High-risk Febrile Neutropenia Research Articles

Patterns of vancomycin use in high-risk febrile neutropenia.

e23224 Background: Febrile neutropenia (FN) is a common complication in patients with hematologic malignancy. ASCO guidelines on the management of FN endorse empiric anti-Pseudomonas coverage while reserving the use of agents targeting gram-positive organisms and methicillin-resistant Staphylococcus aureus (MRSA) for select criteria-defined patients such as those with severe mucositis, hemodynamic instability, radiographic pneumonia, or history of MRSA colonization among others. We sought to examine our institutional management of FN, hypothesizing that local use of empiric vancomycin for high-risk FN will deviate from ASCO guidelines reflected in institutional policy. Methods: Case data from 1/1/2016 – 6/1/2023 was collected retrospectively, comprising patients admitted to the general medical floor with known leukemia, lymphoma, or multiple myeloma meeting ASCO criteria for FN. Patients admitted to intensive care at time of FN or for less than 48-hours were excluded. For each patient, use of vancomycin at time of FN diagnosis (t0) and 48-hours later (t48) was evaluated for congruence with society guidelines. Results: 91 patients were reviewed with a median age of 68 years old (IQR 59-74, 15). Median length of stay (LOS) was 20 days (IQR 7-29, 22) with FN occurring on day seven of hospitalization on average. Most patients receiving vancomycin were admitted to the hematology specialty unit at time of diagnosis (63%). Acute leukemia was the most common malignancy represented (62.8%), while high grade lymphoma comprised 23.1%. 98.9% of patients were on active chemotherapy at time of FN. 81 patients (89%) received vancomycin as empiric treatment for FN with 76 (93.8%) receiving vancomycin at t0. Of this latter cohort, 29.7% of patients received vancomycin at t0 without indication. At t48, vancomycin was discontinued in 28.4% of patients, 44.4% received vancomycin with true indication, and 27.2% were continued on vancomycin without indication. The median duration of therapy for patients receiving vancomycin incongruently at t48 was 4 days. Of those meeting criteria for vancomycin use at t48, severe mucositis and soft tissue infection were each cited in 22.2% of cases, followed by pneumonia, persistent fever, and hemodynamic instability. Notably, the presence of any grade mucositis was significantly associated with the continued use of empiric vancomycin at t48 (p = .025). Admission to hematology specialty unit did not significantly affect adherence to FN management guidelines. Conclusions: These data suggest that the use of vancomycin for FN at our institution deviates from society guidelines including on specialized hematology wards. This study was underpowered to assess adverse outcomes seen with vancomycin use such as renal injury, prolonged LOS and greater cost of care. Given the high complexity of this patient population, detailed provider education is indicated to promote safe, evidence-based care and broader antimicrobial stewardship.

Application value of metagenomic next-generation sequencing in hematological patients with high-risk febrile neutropenia.

Metagenomic next-generation sequencing (mNGS) is a novel non-invasive and comprehensive technique for etiological diagnosis of infectious diseases. However, its practical significance has been seldom reported in the context of hematological patients with high-risk febrile neutropenia, a unique patient group characterized by neutropenia and compromised immune responses. This retrospective study evaluated the results of plasma cfDNA sequencing in 164 hematological patients with high-risk febrile neutropenia. We assessed the diagnostic efficacy and clinical impact of mNGS, comparing it with conventional microbiological tests. mNGS identified 68 different pathogens in 111 patients, whereas conventional methods detected only 17 pathogen types in 36 patients. mNGS exhibited a significantly higher positive detection rate than conventional methods (67.7% vs. 22.0%, P < 0.001). This improvement was consistent across bacterial (30.5% vs. 9.1%), fungal (19.5% vs. 4.3%), and viral (37.2% vs. 9.1%) infections (P < 0.001 for all comparisons). The anti-infective treatment strategies were adjusted for 51.2% (84/164) of the patients based on the mNGS results. mNGS of plasma cfDNA offers substantial promise for the early detection of pathogens and the timely optimization of anti-infective therapies in hematological patients with high-risk febrile neutropenia.

