Therapy For Febrile Neutropenia Research Articles

Adverse Cutaneous Drug Reaction Following Granulocyte Colony-Stimulating Factor Administration in Nasopharynx Cancer Patient with Febrile Neutropenia: A Case Report

Introduction: Several side effects may occur during cancer treatment such as myelosuppression following systemic chemotherapy, which is mainly manifested as neutropenia and is associated with increased infection risk. Febrile neutropenia is associated with a worse prognosis. Granulocyte colony-stimulating factor (G-CSF) may be given prophylactically before chemotherapy in selected cases or as adjuvant therapy in febrile neutropenia. G-CSF administration may be associated with several side effects, including skin manifestation. More rarely, G-CSF administration may induce acute febrile neutrophilic dermatosis is which known as a Sweet syndrome. Case Presentation: A 63-year-old man with nasopharyngeal cancer stage III on chemotherapy and radiotherapy came to our emergency department with a chief complaint of fever, coughing, and shortness of breath. He was diagnosed with community-acquired pneumonia and febrile neutropenia. His white blood cell (WBC) count was 200/mm3 . On the third day of hospitalization and G-CSF administration, he developed a rash and had skin desquamation mainly on his head including the scalp, face, lips, upper trunk, arms, and the surface of both hands. His follow-up laboratory result was WBC 8300/mm3 with a neutrophil count of 87%. Presumable Sweet syndrome diagnosis with differential diagnosis of other drug eruption reactions was made. Systemic and topical were administered, and G-CSF was stopped. Significant improvement was observed. Conclusions: G-CSF administration in febrile neutropenic cancer is generally safe; however, several adverse events may occur. Cutaneous adverse events following G-CSF administration should be recognized and treated accordingly. Sweet syndrome is rare but should be recognized as a possible G-CSF-induced drug skin complication.

Respiratory Viral Infections in Pediatric Acute Leukemia Patients Presenting with Febrile Neutropenia in a Tertiary Hospital in Ankara, Turkey

Background: The prevalence and roles of respiratory viral pathogens in pediatric acute leukemia patients with febrile neutropenia is not well understood and laboratory tests to detect viral agents are not a routine practice in the investigation of these patients.Patients and methods: The medical records of 50 neutropenic episodes in pediatric acute leukemia patients in the Hacettepe University Children’s hospital, Ankara-Turkey, were reviewed. Blood samples were obtained for blood culture, aspergillus antigen and other routine tests. Nasopharyngeal aspirate samples were collected and transferred to the laboratory in a viral transport medium. Therapy for febrile neutropenia was initiated according to our institution’s protocols.Results: Fifty (50) consecutive febrile neutropenic episodes in 44 pediatric ALL and AML patients were included in the study between 1st October 2009 and 31st August 2010. Microbiologically documented infections were found in 36% of the episodes, clinically documented infections in 16% of the episodes and 48% of the episodes were accepted as Fever of Unknown Origin. Twenty-two percent (22%) of the microbiologically documented infections were due to viral agents, 56 % were due to Gram positive bacteria, 21% were due to Gram negative bacteria (E. coli) and only one episode of fungemia was documented.Conclusions: Fever of Unknown Origin constituted nearly 50% of the febrile neutropenic episodes in this study despite the availability of advanced laboratory diagnostic methods. Among the episodes with microbiologically documented infections, bacterial pathogens were especially common. Presenting complaints like cough and rhinorrhea are not specific to a viral etiology and care should be taken not to miss potentially threatening bacterial pathogens in such episodes.

Comparison of Empiric Antibiotic Escalation Therapy with Vancomycin (VAN) versus Linezolid (LIN) in Patients with Febrile Neutropenia.

