High-risk Febrile Neutropenia Research Articles

Lipegfilgrastim in patients with chemotherapy-induced neutropenia

The development of dose-limiting toxicities, including myelotoxicity, can significantly limit cytostatic therapy of malignant tumors. Neutropenia associated with high risk of febrile neutropenia (FN) and infectious complications that may interfere with therapy intensity and significantly increases the cost of diagnosis and treatment. With the development of recombinant forms of human granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor, therapy of iatrogenic neutropenia has undergone significant changes. The use of G-CSF (filgrastim, lenograstim, pegfilgrastim) reduces FN incidence in patients receiving myelosuppressive chemotherapy. Until recently, the only original preparation of G-CSF with prolonged action was pegfilgrastim. Lipegfilgrastim (Lonquex, Teva) is a new highly effective long-acting pegylated G-CSF, which has been approved by European Medicines Agency experts for FN prevention in patients receiving chemotherapy. This review summarizes the characteristics of chemical structure, pharmacokinetics, safety and efficacy of lipegfilgrastim.

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

PurposeAccumulating 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.MethodsData 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.ResultsA 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.ConclusionsIn 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.Electronic supplementary materialThe online version of this article (doi:10.1007/s00520-015-3039-4) contains supplementary material, which is available to authorized users.

Granulocyte Transfusion in Febrile Neutropenia

▪Background: Over last 30 years cure rates are increasing among oncology patients. As the therapy intensifies, infectious complications become more common. Neutropenia is defined as neutrophil counts of <500/mm³ and it is one of the most frequent and severe complications of pediatric cancer therapy. In 12-17% of patients with febrile neutropenia, there are proven bacteremia and fungal infections. Pediatric oncology patients have a frequency of 30 morbidity and 1% mortality due to infections. Granulocyte transfusions (GTX) were found to be an effective protective and therapeutic strategy in prolonged neutropenia. GTX had been shown to be limiting the duration and complications of neutropenic period, maximum levels of CRP and duration of antibiotic usage especially after myeloablative therapy.Materials and methods: In this study that was performed at Kanuni Sultan Süleyman Education and Research Hospital pediatric hematology-oncology unit, 170 granulocyte transfusions applied to 37 high risk febrile neutropenia attack of 23 patients were evalauted retrospectively. Granulocyte transfusions were done when the neutrophile counts were between 0 to 300 /mm³ by taking account the general status, physical examination and cultures of patients. Donors were selected according to blood types and their informed cosent were taken. The donors came to the unit one night before, 8 mg intramuscular dexamethasone and 480 mcg of G-CSF were applied. After 12 hours, granulocytes were taken from the donors by intermittent flow technique and given to patients intraveneously. The time needed for getting away from neutropenia, number of febrile days and observed adverse effects were recorded.Results: For 23 high risk febrile neutropenic patients, granulocyte transfusion was performed at an average of 1-27 times per attack, totally 170 times in 37 attack. Eight of the patients were girls and 15 were boys, ages were ranging between 6 months to 16 years. Product quality qas found to be 1.41 x 1010; 2,14 x 1010/m2. Mean days for subsiding of fever was 6.45 days, mean time for getting rid of neutropenia was 8.15 days. Three patients died during neutropenia attacks. Two of them had both infections and uncontrolled progressive primary disease. Only one patient was lost from infection even though he had antibiotic, antifungal and supportive therapy. Only upper respiratory disease symptoms were noted at 3 of the donors. In one of the patients, transfusion was stopped due to allergic reactions. No other adverse reactions were noted.Conclusion: Our results were similar to the literature and it shows that granulocyte transfusions after myeloablative therapy limits the neutopenic period, decrease complications of neutropenia, maximum level of CRP and the duration and number of antibiotic usage. But stil controlled studies done at larger cohorts are needed. DisclosuresNo relevant conflicts of interest to declare.

Intensive chemotherapy for Burkitt lymphoma in HIV positive patients

Burkitt lymphoma has a low incidence, is highly aggressive, may be endemic, sporadic or associated with immunodeficiency and it has a high frequency of extranodal involvement. Overall and relapse free survival in HIV patients is 72 and 71% respectively. However, the current protocol in Chile considers a positive HIV serology as an exclusion criterion for intensive chemotherapy. To analyze the response to Burkitt lymphoma treatment among HIV positive patients. All HIV positive patients with a Burkitt lymphoma treated using PANDA protocol in a public hospital were analyzed. Eight male patients aged between 25 and 43 years, 63% in stage IV, were analyzed. All patients received an intensified chemotherapy regime, three of them without Rituximab. Complete remission was achieved in 87%. One patient was refractory to treatment and one patient relapsed at 5 months and died. Overall and relapse free survival were 58 and 60% respectively. All patients had episodes of high risk febrile neutropenia, but it did not cause deaths. In this group of HIV patients, intensive chemotherapy for Burkitt lymphoma had a high degree of effectiveness with a low relapse rate and high cure rate.