Microorganisms isolated from blood cultures and resistance profile in children with cancer and high-risk febrile neutropenia. Red PINDA, Chile, 2016-2021

To identify the frequency of microorganisms isolated from blood cultures (BC) and their antimicrobial resistance (R) profile in children with HRFN, compared with the same data from previous studies of the same group. Prospective, multicenter, epidemiological surveillance study of microorganisms isolated from BC in patients under 18 years of age, from 7 PINDA network hospitals, between 2016 and 2021. 284 episodes of HRFN with positive BC were analyzed out of 1091 enrolled episodes (26%). Median age 7.2 years [3.0-12.3]. The main isolates were gram-negative bacilli (GNB) 49.2%, gram-positive cocci (GPC) 43.8%, and fungi 3.6%. The most frequently isolated microorganisms were viridans group Streptococci (VGS) (25.8%), Escherichia coli (19.8%), Pseudomonas spp. (11.2%), Klebsiella spp. (10.9%), and coagulase negative Staphylococci (CoNS) (10.9%). There was an increase in R to third-generation cephalosporins (p = 0.011) in GNB and to oxacillin in CoNS (p = 0.00), as well as a decrease in R to amikacin in non-fermenting GNB (p = 0.02) and to penicillin in VGS (p = 0.04). VGS is the main agent isolated in BC from pediatric patients with cancer and episodes of HRFN, followed by E. coli, Pseudomonas spp., and Klebsiella spp. Having epidemiological surveillance of microorganisms isolated from BC and their antimicrobial R profile is essential to favor the rational use of antimicrobials.

The Use of Granulocyte Colony-Stimulating Factor as Primary Prophylaxis in Patients Undergoing Chemotherapy: An Experience of Moroccan Oncologists.

Febrile neutropenia (FN) is a frequent and serious emergency for oncologic patients undergoing chemotherapy. Using granulocyte colony-stimulating factor (G-CSF) as primary prophylaxis of febrile neutropenia is an integral part of the management of cancer patients. Our study aims to identify the challenges that prevent Moroccan oncologists from prescribing G-CSF for primary prevention. Seventy doctors participated in our study, with a participation rate of 35.35%. Twenty-two participants had at least five years of experience in oncology. Most participants were medical oncologists (82.9%), and two-thirds of them practiced in teaching hospitals. Regarding the use of G-CSF in primary prevention, all participants complied with the recommendations for FN risk assessment and the prescription of G-CSF for prophylaxis in patients at high risk of FN (>20%). However, their use in intermediate-risk patients remains limited mainly by the cost of these drugs (45.7% of participants). FN remains a dreadful complication in oncology. Since the introduction of G-CSF into standard oncology practice, particularly in primary prevention, the management of certain patients has improved considerably. Nevertheless, the indications for G-CSF in our context, essentially in intermediate-risk patients, are uncertain.

Phase II study of the safety and efficacy of discontinuing pegfilgrastim for pancreatic adenocarcinoma treated with FOLFIRINOX.

663 Background: The original FOLFIRINOX regimen (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) for pancreatic ductal adenocarcinoma (PDAC) is associated with a high risk of febrile neutropenia (FN), and pegfilgrastim has been used to reduce the risk. However, it remains unclear how long pegfilgrastim needs to continue. This study evaluated the safety and efficacy of FOLFIRINOX after discontinuing pegfilgrastim in PDAC patients. Methods: This prospective phase II trial included patients with PDAC who received the first three courses of FOLFIRINOX, with primary pegfilgrastim prophylaxis for FN, and did not experience FN. The patients continued on FOLFIRINOX without pegfilgrastim from the fourth course. The primary endpoint was development of FN. The secondary endpoints included relative dose intensity (RDI), objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). The threshold and expected development of FN were 20% and 7%, respectively, at a one-sided significance level of 0.10 and statistical power of 80%. Based on this hypothesis, we calculated the number of patients needed to be 33. Results: In total, 34 patients (20 male, median age 66 years) were enrolled from August 2017 to September 2021. Twenty-three patients were unresectable, and 11 were borderline resectable. FN developed in one patient. Grade 4 neutropenia was observed in six patients, grade 3 neutropenia in 10 (29.4%), anemia in four (11.8%), diarrhea in two (5.9%), and malaise, lung infection, peripheral sensory neuropathy, colitis, and biliary tract infection in one (2.9%) each. Twenty-two patients required dose reduction, mainly because of neutropenia. Mean RDIs at the sixth course of oxaliplatin, irinotecan, leucovorin, acute infusion of fluorouracil, and continuous infusion of fluorouracil were 77.0%, 88.2%, 81.8%, 84.4%, and 87.6%, respectively. ORR, median PFS, and median OS were 44.1%, 15.8 months, and 25.8 months, respectively. Conclusions: FOLFIRINOX can be continued safely with a low incidence of FN after discontinuing pegfilgrastim in PDAC patients who did not experience FN during the first three courses of FOLFIRINOX, if the drug dose is reduced appropriately for neutropenia from the fourth course. Clinical trial information: UMIN000028055 .

Docetaxel, cisplatin, and fluorouracil with pegfilgrastim on day 3 as neoadjuvant chemotherapy for esophageal cancer.