BackgroundIn febrile neutropenia, either linezolid (LIN) or vancomycin (VAN) can be used if a gram-positive infection is suspected. Interestingly there is no literature in which both are compared in the setting of febrile neutropenia. Therefore, we provide here the results of a retrospective analysis of adding VAN versus LIN in patients with febrile neutropenia.MethodsPatients with haematological diseases and febrile neutropenia after myelosuppressive chemotherapy and no clearance of infection after the first empiric broad-spectrum antibiotic were escalated to VAN or LIN from 03/2010 to 03/2014 at the University Hospital Bonn were included in this retrospective analysis.ResultsOut of the 73 patients, 50 had received VAN and 23 LIN. The median hospitalisation time in the LIN cohort was significantly shorter than in the VAN cohort (LIN 16 days vs VAN 20 days p=0.046). Successful defervescence with the escalation to VAN or LIN could be detected in 76% of the LIN cases and 50% in the VAN group (p=0.052). This trend to better efficacy with LIN was also shown by a higher rate of discontinuation of VAN and escalation to another antibiotic scheme (54.2%) than in the LIN cohort (24%, p=0.052).ConclusionThe antibiotic therapy in febrile neutropenia with LIN showed a trend of better efficacy than therapy with VAN. However, because of the small sample size and the retrospective manner, VAN may still be considered a reasonable option in neutropenic fever, and randomised studies are needed in this field.

Usage-evaluation study on Vancomycin among hospitalized pediatric patients: Experience from two tertiary care centers of Eastern India

Background: Vancomycin is a highly effective bactericidal antibiotic with excellent efficacy against resistant Gram-positive microorganisms. It is losing its antimicrobial efficacy due to its rampant usage in Food and Drug Administration/Centers for Diseases Control and Prevention as well as off-label clinical uses. To stop its emerging resistance, judicious use of vancomycin following antibiotic stewardship is required. Aims: This study aims to examine the rationality of vancomycin use with respect to its adherence to Hospital Infection Control Practices Advisory Committee guidelines as well as its dosing, duration, adverse effects, and final outcome. Methodology: A retrospective cross-sectional hospital record-based study was conducted at two medical colleges of Eastern India from January 1, 2020, till June 30, 2020, incorporating all admitted newborns and children till 12 years’ age who received vancomycin for any clinical conditions. However, the patients with renal diseases or incomplete history were excluded from the study. Results: A cohort of 388 patients was included of which majority of them (41.2%) were in the age group of 2–12 years and males (56.9%). Sepsis (24.2%) and pneumonia (20.8%) were the most common indications for vancomycin prescription. Overall, appropriate usage of vancomycin was found in 57.2% of patients with maximum appropriate usage which was seen among neonates (64.5%). The areas of inappropriate usage were empirical therapy in febrile neutropenia, surgical prophylaxis, treatment of coagulase-negative Staphylococcal infection, and failure to withdraw vancomycin even after negative culture report for Gram-positive organisms. The final outcome in terms of clinical improvement was seen in 72.4% of patients irrespective of appropriate/inappropriate usage. Conclusion: Monitoring vancomycin usage should be followed in institutional practice to stop the emergence of resistance of vancomycin.

Correction possibilities of drug-induced liver toxicity in the treatment of patients with blood system tumors

