia.

PubMed

Wang, Xiao Jun; Wong, Ching Man; Chan, Alexandre

2016-09-01

The Functional Assessment of Cancer Therapy-Neutropenia (FACT-N) is a neutropenia-specific questionnaire to assess patients' health-related quality of life. This study aimed to examine the psychometric properties of FACT-N among cancer patients with chemotherapy-induced neutropenia (CIN). This prospective, cross-sectional study included multiethnic Asian cancer patients. Patients completed the questionnaires within seven days after diagnosed with CIN. Eligible patients completed either the English or Chinese version of the EuroQol 5-Dimensions (EQ-5D) and the FACT-N once, according to their language preference. The reliability was evaluated by using Cronbach alpha (α). The known-group validity was assessed based on patient's Eastern Cooperative Oncology Group performance status, neutropenia grade, and experience of fever. The convergent validity was evaluated by contrasting the FACT-N subscales with the EQ-5D domains. Multiple linear regression models were performed to compare the FACT-N total scores between the two language versions. A total of 276 eligible patients (200 English speaking and 76 Chinese speaking) were included in this study. Internal consistencies within the FACT-N subscales were satisfactory (Cronbach α = 0.71-0.85), except for the flu-like symptoms subscale (Cronbach α = 0.67). For known-group validity, the FACT-N total score could differentiate patients according to their Eastern Cooperative Oncology Group performance status (P < 0.001), neutropenia grade (P = 0.028), and experience of fever (P < 0.001). The correlations between the FACT-N subscales and their hypothesized constructs in EQ-5D domains were weak to moderate (|r| = 0.15-0.44). The measurement equivalence between the English and Chinese versions was established for the FACT-N total scores. The FACT-N is a valid and reliable instrument to be used in clinical practice to evaluate the health-related quality of life among multiethnic Asian patients with CIN. Copyright �

Diagnosis of bacteremia in febrile neutropenic episodes in children with cancer: microbiologic and molecular approach.

PubMed

Santolaya, María E; Farfán, Mauricio J; De La Maza, Verónica; Cociña, Manuela; Santelices, Felipe; Alvarez, Ana M; Avilés, Carmen L; Becker, Ana; O'Ryan, Miguel; Román, Paulina; Salgado, Carmen; Silva, Pamela; Topelberg, Santiago; Tordecilla, Juan; Varas, Mónica; Villarroel, Milena; Viviani, Tamara; Zubieta, Marcela; Torres, Juan P

2011-11-01

Bacterial isolation using conventional microbiologic techniques rarely surpasses 25% in children with clinical and laboratory findings indicative of an invasive bacterial infection. The aim of this study was to determine the role of real-time polymerase chain reaction (RT-PCR) from whole blood samples compared with automated blood cultures (BC) in detection of relevant microorganisms causing bacteremia in episodes of high-risk febrile neutropenia (HRFN) in children with cancer. Children presenting with HRFN at 6 hospitals in Santiago, Chile, were invited to participate. Blood samples were obtained at admission for BC, and at admission and 24 hours for RT-PCR targeting DNA of Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa causing bacteremia in children with HRFN. A total of 177 HRFN episodes were evaluated from May 2009 to August 2010, of which 29 (16.3%) had positive BC, 9 (5%) positive for 1 of the 3 selected bacterial species: 5 for E. coli, 3 for S. aureus, and 1 for P. aeruginosa. RT-PCR detected 39 bacteria in 36 episodes (20%): 14 E. coli, 20 S. aureus, and 5 P. aeruginosa. The sensitivity, specificity, and positive and negative predictive values of RT-PCR compared with BC were 56%, 80%, 13%, and 97%. The final clinical diagnosis was compatible with an invasive bacterial infection in 30/36 (83%) RT-PCR-positive episodes. In our series, RT-PCR significantly improved detection of the most relevant bacteria associated with HRFN episodes. Large number of patients and close clinical monitoring, in addition to improved RT-PCR techniques will be required to fully recommend RT-PCR-based diagnosis for the routine workup of children with cancer, fever, and neutropenia.

[Frequency of opportunistic infections in children with immune neutropenia and their mothers].

PubMed

Kalugina, M Iu; Karazhas, N V; Rybalkina, T N; Bosh'ian, R E; Mamedova, E A; Polovtseva, T V; Finogenova, N A

2012-01-01

Determine the frequency of opportunistic infections among children with immune neutropenia and their mothers. 66 mothers and 66 children with immune neutropenia diagnosis were examined for the presence of herpes (HV) and pneumocystic infection. Opportunistic infections markers (IgM, IgG, early and late antigens, virus reproduction) were determined by enzyme immunoassay, immunofluorescence reaction and rapid culture method (vero, u937, human fibroblasts). Pneumocystosis was the most active infection in the group. Among mothers 26 (39.3%) cases of pneumocystic infection in acute form were detected, among children - 18 (27.3%) cases. Infection occurred only in acute form during primary infection; there were no cases of its reactivation, which is an indication of recent pneumocystosis infection. Analysis of data on detection of acute and recent herpes infections showed that HV infection markers were determined in a relatively large number of mothers and their children: herpes simplex virus - 21.2%, Epstein-Barr virus - 12.0%, cytomegalovirus - 15.0%, Human herpesvirus 6 - 10.6%, Pneumocystis carinii - 21.2%. The data provided give evidence on a possible family pattern of the infection. A necessity of examination of mothers and their children suffering from immune neutropenia was shown because the specified opportunistic infections can form intra-family foci. The presence of acute form of infection in mother may be one of the conditions of development of this infection in the child.

Early Changes of Mannose-Binding Lectin, H-Ficolin, and Procalcitonin in Patients with Febrile Neutropenia: A Prospective Observational Study.

PubMed

Işlak Mutcalı, Sibel; Saltoğlu, Neşe; Balkan, İlker İnanç; Özaras, Reşat; Yemişen, Mücahit; Tabak, Fehmi; Mert, Ali; Öztürk, Recep; Öngören, Şeniz; Başlar, Zafer; Aydın, Yıldız; Ferhanoğlu, Burhan; Soysal, Teoman

2016-12-01

The significance of mannose-binding lectin (MBL) and H-ficolin deficiency in febrile neutropenic (FN) patients and the correlation of these markers along with consecutive C-reactive protein (CRP) and procalcitonin (PCT) levels during the infectious process are investigated. Patients with any hematological malignancies who were defined to have "microbiologically confirmed infection", "clinically documented infection", or "fever of unknown origin" were included in this single-center prospective observational study. Serum levels of CRP, PCT, MBL, and H-ficolin were determined on 3 separate occasions: at baseline (between hospital admission and chemotherapy), at the onset of fever, and at the 72nd hour of fever. Forty-six patients (54% male, mean age 41.7 years) with 61 separate episodes of FN were evaluated. Eleven patients (23.9%) had "microbiologically confirmed infection", 17 (37%) had "clinically documented infection", and 18 (39.1%) had "fever of unknown origin". Fourteen (30.4%) patients had low (<500 ng/mL) initial MBL levels and 7 (15.21%) had low (<12,000 ng/mL) H-ficolin levels. Baseline MBL and H-ficolin levels did not significantly change on the first and third days of fever (p=0.076). Gram-negative bacteremia more frequently occurred in those with low initial MBL levels (p=0.006). PCT levels were significantly higher in those with microbiologically documented infections. Mean and median PCT levels were significantly higher in cases with bacteremia. There was no significant difference between hemoculture-positive and-negative patients in terms of CRP levels. Monitoring serum H-ficolin levels was shown to be of no benefit in terms of predicting severe infection. Low baseline MBL levels were correlated with high risk of gram-negative bacteremia; however, no significant correlation was shown in the follow-up. Close monitoring of PCT levels is warranted to provide more accurate and specific data while monitoring cases of bacteremia.

Side Effects: Infection and Neutropenia

Cancer.gov

Infection and neutropenia can be serious side effects during cancer treatment. Chemotherapy can increase your risk. Learn how to prevent infection during treatment. Find out what signs and symptoms to call the doctor about.

TCIRG1 associated Congenital Neutropenia

PubMed Central

Makaryan, Vahagn; Rosenthal, Elisabeth A.; Bolyard, Audrey Anna; Kelley, Merideth L.; Below, Jennifer E.; Bamshad, Michael J.; Bofferding, Kathryn M.; Smith, Joshua D.; Buckingham, Kati; Boxer, Laurence A.; Skokowa, Julia; Welte, Karl; Nickerson, Deborah A.; Jarvik, Gail P.; Dale, David C.

2014-01-01

Severe congenital neutropenia (SCN) is a rare hematopoietic disorder, with estimated incidence of 1 in 200,000 individuals of European descent, many cases of which are inherited in an autosomal dominant pattern. Despite the fact that several causal genes have been identified, the genetic basis for >30% of cases remains unknown. We report a five generation family segregating a novel single nucleotide variant (SNV) in TCIRG1. There is perfect co-segregation of the SNV with congenital neutropenia in this family; all 11 affected, but none of the unaffected, individuals carry this novel SNV. Western blot analysis show reduced levels of TCIRG1 protein in affected individuals, compared to healthy controls. Two unrelated patients with SCN, identified by independent investigators, are heterozygous for different, rare, highly conserved, coding variants in TCIRG1. PMID:24753205

Prevalence of non-febrile seizures in children with idiopathic autism spectrum disorder and their unaffected siblings: a retrospective cohort study.

PubMed

McCue, Lena M; Flick, Louise H; Twyman, Kimberly A; Xian, Hong; Conturo, Thomas E

2016-11-28

Autism spectrum disorder (ASD) is a heterogeneous disorder characterized not only by deficits in communication and social interactions but also a high rate of co-occurring disorders, including metabolic abnormalities, gastrointestinal and sleep disorders, and seizures. Seizures, when present, interfere with cognitive development and are associated with a higher mortality rate in the ASD population. To determine the relative prevalence of non-febrile seizures in children with idiopathic ASD from multiplex and simplex families compared with the unaffected siblings in a cohort of 610 children with idiopathic ASD and their 160 unaffected siblings, participating in the Autism Genetic Resource Exchange project, the secondary analysis was performed comparing the life-time prevalence of non-febrile seizures. Statistical models to account for non-independence of observations, inherent with the data from multiplex families, were used in assessing potential confounding effects of age, gender, and history of febrile seizures on odds of having non-febrile seizures. The life-time prevalence of non-febrile seizures was 8.2% among children with ASD and 2.5% among their unaffected siblings. In a logistic regression analysis that adjusted for familial clustering, children with ASD had 5.27 (95%CI: 1.51-18.35) times higher odds of having non-febrile seizures compared to their unaffected siblings. In this comparison, age, presence of gastrointestinal dysfunction, and history of febrile seizures were significantly associated with the prevalence of non-febrile seizures. Children with idiopathic ASD are significantly more likely to have non-febrile seizures than their unaffected siblings, suggesting that non-febrile seizures may be ASD-specific. Further studies are needed to determine modifiable risk factors for non-febrile seizures in ASD.

Febrile Seizures and Epilepsy: Association With Autism and Other Neurodevelopmental Disorders in the Child and Adolescent Twin Study in Sweden.

PubMed

Gillberg, Christopher; Lundström, Sebastian; Fernell, Elisabeth; Nilsson, Gill; Neville, Brian

2017-09-01

There is a recently well-documented association between childhood epilepsy and earlysymptomaticsyndromeselicitingneurodevelopmentalclinicalexaminations (ESSENCE) including autism spectrum disorder, but the relationship between febrile seizures and ESSENCE is less clear. The Child and Adolescent Twin Study in Sweden (CATSS) is an ongoing population-based study targeting twins born in Sweden since July 1, 1992. Parents of 27,092 twins were interviewed using a validated DSM-IV-based interview for ESSENCE, in connection with the twins' ninth or twelfth birthday. Diagnoses of febrile seizures (n = 492) and epilepsy (n = 282) were based on data from the Swedish National Patient Register. Prevalence of ESSENCE in individuals with febrile seizures and epilepsy was compared with prevalence in the twin population without seizures. The association between febrile seizures and ESSENCE was considered before and after adjustment for epilepsy. Age of diagnosis of febrile seizures and epilepsy was considered as a possible correlate of ESSENCE in febrile seizures and epilepsy. The rate of ESSENCE in febrile seizures and epilepsy was significantly higher than in the total population without seizures (all P < 0.001). After adjusting for epilepsy, a significant association between febrile seizures and autism spectrum disorder, developmental coordination disorder, and intellectual disability remained. Earlier age of onset was associated with all ESSENCE except attention-deficit/hyperactivity disorder in epilepsy but not with ESSENCE in febrile seizures. In a nationally representative sample of twins, there was an increased rate of ESSENCE in childhood epilepsy and in febrile seizures. Febrile seizures alone could occur as a marker for a broader ESSENCE phenotype. Copyright © 2017 Elsevier Inc. All rights reserved.