A high risk of febrile neutropenia (FN) from neoadjuvant chemotherapy with docetaxel, cisplatin, and fluorouracil (DCF) for esophageal cancer has been reported. The optimal timing of prophylactic use of pegfilgrastim remains to be elucidated. To evaluate the effect of pegfilgrastim administered on day 3, we conducted a feasibility study. Chemotherapy consisted of intravenous administration of docetaxel (70 mg/m2 per day) and cisplatin (70 mg/m2 per day) on day 1 and continuous infusion of 5-fluorouracil (750 mg/m2 per day) on days 1-5. Pegfilgrastim was given as a single subcutaneous injection at a dose of 3.6 mg on day 3 during each treatment course. This regimen was repeated every 3 weeks for up to a maximum of three courses. Prophylactic antibiotics were not needed but were allowed to be given at the discretion of the physician. The primary endpoint was the incidence of FN. Twenty-six patients were administered DCF in combination with pegfilgrastim on day 3. After the first course of DCF, 10 out of 26 patients (38.5%) experienced grade 4 neutropenia, and two patients (7.7%) experienced FN. Of the 14 patients who did not receive prophylactic antibiotics, four had grade 4 neutropenia, including two who developed FN. On the contrary, of the 12 patients who received prophylactic levofloxacin, six had grade 4 neutropenia, but no cases of FN were observed. Administration of pegfilgrastim on day 3 was not sufficient to prevent FN due to DCF treatment, and prophylactic administration of both pegfilgrastim and antibiotics could be a solution.

The frequency of regimens associated with high risk of febrile neutropenia and the incidence of dose-limiting neutropenia among patients receiving cytotoxic therapy for malignancies: the FLAME study results

Aim. To assess the proportion and profile of patients at high risk of febrile neutropenia (FN) receiving cytotoxic chemotherapy (CT), as well as the incidence of FN and dose-limiting neutropenia after one cycle of CT.&#x0D; Materials and methods. The paper presents the results of the FLAME study, the first Russian observational study in patients with solid tumors who received only cytotoxic CT or a combination with targeted, immuno-oncological drugs. By random sampling, the study retrospectively included 500 patients with a median age of 59 years (18–83 years) from 25 medical institutions in the Russian Federation.&#x0D; Results. CT regimens with a high (20%) risk of FN were received by 25.2% (126/500) of patients; 53% (265/500) of patients had intermediate risk, and half of them (132/265 [49.8%]) had at least one additional risk FN factor following international NCCN guidelines. Thus, a high risk of FN, according to the therapy and the assessment of individual prognostic adverse factors, was noted in 51.6% (258/500) of patients. 36.8% (95/258) of patients with high risk for FN received primary prophylaxis with granulocyte colony-stimulating factors.&#x0D; Conclusion. The study showed a significant proportion of patients with a high risk of FN, and most of them do not receive primary prophylaxis of FN.

Lower uric acid and adequate hydration are associated with lower risk of febrile neutropenia following autologous bone marrow transplantation in patients with lymphoma

Background. Despite the promising results of autologous bone marrow transplantation (BMT) in patients with lymphoma, infectious complications limit its positive outcomes. This study evaluated the incidence and associated factors of febrile neutropenia (FN) following BMT in patients with lymphoma. Materials and methods. The study consecutively included 147 patients with lymphoma who were candidates for BMT. Clinical and laboratory results were recorded, and after BMT, the occurrence of FN was investigated through the daily evaluation of neutrophil count and body temperature. Results. On average, FN occurred in 91 patients (61.9%) after 12.77 ± 2.45 days after BMT. Lower fluid balance was associated with a higher risk of FN (lowest adjusted odds ratio [OR] at day -2 = 0.602, 95% confidence interval [CI] = 0.299 – 0.870, p-value = 0.007). The higher uric acid level was associated with a higher risk of FN (highest adjusted OR at day -10 = 1.617, 95% CI = 1.328 – 1.963, p-value = 0.035). LDH was also positively correlated with FN (highest adjusted OR at day 0 = 1.501, 95% CI = 1.198 – 2.104, p-value = 0.004). Conclusions. Adequate hydration of the patients is of paramount importance for preventing FN in patients who receive BMT. Furthermore, uric acid and LDH could be considered in future studies for the risk stratification of FN.

Usefulness of Peripheral Blood Cultures in Children With Cancer and Episodes of Fever and Neutropenia.