Background. In modern oncohematology achieved notable success due to the intensification and development of new chemotherapy regimens. However, the side effects of anticancer drugs, due to low selectivity of most of them, are a serious limitation to achieve their maximal therapeutic effect. Although doctors are aware of the possibility of hepatotoxic reactions to various drugs, in clinical practice, the diagnosis of drug-induced liver injury is formulated unreasonably rarely. This speculation is due to several factors: in some cases, the latent course of drug-induced liver injury, often inadequate interpretation of clinical symptoms and laboratory parameters, and sometimes insufficiently thorough collection of anamnesis. A particularly difficult problem for a doctor is the development of drug-induced hepatotoxicity in patients for whom the “causal” drug is prescribed for vital indications, in particular, polychemotherapy in cancer patients, complex antimicrobial therapy and antiviral therapy for febrile neutropenia or sepsis, etc. In these situations, on the one hand, treatment cancellation is impossible due to the risk of disease progression, on the other hand, its continuation is undesirable due to the risk of severe hepatitis. In addition, multicomponent therapy, which is a complex of potentially hepatotoxic substances, often does not allow specifying the substance that caused the pathological reaction. At the same time, it is obvious that the hepatocyte, the main cell of the hepatic parenchyma, remains the center of the organ pathology. The variety of biochemical processes occurring with ademetionine participation served as the basis for conducting clinical studies in order to correct drug-induced liver toxicity in the treatment of patients with blood system tumors.The objective of the study is to assess laboratory and clinical parameters of drug-induced liver injury (DILI), intrahepatic cholestasis in the study of homeostasis disorders in patients with hematological malignancies and chemotherapy-induced hepatotoxicity.Materials and methods. The study involved 45 patients with blood system tumors, who had chemotherapy-induced hepatocellular failure. To describe the population of DILI patients, we collected demographic data, clarified the underlying liver disease in each patient, and analyzed the diagnostic criteria for chronic liver disease due to DILI. Clinical signs and symptoms of cholestasis (jaundice, pruritus, weakness), as well as manifestations of a depressive state and asthenic syndrome – mood (mild, moderate and severe), normalization of sleep rhythm, memory improvement, general health were assessed. Changes in laboratory parameters of liver function were studied. In 20 patients with blood system tumors, the biochemical parameters associated with cell metabolism were analyzed – lipid peroxidation, nitric oxide (NOx ) level, impaired liver detoxification capacity by glutathione level and glutathione-S-transferase activity. The treatment regimens for drug-induced hepatotoxicity included the Heptral, which was prescribed until stable normalization of liver function.Results. All patients with developed liver failure showed metabolic disorders. The use of ademetionine has shown significant effect. The NO and superoxide dismutase in most patients decreased significantly and almost corresponded to the norm. Normalization of the glutathione system parameters was also observed. One of the mechanisms of Heptral protective effect is an increase in the glutathione synthesis. The improvement in laboratory parameters was accompanied by the disappearance of DILI and intrahepatic cholestasis symptoms. This is confirmed by significant statistical correlations between them and indicates the ademetionine efficacy to recovery of hepatocytes function. When using ademetionine, the most pronounced reduction among biochemical parameters was observed in alkaline phosphatase and γ-glutamyl transpeptidase, markers of cholestasis syndrome. In addition, serum bilirubin concentration and alanine and aspartic transaminases activity (albeit to a lesser extent) decreased significantly. Clinical and biochemical effects, as a rule, persisted for several months after completion of therapy. Decrease in biochemical parameters characterizing cholestasis and cytolysis (positive dynamics of alanine and aspartic transaminases, alkaline phosphatase, γ-glutamyl transpeptidase, bilirubin) was accompanied by an improvement and normalization of patients’ well-being. When assessing the depression and asthenic syndrome, it was noted that the duration of Heptral therapy is important.Conclusion. The results obtained were the basis for the development of supportive therapy programs to prevent and reduce liver toxicity during chemotherapy. Rational approaches to the liver metabolic disorders correction – a real way to increase the treatment efficacy and improve the quality of life of patients with blood system tumors.

Commentary on Cefepime versus Cefoperazone/Sulbactam in Combination with Amikacin as Empirical Antibiotic Therapy in Febrile Neutropenia

Commentary on Cefepime versus Cefoperazone/Sulbactam in Combination with Amikacin as Empirical Antibiotic Therapy in Febrile Neutropenia

Microbial Infection with Their Antibiotic Sensitivity Pattern in Febrile Neutropenic Patients Treated in Haematology and BMT Unit in DMCH

