Febrile Neutropenia In Patients Research Articles

Prophylactic Use of Filgrastim on Days 7, 11 and 14 in Patients Receiving R-CHOP for Non-Hodgkin's Lymphoma

Introduction Chemotherapy-induced febrile neutropenia (FN) is a side effect of cytotoxic chemotherapy and a major risk factor for infection as well as a dose-limiting toxicity. One method of reducing the incidence of febrile neutropenia is through the use of granulocyte stimulating factor (G-CSF). Patients with Non-Hodgkin's Lymphoma (NHL) receiving R- CHOP chemotherapy are thought to have a 10-20% risk of FN (Aapro et al 2010). Elderly patients (aged 65 and over) have an elevated risk of FN. The Newcastle upon Tyne Hospitals (NuTH) local guidelines recommend a novel regime prescribing one dose of filgrastim on days 7, 11 and 14 of treatment regime as primary prophylaxis. Several randomised studies and retrospective reviews of practice have examined the question of G-CSF prophylaxis in older patients. There is little doubt that the use of G-CSF as primary prophylaxis in this group reduces the incidence of FN, however the data are conflicting with respect to impact on overall survival (Osby et al 2003. Doorduijn et al 2003) Aims To audit prophylactic G-CSF prescribing against trust guidelines for patients over 65 with NHL receiving R-CHOP chemotherapy. We also assessed the frequency of hospital admissions for FN in patients over 65 receiving curative R-CHOP for NHL. Methods Patients with NHL over 65 who received R-CHOP at NuTH between 01/06/2017 - 31/01/2018 were identified using our electronic chemotherapy prescribing system. Electronic medical records were used to extract patient, chemotherapy, and hospital admission details. A data collection tool was used to record; patient age, cycle number, details about neutropenic sepsis related admissions and neutrophil counts between 1- 4 days prior to a cycle commencing. Results 30 patients with an average age of 73, cumulatively received 138 cycles of R-CHOP during the defined time period. 91.3% (126/138) of G-CSF prescriptions co-prescribed with chemotherapy were in accordance with trust policy. G-CSF on day 7, 11 and 14 corresponded with 8 hospital neutropenic admissions and 0 non-neutropenic. Comparatively 8.7% (12/138) of G-CSF prescriptions were for ≥5 days and corresponded with 5 hospital admissions with FN and 1 non-neutropenic. However, patients who received 5 or more days G-CSF had multiple risk factors for FN or had a previous episode of FN. The average length of admission due to FN was 6 days which has an associated financial implication. 17 chemotherapy prescriptions were dose reduced, of which 82.4% (14/17) were co-prescribed with the day 7, 11 and 14 regime. There were no deaths as a result of neutropenic sepsis in this cohort of 30 patients. Conclusion The NuTH G-CSF regime resulted in FN admission at a rate of 6.35% (8/126). This is lower than the expected rate of 10-20 % in the absence of G-CSF prophylaxis. These data support the use of the modified regimen of filgrastim on days 7, 11 and 14. References Aapro, M.S. et al. 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. European Journal of Cancer, Volume 47, Issue 1, 8 - 32 Doorduijn JK, an der Holt B, Imhoff GW, Hem KG, Kramer MHH, Oers MHJ, et al. CHOP compared to CHOP plus granulocyte colony‐stimulating factor in elderly patients with aggressive Non‐Hodgkin's Lymphoma. Journal of Clinical Oncology 2003;21(16):3041‐50. Ösby K, Hagberg H, Kvaloy S, Teerenhovi L, Anderson H, Cavallin‐Stahl E, et al. CHOP is superior to CNOP in elderly patients with aggressive lymphoma while outcome is unaffected by filgrastim treatment: results of a Nordic Lymphoma Group randomized trial. Blood 2003;101(10):3840‐8. Disclosures Gabriel: Abbvie: Consultancy, Speakers Bureau; Jazz: Consultancy, Speakers Bureau; Kite: Honoraria. OffLabel Disclosure: Filgrastim - granulocyte colony stimulating factor

Doripenem Versus Meropenem As the First-Line Mono-Therapy in High-Risk Febrile Neutropenic Patients with Acute Leukemia: A Randomized, Controlled Trial