The collection of blood cultures (BC) is key for guiding antimicrobial therapy in children with febrile neutropenia (FN), more than 90% have central venous catheters (CVC). There is no consensus on the need for peripheral BC over central BC in this population. The aim of this study was to determine the contribution of peripheral BC over central BC in the diagnosis of bloodstream infections in children with FN. Descriptive, retrospective study, episodes of FN recorded prospectively in 6 hospitals in Santiago, Chile, from 2016 to 2021. Central and peripheral BC were drawn upon admission. All episodes with at least one (+) BC were allocated to one of these groups: consistent (+) BC, inconsistent (+) BC, only CVC (+) BC and only peripheral (+) BC. The volume of the samples was recorded. The analysis included 241 episodes of FN with at least one (+) BC. The median age was 7.2 years, 51% were female, 84% had hematological cancer and 98% had episodes of high-risk FN. Of a total of 241 episodes, 135 (56%) had consistent (+) BC, 13 (5%) had inconsistent (+) BC, 35 (15%) had only CVC (+) BC and 58 (24%) had only peripheral (+) BC. There were no significant differences in the volume of the samples between central and peripheral BC. The proportion of bloodstream infections detected only through peripheral BC was 24%, higher than previously reported, not due to sample volume. We recommend obtaining peripheral as well CVC BC in children with FN.

Selected Frailty Testing Can Predict for Risk of Febrile Neutropenia in Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplant

Introduction: Validated myeloma-specific frailty assessment tools, such as the IMWG geriatric assessment tool (IMW GAT) and the revised myeloma co-morbidity index (R-MCI), can be useful to tailor treatment intensity in MM patients (pts). To date, most MM studies of frailty have focused on older, transplant-ineligible populations, with less known about the utility of frailty assessments to guide therapeutic decision-making in younger, transplant pts. We previously reported that frailty scores largely validated in older MM cohorts correlate well with each other, but generally lack ability to discriminate between unfit and fit patients, when applied to a younger transplant population (Devasia et al ASH 2022). Here, we evaluate the use of pre-transplant frailty assessment, using a battery of subjective and objective tools, for predicting common post-transplant toxicities, such as febrile neutropenia (FN) and organ complications. Methods: 162 consecutive MM pts preparing for ASCT and consented for an ongoing prospective frailty study were included. Prior to ASCT, patients underwent comprehensive frailty assessments including: 1) objective measures of fitness [hand grip strength, 6-min walk test (6MWT), Timed Up and Go (TUG), 2) subjective measures of function (Fried Frailty Phenotype (FFP), Rockwood Frailty, KPS, ECOG, HSCT-CI, ESAS), 3) scoring systems integrating both objective and subjective measures (R-MCI, IMWG geriatric assessment tool (IMWG-GAT), and 4) routine screening for organ function (CrCl, serum albumin, hemoglobin, BNP, PFT, and cardiac imaging). Following ASCT, acute grade 3-4 organ-specific toxicities (including FN) occurring from stem cell infusion through engraftment to discharge were prospectively collected (NCI-CTCAE criteria V5.0). Patient/disease characteristics, stem cell dose, engraftment, and transfusion requirements were also collected from electronic patient records. Chi-square and/or Fisher's exact test, as appropriate, were used to assess the association of categorical covariates with frailty scores/measures. Logistic regression was used to assess the association of potential predictors to binary outcomes. All p-values were 2-sided and p&amp;lt;0.05 was considered statistically significant. Results: In total, 162 pts were included in this analysis, median age 62 yrs (range 35-73). Most pts received melphalan 200 mg/m2 conditioning, with 10 pts (6%) dose-reduced to 140mg/m2. All patients received antibiotic prophylaxis. Median stem cell dose was 2.82 x 10 6 CD34+ cells/kg Median neutrophil and platelet engraftment times were 13(10-17) and 14(8-45) days, respectively. 104(64%) pts developed FN post-transplant. Other grade 3-4 toxicities included: GI (41 pts; 25.3%), cardiac (12 pts; 7.4%), lung (4 pts; 2.4%). When correlating with pre-transplant frailty assessments, ECOG performance status and R-MCI appeared to predict for risk of FN, but not for specific organ toxicity (GI, cardiac) nor presence of &amp;gt;1 grade 3-4 toxicity (Table 1). In pts with ECOG 1-2 at baseline, the incidence of FN was 70.9% (83/117) compared to ECOG 0 pts 46.7% (21/45)(p=0.0039). There were no patients with ECOG 3-4 on study. Similarly, 58% (59/101) with baseline low risk frailty as per R-MCI developed FN, compared to 73.8% (45/61) in either R-MCI intermediate or high risk groups (p=0.050). We then evaluated the combined effect of ECOG and R-MCI on prediction of FN. Patients with ECOG 0 plus R-MCI low risk were grouped as “Low risk FN”, patients with ECOG 1-2 plus R-MCI intermediate/high risk were grouped as “High risk FN”. All other patients were grouped as “Intermediate risk FN” (Table 2). By using 2 scores, we could better predict for FN, with 72.5% in “High risk FN” compared with only 37% in “Low risk FN” (p=0.0008)]. Conclusions: This preliminary analysis of an ongoing frailty study in MM patients undergoing ASCT suggests potential utility of combining ECOG and R-MCI in predicting for development of FN. In pts with both ECOG 0 and R-MCI low risk (21% of total cohort), FN occurred in only 37%. Although further validation in a larger cohort is required, this finding may help to select at-risk patients for prophylactic peri-transplant antibiotics whilst avoiding routine use in all patients. This has clinical significance, given the emerging recognition of potentially detrimental effect on the gut microbiota and risk of antibiotic resistance in this setting.

