7 research outputs found
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Prospective Study Of An Emergency Department Febrile Neutropenia Pathway In Patients With Hematologic Malignancies
Abstract
Background
Febrile neutropenia (FN) is an oncologic emergency associated with high morbidity and mortality, particularly in patients (pts) with hematologic malignancies. Delays in antibiotic administration, which can occur in busy emergency departments (EDs), lead to worse outcomes. We instituted a FN pathway (FNP) in the Cleveland Clinic (CC) ED to reduce antibiotic delays.
Methods
This prospective study comparing patients from 06/12 - 06/13 to historical pts from 02/10 - 05/12, represented a collaboration among cancer center, ED, infectious disease, pharmacy, and electronic medical record representatives. Fever was defined as temperature >38°C either at home or in the ED, while neutropenia as absolute neutrophil count <0.5 x 109/L. All CC cancer pts received a special “Neutropenic Risk Hospital Medical Alert Card,” which they presented upon CC ED registration with fever. The pathway formally recognized “fever with a history of cancer” to be a distinct chief complaint and FN to be categorized as Emergency Severity Index level 2 (equivalent to stroke or myocardial infarction) for immediate triage and care. ED-specific electronic FN order sets were created to facilitate antibiotic, laboratory, and blood culture ordering, with antibiotics administered prior to return of neutrophil count. The primary goal of the FNP is administration of empiric broad-spectrum antibiotics within 120 minutes of ED presentation, per Infectious Diseases Society of America guidelines; and the primary outcomes measured were time intervals related to it, e.g. time to blood draw, physician assessment, and antibiotic order/administration. Group comparisons were made using the chi-square, Kruskal-Wallis, Wilcoxon rank-sum, and log rank tests, as appropriate. All reported times were from ED registration.
Results
In total, 137 consecutive FN episodes in 115 pts with hematologic malignancies occurred during the 12 month study period, 63 episodes in 44 pts in the historical cohort. All pts were triaged and treated using the ED FNP, but use of the specific FN order set was variable: episodes were thus classified as treated per the order set (n=53) or not (n=84 – pts still received antibiotics, but not necessarily per the order set). Overall 60% of pts (n=89) were male and the median age at the time of first ED encounter was 59 years (range 20-88). Cancers were: non-Hodgkin lymphoma (38%), acute myeloid leukemia (21%), other leukemias (15%), and myelodysplastic syndromes (8%). Compared to historical pts, FNP study pts had a higher median ANC (2.0 vs. 0.2, p<0.0001), were less likely to be on growth factors (26% vs. 41%, p=0.06) and more likely to have received prophylactic antibiotics (55% vs. 35%, p=0.006). For the outcome of interest, FNP study pts had significantly shorter time to having blood drawn (median 38.5 vs. 70 minutes, p<0.0001), seeing a doctor (median 44 vs. 71 minutes, p=0.0002) and to receiving antibiotics (median 79 vs. 228 minutes, p<0.0001). Time to admission was also shorter for FNP study pts (4.2 vs. 6.0 hours, p<0.0001), though study pts were less likely to be admitted than historical controls (83% vs. 97%, p=0.005). For FNP pts admitted to the hospital, there was a non-significant decrease in length of stay (median 3.8 vs 4.6 days, p=0.28), ICU admission (7% versus 11%, p=0.26), and length of ICU stay (median 1.9 vs 2.3 days, p=0.83) compared to historical controls.
Comparing the two FNP groups treated or not treated per the order set, those treated using the order set had shorter times to antibiotics being ordered (median 28.0 vs. 60.5 minutes, p0.28).
Conclusion
The FNP significantly decreased time from ED registration to all set time-points, including time to antibiotics by almost three-fold, compared to historical controls in pts with hematologic malignancies. Rate of hospitalization was significantly lower, and ICU and length of stay numerically lower. The FNP is an effective clinical tool to provide prompt antibiotic administration to FN pts and likely represents a significant mechanism for improved outcomes and cost-savings to patients with hematologic malignancies presenting with FN.