BACKGROUND: Febrile neutropenia (FN) is often observed in patients with hematological malignancies (HEM), especially in those with acute leukemia (AL). Monotherapy with antipseudomonal beta-lactams, such as cefepime, carbapenem, or piperacillin-tazobactam, is recommended as first-line empiric antibacterial therapy in FN patients. The efficacy of meropenem (MEPM) as empiric monotherapy for FN patients with cancer has been assessed in randomized comparative trial against cefepime, imipenem/cilastain, ceftazidime with or without amikacin, and piperacillin-tazobactom. Because of those studies, MEPM is considered a standard antibiotic for the empiric treatment of FN patients with HEM.In contrast, doripenem (DRPM) is a relatively new carbapenem, and the clinical study about efficacy and safety of DRPM in FN patients with HEM is limited. 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 AL and myelodysplastic syndrome (MDS). METHODS: One hundred and thirty-three hospitalized patients with acute leukemia or high-risk myelodysplastic syndrome, who developed high-risk FN during or after chemotherapy (AML 77, ALL 43, APL 9, ATL 1, MDS (RAEB-2) 3cases) were randomized to each drug group (DRPM, 65; MEPM, 68). 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 success rate (Resolution of fever within 3 to 5 days without treatment modification: the primary endpoint) was higher in the DRPM group than in the MEPM group (60.0% vs. 45.6%), although the difference was not significant (P = 0.136). However, resolution of fever within 7 days of treatment was significantly higher in the DRPM group than in the MEPM group (78.4% vs. 60.2%, respectively, P = 0.037). Otherwise, the cumulative number of afebrile cases by day14 was 87.7% and 83.8% in the DRPM and MEPM group, respectively (P = 0.523). The success rate did not depend on neutrophil recovery: success rates for the DRPM group were 58.3% and 60.9%, with and without neutrophil recovery, respectively; success rates for the MEPM group were 33.3% and 40.9%, with and without neutrophil recovery, respectively (P = 0.233, P = 0.346). In all, 40.0% of the DRPM group and 32.3% of the MEPM group received anti-MRSA agent, as empiric or targeted antibacterial therapy of persistent or recurrent fever considering of infections by gram-positive bacteria, including methicillin-resistant species. Antifungal medications were added to 21.5% of the DRPM group and 13.2% of the MEPM group, as empiric or preemptive therapy of persistent or recurrent fevers believed to be caused by fungal infections. Survival rates at 30 days after the start of administration were 98.5% and 100% in the DRPM and MEPM group, respectively (P = 0.304). The rates of adverse events did not significantly differ between the DRPM and MEPM group (38.5% vs. 41.2%, respectively, P = 0.749), and 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 therapy in high-risk FN patients with AL and MDS, and both drugs could be well tolerated clinically. Disclosures Oyake: Kyowa-Hakko Kirin: Honoraria; Celgene: Honoraria; Chugai: Honoraria; Astellas: Speakers Bureau. Hanamura:Sanofi: Research Funding; Taiho: Research Funding; MSD: Research Funding; Chugai: Research Funding; Eli Lilly: Research Funding; Fujimoto: Research Funding; Zenyaku: Research Funding; Yamada Yohojo: Research Funding; Chugai: Research Funding; Astellas: Research Funding; Shionogi: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Consultancy, Honoraria, Research Funding; Eisai: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Kyowa-Hakko Kirin: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Ono: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; AbbVie: Honoraria; Mundi: Honoraria; Nihon Shinyaku: Honoraria, Research Funding; Otsuka: Honoraria, Research Funding. Ito:Bristol-Myers Squibb: Honoraria; Ono: Honoraria; Celgene: Honoraria.

The Economic Burden of Short-Term Adverse Events Associated with the CHOP Chemotherapy Regimen in Patients with Lymphoproliferative Disorders in the United States: A Comprehensive Literature Review

Objectives: CHOP (vincristine, cyclophosphamide, prednisone, doxorubicin) is a treatment option for post-transplant lymphoproliferative disorder (PTLD) following solid organ transplant, an aggressive and potentially fatal disease. The most common and impactful CHOP-related adverse events (AEs) are febrile neutropenia (FN), chemotherapy-induced (CI) peripheral neuropathy (PN), infection, CI-anemia (A), and CI-nausea and vomiting (NV). These CHOP-related AEs have a large humanistic burdensignificant impact to quality of life (QoL) of patients, especially shortly after treatment. The evidence for a positive QoL benefit associated with some AE treatments (e.g., erythropoietin stimulating agents [ESA], granulocyte colony stimulating factors) is inconsistent and many patients likely remain with QoL deficits even after treatment. The impact of these short-term CHOP-related AEs is likely to be accompanied by an increase in healthcare resource utilization and costs. The objective of this study was to explore the economic burden of short-term CHOP-associated AEs in PTLD patients. Since PTLD is a rare disease with limited available data, we expanded our search to include all patients with lymphoproliferative disorders (LPD). Methods: Short-term (within several months after treatment) AEs associated with CHOP with an incidence of >4% in patients with LPDs were determined and sourced from the published literature and cancer websites. A comprehensive literature search was conducted using PubMed and EMBASE to identify economic burden studies published from 2010 to 2018 of the AEs associated with CHOP and its components in the United States (US). Studies incorporating rituximab alongside CHOP (CHOP + R) were also included as this is a valid treatment option for PTLD patients. Economic burden was defined as the management costs and resource utilization associated with treating CHOP-emergent adverse events. The conduct of this comprehensive literature review was guided by the PRISMA protocol wherein the research question (using the PICOS format), search strategy, target short-term AEs, and inclusion and exclusion criteria were pre-specified in detail. Results: Overall, 3,946 non-duplicate citations were screened, 39 studies were included for abstraction and no studies included patients with PTLD. Studies were methodologically heterogenous, with approximately half (56%) based on some form of retrospective analysis or prospective observational study. FN was the AE most commonly encountered, followed by CIA, infection, CI-nausea and vomiting, and CIPN. FN was an important driver of hospitalization (proportion of FN patients with hospitalization was up to 83.2%) and extended length of stay (LOS) was substantial for several AEs (LOS range in days: infection, 8.4-23.6; FN, 7.9-19.7). Mean LOS was longer in FN patients with multiple hospitalizations as well as in FN patients with comorbidities. Rates of transfusion in CI-anemia patients varied dramatically, from 10.8% to 47.4%. Transfusion rates were attenuated by ESA use in LPD patients, although a significant proportion of anemic cancer patients receiving ESAs still required transfusions. Total management costs were highly variable, ranging from nominal for events such as CIPN to over $197,000 in hospitalization costs per infection discharge per patients complicated with clostridium difficile. One recent study showed the inpatient costs attributable to FN were $33,006 per patient per episode. Studies identified CINV as a top reason for unplanned service use, but no studies were identified assessing its economic impact in LPD patients. Outpatient care costs for each AE varied but tended to have a low to moderate economic impact. The costs attributable to several AEs (FN, infection) were highest in the first cycle of chemotherapy. Conclusions: Several common short-term AEs due to CHOP in the LPD population were associated with substantial healthcare resource utilization and costs that were primarily driven by increased hospitalization and length of inpatient stays. Costs for FN and infections associated with CHOP ranged from $33,000 to over $197,000, demonstrating the high economic burden to the US healthcare system. No PTLD-specific studies were found, highlighting the absence of published data addressing the economic burden associated with chemotherapy in PTLD patients and the need for effective and tolerable therapies. Disclosures Watson: Atara Biotherapeutics: Employment, Equity Ownership. Barlev:Atara Biotherapeutics: Employment, Equity Ownership. Worrall:Atara Biotherapeutics, Inc: Consultancy. Duff:Atara Biotherapeutics, Inc: Consultancy. Beckerman:Atara Biotherapeutics, Inc: Consultancy.