Impact of treatment experience on patient knowledge of colony-stimulating factors among patients receiving cancer chemotherapy: evidence from S1415CD-a large pragmatic trial.

Primary prophylactic granulocyte colony-stimulating factors (PP-CSFs) are prescribed alongside chemotherapy regimens that carry a significant risk of febrile neutropenia (FN). As part of S1415CD, a prospective, pragmatic trial evaluating the impact of automated orders to improve PP-CSF prescribing, we evaluated patients' baseline knowledge of PP-CSF and whether that knowledge improved following the first cycle of chemotherapy. Adult patients with breast, colorectal, or non-small-cell lung cancer initiating chemotherapy were enrolled in S1415CD between January 2016 and April 2020. Eight questions assessing knowledge of CSF indications, risks, benefits, and out-of-pocket costs were included in a baseline survey and in a follow-up survey at the end of the first cycle of chemotherapy. Responses were stratified by the trial arm and whether chemotherapy was low, intermediate, or high FN risk. Of the 3605 eligible patients, 3580 (99.3%) completed the baseline survey, and 3420 (95.5%) completed the follow-up survey. At baseline, 803 (22.4%) patients responded "Don't know" to all 8 questions, and all patients averaged 2.75 correct questions. At follow-up, knowledge increased by 0.34 in the high-FN-risk group (p < 0.001) but declined for the other FN-risk groups. In multivariate analysis, receiving a high-FN-risk regimen and younger age were significantly associated with knowledge improvement. Chemotherapy patients had poor knowledge of PP-CSF that improved only modestly among recipients of high-FN-risk chemotherapy. Further efforts to inform patients about the risks, benefits, and costs of PP-CSF may be warranted, particularly for those in whom prophylaxis is indicated. NCT02728596, April 6, 2016.

Primary Prevention of Neutropenia by Empegfilgrastim in Patients with Advanced Stages of Classical Hodgkin Lymphoma Treated with Intensive First-Line Chemotherapy with a Modified 6-Cycle Program EACODD-14 Under the Protocol “LKh-Rossiya-1”

Aim. To assess the efficacy of a long-acting form of the granulocyte colony-stimulating factor (G-CSF) empegfilgrastim in primary prevention of neutropenia in patients with advanced stages of classical Hodgkin lymphoma (cHL) who received intensive chemotherapy with reduced inter-cycle interval under the protocol “LKh-Rossiya-1”.&#x0D; Materials &amp; Methods. The study enrolled 35 patients with newly diagnosed cHL. All patients had advanced stages (IIB X/Е and III/IV) of the disease. They were treated at the NI Pirogov National Medical and Surgical Center from March 2013 to August 2022. The primary prevention of neutropenia by long-acting G-CSF (empegfilgrastim) was administered to 21 patients under the protocol “LKh-Rossiya-1”. They received 6 chemotherapy cycles of modified EACODD-14, in total 126 cycles. The control group consisted of 14 patients who received 6 ЕАСОРР-14 chemotherapy cycles (in total 84 cycles) with dacarbazine as substitution for procarbazine. In the control group, the primary prevention of neutropenia was carried out using discrete G-CSF (filgrastim). The median (range) follow-up in the main (n = 21) and control (n = 14) groups was 18 (5–36) and 39 (29–116) months, respectively. The treatment efficacy was assessed based on PET-CT in 31 patients and on CT in 4 patients.&#x0D; Results. By the end of chemotherapy, complete metabolic response was achieved in 28 (80 %) out of 35 patients (95 % in the EACODD-14 and 73 % in ЕАСОРР-14 groups). In 6 (17 %) patients, partial remission was confirmed only by CT scan, and in 1 (3 %) patient, PET/CT showed stabilization. After consolidation radiotherapy, complete remission was reported in all 35 patients. Both groups received the full chemotherapy program per protocol. Without a violation of G-CSF regimen, the EACODD-14 group received 121 (96 %) cycles out of those 126 planned, whereas the ЕАСОРР-14 group received all 84 cycles per protocol. Full implementation of 107 (88.4 %) cycles in the first group and 24 (29 %) cycles in the second group was achieved in 12 (57 %) and 5 (36 %) patients, respectively (p &lt; 0.001). Neutropenia grade 4 was more often identified in filgrastim than in empegfilgrastim recipients (57 % vs. 19 %; p &lt; 0.05) and in a larger number of cycles (15 % vs. 3 %; p &lt; 0.01). The rate of infection episodes in the ЕАСОРР-14 group was higher (50 % vs. 28 %) and in more cycles (15 % vs. 5 %; p &lt; 0.05). Due to the use of long-acting G-CSF (empegfilgrastim) the number of inpatient days could be reduced from 9 to 5.&#x0D; Conclusion. The results of this study demonstrate the advantage of long-acting G-CSF (empegfilgrastim) as compared with its discrete form (filgrastim) in intensified programs with a reduced inter-cycle interval and high risk of febrile neutropenia (EACODD-14 and EACOРР-14). The use of empegfilgrastim allowed to administer three times as many chemotherapy cycles adhering to the principle of dose intensity in a larger number of patients with advanced cHL stages.