Predicting paclitaxel-induced neutropenia using the DMET platform.

PubMed

Nieuweboer, Annemieke J M; Smid, Marcel; de Graan, Anne-Joy M; Elbouazzaoui, Samira; de Bruijn, Peter; Martens, John W; Mathijssen, Ron H J; van Schaik, Ron H N

2015-01-01

The use of paclitaxel in cancer treatment is limited by paclitaxel-induced neutropenia. We investigated the ability of genetic variation in drug-metabolizing enzymes and transporters to predict hematological toxicity. Using a discovery and validation approach, we identified a pharmacogenetic predictive model for neutropenia. For this, a drug-metabolizing enzymes and transporters plus DNA chip was used, which contains 1936 SNPs in 225 metabolic enzyme and drug-transporter genes. Our 10-SNP model in 279 paclitaxel-dosed patients reached 43% sensitivity in the validation cohort. Analysis in 3-weekly treated patients only resulted in improved sensitivity of 79%, with a specificity of 33%. None of our models reached statistical significance. Our drug-metabolizing enzymes and transporters-based SNP-models are currently of limited value for predicting paclitaxel-induced neutropenia in clinical practice. Original submitted 9 March 2015; Revision submitted 20 May 2015.

Effect of therapy on the neutropenia of hyperthyroidism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eakin, D.L.; Peake, R.L.; Weiss, G.B.

Observations in a patient with recurrent hyperthyroidism, each time associated with neutropenia which resolved after therapy, prompted a chart review of other patients referred for radioactive iodine therapy. Of 99 untreated patients, 18 had neutrophil counts of less than 2,000/cu mm. After therapy with either thionamides or /sup 131/I, 41 of 53 (77%) evaluable patients had an increase in neutrophil count. Eleven of these evaluable patients had neutropenia before therapy; after therapy, all 11 had an increase in their neutrophil counts into the normal range, with a mean increase of 170%. In one patient, studies on the mechanism of neutropeniamore » indicate that bone marrow production and reserve remain normal and that circulating neutrophils are normally marginated. A decreased neutrophil circulation time may be the cause of neutropenia associated with hyperthyroidism.« less

The Use of Intravenous Antibiotics at the Onset of Neutropenia in Patients Receiving Outpatient-Based Hematopoietic Stem Cell Transplants

PubMed Central

Hamadah, Aziz; Schreiber, Yoko; Toye, Baldwin; McDiarmid, Sheryl; Huebsch, Lothar; Bredeson, Christopher; Tay, Jason

2012-01-01

Empirical antibiotics at the onset of febrile neutropenia are one of several strategies for management of bacterial infections in patients undergoing Hematopoietic Stem Cell Transplant (HSCT) (empiric strategy). Our HSCT program aims to perform HSCT in an outpatient setting, where an empiric antibiotic strategy was employed. HSCT recipients began receiving intravenous antibiotics at the onset of neutropenia in the absence of fever as part of our institutional policy from 01 Jan 2009; intravenous Prophylactic strategy. A prospective study was conducted to compare two consecutive cohorts [Year 2008 (Empiric strategy) vs. Year 2009 (Prophylactic strategy)] of patients receiving HSCT. There were 238 HSCTs performed between 01 Jan 2008 and 31 Dec 2009 with 127 and 111 in the earlier and later cohorts respectively. Infection-related mortality pre- engraftment was similar with a prophylactic compared to an empiric strategy (3.6% vs. 7.1%; p = 0.24), but reduced among recipients of autologous HSCT (0% vs. 6.8%; p = 0.03). Microbiologically documented, blood stream infections and clinically documented infections pre-engraftment were reduced in those receiving a prophylactic compared to an empiric strategy, (11.7% vs. 28.3%; p = 0.001), (9.9% vs. 24.4%; p = 0.003) and (18.2% vs. 33.9% p = 0.007) respectively. The prophylactic use of intravenous once-daily ceftriaxone in patients receiving outpatient based HSCT is safe and may be particularly effective in patients receiving autologous HSCT. Further studies are warranted to study the impact of this Prophylactic strategy in an outpatient based HSCT program. PMID:23029441

Intermittent chronic neutropenia in a patient with familial Mediterranean fever.

PubMed

Ganiou Tidjani, K; Ailal, F; Najib, J; Bellanné-Chantelot, C; Donadieu, J; Bousfiha, A A

2008-11-01

A 12-year-old daughter of consanguineous Moroccan parents was diagnosed with cyclic neutropenia, based on a combination of recurrent gingivostomatitis, a fluctuating neutrophil count, and several episodes of severe neutropenia. No ELA2 gene mutations were found. At age 19 years she presented with edema of the limbs, proteinuria and renal failure. Renal amyloidosis AA was diagnosed by biopsy. Gene mutations associated with family Mediterranean fever (FMF) were sought, and a homozygous mutation (M694V) was found in the MFEV gene. This is the novel finding of FMF that masqueraded as cyclic neutropenia. (c) 2008 Wiley-Liss, Inc.

CARbon DIoxide for the treatment of Febrile seizures: rationale, feasibility, and design of the CARDIF-study

PubMed Central

2013-01-01

Background 2-8% of all children aged between 6 months and 5 years have febrile seizures. Often these seizures cease spontaneously, however depending on different national guidelines, 20-40% of the patients would need therapeutic intervention. For seizures longer than 3-5 minutes application of rectal diazepam, buccal midazolam or sublingual lorazepam is recommended. Benzodiazepines may be ineffective in some patients or cause prolonged sedation and fatigue. Preclinical investigations in a rat model provided evidence that febrile seizures may be triggered by respiratory alkalosis, which was subsequently confirmed by a retrospective clinical observation. Further, individual therapeutic interventions demonstrated that a pCO2-elevation via re-breathing or inhalation of 5% CO2 instantly stopped the febrile seizures. Here, we present the protocol for an interventional clinical trial to test the hypothesis that the application of 5% CO2 is effective and safe to suppress febrile seizures in children. Methods The CARDIF (CARbon DIoxide against Febrile seizures) trial is a monocentric, prospective, double-blind, placebo-controlled, randomized study. A total of 288 patients with a life history of at least one febrile seizure will be randomized to receive either carbogen (5% CO2 plus 95% O2) or placebo (100% O2). As recurrences of febrile seizures mainly occur at home, the study medication will be administered by the parents through a low-pressure can fitted with a respiratory mask. The primary outcome measure is the efficacy of carbogen to interrupt febrile seizures. As secondary outcome parameters we assess safety, practicability to use the can, quality of life, contentedness, anxiousness and mobility of the parents. Prospect The CARDIF trial has the potential to develop a new therapy for the suppression of febrile seizures by redressing the normal physiological state. This would offer an alternative to the currently suggested treatment with benzodiazepines. This study is an

Role of genetic variation in docetaxel-induced neutropenia and pharmacokinetics.

PubMed

Nieuweboer, A J M; Smid, M; de Graan, A-J M; Elbouazzaoui, S; de Bruijn, P; Eskens, F A L M; Hamberg, P; Martens, J W M; Sparreboom, A; de Wit, R; van Schaik, R H N; Mathijssen, R H J

2016-11-01

Docetaxel is used for treatment of several solid malignancies. In this study, we aimed for predicting docetaxel clearance and docetaxel-induced neutropenia by developing several genetic models. Therefore, pharmacokinetic data and absolute neutrophil counts (ANCs) of 213 docetaxel-treated cancer patients were collected. Next, patients were genotyped for 1936 single nucleotide polymorphisms (SNPs) in 225 genes using the drug-metabolizing enzymes and transporters platform and thereafter split into two cohorts. The combination of SNPs that best predicted severe neutropenia or low clearance was selected in one cohort and validated in the other. Patients with severe neutropenia had lower docetaxel clearance than patients with ANCs in the normal range (P=0.01). Severe neutropenia was predicted with 70% sensitivity. True low clearance (1 s.d.

TCIRG1-associated congenital neutropenia.

PubMed

Makaryan, Vahagn; Rosenthal, Elisabeth A; Bolyard, Audrey Anna; Kelley, Merideth L; Below, Jennifer E; Bamshad, Michael J; Bofferding, Kathryn M; Smith, Joshua D; Buckingham, Kati; Boxer, Laurence A; Skokowa, Julia; Welte, Karl; Nickerson, Deborah A; Jarvik, Gail P; Dale, David C

2014-07-01

Severe congenital neutropenia (SCN) is a rare hematopoietic disorder, with estimated incidence of 1 in 200,000 individuals of European descent, many cases of which are inherited in an autosomal dominant pattern. Despite the fact that several causal genes have been identified, the genetic basis for >30% of cases remains unknown. We report a five-generation family segregating a novel single nucleotide variant (SNV) in TCIRG1. There is perfect cosegregation of the SNV with congenital neutropenia in this family; all 11 affected, but none of the unaffected, individuals carry this novel SNV. Western blot analysis show reduced levels of TCIRG1 protein in affected individuals, compared to healthy controls. Two unrelated patients with SCN, identified by independent investigators, are heterozygous for different, rare, highly conserved, coding variants in TCIRG1. © 2014 WILEY PERIODICALS, INC.

Neutropenia and Neutropenic Complications in ABVD Chemotherapy for Hodgkin Lymphoma

PubMed Central

Vakkalanka, Bhanu; Link, Brian K.

2011-01-01

A combination of Adriamycin (a.k.a. Doxorubicin), Bleomycin, Vinblastine, and Dacarbazine (ABVD) is the most commonly used chemotherapy regime for Hodgkin lymphoma. This highly effective treatment is associated with a significant risk of neutropenia. Various strategies are adopted to counter this commonly encountered problem, including dose modification, use of colony stimulating factors, and prophylactic or therapeutic use of antibiotics. Data to support these approaches is somewhat controversial, and in keeping with the paucity of definitive evidence, there is a wide disparity in the management of neutropenia in patients receiving ABVD chemotherapy. This paper summarizes the evidence for managing ABVD-related neutropenia during the treatment of Hodgkin lymphoma. PMID:21687649

Neutropenia is independently associated with sub-therapeutic serum concentration of vancomycin.

PubMed

Choi, Min Hyuk; Choe, Yeon Hwa; Lee, Sang-Guk; Jeong, Seok Hoon; Kim, Jeong-Ho

2017-02-01

We aimed to identify the impact of the presence of neutropenia on serum vancomycin concentration (SVC). A retrospective study was conducted from January 2005 to December 2015. The study population was comprised of adult patients who were performed serum concentration of vancomycin. Patients with renal failure or using non-conventional dosages of vancomycin were excluded. A total of 1307 adult patients were included in this study, of whom 163 (12.4%) were neutropenic. Patients with neutropenia presented significantly lower SVCs than non-neutropenic patients (P<0.0001). Multiple linear regressions showed significant association between neutropenia and trough SVC (beta coefficients, -2.351; P=0.004). Multiple logistic regression analysis also revealed a significant association between sub-therapeutic vancomycin concentrations (trough SVC values<10mg/l) and neutropenia (odds ratio, 1.75, P=0.029) CONCLUSIONS: The presence of neutropenia is significantly associated with low SVC, even after adjusting for other variables. Therefore, neutropenic patients had a higher risk of sub-therapeutic SVC compared with non-neutropenic patients. We recommended that vancomycin therapy should be monitored with TDM-guided optimization of dosage and intervals, especially in neutropenic patients. Copyright © 2016 Elsevier B.V. All rights reserved.

Diagnosis and Management of Borrelia turicatae Infection in Febrile Soldier, Texas, USA

PubMed Central

Pietralczyk, Elizabeth; Lopez, Job E.; Brooks, Christopher; Schriefer, Martin E.; Wozniak, Edward; Stermole, Benjamin

2017-01-01

In August 2015, a soldier returned from field exercises in Texas, USA, with nonspecific febrile illness. Culture and sequencing of spirochetes from peripheral blood diagnosed Borrelia turicatae infection. The patient recovered after receiving doxycycline. No illness occurred in asymptomatic soldiers potentially exposed to the vector tick and prophylactically given treatment. PMID:28418310

Copeptin as a serum biomarker of febrile seizures.