Lower c-D-Index in Acute Myeloid Leukemia with Febrile Neutropenia during Chemotherapy

Lower c-D-Index in Acute Myeloid Leukemia with Febrile Neutropenia during Chemotherapy

Are We Choosing Mobilization Regimens for Autologous Stem Cell Transplantation in Multiple Myeloma Wisely?: A Single Centre Comparison of GCSF+/-Plerixafor Vs Cyclophosphamide/GCSF+/- Plerixafor

Background: Autologous stem cell transplantation (ASCT) as consolidation post induction is standard of care for eligible multiple myeloma patients. Multiple strategies are employed for mobilization of stem cells in ASCT. Cyclophosphamide/GCSF is an effective standard regimen. However there are reported toxicities associated with cyclophosphamide including risk of febrile neutropenia. Since plerixafor was introduced in Canada, this mobilization agent has been increasingly used as needed with GCSF at Kingston Health Science Centre (KHSC), with elimination of cyclophosphamide. There is however high cost associated with plerixafor. To date, there is no standard mobilization regimen across Canada. This retrospective study evaluates mobilization and ASCT outcomes of multiple myeloma patients who had undergone stem cell mobilization with GCSF+/-plerixafor (GP) vs cyclophosphamide/GCSF+/-plerixafor (CyGP) at KHSC. The goal is to analyze the efficacy of each regimen balanced with adverse events to guide optimal mobilization regimen choice. Method: Patient with multiple myeloma who had ASCT at KHSC were selected consecutively based on date of ASCT in a reverse chronological order starting from Jan 2019. From Oct 2015 to March 2018, CyGP was the mobilization regimen used at KHSC. From March 2017 to January 2019, cyclophosphamide was eliminated and GP was used. Both groups could have received plerixafor as needed based on Cancer Care Ontario funding criteria such as failure to achieve target CD34+ cell count. Retrospective chart review was conducted to collect data on demographics, plerixafor use, days of apheresis, total cell collected, rate of febrile neutropenia, length of transplant hospital stay, time to engraftment, and transfusion requirement. Chi-Square, t-test, or Mann Whitney methods were used for test of statistical significance where appropriate. Results: Total 97 patients were included with 47 in the GP group and 50 in the CyGP group (Table 1). Average age was 64 and 63 respectively. 32% of patients in GP group and 36% of CyGP group required plerixafor rescue. No difference in the number of apheresis days were noted in the two groups. Total cell collection was significantly higher in the CyGP group (P<0.001). Day 1 and 2 cell collections were also significantly higher in the CyGP group (P<0.05) (Fig 1). The cell dose target varied in the CyGP group due to changing practices over time which is a confounding factor. There were no cases of febrile neutropenia in the GP group and 3 cases in the CyGP group (P=0.243). All 3 febrile neutropenia patients required hospitalization with 1 requiring ICU. There was no clinically significant difference in transfusion requirement during ASCT (Fig 2). Median time to engraftment of neutrophil and platelet after ASCT were less by 1 day in the CyGP group (P<0.05) (Fig 3), although there was no difference in length of transplant hospital stay. Conclusions: Stem cell mobilization with CyGP resulted in significantly higher total collection cell count, and more efficient collection with higher yield on the first 2 days of apheresis. However, there was no difference in the total number of apheresis days. It also did not lead to less plerixafor usage and was associated with possibly higher rate of febrile neutropenia. There was no clinically significant difference in transplant outcomes in terms of transfusion support required, days to engraftment, or length of hospitalization for ASCT. Mobilization with GCSF+/-plerixafor without cyclophosphamide is a non-inferior regimen. Disclosures Bhella: Celgene: Consultancy, Honoraria.

Clinical Profile and Microbiologic Spectrum of Febrile Neutropenic Episodes in Children With Severe Aplastic Anemia.