Evaluation of glycopeptide prescription in high-risk febrile neutropenia: A monocentric study of North Africa.

High-risk febrile neutropenia (FN) is one of the main causes of morbidity and mortality in onco-hematology. The initiation of empirical antibiotic therapy is an emergency that can change the prognosis of some patients. Given the emergence of increasingly resistant Gram-positive bacteremia, glycopeptides, as an empirical treatment, have an important place in the management of high-risk FN. The aim of this study is to evaluate the appropriateness of glycopeptide prescription in high-risk FN patients. This study was conducted in the Hematology Department of Fattouma Bourguiba University Hospital of Monastir, Tunisia. Patients with high-risk FN were enrolled during the period between January 1 and December 31, 2020. Of the 29 patients included in this study, 88 FN episodes were noted of which 39 episodes treated with glycopeptides were evaluated. Twenty-four febrile episodes were empirically treated with glycopeptides (27.3%) of which 17 prescriptions (70.8%) were appropriate according to the European Conference on Infection in Leukemia and the Infectious Diseases Society of America recommendations. A therapeutic escalation using glycopeptides was noted in 17% of cases and appropriately opted in 6 FN episodes (40%). Prescriptions of glycopeptides were appropriate according to the international recommendations in 71% of the empirical prescriptions and in 40% of the therapeutic escalation using glycopeptides. In high-risk FN episodes, glycopeptides prescriptions should be rationalized and limited to the indications detailed in the international guidelines to control the emergence of multidrug-resistant bacteria.

Efficacy and safety of PEG-rhG-CSF versus rhG-CSF in preventing granulocytopenia in sarcoma patients receiving doxorubicin combined with ifosfamide: A prospective, randomized, non-inferiority phase II study.