Phase 2 trial of the topoisomerase II inhibitor, amrubicin, as second-line therapy in patients with metastatic urothelial carcinoma

The purpose of this investigator-initiated multicenter phase II study was to determine the activity of the third-generation synthetic anthracycline, amrubicin, administered as second-line therapy in patients with advanced urothelial carcinoma. Patients with progressive metastatic urothelial cancer despite first-line chemotherapy were eligible for enrollment. Amrubicin was initially administered at a dose of 40 mg/m(2)/day daily × 3 every 21 days, and the dose was subsequently reduced to 35 mg/m(2)/day daily × 3 every 21 days. Prophylactic granulocyte colony-stimulating factor was administered to all patients, and prophylactic antibiotics were administered to patients at high risk of febrile neutropenia. Treatment was administered for up to six cycles in the absence of intolerable toxicity or disease progression. The primary endpoint was the objective response rate. A total of 22 patients were enrolled. Among the first three patients enrolled, all developed grade 4 neutropenia and one patient died of neutropenic sepsis. The starting dose of amrubicin was subsequently reduced, there were no further episodes of febrile neutropenia, and only one patient required a subsequent dose reduction. The most common adverse events were hematologic; grade ≥3 neutropenia occurred in 27 %, and other grade ≥3 adverse events were uncommon. Partial responses were achieved in three patients [13.6, 95 % confidence interval (CI) 0-28 %), while stable disease was the best response in 12 patients (54.5, 95 % CI 33.7-75.3 %). The trial was closed prematurely due to a development decision by the funder. Amrubicin as second-line therapy in advanced urothelial carcinoma is associated with modest single-agent activity. While there remains a role for the introduction of novel cytotoxic agents in the management of metastatic urothelial cancer, optimal development of such therapies will likely require patient selection biomarkers.

Appropriate use of granulocyte-colony stimulating factor in treating hematologic malignancies

Granulocyte colony stimulating factor (G-CSF) plays important roles in treating hematologic malignancies including hematopoietic stem cell transplantation (HCT) and intensive chemotherapy. In the situation of peripheral blood cell transplantation (PBSCT), G-CSF mobilizes hematopoietic stem cells and progenitor cells into peripheral blood and thereby accelerates recovery from neutropenia and thus prevents serious infections after transplantation. In the setting of chemotherapy administration for leukemia and lymphoma, G-CSF can be given to prevent febrile neutropenia (FN) in order to maintain drug intensity and thus improve therapeutic outcomes. Based upon the guidelines abroad and in our country, G-CSF should be used as primary or secondary prophylaxis according to the risk of developing FN during chemotherapy. Patients with acute leukemia who received extremely high-risk chemotherapy benefitted from prophylactic treatment with G-CSF, especially those with acute lymphoblastic leukemia. In treating lymphomas for patients given a regimen with a high risk for FN (>20%), administration of G-CSF as primary prophylaxis is recommended. In addition, administration of primary prophylactic G-CSF is also recommended for patients given a regimen with an intermediate risk for FN (10-20%), if they have risk factors for worsening FN or infection.

High-throughput pharmacogenetics identifies SLCO1A2 polymorphisms as candidates to elucidate the risk of febrile neutropenia in the breast cancer RAPP-01 trial.