Febrile neutropenia (FN) is a common life-threatening complication in patients with severe aplastic anemia (SAA). However, few studies have examined the spectrum of infections in FN in patients with SAA, especially in children. Therefore, the current study was planned to study the clinicomicrobiologic profile of FN episodes in these children. Data of 38 episodes of FN that occurred in 31 children with SAA from November 2015 to April 2017 were collected prospectively and analyzed. FN episodes occurred more frequently (54.8%) in patients on immunosuppressive therapy. Clinically documented infections accounted for 21 (55.26%) episodes, microbiologically documented infections for 15 (39.47%), bacteremia for 13 (34.21%), and invasive fungal diseases for 6 (15.78%) episodes. Among clinically documented infections, the lower respiratory tract was the commonest site in 23.68% episodes, followed by skin and soft tissue infections. No focus of infection could be identified in 12 (31.57%) episodes. Gram-negative bacteria (71.42%) were the predominant isolates (commonest Klebsiella pneumoniae) over Gram-positive bacteria (commonest coagulase-negative Staphylococcus). High prevalence of aminoglycoside, piperacillin-tazobactam, and carbapenem resistance was noted among Gram-negative organisms. Gram-positive organisms showed excellent sensitivity to vancomycin, linezolid, and clindamycin. The overall mortality rate was 42%. Empirical antimicrobial therapy should include adequate coverage for Gram-negative pathogens. The antimicrobial regimen should be modified according to the results of the culture and sensitivity testing.

Trends in Incidence and Outcomes of Clostridium difficile Colitis in Hospitalized Patients of Febrile Neutropenia: A Nationwide Analysis.

Clostridium difficile infection (CDI) has been attracting attention lately as the most common hospital acquired infection. Patients with neutropenia because of malignancy seem to be at an increased risk for developing CDI. There is currently limited data that assesses the national burden and outcomes of CDI in Febrile Neutropenia (FN). We analyzed the National Inpatient Sample (NIS) database for all subjects with discharge diagnosis of FN with or without CDI (ICD-9 codes 288.00, 288.03,780.60, and 008.45) as primary or secondary diagnosis during the period from 2008 to 2014. All analyses were performed with SAS, version 9.4 (SAS Institute). From 2008 to 2014 there were total 19422 discharges of FN patients with CDI. There was a rising incidence of CDI in patients with FN from 4.11% (in 2008) to 5.83% (in 2014). The In-hospital mortality showed a decreasing trend from 7.79% (in 2008) to 5.32% (in 2014), likely because of improvements in diagnostics and treatment. The overall mortality (6.37% vs. 4.61%), length of stay >5 days (76.45% vs. 50.98%), hospital charges >50,000 dollars (64.43% vs. 40.29%), colectomy and colostomy (0.35% vs. 0.15%), and discharge to skilled nursing facility (10.47% vs. 6.43%) was significantly more in FN patients with CDI versus without CDI over 7 years (2008 to 2014). Age above 65 years, Hispanic race, hematological malignancies, urban hospital settings, and sepsis were significant predictors of mortality in febrile neutropenia patients with CDI. Despite the significant decrease in mortality, the incidence of CDI is rising in hospitalized FN patients with underlying hematological malignancies. Risk factor modification, with the best possible empiric antibiotic regimen is imperative for reducing mortality and health care costs in this cohort.

Relative dose intensity of R-CHOP treatment and febrile neutropenia incidence: A nation-wide survey

Abstract Background No comprehensive analysis has evaluated the appropriate relative dose intensity (RDI) of R-CHOP treatment in elderly patients. This study aimed to clarify the relationships between the RDI of R-CHOP treatment and susceptibility of febrile neutropenia (FN) using a national inpatient database in Japan. Methods We identified patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) who received the first R-CHOP treatment between July 2007 and March 2017 from the Japanese Diagnosis Procedure Combination Database. RDI was calculated according to a comparison between the actual cyclophosphamide dose and the 100%-dose cyclophosphamide. Multivariable logistic regression analysis was performed to identify factors associated with the incidence of febrile neutropenia (FN). Results FN occurred in 1,465 of the 18,095 (8.1%) patients, at a median of 10 days (IQR, 8-12) from the initiation of the chemotherapy. Compared with the >100% RDI group, multivariate analyses showed that each low-RDI group (80%≤RDI Conclusions Our study suggests that low-RDI R-CHOP treatment decreases the susceptibility of FN in patients who are over 70 years of age.

Efficacy and safety of early administration of pegfilgrastim for esophageal cancer treated with DCF: A phase 2 study