Disclosures:
No relevant conflicts of interest to declare
Reducing Time to Antibiotic Administration for Febrile Neutropenia in the Emergency Department
Purpose: Febrile neutropenia (FN) is an oncologic emergency, and prolonged time to antibiotic administration (TTA) is associated with increased hospital length of stay (LOS) and worse outcomes. We hypothesized that a febrile neutropenia pathway (FNP) quality initiative project would reduce TTA delays for febrile patients with cancer presenting to the emergency department (ED).
Methods: This prospective study compared ED FNP patients (> 18 years old), between June 2012 and June 2013 with both historical and direct admissions (DA) cohorts at a multispecialty academic center. Interventions included providing patients with FN-Alert cards, standardizing the definition of FN and recognizing it as a distinct chief complaint, revising ED triage level for FN, creating electronic FN order sets, administering empiric antibiotics before neutrophil count result, and relocating FN antibiotics to the ED. The primary outcome was TTA, with a target goal of 90 minutes after ED presentation.
Results: In total, 276 FN episodes in 223 FNP patients occurred over the 12-month study period and were compared with 107 episodes in 87 patients and 114 episodes in 101 patients in the historical and DA cohorts, respectively. Use of the FNP reduced TTA from 235 and 169 minutes in historical and DA cohorts, respectively, to 81 minutes, and from 96 to 68 minutes when the order set was not used versus used in the FNP group (P < .001 for all comparisons). Decrease in hospital LOS was not statistically significant.
Conclusion: The ED FNP is a significant quality initiative with sustainable interventions, and was able to demonstrate value by decreasing TTA compared to both historical and DA controls in cancer patients presenting to the ED
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Whole Exome Sequencing to Predict Response to Hypomethylating Agents in MDS
Abstract
Abstract 1698
Hypomethylating agents decitabine and azacitidine are standard treatments for myelodysplastic syndromes (MDS). In their use, one hopes to rectify cytopenias and prolong survival by retarding further disease progression. However, individual treatment responses vary from complete remission (CR) to complete refractoriness. In general, at least 4 cycles of therapy are administered prior to assessing response. Thus, patients may have prolonged exposure to ineffective therapy, suffering toxicities without clinical benefit, while alternative and potentially more effective treatments are delayed. Currently, there are no reliable phenotypic or mutational markers for predicting response to hypomethylating agents.
Once whole exome sequencing (WES) became available for more routine analysis, we theorized that somatic mutational patterns may help identify patients who would most benefit from these drugs, thereby maximizing response rate by rational patient selection. To pursue this hypothesis, we screened a cohort of 168 patients with MDS who received either azacitidine or decitabine for the presence of somatic mutations. Only those who received sufficient therapy, i.e., completed at least 4 cycles, were selected for outcome analysis. Targeted Sanger sequencing, including a panel of up to 19 genes frequently affected by somatic mutations was performed. For a representative subset of 26 patients (this subset is expanding) of whom there were 15 responders and 11 non-responders, mutational analysis was performed by WES to select target genes for further analysis. WES utilizes paired DNA (tumor vs. CD3+ lymphocytes) to produce raw sequence reads aligned using Burrows-Wheeler Aligner (BWA). Variants are detected using the Broad Institute's Best Practice Variant Detection GATK toolkit.
Median age was 68 years (range, 55–85), 50% were female, and MDS subtypes were as follows: RA/RCUD/RARS 13%, RCMD 16%, RAEB-1/2 20%, MDS/MPN & CMML-1/2 31%, and sAML 20%. Response was assessed using IWG 2006 criteria at 4 and 7 months after therapy initiation. Overall response was 48%; rate of CR (including marrow/cytogenetic CR) was 28%, any HI 20%, SD 22%, and no response 29%. The cohort was then dichotomized into “responders” and “non-responders,” with responders classified as those achieving CR or any HI. Baseline patient characteristics were similar between both groups, including average age at treatment initiation, disease subtypes, proportion of abnormal/complex karyotypes, and presence of common cytogenetic aberrations. Overall, the most frequently mutated genes include TET2/IDH1/IDH2, SRSF2, ASXL1, SF3B1, RUNX1, EZH2/EED/SUZ12, SETBP1, CBL, and PPIAF2. The highest rate of refractoriness was noted in mutants of TET2/IDH1/IDH2 (67%), SF3B1 (67%), U2AF1/2 (67%). We also identified several genes whose mutants were few but associated exclusively with refractory disease (100%), including KIT, ZRSR2, PRPF8, LUC7L2.