PubMed

Stöcklin, Benjamin; Fouzas, Sotirios; Schillinger, Paula; Cayir, Sevgi; Skendaj, Roswitha; Ramser, Michel; Weber, Peter; Wellmann, Sven

2015-01-01

Accurate diagnosis of febrile seizures in children presenting after paroxysmal episodes associated with fever, is hampered by the lack of objective postictal biomarkers. The aim of our study was to investigate whether FS are associated with increased levels of serum copeptin, a robust marker of arginine vasopressin secretion. This was a prospective emergency-setting cross-sectional study of 161 children between six months and five years of age. Of these, 83 were diagnosed with febrile seizures, 69 had a febrile infection without seizures and nine had epileptic seizures not triggered by infection. Serum copeptin and prolactin levels were measured in addition to standard clinical, neurophysiological, and laboratory assessment. NCT01884766. Circulating copeptin was significantly higher in children with febrile seizures (median [interquartile range] 18.9 pmol/L [8.5-36.6]) compared to febrile controls (5.6 pmol/L [4.1-9.4]; p < 0.001), with no differences between febrile and epileptic seizures (21.4 pmol/L [16.1-46.6]; p = 0.728). In a multivariable regression model, seizures were the major determinant of serum copeptin (beta 0.509; p < 0.001), independently of clinical and baseline laboratory indices. The area under the receiver operating curve for copeptin was 0.824 (95% CI 0.753-0.881), significantly higher compared to prolactin (0.667 [0.585-0.742]; p < 0.001). The diagnostic accuracy of copeptin increased with decreasing time elapsed since the convulsive event (at 120 min: 0.879 [0.806-0.932] and at <60 min: 0.975 [0.913-0.997]). Circulating copeptin has high diagnostic accuracy in febrile seizures and may be a useful adjunct for accurately diagnosing postictal states in the emergency setting.

Neutropenia associated with osteomyelitis due to Hepatozoon canis infection in a dog.

PubMed

Shimokawa Miyama, Takako; Umeki, Saori; Baba, Kenji; Sada, Kumiko; Hiraoka, Hiroko; Endo, Yasuyuki; Inokuma, Hisashi; Hisasue, Masaharu; Okuda, Masaru; Mizuno, Takuya

2011-10-01

A 4-year-old, intact male Shiba dog was referred to Yamaguchi University Animal Medical Center, Yamaguchi, Japan, for the following complaints: anorexia, lethargy, intermittent fever, gingival bleeding and abdominal purpura. The dog presented with persistent neutropenia. Histopathological examination of a bone marrow sample revealed round to oval structures that resembled Hepatozoon micromerozoites and formed a "wheel-spoke" pattern. Furthermore, mature neutrophils were observed around these structures. PCR and sequencing using bone marrow aspirate confirmed Hepatozoon canis (H. canis) infection. These findings suggest that the neutropenia observed in this case was associated with osteomyelitis due to H. canis infection. This is the first report of neutropenia associated with H. canis infection. H. canis infection can be included in the differential diagnosis in canine cases of neutropenia in areas where the disease is endemic.

Score of liver ultrasonography predicts treatment-related severe neutropenia and neutropenic fever in induction chemotherapy with docetaxel for locally advanced head and neck cancer patients with normal serum transamines.

PubMed

Wang, Ting-Yao; Chen, Wei-Ming; Yang, Lan-Yan; Chen, Chao-Yu; Chou, Wen-Chi; Chen, Yi-Yang; Chen, Chih-Cheng; Lee, Kuan-Der; Lu, Chang-Hsien

2016-11-01

Induction chemotherapy with docetaxel improved outcome in advanced head and neck squamous cell carcinoma (HNSCC) patients, but docetaxel was not recommended in liver dysfunction patients for treatment toxicities. Severe neutropenic events (SNE) including severe neutropenia (SN) and febrile neutropenia (FN) still developed in these patients with normal serum transaminases. Ultrasonography (US) fibrotic score represented degree of hepatic parenchymal damage and showed good correlation to fibrotic changes histologically. This study aims to evaluate the association of US fibrotic score with docetaxel treatment-related SNE in advanced HNSCC patients with normal serum transaminases. Between 1 January 2011 and 31 December 2013, a total of 47 advanced HNSCC patients treated with induction docetaxel were enrolled. The clinical features were collected to assess predictive factors for SNE. The patients were divided into two groups by the US fibrotic score with a cutoff value of 7. The Mann-Whitney U test and logistic regression method were used for the risk factor analysis. The background, treatment, and response were similar in both groups except for lower lymphocyte and platelet count in patients with higher US score. Twenty-seven patients (51 %) developed grade 3/4 neutropenia, and more SNE developed in patients with US score ≧7. In multivariate analysis, only US score ≥7 was independent predictive factor for developing SN (hazard ratio 7.71, p = 0.043) and FN (hazard ratio 20.95, p = 0.008). US score ≥7 is an independent risk factor for SNE in advanced HNSCC patients treated with induction docetaxel. US score could be used for risk prediction of docetaxel-related SNE.

Cost-Effectiveness Analysis of Prophylaxis Treatment Strategies to Reduce the Incidence of Febrile Neutropenia in Patients with Early-Stage Breast Cancer or Non-Hodgkin Lymphoma.

PubMed

Fust, Kelly; Li, Xiaoyan; Maschio, Michael; Villa, Guillermo; Parthan, Anju; Barron, Richard; Weinstein, Milton C; Somers, Luc; Hoefkens, Caroline; Lyman, Gary H

2017-04-01

The objective of this study was to evaluate the cost effectiveness of no prophylaxis, primary prophylaxis (PP), or secondary prophylaxis (SP) with granulocyte colony-stimulating factors (G-CSFs), i.e., pegfilgrastim, lipegfilgrastim, filgrastim (6- and 11-day), or lenograstim (6- and 11-day), to reduce the incidence of febrile neutropenia (FN) in patients with stage II breast cancer receiving TC (docetaxel, cyclophosphamide) and in patients with non-Hodgkin lymphoma (NHL) receiving R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) over a lifetime horizon from a Belgian payer perspective. A Markov cycle tree tracked FN events during chemotherapy (3-week cycles) and long-term survival (1-year cycles). Model inputs, including the efficacy of each strategy, risk of reduced relative dose intensity (RDI), and the impact of RDI on mortality, utilities, and costs (in €; 2014 values) were estimated from public sources and the published literature. Incremental cost-effectiveness ratios (ICERs) were assessed for each strategy for costs per FN event avoided, life-year (LY) saved, and quality-adjusted LY (QALY) saved. LYs and QALYs saved were discounted at 1.5% annually. Deterministic and probabilistic sensitivity analyses (DSAs and PSAs) were conducted. Base-case ICERs for PP with pegfilgrastim relative to SP with pegfilgrastim were €15,500 per QALY and €14,800 per LY saved for stage II breast cancer and €7800 per QALY and €6900 per LY saved for NHL; other comparators were either more expensive and less effective than PP or SP with pegfilgrastim or had lower costs but higher ICERs (relative to SP with pegfilgrastim) than PP with pegfilgrastim. Results of the DSA for breast cancer and NHL comparing PP and SP with pegfilgrastim indicate that the model results were most sensitive to the cycle 1 risk of FN, the proportion of FN events requiring hospitalization, the relative risk of FN in cycles ≥2 versus cycle 1, no history of FN, and the

Neutropenia: occurrence and management in women with breast cancer receiving chemotherapy

PubMed Central

do Nascimento, Talita Garcia; de Andrade, Marceila; de Oliveira, Rosemeire Aparecida; de Almeida, Ana Maria; Gozzo, Thais de Oliveira

2014-01-01

Objectives to identify the prevalence, and describe the management of, neutropenia throughout the chemotherapy treatment among women with breast cancer. Methods observational study, cycles of chemotherapy. 116 neutropenic events were recorded, and 63.3% of the patients presented neutropenia at some point of their treatment, 46.5% of these presenting grade II. The management used was temporary suspension between the cycles and the mean number of delays was 6 days. The study was prospective and longitudinal, where the evaluation of the hematological toxicities was undertaken at each cycle of chemotherapy, whether neoadjuvant or adjuvant. Results 79 women were included, who received 572 cycles. However, the reasons for the suspensions were the lack of a space in the chemotherapy center, followed by neutropenia. Conclusion neutropenia is one of the most common and serious adverse events observed during the chemotherapy. Nursing must invest in research regarding this adverse event and in management strategies for organizing the public health system, so as to offer quality care. PMID:26107839

78 FR 48175 - Retrospective Review of Draft Guidance Documents Issued Before 2010; Withdrawal of Guidances

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-07

...-related bloodstream infections, febrile neutropenia, gonorrhea, Lyme disease, streptococcal pharyngitis...--Developing Antimicrobial Drugs for Treatment''--issued July 1998. 9. ``Streptococcal Pharyngitis and...

Medication management of febrile children: a qualitative study on pharmacy employees' experiences.

PubMed

Stakenborg, Jacqueline P G; de Bont, Eefje G P M; Peetoom, Kirsten K B; Nelissen-Vrancken, Marjorie H J M G; Cals, Jochen W L

2016-10-01

Background While fever is mostly self-limiting, antibiotic prescription rates for febrile children are high. Although every parent who receives a prescription visits a pharmacy, we have limited insight into pharmacy employees' experiences with these parents. Pharmacy employees do however exert an important role in ensuring children receive correct dosages and in advising parents on administration of antibiotics. Objective To describe pharmacists' and pharmacy assistants' experiences with parents contacting a pharmacy for their febrile child, and to identify ways of improving medication management of these children. Setting Community pharmacies in the Netherlands. Method A qualitative study including 24 Dutch pharmacy employees was conducted, performing four focus group discussions among pharmacy employees. Analysis was based on constant comparative technique using open and axial coding. Main outcome measure Pharmacy employees' experiences with parents contacting a pharmacy for their febrile child. Results Three categories were identified: (1) workload and general experience, (2) inconsistent information on antibiotic prescriptions, (3) improving communication and collaboration. Pharmacy employees experienced that dosing errors in antibiotic prescriptions occur frequently and doctors provide inconsistent information on prescriptions. Consequently, they have to contact doctors, resulting in a higher workload for both stakeholders. They believe this can be improved by providing the indication for antibiotics on prescriptions, especially when deviating from standard dosages. Conclusion Pharmacy employees experience a high amount of dosing errors in paediatric antibiotic prescriptions. Providing the indication for antibiotics in febrile children on prescriptions, especially when deviating from standard dosages, can potentially reduce dosage errors and miscommunication between doctors and pharmacy employees.

Treatment of hyperthyroidism with antithyroid drugs corrects mild neutropenia in Graves' disease.

PubMed

Aggarwal, N; Tee, S A; Saqib, W; Fretwell, T; Summerfield, G P; Razvi, S

2016-12-01

Neutropenia secondary to antithyroid drug (ATD) therapy in Graves' disease (GD) is well recognized. However, the effect of hyperthyroidism, prior to and after ATD therapy, on neutrophil counts in patients with GD is unclear. To study the prevalence of neutropenia in newly diagnosed untreated GD and the effect of ATD on the neutrophil count. Prospective study from August 2010 to December 2014. Endocrinology outpatient clinic in a single centre. Consecutive patients (n = 206) with newly diagnosed GD. ATD therapy. Prevalence and factors predicting neutropenia (<2 × 10 9 /l) and change in neutrophil counts following ATD. At diagnosis, 29 (14·1%) of GD individuals had neutropenia. Non-Caucasians [odds ratio (95% CI) of 4·06 (1·14-14·45), P = 0·03] and patients with higher serum thyroid hormone levels [OR 1·07 (1·02-1·13), P = 0·002 for serum FT3] were the only independent predictors of neutropenia. All patients with neutropenia had normalized blood neutrophil levels after achieving euthyroidism with ATD therapy. In patients in whom data were available posteuthyroidism (n = 149), change in neutrophil count after achieving euthyroidism was independently related to reduction in thyroid hormone levels (P < 0·01). GD is associated with neutropenia in one in seven patients at diagnosis, especially in non-Caucasians and those with higher serum thyroid hormone levels. Neutrophil counts increase with treatment with ATD and are related to reduction in thyroid hormone concentrations. It is therefore important to check neutrophil levels in newly diagnosed patients with GD prior to commencing ATD therapy as otherwise low levels may incorrectly be attributed to ATD therapy. © 2016 John Wiley & Sons Ltd.

Evaluation of the Safety of Clozapine Use in Patients with Benign Neutropenia

PubMed Central

Richardson, Charles M.; Davis, Erica A.; Vyas, Gopal R.; DiPaula, Bethany A.; McMahon, Robert P.; Kelly, Deanna L.