Abstract Background It has been reported that docetaxel, cisplatin and 5-fluorouracil (DCF) regimen was effective for advanced esophageal cancer. However, the DCF regimen is associated with a high risk of severe neutropenia or febrile neutropenia (FN). In our retrospective study evaluating the efficacy of pegfilgrastim administration on day 7 (D7) in DCF regimen, the neutrophil count nadir was observed from D7. Thus, the timing of its administration could be too late. In this study, we assess the efficacy and safety of early administration (D3) of pegfilgrastim in DCF therapy for advanced esophageal cancer. Methods In this single-arm phase 2 study, patients with advanced esophageal cancer were recruited. They were treated with DCF therapy (DTX: 70mg/m2 on D1, CDDP: 70mg/m2 on D1, and 5-FU: 750mg/m2 on D1-5), and were administrated pegfilgrastim on D3. The primary endpoint was grade4 neutropenia. The secondary endpoints were the rate of FN and the incidence of other adverse events. This study was registered in UMIN system (UMI23393). Results Between July 2016 and Dec. 2018, we enrolled 23 patients (median age 62y ). The incidence of grade4 neutropenia was 8.7% (95%CI:4.7 - 22.1). The rate of FN was 0%. The rate of grade3 neutropenia was 17.4% (95%CI: 1.7 - 33.1), but no other serious adverse events related to pegfilgrastim were observed. Conclusion Primary prophylaxis with pegfilgrastim is recommended for the prevention of FN in patients receiving high-risk chemotherapy regimens such as DCF. According to the guidelines, G-CSF should be administered 24 h after the completion of chemotherapy. The optimal administration schedule remains unclear in regimens including IV continuous 5-FU administration like DCF. These results have shown that early administration (D3) of pegfilgrastim was safe and seemed to be more effective than D7 in DCF therapy. Further clinical studies with a larger sample size should be conducted to confirm our results.

D-index-guided early antifungal therapy for persistent FN in patients with hematological malignancies (CEDMIC trial)

Abstract Introduction Empiric antifungal therapy (EAT) is recommended for persistent febrile neutropenia (FN) based on some large-scale randomized studies. However, EAT sometimes results in overtreatment and unnecessary expense. On the other hand, preemptive therapy triggered by positive fungal tests or radiological findings can increase the incidence of invasive fungal infection (IFI), so an adequate risk-based approach is essential. D-index, recently developed as a parameter reflects both the duration and depth of neutropenia, enables real-time monitoring. We prospectively investigated this novel D-index-guided early antifungal therapy (DET). Methods 423 patients underwent chemotherapy or hematopoietic stem cell transplantation for hematological malignancies were randomized into EAT or DET group, and 413 were eligible for ITT analyses (EAT: 201, DET: 212). The primary endpoint was the incidence of proven/probable IFI. Micafungin at 150 mg/day was administered for FN patients as EAT or DET. Results IFI (proven/probable/possible) was observed in 12 (6.0%) in EAT and 5 (2.4%) in DET, respectively. Proven/probable IFI was identified in 5 (2.5%) of EAT and 1 (0.5%) of DET, which fulfilled the predetermined criteria of non-inferiority of DET group. The survival rate of EAT and DET group was 98.0% vs. 98.6% at day 42 and 96.4% vs. 96.2% at day 84, respectively. The rate of micafungin use was significantly lower in DET group than that in EAT group (29.5% vs. 60.6%, P Conclusions DET was safe and successfully reduced the use of antifungal agents and total cost. DET is a reasonable alternative strategy for persistent FN.

Incidence, risk factors and clinical features of febrile neutropenia in malignant lymphoma patients in our institution

Abstract Background Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) is the standard treatment regimen for malignant lymphoma. CHOP-induced neutropenia is a common clinical complication that often develops into life-threatening febrile neutropenia (FN). The incidence rate of FN in malignant lymphoma patients receiving a CHOP + rituximab regimen is approximately 10%–20% in clinical trials. Assessing FN-related factors in an individual hospital is an important step towards ensuring appropriate treatment. Therefore, we aimed to evaluate the incidence, risk factors, and clinical features related to FN in our institution and to determine the rate of treatment success in FN patients receiving antibiotics. Methods FN-related characteristics were investigated in 182 malignant lymphoma patients who were treated with the CHOP regimen between January 2013 and December 2018. All data were retrospectively collected from the electronic medical record system. Categorical factors were compared using the Fisher’s exact test and Mann-Whitney U test. Logistic regression analysis was used to analyze FN-related risk factors. Results Among 182 patients, 79 (43.4%) were men. Median age was 67 years. Most patients (90.7%) had an Eastern Cooperative Oncology Group performance status (PS) of 0–2. We noted 80 FN episodes in 60 patients (33.0%). On multivariate analysis, lack of granulocyte colony stimulating factor (G-CSF) prophylaxis in cycle 1 and poor PS were significantly associated with FN occurrence. Documented infections were observed in case of 35 FN episodes (43.8%), and median fever duration was 3 days. Treatment was successful without any modifications in case of 64 episodes (80%). No deaths were observed. Conclusion FN incidence was 33.3% at our institution. Lack of G-CSF prophylaxis and poor performance status were risk factors for FN in this setting. Use of G-CSF prophylaxis in patients with poor PS may help in decreasing FN incidence.

Timely administration of antibiotics in febrile neutropenia per updated ASCO/IDSA guidelines.