Background: Because of great concerns about mortality and morbidity due to infection in febrile neutropenic patients, the appropriate empirical antibiotic should be started immediately. Although there are established guidelines for the use of empirical therapy in febrile neutropenia, local microbiological pattern and antibiotic susceptibility should be considered for better outcome. There is paucity of data regarding the organism isolated and sensitivity in febrile neutropenic patients in Dhaka Medical College Hospital (DMCH). Objectives: The current study aimed to find out causative organisms for febrile neutropenia and to observe their antimicrobial sensitivity pattern. Materials and method: This was a prospective observational study carried out in department of haematology and BMT of Dhaka Medical college hospital during the period of October, 2014 to July, 2015. Total 104 patients experienced febrile neutropenia and both febrile blood and urine samples were collected and sent for culture. Results: Out of 104 patients male were 65 and female were 39 (M:F ratio 1.6:1) with a mean age of patients were 31.3 (±15.43) years. Majority (86.5%) of febrile neutropenic patients were post-chemotherapy of acute leukaemia. Out of 104 case 29 were positive growth in both blood and urine samples. Out of 25 blood culture positive patients’ organisms isolated were predominantly gram negative (78.6%) whereas 21.4% were gram negative. However, in urine culture equal number of organisms (4 vs 4) from both gram positive and gram negative were isolated. Gram negative microorganisms were resistance to antibiotic such as amoxicillin, ceftazidime, ceftriaxone, cefixime, cotrimoxazole and gentamicin and sensitive to antibiotic like meropenem, amikacin, ciprofloxacin and colistin. Gram positive microorganisms were almost resistance to azithromycin, cefixime, ciprofloxacin, cotrimoxazole, gentamicin and moxifloxacin but were sensitive to chloramphenicol, clindamycin and linezolid. Conclusions: Gram negative organisms were the predominant organisms in febrile neutropenic patients at our institute. They are resistant to a good number of commonly used antibiotics and sensitive to only a few antibiotics.

Pre-emptive antifungal therapy versus empirical antifungal therapy for febrile neutropenia in people with cancer

Pre-emptive antifungal therapy versus empirical antifungal therapy for febrile neutropenia in people with cancer

Antimicrobial de-escalation in adult hematopoietic cell transplantation recipients with febrile neutropenia of unknown origin.

The optimal duration of empiric antimicrobial therapy in febrile neutropenia of unknown origin is unclear. This study evaluated outcomes in autologous and allogeneic hematopoietic cell transplantation recipients with febrile neutropenia of unknown origin who received early de-escalation of broad-spectrum antimicrobials prior to hematopoietic recovery versus those who continued broad-spectrum antimicrobials until hematopoietic recovery. A single-center, retrospective study assessed hematopoietic cell transplantation recipients with febrile neutropenia of unknown origin. Patients were categorized into either cohort 1, representing early de-escalation prior to hematopoietic recovery, or cohort 2, representing continuation of broad-spectrum antimicrobials until hematopoietic recovery. A total of 107 patients were included (22.4% in cohort 1 and 77.6% in cohort 2). Most patients (87.5%) in cohort 1 underwent haploidentical hematopoietic cell transplantation, whereas 84.3% of patients in cohort 2 received autologous hematopoietic cell transplantation. There were no significant differences in rates of recurrent fever (4.2% versus 7.2%, in cohorts 1 and 2, respectively, adjusted odds ratio = 0.84, P = 0.85), re-escalation (4.2% versus 4.8%, adjusted odds ratio = 1.57, P = 0.64), and Clostridioides difficile-associated infections (4.2% versus 2.4%, adjusted odds ratio = 2.27, P = 0.43). No patient experienced in-hospital mortality, intensive care unit admission, or bacteremia. Hematopoietic cell transplantation recipients with febrile neutropenia of unknown origin in which broad-spectrum antimicrobials were de-escalated prior to hematopoietic recovery did not experience adverse outcomes. These results concur with recently published studies and the Fourth European Conference on Infections in Leukemia guidelines. An early de-escalation approach in haploidentical hematopoietic cell transplantation recipients specifically appears safe and may result in a reduction in antimicrobial utilization.

Blood Stream Infections and Antibiotic Utilization in Pediatric Leukemia Patients With Febrile Neutropenia.