The RAPP-01 clinical trial compared two adjuvant chemotherapies, doxorubicin plus docetaxel (arm A) versus doxorubicin plus cyclophosphamide (arm B), in 627 women with breast cancer. It stopped prematurely when three severe adverse events occurred among patients with febrile neutropenia (FN), all in the arm A. FN occurred in 40.8% (126/311) in arm A versus 7.1% (22/316) in arm B. We investigated Single Nucleotide Polymorphisms (SNPs) in drug transporter and metabolism genes potentially incriminated in this excess of FN. Using a dedicated DNA chip, we tested association of SNPs belonging to 97 transporter and 68 metabolizing genes with FN occurrence in 155 patients enrolled in the RAPP-01 trial, 85 in arm A and 70 in arm B. Association study in the 85 patients receiving docetaxel identified two SNPs, rs4762699 and rs2857468, both located in the SLCO1A2 gene. Haplotype T-T was associated with a high risk of FN: 83.3% of patients with at least one copy of T-T versus 32.8% in patients with other haplotypes (odds ratio = 10.25, P = 1.4e-4). In a multivariate logistic model adjusted for treatment arm, effect of haplotype T-T remained significant (odds ratio = 6.84, P = 1.15e-4). FN in patients receiving docetaxel in the RAPP-01 trial is significantly associated with the haplotype T-T in rs4762699 and rs2857468 in the SLCO1A2 transporter gene. This result should be validated in an independent cohort.

Phase III, randomized, double-blind, placebo-controlled, multicenter study of lipegfilgrastim in patients with non-small cell lung cancer receiving myelosuppressive therapy.

PurposeThe aim of this study was to demonstrate lipegfilgrastim superiority versus placebo in adults with non-small cell lung cancer receiving myelosuppressive chemotherapy.MethodsThis phase III, double-blind study randomized chemotherapy-naive patients to receive cisplatin and etoposide with either lipegfilgrastim 6 mg or placebo. Because of the placebo control, patients at individual high risk for febrile neutropenia (FN; ≥20%) were excluded. Study drug was administered on day 4 (24 h after chemotherapy) of a 21-day cycle for ≤4 cycles. Primary efficacy measure was FN incidence in cycle 1. Secondary assessments included duration of severe neutropenia (DSN), absolute neutrophil count (ANC) profile, and adverse events (AEs).ResultsThe study included 375 patients (lipegfilgrastim, n = 250; placebo, n = 125). Lipegfilgrastim superiority for FN incidence in cycle 1 was not achieved but incidence was lower (2.4%) versus placebo (5.6%). Cycle 1 mean DSN was significantly shorter for lipegfilgrastim (0.6 ± 1.1 days) versus placebo (2.3 ± 0.5 days; p < 0.0001). Incidence of severe neutropenia was significantly lower for lipegfilgrastim versus placebo overall and in each cycle (all, p < 0.0001). Mean ANC nadir was lowest in cycle 1 but significantly higher for lipegfilgrastim (1.60 ± 1.64) than placebo (0.67 ± 0.85; p < 0.0001). Mean time to ANC recovery was shorter with lipegfilgrastim in each cycle. Treatment-emergent AEs were similar between treatment groups.ConclusionsLipegfilgrastim was not statistically superior to placebo for incidence of FN in cycle 1, but was more effective in reducing incidence of severe neutropenia, DSN, and time to ANC recovery, with an acceptable safety profile.Controlled-trials.com identifier: ISRCTN55761467.

Febrile Neutropenia in Hematological Malignancies: Clinical and Microbiological Profile and Outcome in High Risk Patients.

Background and Objectives:Febrile neutropenia (FN) is considered a medical emergency. Patients with hematological malignancies (HM) commonly experience FN. Broad spectrum antibiotics have to be started empirically to prevent complications. This study depicts the clinical profile, microbiological profile, antibiotic sensitivity pattern, and outcome in high risk HM.Materials and Methods:In this prospective study, 72 patients with hematologic malignancies, diagnosed and treated for 108 high risk febrile neutropenic episodes from August 2011 to January 2013 at a Regional Cancer Center, in South India were analyzed. Cefoperazone-sulbactum was used as a first-line empiric antibiotic.Results:Majority of the patients with FN episodes had acute myeloid leukemia. Overall culture positivity was 29.62%. The most common organisms isolated were Gram-negative bacilli (63.64%), with Escherichia coli being the most frequent pathogen. All Gram-negative organisms were sensitive to imipenem, whereas sensitivity pattern to other antibiotics were as follows: 85.71%, 78.26%, 69.52%, 63.64%, 41.66% and 47.05% for pipercillin-tazoactum, meropenem, cefoperazone-sulbactum, amikacin, ceftazidime, ciprofloxacin respectively. Overall mortality was 13.5%. Most of the patients responded to empiric antibiotic cefoperazone-sulbactum.Conclusions:In the hematologic malignancies particularly in acute leukemia, there is high risk of developing FN. Empiric therapy with cefoperazone-sulbactum as a first line leads to satisfactory outcome in high risk FN and therapy should be tailored to the most appropriate antibiotics according to the bacterial culture results.