41 Background: Current ASCO guidelines for management of febrile neutropenia (FN) recommend initial antibiotic administration within one hour of triage, and initial assessment within 15 minutes of triage for patients presenting with FN within 6 weeks of chemotherapy. The University of Illinois Cancer Center (UICC) implemented an early identification and management strategy in the ambulatory setting for FN in 2017, with success in increasing the percentage of FN patients receiving antibiotics within 2 hours from 50% to 92% over a 6 months (05/2017-11/2017) period. Given updated joint ASCO/IDSA guidelines, we aimed to increase percentage of FN patients receiving antibiotics within 1 hour from 56% to more than 90% over 16 months. Methods: A multidisciplinary team involving oncology, hematology (attendings and fellows), pharmacy, and nursing met quarterly to review FN cases including time to antibiotic administration and documentation of prompt assessment. Two Plan-Do-Study-Act (PDSA) cycles were completed, including development and deployment of an electronic medical record automated order set and targeted education for fellows and nurses. Results: Between 12/17 and 04/19, of 7 patients with FN, 100% (N = 7) received antibiotics in clinic. The percentage of FN patients receiving antibiotics within 1 hour of triage post first and second interventions was as follows: 25% (N = 1), 100% (N = 4). 100% (N = 7) of FN patients had documentation of prompt assessment, but time from triage was not specified. Conclusions: We were successful in improving the percentage of FN patients receiving antibiotics from 56% to more than 90% over 16 months. We are targeting our next PDSA cycle to increase assessments within 15 minutes of triage. Additional future interventions include tailoring antibiotics based on FN with low or high risk of complication via focus group and root case analyses discussion with our attendings, fellows, and nurses, and collaborating with ED on a standard care pathway for FN management.

Comparison of Presepsin, Procalcitonin, Interleukin-8 and C-Reactive Protein in Predicting Bacteraemia in Febrile Neutropenic Adult Patients with Haematological Malignancies.

Bacterial infections represent life-threatening complications in patients with febrile neutropenia (FN). Diagnostic biomarkers of infections may help to differentiate bacteraemia from non-bacteraemia FN. We aimed to evaluate the utility of procalcitonin (PCT), presepsin (PS), C-reactive protein (CRP) and interleukin-8 (IL-8) as biomarkers of bacteraemia in adult FN patients with haematological malignancies.Concentrations of PCT, PS, CRP and IL-8 were prospectively measured in 36 FN episodes experienced by 28 oncohaematological patients.11 out of 36 episodes were classified as bacteraemia. PCT was the best biomarker to predict bacteraemia with the area under the curve (AUC) ROC of 0,9; specificity 100% and positive predictive value 100%, while the most sensitive was IL-8 (90,9%) with AUC ROC of 0,88 and negative predictive value 95,2%. All patients with PCT concentrations above 1,6 μg/l had bacteraemia. Patients with IL-8 concentrations superior to 170 pg/ml had a 40 times higher risk for bacteraemia than the ones with lower levels. Patients with PS concentrations superior to 410 pg/ml had 24 times higher risk for bacteraemia than the patients with lower levels.PCT has higher accuracy than CRP, IL-8 and PS in predicting bacteraemia in adult hematologic patients with FN.

Retrospective Analysis of Clinical Outcomes Associated With the Use of Pegfilgrastim On-body Injector in Patients Receiving Chemotherapy Requiring Granulocyte Colony-Stimulating Factor Support.

Objectives: Pegfilgrastim is a granulocyte colony-stimulating factor (G-CSF) used as primary prophylaxis in patients receiving myelosuppressive chemotherapy regimens that have greater than 20% risk of developing febrile neutropenia (FN). Historically, pegfilgrastim has been administered 24 to 72 hours after chemotherapy, necessitating a return to clinic to receive the provider-administered injection. An alternative option is the pegfilgrastim on-body injector (OBI). With the OBI device, patients have their pegfilgrastim administered 27 hours after receiving chemotherapy while remaining at home, avoiding an additional clinic appointment. Concerns with pegfilgrastim OBI include lack of experience with the device in both the patient and provider, device-related failures, and the success of delivery. This study evaluates pegfilgrastim OBI failure rates through associated patient outcomes among cancer patients receiving chemotherapy requiring G-CSF. Methods: A retrospective electronic chart review was conducted of adult patients with cancer who received chemotherapy and pegfilgrastim OBI from July 1, 2016, to July 31, 2018. The primary objective of this study was the incidence of FN in patients receiving pegfilgrastim OBI. Results: There were no reported cases of hospitalization due to FN in patients who received pegfilgrastim OBI. Dose delays and dosage modifications were not observed in our review. The OBI device failure rate was found to be low (1.92%). Conclusion: The low device failure rate from this study suggests that the OBI is a viable option for administration of pegfilgrastim in patients receiving chemotherapy requiring G-CSF.

Platelet-lymphocyte Ratio After Granulocyte Colony Stimulating Factor Administration: an Early Prognostic Marker in Septic Shock Patients With Chemotherapy-Induced Febrile Neutropenia.

Chemotherapy-induced febrile neutropenia (FN) causes life-threatening complications, but little is known in septic shock patients with FN. The aim of this study was to investigate the prognostic value of inflammatory markers, including C-reactive protein level, immature granulocyte count, white blood cell (WBC) count, absolute neutrophil count (ANC), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR), in septic shock patients with FN at admission and after granulocyte colony-stimulating factor (G-CSF) administration. Data on consecutive adult septic shock patients with FN treated with G-CSF between June 2012 and June 2017 were extracted from a prospectively compiled septic shock registry. Clinical and serial laboratory data at admission and <24 h after G-CSF administration were compared between nonsurvivor and 1-month survivor groups. Of 1,671 septic shock patients, 158 FN patients were treated with G-CSF and 114 (72.2%) survived for 1 month. At admission, no clinical and serial laboratory data were significant to predict survival. After G-CSF administration, PLR and APACHE II were independent predictors for 1-month survival. PLR after administration of G-CSF >100 (adjusted odds ratio [aOR], 9.394; 95% CI, 2.821-31.285, P < 0.001) showed sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 89.4%, 46.2%, 82.9%, and 60.0%, respectively, and APACHE II <28 (aOR, 6.944; 95% CI, 2.351-20.511, P < 0.001) showed sensitivity, specificity, PPV, and NPV of 86.8%, 63.6%, 86.1%, and 65.1%, respectively. After G-CSF administration in septic shock patients with chemotherapy-induced FN, PLR may be used as an early prognostic marker for mortality.

