David J. Seastone

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.

Genomic patterns associated with hypoplastic compared to hyperplastic myelodysplastic syndromes.

While the bone marrow in most patients with myelodysplastic syndromes (MDS) has normal or increased cellularity (hyper-MDS), approximately 10%–15% of MDS patients will present with a hypocellular bone marrow (hypo-MDS).[1][1] Since the diagnosis of MDS relies mainly on the presence of dyplastic

Darbepoetin alfa for anemia with myelodysplastic syndrome

The myelodysplastic syndromes are characterized by refractory cytopenias that lead to symptomatic anemia, bleeding, and increased risk for infections. For almost two decades, the use of darbepoetin and other erythropoietin stimulating agents to treat symptomatic anemia in lower-risk myelodysplastic syndromes has been a standard of care. This practice is supported by numerous Phase I/II studies and one Phase III study demonstrating the benefit of using erythropoietin stimulating agents alone, or in combination with granulocyte colony stimulating factor, for treatment of symptomatic anemia with the goal of decreasing red blood cell transfusion requirements. This review summarizes the published experience regarding the use of erythropoietin stimulating agents, with a special focus on darbepoetin, in patients with myelodysplastic syndrome and symptomatic anemia.

Abstract 5575: Obesity and genomic changes in patients with myelodysplastic syndromes

Obesity is rapidly overtaking smoking as the leading preventable cause of cancer, particularly in cancers of the breast and colon. In a large cohort of individuals participating in the National Institutes of Health-AARP Diet and Health Study, a higher incidence of MDS and an increased mortality was observed in individuals with body mass index (BMI) >30 compared to those with BMI We performed genomic analyses by using next-generation targeted deep sequencing (NGS) and whole exome sequencing (WES) of 62 significantly affected genes that play an important role in MDS pathogenesis. Mutations were considered individually and grouped into several functional pathways. Overweight (BMI 25-29) and obese (BMI >30) were combined in one group (BMI-H). Of 205 pts with MDS treated at our institution between 1/2000 - 1/2013, 146 (71%) were BMI-H. Interestingly, only 2 patients had BMI Overall, 74% of pts had at least one of the 62 screened mutations, the most common being: SF3B1 (17%), TET2 (17%), ASXL1 (14%), STAG2 (12%), DNMT3A (9%), U2AF1/2 (8%), GPR98 (8%), and RUNX1(7%). Mutations in IDH1/2 (5% vs. 0%), DNMT3A (11% vs. 5%), TET2 (18% vs. 14%) occurred more frequently in BMI-H, where SF3B1 (25% vs. 13%), and NRAS (7% vs. 2%) mutations were more common in BMI-N. Within functional groups, mutations in splicing machinery genes were less common in BMI-H compared to BMI-N (32% vs. 41%, p = .05) and mutations in DNA methylation genes were more common in BMI-H (20% vs. 34%, p = .02). Clonal architecture analysis points to the presence of different dominant clones between the two groups. In the dominant MDS clones, mutations in TET2 and DNMT3A were observed more frequently in pts with BMI-H, whereas mutations in SF3B1 were more frequently observed in BMI-N pts. In conclusion, overweight and obese pts with MDS have a trend for inferior survival and higher rate of progression to AML as compared to MDS pts with normal weight. Genomic differences in clonal architecture and distribution of somatic mutations were observed in the BMI-H group. Further exploration including germline mutations and previously described familial obesity genes is needed to expound on the interaction between the biology of obesity and leukemogenesis of MDS. Citation Format: Aziz Nazha, David Seastone, Hideki Makishima, Matt Kalaycio, Hetty E. Carraway, Anjali S. Advani, Ahamd Zarzour, Jennifer Carew, Aaron T. Gerds, Sudipto Mukherjee, Jaroslaw P. Maciejewski, Mikkael A. Sekeres. Obesity and genomic changes in patients with myelodysplastic syndromes. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5575. doi:10.1158/1538-7445.AM2015-5575