2017-01-01

Objective Determine if clozapine can be safely utilized in a population of psychiatric patients with current or a history of benign neutropenia. Method A single-center, retrospective chart review was conducted in an inpatient psychiatric hospital. Patients included had benign neutropenia prior to receiving clozapine and received clozapine using modified monitoring guidelines. All available laboratory values for absolute neutrophil count (ANC) before clozapine initiation and during treatment were evaluated. The primary endpoint was the difference in ANC after initiation of clozapine compared to before clozapine treatment. Results A total of 26 patients were reviewed. Mean age was 34 years at clozapine initiation. The majority were African-American (73%), with more males than females (73% vs. 27%). The mean lowest ANC value was not significantly different after clozapine initiation compared to before (1.5 and 1.4×103 cells/mm3, respectively; p=0.22). There were no cases of agranulocytosis (ANC <0.5 ×103 cells/mm3) and no patients were discontinued for falling below limits set by modified guidelines. There were fewer occurrences of mild neutropenia (ANC <2.0×103 cells/mm3) after clozapine initiation than before (16% and 31.4%, respectively; p<0.001). There were also fewer occurrences of moderate neutropenia (ANC <1.5×103 cells/mm3) with 2.1% after clozapine and 13.3% before (p<0.001). Occurrence of ANC <1.0×103 cells/mm3 did not differ (0.4% before, 0.3% after, p=0.79). Conclusion Twenty-six patients with benign neutropenia were safely treated with clozapine. Their pre-clozapine neutropenia did not predict increased risk for agranulocytosis with clozapine. Patients had significantly fewer episodes of mild and moderate neutropenia after receiving clozapine compared to before. PMID:27736047

Co-administration of dexamethasone increases severity and accelerates onset day of neutropenia in bladder cancer patients on methotrexate, vinblastine, adriamycin and cisplatin chemotherapy: a retrospective cohort study.

PubMed

Itai, Shingo; Suga, Yukio; Hara, Yusuke; Izumi, Kouji; Maeda, Yuji; Kitagawa, Yasuhide; Ishizaki, Junko; Shimada, Tsutomu; Mizokami, Atsushi; Sai, Yoshimichi

2017-01-01

Bladder cancer patients receiving methotrexate, vinblastine, adriamycin and cisplatin (MVAC) chemotherapy are co-administered with dexamethasone as an anti-emetic. We examined whether or not dexamethasone affects the severity and onset day of MVAC-induced severe neutropenia. This was a retrospective study of bladder cancer patients treated with MVAC chemotherapy with or without dexamethasone as an antiemetic at Kanazawa University Hospital during January 2005 - December 2009. Patients were categorized into three groups; no dexamethasone use (Dex (-)), dexamethasone on day 2 (Dex 1 day), and dexamethasone on days 2, 3 and 4 (Dex multiday). We evaluated the incidence of grade 3/4 neutropenia and the day of onset of first severe neutropenic episode during the first course of MVAC chemotherapy. Logistic regression was used to investigate whether co-administration of dexamethasone was a risk factor for severe neutropenia. Episodes of grade 3/4 neutropenia occurred in 3 out of 6 (50.0%), 11 out of 12 (91.7%) and 6 out of 6 (100%) patients in the Dex (-), Dex 1 day, and Dex multiday groups, respectively. The appearance day of first severe neutropenia in the Dex multiday group (13.2 ± 1.0) was significantly accelerated compared to the Dex (-) group (17.7 ± 2.1). Univariate logistic regression analysis revealed that dexamethasone is a risk factor for severe neutropenia (OR 17.0; 95%CI: 1.3-223.1). Co-administration of dexamethasone for anti-emesis brings forward the first appearance of neutropenia, and increases the severity of neutropenia, in bladder cancer patients receiving MVAC chemotherapy.

New monogenic disorders identify more pathways to neutropenia: from the clinic to next-generation sequencing

PubMed Central

Corey, Seth J.; Oyarbide, Usua

2018-01-01

Neutrophils are the most common type of leukocyte in human circulating blood and constitute one of the chief mediators for innate immunity. Defined as a reduction from a normal distribution of values, neutropenia results from a number of congenital and acquired conditions. Neutropenia may be insignificant, temporary, or associated with a chronic condition with or without a vulnerability to life-threatening infections. As an inherited bone marrow failure syndrome, neutropenia may be associated with transformation to myeloid malignancy. Recognition of an inherited bone marrow failure syndrome may be delayed into adulthood. The list of monogenic neutropenia disorders is growing, heterogeneous, and bewildering. Furthermore, greater knowledge of immune-mediated and drug-related causes makes the diagnosis and management of neutropenia challenging. Recognition of syndromic presentations and especially the introduction of next-generation sequencing are improving the accuracy and expediency of diagnosis as well as their clinical management. Furthermore, identification of monogenic neutropenia disorders is shedding light on the molecular mechanisms of granulopoiesis and myeloid malignancies. PMID:29222253

Childhood Epilepsy, Febrile Seizures, and Subsequent Risk of ADHD.

PubMed

Bertelsen, Elin Næs; Larsen, Janne Tidselbak; Petersen, Liselotte; Christensen, Jakob; Dalsgaard, Søren

2016-08-01

Epilepsy, febrile seizures, and attention-deficit/hyperactivity disorder (ADHD) are disorders of the central nervous system and share common risk factors. Our goal was to examine the association in a nationwide cohort study with prospective follow-up and adjustment for selected confounders. We hypothesized that epilepsy and febrile seizures were associated with subsequent ADHD. A population-based cohort of all children born in Denmark from 1990 through 2007 was followed up until 2012. Incidence rate ratios (IRRs) and 95% confidence intervals (95% CIs) for ADHD were estimated by using Cox regression analysis, comparing children with epilepsy and febrile seizure with those without these disorders, adjusted for socioeconomic and perinatal risk factors, as well as family history of neurologic and psychiatric disorders. A total of 906 379 individuals were followed up for 22 years (∼10 million person-years of observation); 21 079 individuals developed ADHD. Children with epilepsy had a fully adjusted IRR of ADHD of 2.72 (95% CI, 2.53-2.91) compared with children without epilepsy. Similarly, in children with febrile seizure, the fully adjusted IRR of ADHD was 1.28 (95% CI, 1.20-1.35). In individuals with both epilepsy and febrile seizure, the fully adjusted IRR of ADHD was 3.22 (95% CI, 2.72-3.83). Our findings indicate a strong association between epilepsy in childhood and, to a lesser extent, febrile seizure and subsequent development of ADHD, even after adjusting for socioeconomic and perinatal risk factors, and family history of epilepsy, febrile seizures, or psychiatric disorders. Copyright © 2016 by the American Academy of Pediatrics.

Idiosyncratic drug-induced agranulocytosis or acute neutropenia.

PubMed

Andrès, Emmanuel; Maloisel, Frédéric

2008-01-01

Idiosyncratic drug-induced agranulocytosis or acute neutropenia is an adverse event resulting in a neutrophil count of under 0.5 x 10/l. Patients with such severe neutropenia are likely to experience life-threatening and sometimes fatal infections. Over the last 20 years, the incidence of idiosyncratic drug-induced agranulocytosis or acute neutropenia has remained stable at 2.4-15.4 cases per million, despite the emergence of new causative drugs: antibiotics (beta-lactam and cotrimoxazole), antiplatelet agents (ticlopidine), antithyroid drugs, sulfasalazine, neuroleptics (clozapine), antiepileptic agents (carbamazepine), nonsteroidal anti-inflammatory agents and dipyrone. Drug-induced agranulocytosis remains a serious adverse event due to the occurrence of severe sepsis with severe deep infections (such as pneumonia), septicemia and septic shock in around two thirds of patients. In this setting, old age (>65 years), septicemia or shock, metabolic disorders such as renal failure, and a neutrophil count under 0.1 x 10/l are poor prognostic factors. Nevertheless with appropriate management using preestablished procedures, with intravenous broad-spectrum antibiotic therapy and hematopoietic growth factors, the mortality rate is currently around 5%. Given the increased life expectancy and subsequent longer exposure to drugs, as well as the development of new agents, healthcare professionals should be aware of this adverse event and its management.

Population pharmacokinetics and dosing simulations of imipenem in serious bacteraemia in immunocompromised patients with febrile neutropenia.

PubMed

Jaruratanasirikul, Sutep; Wongpoowarak, Wibul; Jullangkoon, Monchana; Samaeng, Maseetoh

2015-02-01

The aims of this study were to i) reveal the population pharmacokinetics; and ii) assess the probability of target attainment (PTA) and cumulative fraction of response (CFR) (defined as the expected population PTA for a specific drug dose and a specific population of microorganisms) of imipenem in febrile neutropenic patients with bacteraemia. Ten patients were randomised into two groups: Group I received a 0.5-h infusion of 0.5 g of imipenem every 6 h (q6h) for 8 doses; and Group II received a 4-h infusion of 0.5 g q6h for 8 doses. A Monte Carlo simulation was performed to determine the PTA. The volume of distribution and total clearance of imipenem were 20.78 ± 1.35 l and 23.19 ± 1.34 l/h, respectively. Only a 4-h infusion of 1 g q6h regimen achieved a PTA >93% for 80% T>MIC for a MIC of 2 μg/ml. A 4-h infusion of all simulated regimens and a 0.5-h infusion of 0.5 g q6h and 1 g q6h achieved targets (CFR ≥ 90%) against Escherichia coli and Klebsiella spp. However, against Pseudomonas aeruginosa and Acinetobacter spp., no regimens achieved their targets. In conclusion, the results indicate that a higher than manufacturer's dosage recommendation is required to maximize the activity of imipenem. Copyright © 2014 Japanese Pharmacological Society. Production and hosting by Elsevier B.V. All rights reserved.

Severe neutropenia revealing a rare presentation of dengue fever: a case report.

PubMed

Shourick, J; Dinh, A; Matt, M; Salomon, J; Davido, B

2017-08-17

Arboviruses are a common cause of fever in the returned traveler often associated with leucopenia, especially lymphopenia and thrombocytopenia. Transient neutropenia has been described in a few cases of arboviruses. However, prolonged and severe neutropenia (<500/mm 3 ) has rarely been reported in dengue fever, especially in the returned traveler in Europe. A 26-year-old healthy female without any medical past history, flying back from Thailand, presented a transient fever with severe neutropenia (<500/mm 3 ). Laboratory tests showed a mild hepatic cytolysis and thrombocytopenia, mimicking malaria or viral hepatitis. While she underwent protective isolation, NS1 antigen returned positive in favor of a dengue fever. Outcome was favorable without any antimicrobial therapy. Physicians should be wary of possible unusual presentation of dengue fever with prolonged neutropenia. Although such biological sign is more often associated with malaria or severe bacterial infection, it may be a sign of arbovirus.

Serious neutropenia following etanercept administration in a 62 years female patient of rheumatoid arthritis.

PubMed

Datta, K; Ghosh, R K; Ghosh, S M

2010-10-01

Tumor necrosis factor (TNF) plays an important role in the inflammatory process of RA and the resulting joint pathology. Etanercept is a member of anti TNF family which is indicated in patients with moderate to severe active rheumatoid arthritis either alone or in combination with MTX. Very few cases of neutropenia with etanercept treatment have been reported worldwide so far. The mechanism of etanercept induced neutropenia is not yet established. We report a case of 62 year female patient, developing etanercept induced neutropenia after 1 month of starting treatment. The absolute neutrophil count (ANC) came down to 150/microl on the 6th day of diagnosis. Bone marrow examination revealed a maturation arrest of granulocytic cells. Other marrow components were normal. Causality assessment of adverse drug reactions was done as per Naranjo's Algorithm. It was a probable ADR. We propose the possible mechanism of neutropenia is bone marrow toxicity. This is contrary to a previous case report which suggested peripheral consumption of neutrophil as a cause of neutropenia. Recently, there are some reports of leukemia and other hematological malignancies associated with the use of etanercept and in those conditions neutropenia could be the first manifestation. Neither product label of the drug nor US FDA warns for periodic blood investigation during etanercept therapy. There is a definite need for total and differential count estimation at the beginning and regular interval during etanercept treatment to rule out possibilities of neutropenia.

[Anaemia and neutropenia in a cohort of non-infected children of HIV-positive mothers].

PubMed

Fernández Ibieta, M; Ramos Amador, J T; González Tomé, M I; Guillén Martín, S; Bellón Cano, J M; Navarro Gómez, M; de José, M I; Beceiro, J; Iglesias, E; Rubio, B; Relaño Garrido, P; Santos, M J; Martínez Guardia, N; Roa, M A; Regidor, J

2008-12-01

Mother-to-child HIV transmission is currently around 1% in western countries, due to prevention measures. Antiretroviral drugs do have adverse effects, anaemia and myelosupression caused by AZT being the most observed effects. In the present study, we analyse the prevalence of anaemia and neutropenia in an uninfected children cohort born to HIV-infected women. We followed up 623 uninfected children belonging to the FIPSE cohort according to standardised protocols. This cohort groups 8 hospitals from Madrid and follows up HIV infected pregnant women and their children. Anaemia and neutropenia were defined according to the ACTG (AIDS Clinical Trails Group) toxicity tables. Children were classified according to prematurity, ethnic origin, birth weight, withdrawal syndrome, in-utero treatment and neonatal prophylaxis. Categorical variables were compared with the chi2 or the Fisher tests. Anaemia was observed in 188 (30.1%) children during follow-up and 161 (25.8%) had anaemia grade 2 or higher. Prematurity (p < 0.001), low birth weight (p = 0.005) and Highly Active Antiretroviral Treatment (HAART) with Protease Inhibitors (p = 0.016) were associated with higher percentages of anaemia in children. Nadir haemoglobin values were reached by 6 weeks of life and anaemia was transient and disappeared by six months of age. Neutropenia was present in 41.9% (261 children) and 22.7% of the children had moderate-severe neutropenia. Prematurity was again associated with neutropenia (p = 0.01) and low birth weigh was associated only with moderate-severe neutropenia (p = 0.023). African infants had a higher percentage of neutropenia than the rest of the children (50% vs. 44%), although the differences were not significant. The type of in-utero treatment did not appear to influence the neutropenia. Neutropenia was still present in 12.5% of infants at 18 months of age. The type of neonatal prophylaxis to prevent mother-to-child transmission (monotherapy, dual therapy or triple therapy

Conflicting Data on the Incidence of Leukopenia and Neutropenia After Heated Intraperitoneal Chemotherapy with Mitomycin C.