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

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.

A Randomized Controlled Study to Determine the Efficacy of Garlic Compounds in Patients With Hematological Malignancies at Risk for Chemotherapy-Related Febrile Neutropenia.

Patients receiving chemotherapy for hematological malignancies are at high risk for febrile neutropenia (FN). Garlic extracts (GEs) are natural food substances showing antimicrobial effects in vivo. We explored whether adding GE may be efficacious in reducing the risk or severity of infections. This was a placebo-controlled double-blind randomized study. Of 95 patients randomized to receive GE or placebo following chemotherapy, a febrile episode was documented in 50% of patients receiving GE and 63.3% receiving placebo (P = .89). There was a higher risk of developing a third and fourth febrile episode in the GE group (P = .01). However, among those at a lower risk for FN, those receiving GE developed fewer FN episodes (P = .075), especially those with severe neutropenia (P = .05). Major adverse events were distributed equally, but nonadherence was more common in the GE than in the placebo group: 19.5% versus 4%, respectively (P = .05). GE was safe and did not reduce FN risk in the entire cohort, but yet appeared to exert a protective effect in the lower-risk subgroup. We do not recommend the use of GE for FN prevention in higher-risk patients. A larger-scale clinical trial for the lower-risk subgroup of patients is advocated. (This trial was registered at www.clinicaltrials.gov as NCT00247039.).

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

9626 Background: Guidelines recommend primary prophylaxis (PP) with granulocyte colony stimulating factors (G-CSF) for patients above a febrile neutropenia (FN) risk threshold of 20%. When consider...

The efficacy of prophylactic GCSF for FOLFIRINOX.

274 Background: Granulocyte Colony-Stimulating Factors (GCSF) is used as supportive care in cancer management when patients (pts) receive chemotherapy with high risk of febrile neutropenia (FN). Peg-GCSF is unapproved in Japan at the time of Aug 2014. Hence, phase II study of combination chemotherapy regimen consisting of oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) for Japanese pts with advanced pancreatic cancer showed FN; 22% and severe neutropenia; 77.8%. Purpose of this retrospective study was to describe the incidence of FN and severe neutropenia during the first cycle of FOLFIRINOX with prophylactic GCSF (pGSF). Methods: Between January 2014 and August 2014, the pts who received FOLFIRINOX with pGCSF were examined retrospectively. The adverse events and detail of pGCSF administration during first cycle were investigated. Results: Among five pts administered FOLFIRINOX, 4 pts received pGSF in first cycle. All patients received FOLFIRINOX without dose reduction. The patient characteristics were as follows: median age (range), 58 (50-66); male/ female, 3/1; PS 0/1, 1/3. The detail of UTG1A1 (*6/ *28) was as follows: (wild type/ wild type), 2pts; (wild/ hetero), 1pt; (hetero/ hetero), 1pt. Hematological adverse events (grade 1/2/3/4) were as follows: leukopenia (0/1/2/0), neutropenia (0/1/0/1), thrombocytopenia (0/4/0/0), FN (0/0/1/0). The patient who occurred grade4 neutropenia and grade3 febrile neutropenia had UTG1A1 *6 hetero/ *28 hetero. Non-hematological adverse events (grade 1/2/3/4) were as follows: elevated GOT (2/1/0/0), elevated GPT (2/1/0/0), elevated T-Bil (0/0/0/0), anorexia (1/2/1/0), fatigue (2/1/0/0), nausea (0/1/2/0), diarrhea (1/1/0/0). The median starting date of pGSF administration was 4.5 (3-7). The median number of pGSF administration was 7.5 (6-9). Conclusions: Although this was retrospective and small study, pGSF appeared to be effective for prevention of severe neutropenia and FN. Hence pGSF might increase dose intensity of FOLFIRINOX.

Management of chemotherapy-induced neutropenia: measuring quality, cost, and value.