Frequent surveillance of bacterial pathogens responsible for microbiologically defined-blood stream infections (MD-BSI), and their respective antibiotic susceptibilities is central to tailoring empiric antibiotic therapy in febrile neutropenia (FN) episodes in pediatric patients with leukemia. The safety of deescalating antibiotic therapy in pediatric patients with leukemia and neutropenia is incompletely understood. A retrospective chart review of 194 FN episodes occurred between the years of 2013 and 2016 in 67 patients with leukemia. Clinical and microbiologic data were recorded. MD-BSI occurred in 36 of 194 (18%) of FN episodes. Deescalation of empiric antibiotic therapy based on antibiotic susceptibilities was possible in 25 of 36 (69.4%) episodes. In those 25 episodes, where there was an opportunity to deescalate the antibiotic spectrum, it was clinically appropriate to do so in 19. Deescalation occurred in 9 (47.4%) of these episodes without complication. The remaining 10 patients received a median of 20 additional days of broad-spectrum antibiotic therapy (range, 12 to 30 d). In our small cohort of patients, deescalation of antibiotic therapy based on antimicrobial susceptibilities did not result in complication. Larger prospective studies are needed to address the safety of deescalating antibiotic therapy in this population.

Cefepime vs. cefoperazone/sulbactam in combination with amikacin as empirical antibiotic therapy in febrile neutropenia.

Beta lactams are standard empirical therapy for febrile neutropenia (FN). The aim of this study was to evaluate the efficacy and safety of cefepime monotherapy compared with cefoperazone/sulbactam plus amikacin (CS + A) for empirical treatment of high risk FN. One hundred seventy-five patients with 336 FN episodes were randomized to receive either cefepime (2g q8h for adults and 50mg/kg q8h for children) or CS (2g q8h for adults and 50mg/kg q8h for children) plus amikacin (15mg/kg once a day). Positive response was defined as afebrile within 72h of starting antibiotics, persistent afebrile status more than 48h and no requirement of second-line antibiotics and antifungal agents. Three hundred thirty-six episodes were assessable for efficacy (168 cefepime, 168 CS + A). The positive response to antibiotics was identical for cefepime (53%) and CS + A (53%). Positive response was similar in MDI (microbiologically documented infection), 50 vs. 35% (p = 0.248), CDI (clinically documented infection), 50 vs. 35% (p = 0.259), combination CDI + MDI, 25 vs. 15% (p = 0.400), FUO (fever of unknown origin), 68 vs. 72% (p = 0.577) respectively in the two groups. The successful discontinuation of antibiotics at 72h in FUO was similar in both groups (60 vs. 59%, p = 0.544). Total drug-related adverse events were similar in both groups (8 vs. 6%) except renal dysfunction was high in CS + A (1 vs. 7 events). Mortality was the same between two groups (8 vs 7%). Cefepime monotherapy and CS + A had similar efficacy as first-line therapy for FN. Discontinuation of empirical antibiotics is safe and feasible approach in selected group of FUO patients.

Management of infection during chemotherapy for acute leukemia in Japan: a nationwide questionnaire-based survey by the Japan Adult Leukemia Study Group

We performed a nationwide questionnaire-based survey to evaluate the current clinical practices of infectious complications during chemotherapy for acute leukemia in Japan. We e-mailed a questionnaire to member institutions of the Japan Adult Leukemia Study Group in September, 2013. The questionnaire consisted of 50 multiple-choice questions covering therapeutic environment, antimicrobial prophylaxis, screening test during neutropenia, empirical therapy for febrile neutropenia, and the use of granulocyte-colony stimulating factor. The results were compared to those of previous surveys conducted in 2001 and 2007, and also to the recommendations described in the guidelines. Usable responses were received from 141 out of 222 (63.5%) institutions. Chemotherapy for acute myeloid leukemia was performed in protective environment in 90% of the institutions, which increased compared to previous survey (76%). Fluoroquinolones and fluconazole were the most commonly used antimicrobial agents for antibacterial and antifungal prophylaxis, followed by sulfamethoxazole-trimethoprim and itraconazole, respectively. In empirical therapy for febrile neutropenia, monotherapy with β-lactum antibiotics was the first-line therapy in most of the institutions. While empirical antifungal therapy was adopted for persistent fever in more than half of the institutions, preemptive/presumptive therapy was also used in approximately 40% of the institutions. Most of the clinicians were reluctant to use granulocyte-colony stimulating factor routinely in chemotherapy for acute myeloid leukemia. This study clarified the current clinical practices of infectious complications during chemotherapy for acute leukemia and would provide important information for the development of a suitable guideline in Japan.