e24173 Background: Prophylactic use of rhG-CSF is routinely recommended in patients with a high risk of febrile neutropenia (FN) after chemotherapy. Currently, rhG-CSF is mostly used in clinical practice. However, PEG-rhG-CSF tends to be a substitute due to its convenience and long-acting effect. Regarding concerns about its efficacy and safety, whether PEG-rhG-CSF could be prophylactically used after these regimens with a high risk of FN is still in doubt. Doxorubicin combined with ifosfamide is commonly applied in sarcoma patients and is one of the most serious myelosuppressive chemotherapy regimens in solid tumors. We compared the efficacy and safety of PEG-rhG-CSF with rhG-CSF in the prevention of severe granulocytopenia and FN, in patients receiving this representative regimen. Methods: This was a single-center, prospective, randomized, crossover, non-inferiority phase II trial. Patients with sarcoma suitable for doxorubicin combined with ifosfamide treatment were enrolled. All patients received 2 cycles of chemotherapy and were randomly assigned to either the AOB group (PEG-rhG-CSF used in 1st cycle and rhG-CSF in 2nd cycle) or BOA group (rhG-CSF used in 1st cycle and PEG-rhG-CSF in 2nd cycle). Blood monitoring every other day until ANC ≥ 2×109/L in two consecutive tests. The primary endpoints were the frequency and duration of grade 4 granulocytopenia after prophylactic use of PEG-rhG-CSF and rhG-CSF respectively, the secondary endpoints were the frequency and duration of febrile neutropenia, and proportion of antibiotic use. Results: From Jan 1, 2018 to Aug 31, 2021, 70 patients were enrolled, 35 each in AOB and BOA. There were no statistical differences in the incidence and duration of grade 4 granulocytopenia (85.7% vs. 77.0%, p = 0.1; 1.34d vs. 1.41d, p = 0.70), the proportion and duration of febrile neutropenia (12.8% vs. 8.2%, p = 0.77; 0.6d vs. 0.8d, p = 0.74), and the proportion of antibiotics used (19.1% vs. 14.9%, p = 0.79) when comparing PEG-rhG-CSF vs. rhG-CSF in prophylactical use. The incidence of grade 4 granulocytopenia in both groups was comparable in 1st cycle (90.9% vs. 96.0%, p = 0.47), but in 2nd cycle it was significantly lower in AOB than that in BOA (54.5% vs. 88.0%, p = 0.01). The lowest value of ANC was higher in AOB in 2nd cycle (0.32G/L vs. 0.12G/L, p = 0.03). Conclusions: This study demonstrated PEG-rhG-CSF could prevent granulocytopenia and FN in sarcoma patients receiving doxorubicin combined with ifosfamide, with comparable efficacy and toxicities as rhG-CSF. Considering the convenience in use and patient compliance, PEG-rhG-CSF could be an effective and reasonable alternative to rhG-CSF. Clinical trial information: ChiCTR1900021945 .

Prevention of febrile neutropenia in oncological patients: real-world data

Aim. To assess the effect of febrile neutropenia (FN) prophylaxis with granulocyte colony-stimulating factors (G-CSF) in real-world cancer patients.&#x0D; Materials and methods. We conducted a statistical analysis of anonymized medical records collected in the Webiomed platform. Before analysis, the cards were validated by clinical experts. Electronic records were extracted according to two principles: mentioning D70 in the diagnosis or mentioning a chemotherapy regimen associated with a high risk of FN (20%), requiring the primary prevention of neutropenia. Thus, we obtained two datasets comprising 47.085 (590 patients) and 30.523 (398 patients) records, respectively.&#x0D; Results. Based on the analysis results, the most common risk factors for FN development were highly hematologically toxic chemotherapy regimens and elderly age about 50% in the adult population. In both datasets, the number of female patients prevailed (63.7% in dataset 1, 91.2% in dataset 2), so the most common was breast cancer. Less common were cervical cancer, digestive cancer, and lung cancer. Despite the indications for primary prevention of FN, for safety and importance of achieving the planned dose intensity, it was administered in 18.3% of patients in dataset 1 and 2.3% in dataset 2. No FN or G-CSF-related adverse events were reported in patients who received adequate primary prevention.&#x0D; Conclusion. Some issues related to G-CSF administration in cancer patients were identified. We identified the insufficient provision of patients with primary prevention of FN, which negatively affects survival rates and reduces adherence to antitumor therapy. Real-world data demonstrate the efficacy and safety of FN prevention and planned dose intensity maintance in cytotoxic therapy regimens.

CE: Febrile Neutropenia in the Chemotherapy Patient.

Febrile neutropenia is a serious complication of chemotherapy treatment and may present as the only clinical sign of infection. If not addressed in a timely manner, it may progress to multisystem organ failure and may be fatal. Initial assessment of fever in those receiving chemotherapy requires prompt administration of antibiotics, ideally within one hour of presentation. Depending on the clinical status of the patient, antibiotic treatment may occur in the inpatient or outpatient setting. Nurses play an important role in the identification and treatment of patients at high risk for febrile neutropenia through assessment and adherence to clinical practice guidelines. In addition, nurses play an active role in patient education regarding risk factors, protective measures, and signs and symptoms of infection in the immunocompromised oncology patient.

Outcomes in Patients With Curative Malignancies Receiving Filgrastim as Primary Prophylaxis.