We next applied a recursive partitioning algorithm to construct a decision tree for identifying the most pivotal mutations associated with response: we found mutant CBL and PPFIA2 to be strongly associated with response, whereas mutant U2AF1/2, SF3B1 and PRPF8 were strongly associated with refractoriness. Our final approach was to dichotomize the cohort by the presence/absence of each mutation/group of mutations, and response within mutant vs. wild type cases was compared. Among refractory cases, TET2/IDH1/IDH2 (26%) and SF3B1 (17%) were most frequently mutated; among responders, mutations in RUNX1 (19% vs. 4%]), CBL (14% vs. 0%), SRSF2 (23% vs. 9%), and SETBP1 (18% vs. 4%) were most frequent. When multiple genes were combined in “either-or” fashion, mutation in TET2, SF3B1, PRPF8, or LUCL71 was significantly associated with refractoriness (52%, p=.0287), whereas mutations of RUNX1, CBL, SRSF2, SETBP1, or PPFIA2 mutation was significantly associated with response (86%, p=.0001).
Mutational patterns appear to predict response to standard hypomethylating agents. Identification of the most predictive genes could guide development of molecular maker-based selection of patients for hypomethylating agent therapy, but will require ongoing analysis and additional prospective testing for validation.
Disclosures:
Advani: Genzyme: Honoraria, Research Funding; Immunomedics: Research Funding. Maciejewski:NIH: Research Funding; Aplastic Anemia&MDS International Foundation: Research Funding
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Defining quality and value in a prospective study of an emergency department (ED) febrile neutropenia pathway (FNP)
Defining quality and value in a prospective study of an emergency department (ED) febrile neutropenia pathway (FNP).
Pilot study on the efficacy of an ondansetron- versus palonosetron-containing antiemetic regimen prior to highly emetogenic chemotherapy
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Use of targeted therapies for advanced renal cell carcinoma in the Veterans Health Administration
BackgroundThe objective of this study is to describe the use of targeted therapies for the treatment of advanced renal cell carcinoma (RCC) and overall survival (OS) among patients in clinical practice in the Veterans Health Administration (VHA).MethodsA retrospective cohort of 286 patients from 24 VHA Medical Centers diagnosed with advanced clear cell RCC between Fiscal Year (FY) 2010 and FY2014 was followed through September 30, 2016. Among patients who received targeted therapy, we described the medications taken, duration of therapy, and overall survival. We also assessed the effect of the first therapy received on overall survival using Cox Proportional Hazards models.ResultsThere were 66 patients who did not receive therapy for their advanced RCC. Of the 220 treated patients, the mean (sd) number of medications received was 1.9 (1.1). The medications most commonly used first were sunitinib (61.8%), pazopanib (17.3%), and temsirolimus (10.9%). The median duration of first-line therapy was 86 days (interquartile range [IQR] 42, 210). Median total duration of therapy was 159 days (IQR 58, 397). 62.3% of patients had ≥ 1 dose of therapy held or reduced, mainly due to an adverse drug event (ADE). Median survival from the start of treatment to death was 1.08 years (IQR 0.80, 1.31). Finally, receipt of temsirolimus vs sunitinib (HR 1.95 [95%CI 1.09,3.47]) as the first targeted therapy was independently associated with an increased hazard of death.ConclusionOur analysis of targeted therapies for advanced RCC in VHA suggests duration of treatment is shorter in a real-world setting than in clinical trials, and dose reductions and ADEs are more common