PubMed

Feferman, Yael; Bhagwandin, Shanel; Kim, Joseph; Aycart, Samantha N; Feingold, Daniela; Labow, Daniel M; Sarpel, Umut

2017-12-01

During heated intraperitoneal chemotherapy (HIPEC), neutropenia rates of 20 to 40% have been reported when mitomycin C (MMC) is dosed by weight or body surface area (BSA). This study investigated the authors' HIPEC experience using a fixed 40-mg dose of MMC, per consensus guidelines, and analyzed predictors for severe leukopenia and neutropenia. Patients who underwent MMC-HIPEC from 2007 to 2016 at a single tertiary care center were retrospectively reviewed. Among 314 MMC-HIPEC cases, 72 patients in the early era of the authors' program received routine prophylactic postoperative granulocyte-colony-stimulating factor (GCSF). This early cohort had five severe leukopenic reactions and one neutropenic reaction. In the subsequent 242 cases without GCSF prophylaxis, severe leukopenia developed in 16 patients (7%), with neutropenia occurring in 11 (4.5%) of these cases. A history of prior systemic chemotherapy was noted in 9 (56%) of the 16 leukopenic patients compared with 112 (46%) of the patients who had no leukopenia (nonsignificant difference). The median nadir of leukopenia was 5 days (range 1-11 days). Of the 11 neutropenic patients, 6 received therapeutic GCSF, and 5 recovered without intervention. The 30-day postoperative mortality of the patients with leukopenia was 0%. In this study, the incidence of neutropenia after HIPEC with 40 mg of MMC was markedly lower than reported in the literature for doses adjusted by BSA or weight. The authors report that GCSF is not necessary for routine prophylaxis of all MMC-HIPEC patients. The findings suggest that a fixed 40-mg dose of MMC allows HIPEC to be performed with less risk of immunosuppression.

Comparison of EP2006, a filgrastim biosimilar, to the reference: a phase III, randomized, double-blind clinical study in the prevention of severe neutropenia in patients with breast cancer receiving myelosuppressive chemotherapy

PubMed Central

Blackwell, K.; Semiglazov, V.; Krasnozhon, D.; Davidenko, I.; Nelyubina, L.; Nakov, R.; Stiegler, G.; Singh, P.; Schwebig, A.; Kramer, S.; Harbeck, N.

2015-01-01

Background Biosimilars of filgrastim are in widespread clinical use in Europe. This phase III study compares biosimilar filgrastim (EP2006), with the US-licensed reference product, Neupogen®, in breast cancer patients receiving (neo)adjuvant myelosuppressive chemotherapy (TAC). Patients and methods A total of 218 patients receiving 5 µg/kg/day filgrastim over six chemotherapy cycles were randomized 1:1:1:1 into four arms. Two arms received only one product (nonalternating), biosimilar or reference, and two arms (alternating) received alternating treatments during each cycle (biosimilar then reference or vice versa). The primary end point was duration of severe neutropenia (DSN) during cycle 1. Results The baseline characteristics were balanced between the four treatment arms. Noninferiority of biosimilar versus the reference was demonstrated: DSN (days) in cycle 1 was 1.17 ± 1.11 (biosimilar, N = 101) and 1.20 ± 1.02 (reference, N = 103), 97.5% confidence interval lower boundary for the difference was −0.26 days (above the predefined limit of −1 day). No clinically meaningful differences were observed regarding any other efficacy parameter: incidence of febrile neutropenia (FN); hospitalization due to FN; incidence of infections; depth and time of absolute neutrophil count (ANC) nadir and time to ANC recovery during cycle 1 and across all cycles. The pattern and frequency of adverse events were similar across all treatments. Conclusion This study demonstrates that biosimilar and the reference filgrastim are similar with no clinically meaningful differences regarding efficacy and safety in prevention of severe neutropenia. Biosimilar filgrastim could represent an important alternative to the reference product, potentially benefiting public health by increasing access to filgrastim treatment. Study number NCT01519700. PMID:26122726

Drug-related genetic polymorphisms affecting severe chemotherapy-induced neutropenia in breast cancer patients

PubMed Central

Tsuji, Daiki; Ikeda, Midori; Yamamoto, Keisuke; Nakamori, Harumi; Kim, Yong-Il; Kawasaki, Yohei; Otake, Aki; Yokoi, Mari; Inoue, Kazuyuki; Hirai, Keita; Nakamichi, Hidenori; Tokou, Umi; Shiokawa, Mitsuru; Itoh, Kunihiko

2016-01-01

Abstract Chemotherapy-induced neutropenia (CIN) is one of the major adverse events that necessitate chemotherapy dose reduction. This study aimed to evaluate the association between grade 4 neutropenia and genetic polymorphisms in breast cancer patients. In this genetic polymorphism association study, peripheral blood samples from 100 consecutive breast cancer outpatients, between August 2012 and September 2014, treated with doxorubicin and cyclophosphamide (AC) combination chemotherapy were genotyped for polymorphisms in adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1), cytochrome P450 (CYP) enzyme-coding genes (CYP2B6 and CYP3A5), glutathione S-transferase (GST), and excision repair cross-complementing 1 (ERCC1). Associations between grade 4 neutropenia and genotypes as well as risk factors were examined using multivariate logistic regression. From 100 patients, 32.0% had grade 4 neutropenia. Multivariate logistic regression analysis revealed that ERCC1 118C > T (odds ratio [OR], 3.43; 95% confidence interval [CI], 1.22–9.69; P = 0.020), CYP2B6∗6 (OR, 4.51; 95% CI, 1.21–16.95; P = 0.025), body mass index (BMI) (OR, 6.94; 95% CI, 1.15–41.67; P = 0.035), and baseline white blood cell (WBC) count (OR, 2.99; 95% CI, 1.06–8.40; P = 0.038) were significant predictors of grade 4 neutropenia. ERCC1 and CYP2B6 gene polymorphisms were associated with the extent of grade 4 neutropenia in patients receiving AC chemotherapy. In addition to previously known risk factors, BMI and WBC counts, ERCC1 and CYP2B6 gene polymorphisms were also identified as independent strong predictors of grade 4 neutropenia. PMID:27858847

Febrile status epilepticus due to respiratory syncytial virus infection.

PubMed

Uda, Kazuhiro; Kitazawa, Katsuhiko

2017-08-01

Febrile status epilepticus can have neurological sequelae. The type of sequelae, however, depend on the etiology, including infection due to viral agents such as the influenza virus. Respiratory syncytial virus (RSV) infection in childhood may also contribute to this. The aim of this study was therefore to characterize febrile status epilepticus associated with RSV infection, and to determine whether this type of infection is a risk factor for neurological sequelae in febrile status epilepticus. We reviewed the medical records of children aged ≤3 years with febrile status epilepticus who were admitted to a tertiary hospital between January 2007 and December 2011. The differences between the RSV-positive and RSV-negative groups were evaluated according to the demographic and clinical data. A total of 99 patients with febrile status epilepticus who had been tested for RSV infection were identified. Three patients in the RSV-positive group (n = 19) and four in the RSV-negative group (n = 80) presented with bronchiolitis. The incidence of intubation and anti-seizure drug treatment in the RSV-positive group was significantly higher than in the -negative group. While all of the patients in the RSV-negative group recovered completely, six patients in the RSV-positive group developed encephalopathy and profound neurological sequelae. In five of the six patients, diffusion-weighted magnetic resonance imaging showed subcortical white matter lesions. RSV infection in the absence of bronchiolitis can initially present as febrile status epilepticus and subsequently develop into acute encephalopathy with profound neurological sequelae. © 2017 Japan Pediatric Society.

Diagnosis and management of primary autoimmune neutropenia in children: insights for clinicians

PubMed Central

Dufour, Carlo

2015-01-01

Autoimmune neutropenia of infancy (AIN), also called primary autoimmune neutropenia, is a disease in which antibodies recognize membrane antigens of neutrophils, mostly located on immunoglobulin G (IgG) Fc receptor type 3b (FcγIIIb receptor), causing their peripheral destruction. It is the most frequent type of neutropenia in children under 3–4 years of age and in most cases shows a benign, self-limited course. The diagnosis is based on evidence of indirect antineutrophil antibodies, whose detection frequently remains difficult. In this review we have analyzed the literature regarding AIN and present our personal experience in diagnosis and management. PMID:25642312

[Clinical significance of peak body temperature, white blood cell count, and C-reactive protein level in febrile episodes among geriatric inpatients].

PubMed

Ikematsu, H; Nabeshima, A; Yamaga, S; Yamaji, K; Kakuda, K; Ueno, K; Hayashi, J; Shirai, T; Hara, H; Kashiwagi, S

1997-06-01

To investigate the clinical implication of peak body temperature, peripheral blood white blood cell (WBC) count, and serum C-reactive protein (CRP) level in febrile symptoms among geriatric hospitalized patients, they were analyzed in 968 febrile episodes obtained from 433 hospitalized patients in the referred hospital. Episodes of one day duration were most frequent (41.6%). WBC count was elevated over 8000/microliters in 475 episodes (49.1%) and CRP exceeded 1.0 mg/dl in 770 episodes (79.5%). Frequency of WBC elevation decreased and frequency of CRP elevation increased according to the time course. The mean value of CRP increased significantly according to the time course. The frequency of WBC count increase and CRP elevation and their averages correlated to the peak body temperature. The peak body temperature displayed the most striking correlation to the length of febrile episodes among three clinical indicators, peak body temperature, WBC count, and CRP level. These results indicate that the elevation of WBC count and/or CRP level is frequent in geriatric patients with febrile symptoms. Peak body temperature may serve as a clinical indicator of the severy of the febrile disease occurring in geriatric patients.

The Cellular and Molecular Mechanisms for Neutropenia in Barth Syndrome

PubMed Central

Makaryan, Vahagn; Kulik, Willem; Vaz, Frederic M.; Allen, Christopher; Dror, Yigal; Dale, David C.; Aprikyan, Andranik A.

2015-01-01

Barth syndrome (BTHS), a rare, X-linked, recessive disease characterized by neutropenia and cardiomyopathy. BTHS is caused by loss-of-function mutations of the tafazzin (TAZ) gene. We developed a model of BTHS by transfecting human HL60 myeloid progenitor cells with TAZ-specific shRNAs. Results demonstrate a significant down-regulation in TAZ expression, mimicking the effects of naturally-occurring truncation mutations in TAZ. Flow cytometry analyses of cells with TAZ-specific, but not scrambled, shRNAs demonstrate nearly two-fold increase in proportion of annexin-V positive cells and significantly increased dissipation of mitochondrial membrane potential as determined by DIOC6-staining. Transfection of TAZ specific shRNA had similar effects in U937 myeloid cells but not in lymphoid cell lines. Further studies in HL60 myeloid progenitor cells revealed aberrant release of cytochrome c from mitochondria and significantly elevated levels of activated caspase-3 in response to TAZ knock-down. Treatment with caspase-specific inhibitor zVAD-fmk resulted in substantially reduced apoptosis to near-normal levels. These data suggest that neutropenia in BTHS is attributable to increased dissipation of mitochondrial membrane potential, aberrant release of cytochrome c, activation of caspase-3 and accelerated apoptosis of myeloid progenitor cells, and that this defect can be partially restored in vitro by treatment with caspase-specific inhibitors. PMID:22023389

[Effectiveness of palifermin in the prevention of oral mucositis in patients with haematological cancers].

PubMed

Ayago Flores, D; Ferriols Lisart, R

2010-01-01

To assess the effectiveness of palifermin for the prevention of oral mucositis in patients with haematological cancers. Retrospective observational study of cohorts of patients with haematological cancer undergoing cytotoxic therapy causing hematopoietic ablation. The main variable assessed was the duration of the oral mucositis. Secondary variables assessed were incidence of mucositis, febrile or septic neutropenia and the administration of opioids and parenteral nutrition. We included 36 patients in this study, 11 in the group that received palifermin and 25 in the control group. The duration of oral mucositis was 4.6+/-3.1 days (median: 5 days) in the patients treated with palifermin in comparison with 7.4+/-4.0 days (median: 6 days) in patients treated with conventional prophylactic therapy (p<0.05). However, no significant differences were seen in the incidence of mucositis, febrile or septic neutropenia, opioid administration of the use of parenteral nutrition. Prophylactic treatment with palifermin reduces the duration of oral mucosities in patients with haematological cancer. Further studies are necessary with larger samples to be able to assess palifermin and its influence on other variables, such as incidence of mucositis, sepsis, febrile neutropenia, etc. Copyright © 2009 SEFH. Published by Elsevier Espana. All rights reserved.