Granulocyte colony-stimulating factor prophylaxis has been shown to reduce the risk and duration of chemotherapy-induced neutropenia and febrile neutropenia and is recommended for at-risk patients receiving chemotherapy. Within the South Texas Veterans Health Care System, daily filgrastim injections remain the preferred formulation of granulocyte colony-stimulating factor for primary prophylaxis of febrile neutropenia. This retrospective, single-center cohort study included 59 patients who received daily filgrastim as primary prophylaxis with a curative cancer diagnosis and a chemotherapy regimen at the South Texas Veterans Health Care System from September 1, 2015 to September 24, 2020. Patients had either a high risk for febrile neutropenia or a chemotherapy regimen with an intermediate risk for febrile neutropenia and additional risk factors. The primary outcome was the incidence of neutropenia/febrile neutropenia leading to treatment delays. Secondary outcomes included chemotherapy dose decreases or discontinuations, hospitalizations, days of hospitalization, infections, extended duration of filgrastim, and transitions to pegfilgrastim due to neutropenia/febrile neutropenia. Patients received a median (IQR) of 7 (5-10) doses of filgrastim for primary prophylaxis. Overall, 10 patients (17%) experienced treatment delays due to neutropenia/febrile neutropenia. Fifteen patients (25%) were hospitalized with a median (IQR) length of stay of 5 (4-7) days, 9 patients (15%) had documented infections, and 2 patients (3%) required a chemotherapy dose reduction. Additionally, 9 patients (15%) required an additional median (IQR) of 2 (2-5) doses of filgrastim, and 9 (15%) patients were transitioned to pegfilgrastim. These results suggest that additional measures such as tracking postnadir absolute neutrophil counts should be performed to ensure patients receive an appropriate number of filgrastim doses to prevent complications associated with neutropenia/febrile neutropenia.

Grade 4 Neutropenia Frequency as a Binary Risk Predictor for Adverse Clinical Consequences of Chemotherapy‑Induced Neutropenia: A Meta-analysis

Neutropenia is the major toxicity of myelosuppressive cancer chemotherapy. Grade 4 neutropenia (Gr4N) is a measure of chemotherapy-induced neutropenia (CIN) severity. We conducted a meta-analysis of CIN data. Gr4N incidence was significantly correlated with febrile neutropenia (FN), days of severe neutropenia (DSN), and nadir absolute neutrophil count (ANC), which are all important predictors of morbidity. With a Gr4N threshold of 65%, both FN and DSN were below levels for low risk of adverse CIN outcomes. Gr4N was highly predictive for adverse CIN outcomes, and a 65% threshold demarcated low vs. high risk for FN and other adverse CIN outcomes.

Adverse effects of antibiotics in children with cancer: are short-course antibiotics for febrile neutropenia part of the solution?

Introduction : Febrile neutropenia is a common complication experienced by children with cancer or those undergoing hematopoietic stem cell transplantation. Repeated episodes of febrile neutropenia result in cumulative exposure to broad-spectrum antibiotics with potential for a range of serious adverse effects. Short-course antibiotics, even in patients with high-risk febrile neutropenia, may offer a solution. Areas covered : This review addresses the known broad effects of antibiotics, highlights developments in understanding the relationship between cancer, antibiotics and the gut microbiome and discusses emerging evidence regarding long-term adverse antibiotic effects. The authors consider available evidence to guide the duration of empiric antibiotics in pediatric febrile neutropenia and directions for future research. Expert opinion : Broad-spectrum antibiotics are associated with antimicrobial resistance, Clostridioides difficile infection, invasive candidiasis, significant disturbance of the gut microbiome and may seriously impact outcomes in children with cancer or undergoing allogenic hematopoietic stem cell transplant. Short-course empiric antibiotics are likely safe in most children with febrile neutropenia and present a valuable opportunity to reduce the risks of antibiotic exposure.

Low pretherapy skeletal muscle mass index is associated with an increased risk of febrile neutropenia in patients with esophageal cancer receiving docetaxel + cisplatin + 5-fluorouracil (DCF) therapy

PurposeDocetaxel + cisplatin + 5-fluorouracil (DCF) therapy, a frequently prescribed regimen for esophageal cancer, is associated with a high risk of febrile neutropenia (FN). This study investigated whether a low skeletal muscle mass index (SMI) is an independent risk factor for FN.MethodsThis retrospective, observational study investigated the SMI of patients with esophageal cancer who received DCF therapy between March 2018 and July 2020. Based on the Asian sarcopenia criteria, patients were divided into two groups: high and low SMI (SMI of < 7.0 and 5.7 kg/m2 for males and females, respectively). The incidence of FN was then compared between the two groups.ResultsThirty-nine patients (20 and 19 in the high- and low-SMI groups, respectively) were included in this study. The incidence of FN was significantly higher in the low-SMI group (63.2% vs. 20.0%, P = 0.006). Univariable and multivariable logistic regression analyses revealed that a low SMI was an independent risk factor for FN (odds ratio, 7.178; 95% confidence interval, 1.272–40.507; P = 0.026). In addition, the frequency of dose reduction in DCF therapy was significantly higher in the low-SMI group (68.4% vs. 35.0%, P = 0.037).ConclusionLow SMI is an independent risk factor for FN in patients with esophageal cancer receiving DCF therapy.