Oпыт внедрения алгоритма эмпирической антибактериальной терапии при развитии фебрильной нейтропении в Центре детской гематологии/онкологии

Oпыт внедрения алгоритма эмпирической антибактериальной терапии при развитии фебрильной нейтропении в Центре детской гематологии/онкологии

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

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 9.0days and control group 8.0days, p = 0.67), and median number of days without ATB (0days, IQR 0-2days 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 28days (p = 0.39) and at 90days (p = 0.72). Considering the cut-off of 0.5ng/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.

Viridans Group Streptococcal Infections in Children After Chemotherapy or Stem Cell Transplantation: A 10-year Review From a Tertiary Pediatric Hospital.

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.

Pharmacoeconomics biosimilars in Oncology

PhArmACoeCoNomiCS bioSimilArS iN oNCology E. Janekova InClinic s.r.o, Bratislava, Slovakia Background: Population growth, long life spans, an increased morbidity cause an increased incidence of cancer diseases. Bio-similar drugs come to the market after the patent protection of biological drugs expires. In general, they reduce the price of the original drugs by 20%. Prior to a practical use they require clinical studies that demonstrate the quality, safety and efficacy biosimilar to that of the original. The price of development and production is 10 times higher than the price of generics. Material and Methods: For the treatment and prophylaxis of febrile neutropenia the original drugs are used; such as pegfilgrastim and filgrastim and filgrastim biosimilars. The study compared the costeffectiveness of 5 EU countries of filgrastim, pegfilgrastim and biosimilar filgrastim in different modes with cost efficiency in the Slovak Republic with a differentiating pricing policy of drugs over the years 2011.2012, 2013. Results: The prophylaxis and therapy of febrile neutropenia with biosimilar filgrastim is cost-effective when related to filgrastim and pegfilgrastim. Both the international and internal analysis puts the biosimilar filgrastim to a position of a cost-effective treatment even in with the absence of evidence provided by a pharmacological and therapeutical priority. Conclusions: The administration of an adequate treatment using pegfilgrastin and biosimilar filgrastim is a cost difference of 289 Euros in the Slovak Republic. Savings during the administration of the biosimilar drug for years: 2011 is 3703 thousand Euro thus, 70% of expenditure, in 2012 it was 4079 thousand. 68%. In 2013 it is 3847 thousand Euro, which is 60% of the cost for treating febrile neutropenia. Biosimilar drugs are the solution for oncologists as how to regulate the cost of oncological treatment while maintaining the effectiveness of said treatment.

PWSF2-7 - Appropriate Use of G-Csf in Cancer Treatment: an Evidence-Based Clinical Practice Guideline-2013

Purpose: To provide recommendations for appropriate use of granulocyte- colony stimulating factors (G-CSF) for patients with cancer treated by chemotherapy and/or radiotherapy.Methods: The 2013 Update Working Group (WG) in the Japan Society of Clinical Oncology (JSCO) completed a review and analysis of data published in the both international and domestic journals from 2005 through February 2013. The WG referred guidelines of G-CSF provided by ASCO-2006, EORTC-2010 and NCCN-2012. Guided by these guidelines and Minds in Japan, WG formulated recommendations based on improvement in survival, quality of life, reduction of toxicity and cost-effectiveness related to national insurance system in Japan.Recommendations: The use of G-CSFs is justified for a. prophylaxis and therapy of febrile neutropenia (FN) during chemotherapy for various malignant diseases, b. mobilization of peripheral-blood progenitor cells for peripheral blood stem cell transplantation, c. supportive therapy for severe neutropenia during treatment of myeloid and lymphoid malignancies, and d. improvement of prolonged neutropenia by radiation therapy. As primary prophylaxis, G-CSF is recommended to use for prevention of FN in patients who receive chemotherapeutic regimen having the risk of FN as 20% or grater, who receive the regimen expected to prolong survival time for maintaining intensity by management of neutropenia with G-CSF such as treatment for acute leukemias and aggressive lymphomas. G-CSF should be considered in patients with FN who are at high-risk for infection-related complications, however G-CSF should not be routinely used as adjunctive treatment for infection. Currently, there are three types of G-CSF (filgrastim, lenograstim, and nartograstim), one pegylated G-CSF (pegfilgrastim) and a few biosimilars of filgrastim for clinically available in Japan. All these G-CSFs have efficacy in management for patients with FN.