Clinical Characteristics and Associated Factors of Mortality in Febrile Neutropenia Patients; a Cross Sectional Study.

The duration and severity of neutropenia directly correlate with the incidence of life-threatening infections. This study aimed to evaluate the clinical characteristics and associated factors of mortality in febrile neutropenia patients. This retrospective cross sectional study was conducted on all febrile neutropenia patients who were admitted to oncology department of two educational hospitals, Tehran, Iran, from 2011 to 2016. Available patients' data regarding baseline characteristics, treatment, and outcome were collected and analyzed using SPSS 21. 357 patients with the mean age of 50.9±17.7 years were studied (59.7% female). Mean white blood cell count of the studied patients was 715.1 ± 270.4 (100 - 1400) cells/mm3. The absolute neutrophil count (ANC) of all patients was <500 cells/mm3. The most frequent sources of malignancy in studied patients were gastrointestinal (35.9%), breast (22.4%), and sarcoma (15.7%), respectively. The mean time interval between initiation of treatment in ED and increase of ANC to > 500 cells/mm3 was 2.45 ± 2.1 (1 - 16) days. 186 (52.1%) subjects reached ANC>500 cells/ mm3 after 2-5 days of hospitalization. The rate of hospital mortality was 5.3% (338 (94.7%) survived). The correlation between gender (p = 0.11), temperature (p = 0.123), number of ED visits (p = 0.765), presenting clinical manifestation (p = 0.201), source of malignancy (p= 0.328), presence of metastasis (p = 0.69), positive urine culture (p = 0.45), positive blood culture (p = 0.62), time from last chemotherapy (p = 0.677), and time to reach ANC>500 cells/mm3 (p = 0.739) with mortality was not significant. Based on the findings of the present study, the rate of hospital mortality in patients with febrile neutropenia was 5.3%. Older age and lower white blood cell count were among the significant associated factors of mortality in this series.

Risk factors for febrile neutropenia and effectiveness of primary prophylaxis with pegfilgrastim in patients with esophageal cancer treated with docetaxel, cisplatin, and 5-fluorouracil

BackgroundThe docetaxel, 5-fluorouracil, and cisplatin (DCF) regimen is an effective form of chemotherapy for advanced esophageal cancer. However, the incidence of adverse events such as febrile neutropenia and hematological toxicity is high.MethodsAmong 937 patients with esophageal cancer at Toranomon Hospital between January 2011 and December 2018, 92 who underwent the DCF regimen as initial treatment were selected. We investigated the risk factors for febrile neutropenia in patients with esophageal cancer treated with DCF regimen and the effectiveness of pegfilgrastim as primary prophylaxis.ResultsAdverse events (CTCAE grade ≥ 3) were observed in 45 of the 92(48.9%) patients with esophageal cancer treated with an initial DCF regimen. Febrile neutropenia was observed in 20 (21.7%) patients. Non-use of pegfilgrastim (odds ratio = 16.393; 95% confidence interval 2.049–125.0) as primary prophylaxis was identified as an independent factor predictive of febrile neutropenia. The pegfilgrastim group had a significantly lower incidence of neutropenia than the control group (9.1% vs 61.0%; p < 0.001). The incidence of febrile neutropenia was 3.0% in the pegfilgrastim group and 32.2% in the control group (p = 0.001). In addition, the incidence of any adverse effect ≥ CTCAE grade3 was also significantly lower in the pegfilgrastim group (12.1% vs 69.5%; p < 0.001). The reduced/interruption rate of next DCF therapy was 6.1% in the pegfilgrastim group and 30.5% in the control group (p = 0.006).ConclusionThis study revealed that the non-use of pegfilgrastim was an independent factor predictive of febrile neutropenia in multivariate analysis. Pegfilgrastim as primary prophylaxis prevents severe neutropenia and febrile neutropenia in patients with esophageal cancer treated with the DCF regimen.

Evaluation of Pulmonary Infiltrate in Febrile Neutropenic Patients of Hematologic Malignancies

Abstract Background: Pulmonary infection is the major risk during neutropenia induced by chemotherapy as well as stem cell transplantation. In spite of potent new-generation antifungal and broad-spectrum antibiotics, one-third of patients usually die from infectious complications. Early diagnosis and prompt administration of appropriate therapy improve the survival. Materials and Methods: We prospectively carried out the study to identify the infectious etiology of pulmonary infiltrates in febrile neutropenia patients by imaging and bronchoscopy. Bacterial culture, fungal culture, galactomannan and molecular diagnosis for pneumocystis, and other infectious agent were carried out in the bronchoalveolar lavage (BAL) fluid and blood. Results: A total of 27 patients were evaluated. Half of the patients belonged to acute leukemia (46%). We had a diagnostic yield of 65% with the most common isolates being Gram-negative bacteria and Aspergillus species. Conclusion: Gram-negative organisms were the predominant infectious agents of pulmonary infection. Our finding emphasizes the importance of BAL in evaluating pulmonary infiltrates in neutropenic patients with hematological malignancies.