Cyclic neutropenia and severe congenital neutropenia in patients with a shared ELANE mutation and paternal haplotype: evidence for phenotype determination by modifying genes.

PubMed

Newburger, Peter E; Pindyck, Talia N; Zhu, Zhiqing; Bolyard, Audrey Anna; Aprikyan, Andrew A G; Dale, David C; Smith, Gary D; Boxer, Laurence A

2010-08-01

Cyclic neutropenia (CN) and severe congenital neutropenia (SCN) are disorders of neutrophil production that differ markedly in disease severity. Mutations of the ELANE gene (the symbol recently replacing ELA2) are considered largely responsible for most cases of CN and SCN, but specific mutations are typically associated with one or the other. We performed ELANE genotyping on all individuals and paternal sperm in an SCN kindred with eight SCN progeny of a sperm donor and six different mothers. One patient with CN had the same S97L ELANE mutation as seven patients with the SCN phenotype. The mutant allele was detected in the donor's spermatozoa, representing 18% of the ELANE gene pool, but not in DNA from his lymphocytes, neutrophils, or buccal mucosa, indicating gonadal mosaicism. The coexistence of CN and SCN phenotypes in this kindred with a shared paternal haplotype strongly suggests both a role for modifying genes in determination of congenital neutropenia disease phenotypes, and the classification of CN and SCN within a spectrum of phenotypes expressing varying degrees of the same disease process. (c) 2010 Wiley-Liss, Inc.

Neutropenia and agranulocytosis during treatment of schizophrenia with clozapine versus other antipsychotics: an observational study in Iceland.

PubMed

Ingimarsson, Oddur; MacCabe, James H; Haraldsson, Magnús; Jónsdóttir, Halldóra; Sigurdsson, Engilbert

2016-12-12

Data on the haematological outcomes of patients who continue clozapine treatment following neutropenia are very rare as even mild neutropenia results in mandatory discontinuation of clozapine in most countries. However, in Iceland where clozapine monitoring is less stringent allows an observational study to be done on the risk of agranulocytosis and neutropenia during treatment with clozapine compared with other antipsychotics among patients with schizophrenia. The present study is a part of a wider ongoing longitudinal study of schizophrenia in Iceland. We identified 201 patients with schizophrenia treated with clozapine and 410 patients with schizophrenia who had never been on clozapine by searching the electronic health records of Landspitali, the National University Hospital. Neutrophil counts were searched in electronic databases to identify patients who developed neutropenia/agranulocytosis and the frequency of neutrophil measurements was examined as well. The median number of days between neutrophil measurements during the first 18 weeks of clozapine treatment was 25 days but after the first 18 weeks on the drug the median became 124 days. Thirty four cases of neutropenia were identified during clozapine treatment with an average follow up time of 9.2 years. The majority, 24 individuals developed mild neutropenia (1500-1900 neutrophils/mm 3 ). None of these progressed to agranulocytosis. The remaining 10 patients developed neutropenia in the range 500-1400 /mm 3 of whom one developed agranulocytosis, three stopped clozapine use and 6 patients continued on clozapine for at least a year without developing agranulocytosis. Unexpectedly, schizophrenia patients on other antipsychotics had an equal risk of developing neutropenia as those on clozapine. Neutropenia is common both in patients with schizophrenia on clozapine treatment and in those never on clozapine. Therefore a large part of neutropenia during clozapine treatment is probably not caused by

Incidence of Neutropenia With Valproate and Quetiapine Combination Treatment in Subjects With Acquired Brain Injuries.

PubMed

Park, Hee Jung; Kim, Jung Yoon

2016-02-01

To investigate whether the incidence of neutropenia was higher in subjects who received a combination treatment with valproate and quetiapine than in those who were administered monotherapy. Retrospective cohort study. Rehabilitation department of a university hospital. Patients with acquired brain injuries who had taken valproate for seizures or quetiapine for delirium for >7 days (N=101). Data were extracted from electronic medical records of the hospital. Not applicable. Incidence of neutropenia (absolute neutrophil count<2000 cells/μL) was elicited from the weekly complete blood cell records for 71.07±43.71 days of observation. The odds ratio for neutropenia development was calculated and adjusted for variables that showed significant differences between patients with or without neutropenia. The incidence of neutropenia was significantly higher in the group receiving the combination treatment than in those receiving the monotherapy (32.26% vs 12.90%, adjusted P=.036), despite a lack of any differences in the daily doses of the medications. Coadministration of quetiapine and valproate was the predictor of neutropenia development when age, body weight, and underlying diseases were adjusted in the logistic regression model (odds ratio=3.749; 95% confidence interval, 1.161-12.099; P=.027). Administration of quetiapine together with valproate in patients with acquired brain injury could increase the incidence of medication-induced neutropenia. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Semimechanistic Bone Marrow Exhaustion Pharmacokinetic/Pharmacodynamic Model for Chemotherapy-Induced Cumulative Neutropenia.

PubMed

Henrich, Andrea; Joerger, Markus; Kraff, Stefanie; Jaehde, Ulrich; Huisinga, Wilhelm; Kloft, Charlotte; Parra-Guillen, Zinnia Patricia

2017-08-01

Paclitaxel is a commonly used cytotoxic anticancer drug with potentially life-threatening toxicity at therapeutic doses and high interindividual pharmacokinetic variability. Thus, drug and effect monitoring is indicated to control dose-limiting neutropenia. Joerger et al. (2016) developed a dose individualization algorithm based on a pharmacokinetic (PK)/pharmacodynamic (PD) model describing paclitaxel and neutrophil concentrations. Furthermore, the algorithm was prospectively compared in a clinical trial against standard dosing (Central European Society for Anticancer Drug Research Study of Paclitaxel Therapeutic Drug Monitoring; 365 patients, 720 cycles) but did not substantially improve neutropenia. This might be caused by misspecifications in the PK/PD model underlying the algorithm, especially without consideration of the observed cumulative pattern of neutropenia or the platinum-based combination therapy, both impacting neutropenia. This work aimed to externally evaluate the original PK/PD model for potential misspecifications and to refine the PK/PD model while considering the cumulative neutropenia pattern and the combination therapy. An underprediction was observed for the PK (658 samples), the PK parameters, and these parameters were re-estimated using the original estimates as prior information. Neutrophil concentrations (3274 samples) were overpredicted by the PK/PD model, especially for later treatment cycles when the cumulative pattern aggravated neutropenia. Three different modeling approaches (two from the literature and one newly developed) were investigated. The newly developed model, which implemented the bone marrow hypothesis semiphysiologically, was superior. This model further included an additive effect for toxicity of carboplatin combination therapy. Overall, a physiologically plausible PK/PD model was developed that can be used for dose adaptation simulations and prospective studies to further improve paclitaxel/carboplatin combination

Neutropenia in Patients with Common Variable Immunodeficiency: a Rare Event Associated with Severe Outcome.

PubMed

Guffroy, Aurélien; Mourot-Cottet, Rachel; Gérard, Laurence; Gies, Vincent; Lagresle, Chantal; Pouliet, Aurore; Nitschké, Patrick; Hanein, Sylvain; Bienvenu, Boris; Chanet, Valérie; Donadieu, Jean; Gardembas, Martine; Karmochkine, Marina; Nove-Josserand, Raphaele; Martin, Thierry; Poindron, Vincent; Soulas-Sprauel, Pauline; Rieux-Laucat, Fréderic; Fieschi, Claire; Oksenhendler, Eric; André-Schmutz, Isabelle; Korganow, Anne-Sophie

2017-10-01

Common variable immunodeficiency (CVID) is characterized by infections and hypogammaglobulinemia. Neutropenia is rare during CVID. The French DEFI study enrolled patients with primary hypogammaglobulinemia. Patients with CVID and neutropenia were retrospectively analyzed. Among 473 patients with CVID, 16 patients displayed neutropenia (lowest count [0-1400]*10 6 /L). Sex ratio (M/F) was 10/6. Five patients died during the follow-up (11 years) with an increased percentage of deaths compared to the whole DEFI group (31.3 vs 3.4%, P < 0.05). Neutropenia was diagnosed for 10 patients before 22 years old. The most frequent symptoms, except infections, were autoimmune cytopenia, i.e., thrombopenia or anemia (11/16). Ten patients were affected with lymphoproliferative diseases. Two patients were in the infection only group and the others belonged to one or several other CVID groups. The median level of IgG was 2.6 g/L [0.35-4.4]. Most patients presented increased numbers of CD21 low CD38 low B cell, as already described in CVID autoimmune cytopenia group. Neutropenia was considered autoimmune in 11 cases. NGS for 52 genes of interest was performed on 8 patients. No deleterious mutations were found in LRBA, CTLA4, and PIK3. More than one potentially damaging variant in other genes associated with CVID were present in most patients arguing for a multigene process. Neutropenia is generally associated with another cytopenia and presumably of autoimmune origin during CVID. In the DEFI study, neutropenia is coupled with more severe clinical outcomes. It appears as an "alarm bell" considering patients' presentation and the high rate of deaths. Whole exome sequencing diagnosis should improve management.

Neutropenia as a Predictive Factor in Metastatic Colorectal Cancer Treated With TAS-102.

PubMed

Hamauchi, Satoshi; Yamazaki, Kentaro; Masuishi, Toshiki; Kito, Yosuke; Komori, Azusa; Tsushima, Takahiro; Narita, Yukiya; Todaka, Akiko; Ishihara, Makoto; Yokota, Tomoya; Tanaka, Tsutomu; Machida, Nozomu; Kadowaki, Shigenori; Fukutomi, Akira; Ura, Takashi; Onozawa, Yusuke; Ando, Masashi; Tajika, Masahiro; Muro, Kei; Yasui, Hirofumi; Mori, Keita; Taniguchi, Hiroya

2017-03-01

TAS-102 significantly improves overall survival in patients with metastatic colorectal cancer. The most common treatment-related adverse event of TAS-102 is bone marrow suppression, which leads to neutropenia. The potential predictive value of neutropenia caused by cytotoxic drugs has been reported in various types of cancer. We retrospectively analyzed 95 consecutive patients with metastatic colorectal cancer who received TAS-102 at 2 Japanese institutions between May 2014 and May 2015. To evaluate the association between efficacy and neutropenia, patients were divided into 4 categories according to the grade of neutropenia during the first cycle of TAS-102: Category A (grade 0-1), B (grade 2-4), C (grade 0-2), and D (grade 3-4). Patient characteristics were as follows: median age, 64 years; male, 58%; Eastern Cooperative Oncology Group performance status 0 to 1, 91%; primary site colon, 49%; KRAS exon 2 wild, 57%; and number of metastatic site ≥ 3, 55%. The disease control rate was significantly different between Category A and B (29.2% vs. 52.6%; P = .045) and between Category C and D (30.9% vs. 72.2%; P = .002). In multivariate analysis, Category D remained a significant predictive factor for progression-free survival compared with Category C (4.3 vs. 2.0 months; hazard ratio, 0.45; P = .01). Neutropenia caused by TAS-102 during the first cycle was associated with better efficacy. Neutropenia may be a surrogate marker for adequate antitumor doses of TAS-102. Copyright © 2016 Elsevier Inc. All rights reserved.

[Treatment of severe neutropenias in dogs and cats with filgrastim].

PubMed

Kraft, W; Kuffer, M

1995-12-01

The recombinant hG-CSF Filgrastim was used in severe cases of neutropenia in the dog caused by parvovirosis, hyperestrogenism, treatment with antineoplastic agents, an aplastic syndrome and in the cat in cases of infectious panleukopenia. Increases of the numbers of leukocytes were observed in all groups of diseases in the dog, but not in feline infectious panleukopenia. Filgrastim is indicated in neutropenias associated with disturbance of the general condition accompanied by fever, but not in cases of transitory leukopenias.

Dipstick screening for urinary tract infection in febrile infants.