Treatment-associated neutropenia continues to represent the most common dose-limiting toxicity of cancer chemotherapy. It often leads to fever and infection, prompting hospitalization and occasionally resulting in serious morbidity, and even mortality, despite modern broad-spectrum antibiotic treatment and supportive care. Neutropenia and its complications may also lead to chemotherapy dose reductions, treatment delays, or early treatment termination, compromising disease control and the potential for cure. NCCN Clinical Practice Guidelines in Oncology recommend administration of primary prophylaxis with a myeloid growth factor in patients receiving regimens associated with a high risk for febrile neutropenia, and consideration of prophylaxis in patients receiving lower-risk regimens who have other risk factors that might place them at higher risk for febrile neutropenia. Although these agents have been shown to be effective and safe in numerous randomized controlled trials, they are expensive and contribute significantly to increasing health care costs. Regulatory agencies and guideline organizations do not currently address the issue of cost. However, with the relentless increase in health care use and current efforts to reform health care, it has become increasingly important to assess both the cost and the net benefit of interventions related to an episode of care in order to compare the overall value of therapeutic options. This article defines and discusses the intersection of quality, costs, and value in the context of prophylactic myeloid growth factor use in patients with cancer receiving myelosuppressive chemotherapy.

High-risk febrile neutropenia and its management in children with solid tumors and lymphoma.

The clinical characteristics and treatment results of febrile neutropenia attacks that occurred in patients with lymphoma and solid tumors were analyzed. A total of 50 patients with 94 high-risk attacks were evaluated for malignant diseases in this study. The fever etiology was determined as clinical (50%), microbiological (5.31%), clinical-microbiological (5.31%), or unknown (39.3%). A few of the attacks (21.3%) were observed in lymphoma cases and 77.7% were observed in patients with solid tumors. Patients who were in remission had 59.6% of the attacks, and 39.4% occurred in patients not in remission. Among the groups tested, 73% (the imipenem/amikacin group) and 47.9% (the piperacillin-tazobactam/amikacin group) of patients were in remission. Glycopeptide addition rates in these groups were 22.2% and 40.8% and antifungal addition rates were 8.8% and 18.3%, respectively. Clinical progress was more problematic in patients who were not in remission during the attacks. This was due to the fact that some patients had other factors that placed them in the high-risk group, as well as increased C reactive protein and procalcitonin values on the first day. Therefore, it may not be accurate to associate the success achieved in the different treatment regimens with antibiotics alone.

Doripenem Versus Meropenem As the First-Line Empirical Therapy in High-Risk Febrile Neutropenic Patients with Hematological Malignancy: A Randomized, Controlled Trial

BACKGROUND: Febrile neutropenia (FN) is often observed in cases of hematological malignancy such as acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL) and myelodysplastic syndrome (MDS). Carbapenem antibiotics having a potent and broad antimicrobial activity against both gram-positive and gram-negative bacteria including Pseudomonas aeruginosa, are good candidates as the first-line therapy drug in high-risk FN patients. In the IDSA guideline 2010 on the use of antimicrobial agents in FN, mono-therapy with an anti-pseudomonal beta-lactam, such as piperacillin-tazobactam, cefepime or carbapenem [only meropenem (MEPM) and imipenem-cilastatin], is recommended as an empirical therapy for high-risk FN patients. Doripenem (DRPM) is a newer carbapenem with few data available as for the efficacy and safety in the setting of FN patients. Therefore, we conducted a randomized, cooperative group, open-label trial comparing DRPM (1.0 g every 8 hours) with MEPM (1.0 g every 8 hours) as the first-line empirical antibacterial therapy for high-risk FN patients with hematological malignancy including AML, ALL and high-risk MDS.PATIENTS and METHODS: One hundred and forty-six hospitalized high-risk FN patients with hematological malignancy (AML 76, ALL 43, APL 13, MDS-AML 9, MDS-RAEB 5 cases) during or after chemotherapy were randomized to each drug group (DRPM: n=73, MEPM: n=73). The study drug was started to administer as a mono-therapy and continued at least for 5 days without drug toxicity, and the efficacy and safety were evaluated.RESULTS: The overall response rate at 7 days in DRPM and MEPM group were not significantly different (DRPM: 67.6%, MEPM: 52.9%, respectively, P=0.098). Both the resolution of fever by mono-therapy at day 3 to 5 (DRPM: 56.9%, MEPM: 47.0%, respectively, p=0.26), and survival at day 30 (DRPM: 98.4%, MEPM: 98.5%, respectively, p=0.312) were not significantly different in the two groups. The frequency of cases needed for anti-MRSA agent and antifungal agent were a little less often in DRPM rather than in MEPM group [DRPM: 36.9%, MEPM: 50.0% (p=0.185), DRPM: 26.1%, MEPM: 32.3% (p=0.535), respectively]. Only grade 1-2 adverse events were observed in both groups (liver dysfunction, renal dysfunction, diarrhea and rash), and they were less often in DRPM group significantly (DRPM: 29.8%, MEPM: 40.8%, respectively, p=0.046). These adverse events were clinically acceptable in the two groups, and most of patients could continue the treatment by both study drugs.CONCLUSIONS: Our clinical study suggested that DRPM had the non-inferiority of efficacy in comparison with MEPM as the first-line empirical therapy in high-risk FN patients with hematological malignancy, and both drugs could be generally well tolerated. DisclosuresNo relevant conflicts of interest to declare.