PB1828 PRIMARY PROPHYLAXIS OF CHEMOTHERAPY‐INDUCED FEBRILE NEUTROPENIA IN ADULT PATIENTS WITH LYMPHOPROLIFERATIVE DISORDERS ‐ CLINICAL EXPERIENCE IN UNIVERSITY HOSPITAL SPLIT

Background:Febrile neutropenia (FN) is the development of fever in a patient with an abnormally low number of neutrophil granulocytes. It can be associated with other signs of infection and is often consequence of chemotherapy treatment. Granulocyte colony‐stimulating factors (G‐CSF) are used for prophylaxis of FN. We analyzed data of adult patients with lymphoproliferative disorders who were treated with chemotherapy regimens of high or intermediate risk for developing FN, according to guidelines of European organization for research and treatment of cancer (EORTC).Aims:To investigate the benefit of primary prophylaxis of chemotherapy‐induced FN in patients with lymphoproliferative disoders. To evaluate the incidence of FN following chemotherapy regimens of high or intermediate risk for developing FN.Methods:We analyzed medical history of all 97 adult patients (M = 55; F = 42, aged 21 – 81 (mean, 54) years) with lymphoproliferative disorders who were treated with chemotherapy regimens of high or intermediate risk for developing FN in the period from 1st November 2017 till 1st November 2018. Incidence of FN was analyzed according to type of chemotherapy regimen and administration of primary prophylaxis.Results:Primary prophylaxis with G‐CSF was administered to all (N = 12) patients who were treated with high risk chemotherapy regimens, in compare to only 24 (28%) patients who received intermediate risk regimens. FN was registered in total of 24 (25%) patients, of whom 20 were treated with intermediate risk regimens. Among patients who received primary prophylaxis after intermediate risk regimens, only 4 (17%) of them developed FN, in compare to 16 (26%) of patients who previously did not receive primary prophylaxis after same regimens. Incidence of FN was higher in females (N = 14) and after the first cycle of chemotherapy regimen (N = 15).Summary/Conclusion:Primary prophylaxis with G‐CSF reduces the risk of developing FN, so it is recommended to administer primary prophylaxis to all patients who are treated with high risk chemotherapy regimens. Primary prophylaxis in patients receiving intermediate risk regimens should be carefully considered because of the high incidence of FN in those who did not receive prophylaxis. In those circumstances, other risk factors (such as comorbidities, age of patient, history of previous infections and FN, stage of the disease and others) should be evaluated before the decision whether to administer primary prophylaxis or not. In our patients, low incidence of FN was observed in the group who received primary prophylaxis after intermediate risk regimens.

PF316 THE CLINICAL CHARACTERISTICS AND OUTCOMES OF PATIENTS WITH AGGRESSIVE LARGE CELL LYMPHOMA AND DIABETES MELLITUS

Background:Epidemiological studies suggest that patients with diabetes mellitus (DM) are at‐risk to develop several types of cancers, including non‐Hodgkin lymphoma. Whether DM affects the clinical presentation or outcome of patients with lymphoma is unknown. Since patients with DM are prone to develop infectious complications, we hypothesize that the co‐occurrence of DM would increase the rate and/or severity of infectious complications in patients with lymphoma who receive chemotherapy.Aims:To describe the clinical characteristics and outcomes of patients with DM who received treatment for aggressive large cell lymphoma.Methods:This is a single center retrospective single center study. We included all consecutive patients who were diagnosed with aggressive large cell lymphoma and were treated at our institute between 2013 and 2017. Demographics, disease‐related and outcome data were extracted from the electronic medical records. Additional data and lab results were extracted from the hospital database. Categorical variables were compared using the χ2 or the Fischer exact test, and Mann Whitney was used to compare medians.Results:Between the years 2013 and 2017 we treated 226 patients with aggressive large cell lymphoma, most (n = 219, 96%) with diffuse large B cell lymphoma. In this cohort 49 patients (22%) had type 2 DM. None of our patients had type 1 DM. The median age of patients with DM was 70 years, and of non‐DM patients 65 years (P = 0.001). Patients with DM tended to have higher baseline BMI values (P = 0.057), but were comparable in all other demographic characteristics. Likewise, response to therapy, relapse rates and survival outcomes were similar in patients with DM compared to non‐DM patients.There were 133 hospital admissions due to febrile neutropenia (FN) in the entire cohort. Patients with DM had higher rates of admissions due to FN (P = 0.004). The admission rate in patients with DM remained higher after age‐matched subgroup analysis (P = 0.005). Yet, the duration of hospitalizations and number of admissions to the ICU were similar in patients with or without DM. In patients with DM, improved glycemic control during FN hospitalizations was associated with shorter hospital duration (P = 0.007). However, Hemoglobin A1C levels were not associated with increased risk for FN or infectious complications.Summary/Conclusion:Patients with aggressive large cell lymphoma and DM have higher rates of hospitalizations due to FN. In this high risk population, perhaps more aggressive measures should be made to avoid infectious complications. Furthermore, our data suggests that improved glycemic control during hospitalization is associated with shorter length of hospitalization due to FN in patients with DM.