PubMed

Glissmeyer, Eric W; Korgenski, E Kent; Wilkes, Jacob; Schunk, Jeff E; Sheng, Xiaoming; Blaschke, Anne J; Byington, Carrie L

2014-05-01

This study compares the performance of urine dipstick alone with urine microscopy and with both tests combined as a screen for urinary tract infection (UTI) in febrile infants aged 1 to 90 days. We queried the Intermountain Healthcare data warehouse to identify febrile infants with urine dipstick, microscopy, and culture performed between 2004 and 2011. UTI was defined as >50 000 colony-forming units per milliliter of a urinary pathogen. We compared the performance of urine dipstick with unstained microscopy or both tests combined ("combined urinalysis") to identify UTI in infants aged 1 to 90 days. Of 13 030 febrile infants identified, 6394 (49%) had all tests performed and were included in the analysis. Of these, 770 (12%) had UTI. Urine culture results were positive within 24 hours in 83% of UTIs. The negative predictive value (NPV) was >98% for all tests. The combined urinalysis NPV was 99.2% (95% confidence interval: 99.1%-99.3%) and was significantly greater than the dipstick NPV of 98.7% (98.6%-98.8%). The dipstick positive predictive value was significantly greater than combined urinalysis (66.8% [66.2%-67.4%] vs 51.2% [50.6%-51.8%]). These data suggest 8 febrile infants would be predicted to have a false-positive combined urinalysis for every 1 infant with UTI initially missed by dipstick screening. Urine dipstick testing compares favorably with both microscopy and combined urinalysis in febrile infants aged 1 to 90 days. The urine dipstick test may be an adequate stand-alone screen for UTI in febrile infants while awaiting urine culture results. Copyright © 2014 by the American Academy of Pediatrics.

Increasing Antimicrobial Resistance Monitored in Surveillance Analysis of Blood Stream Infections in Febrile Neutropenic Pediatric Oncology Patients.

PubMed

El-Mahallawy, Hadir A; Hassan, Safaa Shawky; El-Wakil, Mohamed; Moneer, Manar M; Shalaby, Lobna

2015-01-01

Continuous surveillance of pattern of blood stream infection is necessary in febrile neutropenia (FN)especially with the recent escalating trend in the management of pediatric cancer patients towards intensified regimens and with the increase in infections caused by resistant organisms limiting the choice of antibiotics. To monitor change in pattern of blood stream infections (BSI) in FN pediatric cancer patients. Surveillance of FN episodes with positive BSI was prospectively monitored and compared to a previous surveillance in the same pediatric oncology unit. A total of 232 BSI positive episodes were documented in 192 patients during a 6 months period. The results of recent surveillance analysis showed an increase in intensified regimens of chemotherapy, antimicrobial resistance, fungal infections, and prolonged duration of episodes when compared to previous surveillance, with p value sof <0.001, 0.005, 0.021, and <0.001, respectively. There was an apparent decrease in the crude mortality but this was not statistically significant, to 6% in 2011 from 10 % in 2006. The pattern of BSI at our institution is still inclining towards gram positive organisms but is showing a shift towards more antibiotic resistance and fungal infections.

Dental findings and treatment in consanguinity associated congenital chronic familial neutropenia.

PubMed

Buduneli, Nurcan; Cogulu, Dilsah; Kardesler, Levent; Kütükçüler, Necil

2006-01-01

The purpose of this report is to describe dental findings and treatment of an 11-year old male patient and a 5-year old female patient, children of first cousins, suffering from severe benign congenital chronic familial neutropenia. This case report emphazises the importance of differential diagnosis of immunodeficiencies including congenital chronic familial neutropenia in the background of severe periodontal diseases and/or diffuse carious lesions in children.

[Clinical significance of leukopenia and neutropenia patients with chronic hepatitis "C" in the various regimes antiretroviral therapy].

PubMed

Bakulin, I G; Sharabanov, A S

2010-01-01

To estimate the prevalence and clinical significance of leukopenia and neutropenia in patients with chronic hepatits C, to analyze the impact of different regimens of antiviral therapy by standart or induction doses of pegylated interferon alpha-2a (PegIFNalpha-2a) to optimize curative measures. 24 patients with genotype 1 HCV and different therapeutic regimens of PegIFNalpha-2a were investigated with analysis of kinetics and prevalence of leukopenia and neutropenia. On an average 66,7% patients meet neutropenia during antiviral therapy, and 37,5% and 16,7% among them was the moderate and severe grade accordingly. The major prevalence of leukopenia and neutropenia was evidenced between 12 and 24 weeks of antiviral therapy, the marked severity of neutropenia was noted. It was no correlation between the prevalence of leukopenia and neutropenia and the induction treatment regimens of PegIFNalpha-2a; the tendency for more severity in patients with advanced fibrosis and cirrhosis was detected. It was no infection complications during the therapy observed so it may be provided with full doses of PegIFNalpha-2a in case of mild and moderate grades of leukopenia and neutropenia.

Management of fever and neutropenia in children with cancer.

PubMed

Vedi, A; Pennington, V; O'Meara, M; Stark, K; Senner, A; Hunstead, P; Adnum, K; Londall, W; Maurice, L; Wakefield, Claire; Cohn, R J

2015-07-01

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. 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. 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. 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.

A randomized, multicenter, phase II/III study to determine the optimal dose and to evaluate the efficacy and safety of pegteograstim (GCPGC) on chemotherapy-induced neutropenia compared to pegfilgrastim in breast cancer patients: KCSG PC10-09.

PubMed

Lee, Ki Hyeong; Kim, Ji-Yeon; Lee, Moon Hee; Han, Hye Sook; Lim, Joo Han; Park, Keon Uk; Park, In Hae; Cho, Eun Kyung; Yoon, So Young; Kim, Jee Hyun; Choi, In Sil; Park, Jae Hoo; Choi, Young Jin; Kim, Hee-Jun; Jung, Kyung Hae; Kim, Si-Young; Oh, Do-Youn; Im, Seock-Ah

2016-04-01

Pegylated granulocyte-colony-stimulating factor (G-CSF) is frequently used to prevent febrile neutropenia (FN) in patients undergoing chemotherapy with a high risk of myelosuppression. This phase II/III study was conducted to determine the adequate dose of pegteograstim, a new formulation of pegylated G-CSF, and to evaluate the efficacy and safety of pegteograstim compared to pegfilgrastim. In the phase II part, 60 breast cancer patients who were undergoing DA (docetaxel and doxorubicin) or TAC (docetaxel, doxorubicin, and cyclophosphamide) chemotherapy were randomly selected to receive a single subcutaneous injection of 3.6 or 6.0 mg pegteograstim on day 2 of each chemotherapy cycle. The phase III part was seamlessly started to compare the dose of pegteograstim at selected in phase II with 6.0 mg pegfilgrastim in 117 breast cancer patients. The primary endpoint of both the phase II and III parts was the duration of grade 4 neutropenia in the chemotherapy cycle 1. The mean duration of grade 4 neutropenia for the 3.6 mg pegteograstim (n = 33) was similar to that for the 6.0 mg pegteograstim (n = 26) (1.97 ± 1.79 days vs. 1.54 ± 0.95 days, p = 0.33). The 6.0 mg pegteograstim was selected to be compared with the 6.0 mg pegfilgrastim in the phase III part. In the phase III part, the primary analysis revealed that the efficacy of pegteograstim (n = 56) was non-inferior to that of pegfilgrastim (n = 59) [duration of grade 4 neutropenia, 1.64 ± 1.18 days vs. 1.80 ± 1.05 days; difference, -0.15 ± 1.11 (p = 0.36, 97.5 % confidence intervals = 0.57 and 0.26)]. The time to the absolute neutrophil count (ANC) recovery of pegteograstim (≥2000/μL) was significantly shorter than that of pegfilgrastim (8.85 ± 1.45 days vs. 9.83 ± 1.20 days, p < 0.0001). Other secondary endpoints showed no significant difference between the two groups. The safety profiles of the two groups did not differ significantly. Pegteograstim was shown to be as effective as pegfilgrastim in the

Phase I Results of Vinorelbine With Concurrent Radiotherapy in Elderly Patients With Unresectable, Locally Advanced Non-Small-Cell Lung Cancer: West Japan Thoracic Oncology Group (WJTOG3005-DI)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harada, Hideyuki, E-mail: h.harada@scchr.jp; Seto, Takashi; Igawa, Satoshi

Purpose: To investigate the safety and efficacy of concurrent vinorelbine and thoracic radiotherapy in elderly patients with locally advanced non-small-cell lung cancer (NSCLC). Methods and Materials: Eligible patients were 71 years of age or older with unresectable Stage III NSCLC. Patients were treated with thoracic radiotherapy (60 Gy) and concurrent vinorelbine (20 mg/m{sup 2} in Level 1 and 25 mg/m{sup 2} in Level 2) on Days 1 and 8 every 3 weeks for two cycles, followed by adjuvant vinorelbine (25 mg/m{sup 2}) on Days 1 and 8 every 3 weeks for two cycles. Results: Four patients were enrolled at Levelmore » 1. One patient experienced Grade 3 febrile neutropenia at Level 1 and the dose was escalated to Level 2. At Level 2, 2 of 6 patients experienced dose-limiting toxicities (Grade 4 neutropenia in 1 patient and Grade 3 infection in another). Three of 6 patients developed late Grade 2 or 3 pneumonitis. Therefore, the dose was de-escalated to Level 1. An additional 6 patients were enrolled at Level 1, 4 of whom experienced dose-limiting toxicities (incomplete radiotherapy because of Grade 2 pneumonitis in 1 patient and Grade 3 infection in 1, Grade 3 febrile neutropenia in 1, and Grade 3 esophagitis in 1). Moreover, late Grade 3 pneumothorax and Grade 5 pneumonitis occurred in 1 and 1 patient, respectively. Overall, Grade 2, 3 and 5 pneumonitis occurred in 3, 3, and 1 among 16 patients, respectively. Conclusions: Concurrent vinorelbine and thoracic radiotherapy resulted in a high incidence of severe pneumonitis when the standard dose of this agent was used for elderly patients. We therefore recommend caution in the use of this regimen and schedule for elderly patients.« less

Low bacterial diet versus control diet to prevent infection in cancer patients treated with chemotherapy causing episodes of neutropenia.

PubMed

van Dalen, Elvira C; Mank, Arno; Leclercq, Edith; Mulder, Renée L; Davies, Michelle; Kersten, Marie José; van de Wetering, Marianne D

2016-04-24

Neutropenia is a potentially serious side effect of chemotherapy and a major risk factor for infection, which can be life-threatening. It has been hypothesised that a low bacterial diet (LBD) can prevent infection and (infection-related) mortality in cancer patients receiving chemotherapy that causes episodes of neutropenia, but much remains unclear. This review is an update of a previously published Cochrane review. The primary objective of this review was to determine the efficacy of an LBD versus a control diet in preventing infection and in decreasing (infection-related) mortality in adult and paediatric cancer patients receiving chemotherapy that causes episodes of neutropenia. Secondary objectives were to assess time to first febrile episode, need for empirical antibiotic therapy, diet acceptability and quality of life. We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 4), the Database of Abstracts of Reviews of Effects (DARE) (2015, Issue 4), PubMed (from 1946 to 4 May 2015), EMBASE (from 1980 to 4 May 2015) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (from 1981 to 4 May 2015).In addition, we searched the reference lists of relevant articles and conference proceedings of American Society of Hematology (ASH; from 2000 to 2015), European Bone Marrow Transplantation (EBMT; from 2000 to 2015), Oncology Nurses Society (ONS; from 2000 to 2015), International Society for Paediatric Oncology (SIOP; from 2000 to 2014), Multinational Association of Supportive Care in Cancer (MASCC; from 2000 to 2015), American Society of Clinical Oncology (ASCO; from 2000 to 2015), Interscience Conference of Antimicrobial Agents and Chemotherapy (ICAAC; from 2000 to 2015), European Society for Clinical Nutrition and Metabolism (ESPEN; from 2000 to 2015), American Society for Parenteral and Enteral Nutrition (ASPEN; from 2000 to 2015) and European Hematology Association (EHA; from 2000

Guidelines of the National Comprehensive Cancer Network on the use of myeloid growth factors with cancer chemotherapy: a review of the evidence.

PubMed

Lyman, Gary H

2005-07-01

The prophylactic use of myeloid growth factors reduces the risk of chemotherapy-induced neutropenia and its complications, including febrile neutropenia and infection-related mortality. Perhaps most importantly, the prophylactic use of colony-stimulating factors (CSFs) has been shown to reduce the need for chemotherapy dose reductions and delays that may limit chemotherapy dose intensity, thereby increasing the potential for prolonged disease-free and overall survival in the curative setting. National surveys have shown that the majority of patients with potentially curable breast cancer or non-Hodgkin's lymphoma (NHL) do not receive prophylactic CSF support. In this issue, the National Comprehensive Cancer Network presents guidelines for the use of myeloid growth factors in patients with cancer. These guidelines recommend a balanced clinical evaluation of the potential benefits and harms associated with chemotherapy to define the treatment intention, followed by a careful assessment of the individual patient's risk for febrile neutropenia and its complications. The decision to use prophylactic CSFs is then based on the patient's risk and potential benefit from such treatment. The routine prophylactic use of CSFs in patients receiving systemic chemotherapy is recommended in patients at high risk (>20%) of developing febrile neutropenia or related complications that may compromise treatment. Where compelling clinical indications are absent, the potential for CSF prophylaxis to reduce or offset costs by preventing hospitalization for FN should be considered. The clinical, economic, and quality of life data in support of these recommendations are reviewed, and important areas of ongoing research are highlighted.