G-CSF utilization rate and prescribing patterns in United States: associations between physician and patient factors and GCSF use.

Febrile neutropenia (FN) is a common complication among patients with chemotherapy-induced myelotoxicity and is associated with a number of negative outcomes including prolonged hospitalization, increased medical costs, increased risk of mortality, dose reductions, and delays. Granulocyte-colony-stimulating factor (G-CSF), granulocyte–macrophage-colony stimulating factor (GM-CSF), and pegylated G-CSF are effective at reducing risk and duration of neutropenia-related events. However, despite guidelines, the use of G-CSF and pegylated G-CSF in the United States has not been consistent and pattern of care studies have focused primarily on G-CSF. A number of studies found that G-CSF is underutilized in patients undergoing chemotherapy treatments associated with a high risk of FN, while being over utilized in patients with a low-risk FN. Wide variations in overuse, underuse, and misuse of G-CSF are associated with a number of physician and patient factors. Improved awareness of the guidelines, feedback to providers regarding proper usage, and understanding of chemotherapy regimens associated with very low risks as well as high risks (>20%) of FN is some of the approaches that could lead to improving care.

Granulocyte colony-stimulating factors as prophylaxis against febrile neutropenia.

Myelosuppression secondary to chemotherapy remains a serious adverse effect of cancer therapy that causes high morbidity and mortality. Several current European and American guidelines recommend consideration of primary prophylaxis with colony-stimulating factors (CSFs) when the risk of febrile neutropenia is higher than 20 %. The main factors associated with a high risk of febrile neutropenia include the chemotherapy regimen, tumor type, and patient-related factors such as old age and/or comorbidities. The purpose of this paper is to summarize the most relevant clinical trials and updated recommendations of the main guidelines on the role of granulocyte colony-stimulating factors (G-CSFs) in febrile neutropenia, examining whether the combination of G-CSF with chemotherapy improves overall survival. Future directions for G-CSF use are also discussed.

Efficacy of an Alternative Dosing Strategy of Meropenem in the Treatment of High-Risk Febrile Neutropenia in Adult Subjects

Efficacy of an Alternative Dosing Strategy of Meropenem in the Treatment of High-Risk Febrile Neutropenia in Adult Subjects

Evaluation of a Once-Daily Vancomycin Regimen in an Outpatient Leukemia/Bone Marrow Transplant Clinic (OD-VANCO Study).

The Leukemia/Bone Marrow Transplant Program of British Columbia manages patients with high-risk febrile neutropenia and those with non-neutropenic immunocompromised states in an outpatient clinic setting. Because the program treats outpatients only, once-daily administration of IV antibiotics is desirable. A high-dose, once-daily vancomycin nomogram was developed and implemented as part of the antibiotic treatment regimen. To determine if therapeutic vancomycin trough levels could be achieved with a high-dose, once-daily regimen in this outpatient setting. A prospective, single-centre, observational cohort study was conducted over a 7-month period. Outpatients in the Leukemia/Bone Marrow Transplant Program were started on IV vancomycin with the high-dose, once-daily vancomycin nomogram, and outcomes were assessed. Of 48 outpatients treated over the 7-month period, 10 (21%) had therapeutic vancomycin trough concentrations (i.e., greater than 10 mg/L). Thirty-five (90%) of the 39 patients with suspected clinical infection experienced clinical cure, and 6 (67%) of the 9 patients with documented microbiological infection experienced microbiological cure. Thirty (62%) of the 48 patients experienced symptoms of "red man syndrome", and 7 (15%) experienced some degree of nephrotoxicity. Two of 3 patients with laboratory-reported minimum inhibitory concentration (MIC) for identified pathogens had a calculated area under the curve to MIC ratio greater than or equal to 400. The high-dose, once-daily vancomycin nomogram was effective in attaining trough levels greater than 10 mg/L in only 21% of patients in this study. A substantial number of adverse drug reactions were observed. Given these results, high-dose, once-daily vancomycin is no longer recommended for outpatient therapy.