Deviations from guideline-based therapy for febrile neutropenia in cancer patients.

6078 Background: Febrile neutropenia (FN) is a common cause of morbidity in cancer patients. We examined guideline and non-guideline based care for cancer patients hospitalized with FN and examined how treatment influenced outcomes. Methods: The Perspective database was used to examine the treatment of solid tumor patients with FN from 2000-2010. To capture initial decision-making, we examined treatment within 48 hrs of admission. Based on evidence-based guidelines we determined the appropriate use of guideline-based antibiotics as well as use of treatments not routinely recommended, vancomycin and granulocyte-colony stimulating factors (GCSF). Hierarchical mixed effects models were developed to examine the influence of patient, physician, and hospital characteristics on the quality of treatment. Patients were stratified into low and high-risk groups and the effect of initial treatment on outcome (nursing home discharge and death) examined. Results: Among 25,231 patients with FN, within 48 hours of admission blood cultures were obtained in 90%, guideline-based antibiotic administered to 79%, vancomycin to 37%, and GCSF to 63%. Patients treated at high-volume hospitals, by high-volume physicians and patients managed by hospitalists were more likely to receive guideline-based antibiotics (p<0.05). Vancomycin use increased with time from 17% in 2000 to 55% in 2010 while GCSF use only decreased from 73% to 55%. Patients treated by internists and hospitalists were more likely to receive vancomycin; high-volume physicians were less likely to treat with both vancomycin and GCSF (p<0.05). Among patients who received GCSF, 15% received only one dose and 22% received 2 doses of filgrastim. Among low-risk patients prompt initiation of guideline-based antibiotics decreased the risk of discharge to a nursing facility (OR=0.78; 95% CI, 0.66-0.91) and death (OR=0.65; 95% CI, 0.50-0.85). Conclusions: There is substantial variability in the initial treatment for FN in cancer patients. While use of appropriate empiric antibiotics is high, use of non guideline-based treatments such as vancomycin and GCSF are common. Physician and hospital factors are the most important predictors of both guideline and non guideline-based treatment.

Current Role of Echinocandins in the Management of Invasive Aspergillosis

Echinocandins are parenteral antifungals with a unique site of action targeting the cell wall synthesis. There are three molecules available, anidulafungin, caspofungin, and micafungin, which have fungicidal and fungistatic activity against Candida and Aspergillus, respectively, and an excellent safety profile. There is consistent proof of clinical activity against Aspergillus for caspofungin, while less is known for micafungin and even lees for anidulafungin. Micafungin and caspofungin have been successfully used in targeted treatment of aspergillosis, prophylaxis, and empirical therapy, both as monotherapy and in combination with other antifungals. Caspofungin is approved for empirical therapy of febrile neutropenia and salvage treatment of invasive aspergillosis, whereas micafungin is only licensed for antifungal prophylaxis in stem cell transplantation.

Nanotechnology for therapy and imaging of liver diseases

Nanotechnology has been considered for the improved delivery of various therapeutic agents, including drugs and genes. Indeed, liposomes and nanoparticles equipped with homing devices for the targeting of receptors over-expressed on the hepatic tissue have improved the treatment of various liver diseases. In this review, various nanotechnology approaches employed for the treatment/imaging of liver disease, either in preclinical or in clinic are discussed.