Prevalence of malaria, typhoid, toxoplasmosis and rubella among febrile children in Cameroon.

PubMed

Achonduh-Atijegbe, Olivia A; Mfuh, Kenji O; Mbange, Aristid H E; Chedjou, Jean P; Taylor, Diane W; Nerurkar, Vivek R; Mbacham, Wilfred F; Leke, Rose

2016-11-08

44 %. There was a significant association between ITN non-usage and malaria (p = 0. 029) as well as drinking water and presence of typhoid (p = 0.047). No association was observed between type of housing and malaria, or toxoplasmosis and raising cats. Though malaria still remains the major cause of fever in children, using RDTs for other treatable febrile illnesses like typhoid and toxoplasmosis could facilitate the optimal management of febrile illnesses in children especially when these occur as co-infections with malaria.

Bladder volume at onset of vesicoureteral reflux is an independent risk factor for breakthrough febrile urinary tract infection.

PubMed

Alexander, Siobhan E; Arlen, Angela M; Storm, Douglas W; Kieran, Kathleen; Cooper, Christopher S

2015-04-01

Improved identification of children with vesicoureteral reflux at risk for recurrent febrile urinary tract infection may impact management decisions. We hypothesized that reflux occurring earlier during bladder filling increases the duration of exposure of the kidneys to bacteria, and, therefore, increases the risk of pyelonephritis. Children with vesicoureteral reflux and detailed voiding cystourethrogram data were identified. Bladder volume at onset of reflux was normalized for age. Demographics, reflux grade, laterality, presence/absence of bladder-bowel dysfunction and breakthrough febrile urinary tract infections were assessed. Median followup was 24 months (IQR 12 to 52). A total of 208 girls and 47 boys were analyzed with a mean ± SD age at diagnosis of 3.1 ± 2.6 years. On univariate analysis history of febrile urinary tract infection (HR 2.17, 95% CI 1.33-2.85, p = 0.01), dilating vesicoureteral reflux (HR 1.6, 95% CI 1.05-2.42, p = 0.03) and bladder-bowel dysfunction (HR 1.66, 95% CI 0.99-2.75, p = 0.05) were associated with an increased risk of breakthrough febrile urinary tract infection. Median bladder volume at onset of reflux in children with breakthrough febrile urinary tract infection was significantly less (33.1%) than in those without infection (49.5%, p = 0.003). Reflux onset at 35% predicted bladder capacity or less was associated with a significantly increased risk of breakthrough febrile urinary tract infection on multivariate analysis (HR 1.58, 95% CI 1.05-2.38, p = 0.03). Children with early filling vesicoureteral reflux are at increased risk for breakthrough febrile urinary tract infection independent of reflux grade. Bladder volume at onset of reflux should be recorded during cystograms since it provides additional prognostic information about the risk of pyelonephritis and resolution, and may assist with counseling and clinical decision making. Copyright © 2015 American Urological Association Education and Research, Inc. Published by

Prevalence of HHV-6 in cerebrospinal fluid of children younger than 2 years of age with febrile convulsion.

PubMed

Mamishi, Setareh; Kamrani, Laura; Mohammadpour, Masoud; Yavarian, Jila

2014-04-01

Febrile convulsion is a common disorder in children. Viral infections such as human herpes virus 6 (HHV-6) which results in roseola infantum may contribute to developing seizure. The objective of this study was to determine the prevalence of HHV-6 by detecting DNA in cerebrospinal fluid (CSF) of children with febrile convulsion and without any rash of roseola infantum. In this descriptive cross-sectional study, CSF of 100 children younger than 2 years of age with febrile convulsion was evaluated for detecting HHV-6 DNA by PCR. All of them were referred to emergency ward in Pediatric Medical Center from March 2010 to March 2011. General information, clinical manifestations, laboratory tests and outcomes were collected in the questionnaires. One hundred children including 59 males and 41 females were evaluated. HHV-6 was detected from CSF in six patients (6%) by PCR. Mean age was 8 months old. All children were younger than 12 months old. The most common primary manifestation was fever alone. None of them had rash. Majority of cases occurred in winter. All patients recovered without any encephalitis. These findings showed that primary infection with HHV-6 is frequently associated with febrile convulsion in infants which may be at risk for subsequent development of epilepsy.

Serological evidence of rift valley fever virus among acute febrile patients in Southern Mozambique during and after the 2013 heavy rainfall and flooding: implication for the management of febrile illness.

PubMed

Gudo, Eduardo Samo; Pinto, Gabriela; Weyer, Jacqueline; le Roux, Chantel; Mandlaze, Arcildo; José, Américo Feriano; Muianga, Argentina; Paweska, Janusz Tadeusz

2016-06-08

Rift Valley fever virus (RVFV) remains heavily neglected in humans in Mozambique, even though recent outbreaks were reported in neighboring countries in humans and several cases of RVFV in cattle were reported in several districts in Mozambique. We conducted a cross sectional study during and after severe flooding that occurred in 2013 in Mozambique. Paired acute and convalescent serum samples were tested from febrile patients attending a primary health care unit in a suburban area of Maputo city for the presence of IgG and IgM antibodies against Rift Valley fever virus (RVFV) using enzyme-linked immunosorbent assay (ELISA). Seroconversion of IgG anti-RVFV was observed in 5 % (10/200) of convalescent patients and specific IgM anti-RVFV was detected in one acute patient (0.5 %; 1/200). All sera from acute patient tested negative by real time PCR. In conclusion, our results suggest that RVF represent an important but neglected cause of febrile illness following periods of flooding in southern Mozambique.

Transfusion-related alloimmune neutropenia with no pulmonary complications: one donor-five cases.

PubMed

Hauck-Dlimi, Barbara; Ruppel, Renate; Zimmermann, Robert; Strobel, Julian; Reil, Angelika; Eckstein, Reinhold; Zingsem, Juergen

2016-01-01

Neutrophil alloantibodies are well-known triggers of transfusion-related acute lung injury (TRALI) and also cause immune neutropenia. Alloimmune neutropenia due to transfusion is an isolated phenomenon that is only rarely identified. Its incidence is specified in the literature as being less than one in 10,000 transfused plasma-containing units. We expect that this phenomenon is underreported. We observed five cases of alloimmune neutropenia with no respiratory complications with only one case initially reported as a suspected transfusion reaction. The other four cases were detected in the course of the subsequent lookback investigation. The first case was reported as a potential transfusion reaction when a female patient showed a decrease in the white blood cell count after a platelet (PLT) transfusion. Examinations of the donor blood revealed an antibody against the human neutrophil antigen HNA-1b; the recipient was typed HNA-1b positive and HNA-1a negative. After examining the blood counts of other patients who previously received PLT concentrates from the same donor, we identified four other patients with an unreported decrease in the leukocyte and/or granulocyte count of more than approximately 50% after transfusion. HNA antibodies are generally regarded as potential triggers of TRALI. Here we describe an HNA antibody that reproducibly caused transfusion-related neutropenia only without pulmonary complications. Factors predisposing patients to TRALI development are widely discussed. Our case suggests that antibody characteristics are also relevant in the development of TRALI. Current measures to prevent TRALI should also prevent transfusion-related alloimmune neutropenia. © 2015 AABB.

Clonal predominance of CD8+ T cells in patients with unexplained neutropenia

PubMed Central

Wlodarski, Marcin Wojciech; Nearman, Zachary; Jiang, Ying; Lichtin, Alan; Maciejewski, Jaroslaw Pawel

2008-01-01

Objective T-cell-mediated autoimmunity may be involved in some cases of idiopathic neutropenia. We hypothesized that a precise T-cell receptor repertoire analysis may uncover cytotoxic T-cell (CTL) expansions that are less pronounced than those seen in T large granular lymphocyte leukemia (T-LGL), but are pathophysiologically analogous and thus can serve as markers of a T-cell-mediated process. Materials and Methods Using rational algorithms for T-cell receptor analysis and in vivo tracking of CTL responses previously established in our laboratory, we studied patients with unexplained chronic neutropenia (n = 20), T-LGL (n = 15), and healthy controls (n = 12). We further investigated the involvement of soluble inhibitory factors by coculture assays. To determine the level of immune activation, we studied interferon-g expression in CD8+cells using Taqman polymerase chain reaction. Results Fifteen expanded (immunodominant) CTL clones were detected in 12 of 20 patients. In comparison to LGL leukemia, these clones were less immunodominant, but clearly discernible from subclinical lymphoproliferations in controls. As a surrogate of cytotoxic activity, we found markedly increased production of interferon-γ in most of the neutropenia patients, irrespective of the presence of immunodominant CTL clones. Conclusions These results suggest that, while immunodominant CTL clones are detectable in a proportion of patients only, CTL-mediated pathophysiology may be a general mechanism operating in idiopathic neutropenia. Oligogoclonal CTL expansions in chronic neutropenia may indicate an ongoing autoimmune process, while highly polarized monoclonalities in a subset of neutropenic LGL patients may represent the “extreme” end of the clonal continuum. PMID:18279717

Chemoradiotherapy versus chemotherapy as adjuvant treatment for localized gastric cancer: a propensity score-matched analysis.

PubMed

Girardi, Daniel M; de Lima, Mariana A; Pereira, Gabriel C B; Negrão, Marcelo V; López, Rossana V M; Capareli, Fernanda C; Sabbaga, Jorge; Hoff, Paulo Marcelo G

2018-04-03

Treatment of localized gastric cancer (LGC) consists of surgical resection followed by adjuvant treatment. Both chemoradiation (CRT) and chemotherapy (CT) regimens have shown benefit in survival outcomes versus observation. However, there are few data comparing these approaches. This study included consecutive patients with LGC treated at Instituto do Cancer do Estado de Sao Paulo (ICESP) from 2012 to 2015. CRT was based on the INT-0116 regimen and CT consisted of a platinum and fluoropyrimidine doublet. Treatment choice was based on physician preference. Toxicity was evaluated for every cycle. Overall survival (OS) analysis was performed by Kaplan-Meier. A propensity score-matched analysis was performed to minimize selection bias. A total of 309 patients were evaluated, 227 in CRT group and 82 in CT group. The most prevalent grade 3/4 toxicities in CRT and CT groups were: nausea/vomiting (9.25 vs 4.9%), fatigue (9.3% vs 2.4%), mucositis (4.4% vs 1.2%), neutropenia (37.8% vs 20.9%), febrile neutropenia (3.9% vs 0%), anemia (4.3% vs 6.1%), thrombocytopenia (2.6% vs 4.9%), neuropathy (0 vs 2.4%) and hand-foot syndrome (0.4% vs 2.4%). Two grade 5 toxicities (febrile neutropenia and anemia) occurred in CRT group. There was no difference in the pattern of recurrence. After a median follow-up of 23.5 months (CRT) and 20.6 months (CT), there was no difference in OS between groups. CT and CRT present similar efficacy and tolerability as adjuvant treatment for LGC.

Viridans Group Streptococcal Infections in Children After Chemotherapy or Stem Cell Transplantation: A 10-year Review From a Tertiary Pediatric Hospital.

PubMed

Nielsen, Maryke J; Claxton, Sarah; Pizer, Barry; Lane, Steven; Cooke, Richard P D; Paulus, Stéphane; Carrol, Enitan D

2016-03-01

Viridans Group Streptococci (VGS) are associated with high mortality rates in febrile neutropenia; yet there are no recent European pediatric studies to inform antimicrobial therapy. The aim of this study was to describe the characteristics, outcome, and resistance patterns of children with VGS bacteremia (VGSB) undergoing treatment of malignancy or hematopoietic stem cell transplant. Patients aged 0 to 18 years, admitted to a tertiary pediatric hemato-oncology center with VGSB, from 2003 to 2013, were included in the study. All data were collected retrospectively from medical records. A total of 54 bacteremic episodes occurred in 46 patients. The most common underlying diagnosis was relapsed acute lymphoblastic leukemia. Streptococcus mitis was the most frequent organism. A total of 30% of isolates were resistant to penicillin and 100% sensitive to vancomycin. There were 8 episodes (14.8%) of Viridans Group Streptococcal Shock Syndrome; 6 resulted in admission to intensive care and 3 of these patients died of multiorgan failure. The potentially fatal nature of VGSB is confirmed. The high risk in relapsed acute lymphoblastic leukemia is of note. Research is needed to develop risk-stratification scores that identify children at risk of Viridans Group Streptococcal Shock Syndrome to guide empirical antimicrobial therapy in febrile neutropenia.

Viridans Group Streptococcal Infections in Children After Chemotherapy or Stem Cell Transplantation