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The Oncologist Aug 2022Neutropenia and febrile neutropenia (FN) are common complications of myelosuppressive chemotherapy. This review provides an up-to-date assessment of the patient and cost... (Review)
Review
Neutropenia and febrile neutropenia (FN) are common complications of myelosuppressive chemotherapy. This review provides an up-to-date assessment of the patient and cost burden of chemotherapy-induced neutropenia/FN in the US, and summarizes recommendations for FN prophylaxis, including the interim guidance that was recommended during the coronavirus disease 2019 (COVID-19) pandemic. This review indicates that neutropenia/FN place a significant burden on patients in terms of hospitalizations and mortality. Most patients with neutropenia/FN presenting to the emergency department will be hospitalized, with an average length of stay of 6, 8, and 10 days for elderly, pediatric, and adult patients, respectively. Reported in-hospital mortality rates for neutropenia/FN range from 0.4% to 3.0% for pediatric patients with cancer, 2.6% to 7.0% for adults with solid tumors, and 7.4% for adults with hematologic malignancies. Neutropenia/FN also place a significant cost burden on US healthcare systems, with average costs per neutropenia/FN hospitalization estimated to be up to $40 000 for adult patients and $65 000 for pediatric patients. Evidence-based guidelines recommend prophylactic granulocyte colony-stimulating factors (G-CSFs), which have been shown to reduce FN incidence while improving chemotherapy dose delivery. Availability of biosimilars may improve costs of care. Efforts to decrease hospitalizations by optimizing outpatient care could reduce the burden of neutropenia/FN; this was particularly pertinent during the COVID-19 pandemic since avoidance of hospitalization was needed to reduce exposure to the virus, and resulted in the adaptation of recommendations to prevent FN, which expanded the indications for G-CSF and/or lowered the threshold of use to >10% risk of FN.
Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Biosimilar Pharmaceuticals; Chemotherapy-Induced Febrile Neutropenia; Child; Granulocyte Colony-Stimulating Factor; Humans; Neoplasms; Pandemics; COVID-19 Drug Treatment
PubMed: 35552754
DOI: 10.1093/oncolo/oyac074 -
Revista Espanola de Quimioterapia :... Sep 2019Febrile neutropenia is a common complication in patients with hematologic malignancies receiving chemotherapy, and is associated with high morbidity and mortality.... (Review)
Review
Febrile neutropenia is a common complication in patients with hematologic malignancies receiving chemotherapy, and is associated with high morbidity and mortality. Infections caused by multidrug-resistant bacteria represent a therapeutic challenge in this high-risk patient population, since inadequate initial empirical antibiotic treatment can seriously compromise prognosis. Besides, reducing antimicrobial exposure is a cornerstone in the fight against resistance.
Topics: Antineoplastic Agents; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Febrile Neutropenia; Hematologic Neoplasms; Humans; Immunocompromised Host
PubMed: 31475812
DOI: No ID Found -
Journal of Clinical Oncology : Official... Mar 2023To update a clinical practice guideline (CPG) for the empiric management of fever and neutropenia (FN) in pediatric patients with cancer and hematopoietic cell...
PURPOSE
To update a clinical practice guideline (CPG) for the empiric management of fever and neutropenia (FN) in pediatric patients with cancer and hematopoietic cell transplantation recipients.
METHODS
The International Pediatric Fever and Neutropenia Guideline Panel reconvened to conduct the second update of this CPG. We updated the previous systematic review to identify new randomized controlled trials (RCTs) evaluating any strategy for the management of FN in pediatric patients. Using the Grading of Recommendations Assessment, Development and Evaluation framework, evidence quality was classified as high, moderate, low, or very low. The panel updated recommendations related to initial management, ongoing management, and empiric antifungal therapy. Changes from the 2017 CPG were articulated, and good practice statements were considered.
RESULTS
We identified 10 new RCTs in addition to the 69 RCTs identified in previous FN CPGs to inform the 2023 FN CPG. Changes from the 2017 CPG included two conditional recommendations regarding (1) discontinuation of empiric antibacterial therapy in clinically well and afebrile patients with low-risk FN if blood cultures remain negative at 48 hours despite no evidence of marrow recovery and (2) pre-emptive antifungal therapy for invasive fungal disease in high-risk patients not receiving antimold prophylaxis. The panel created a good practice statement to initiate FN CPG-consistent empiric antibacterial therapy as soon as possible in clinically unstable febrile patients.
CONCLUSION
The updated FN CPG incorporates important modifications on the basis of recently published trials. Future work should focus on addressing knowledge gaps, improving CPG implementation, and measuring the impact of CPG-consistent care.
Topics: Child; Humans; Antifungal Agents; Neutropenia; Neoplasms; Fever; Anti-Bacterial Agents; Hematopoietic Stem Cell Transplantation; Febrile Neutropenia
PubMed: 36689694
DOI: 10.1200/JCO.22.02224 -
Revista Chilena de Infectologia :... 2018Febrile neutropenia is a life-threatening condition that requires immediate attention, especially in patients with chemotherapy-related neutropenia. Patients with... (Review)
Review
Febrile neutropenia is a life-threatening condition that requires immediate attention, especially in patients with chemotherapy-related neutropenia. Patients with febrile neutropenia have a much greater risk of developing bacterial disease, and fever may be the only indicator of severe bacterial infection. Adequate management of febrile neutropenia emphasizes early recognition of patients, risk stratification, and antibiotic therapy administration during the first 60 minutes of admission to an emergency room. Not all children with febrile neutropenia carry the same risk of morbidity and mortality, so in recent years, efforts have been made to distinguish between high-risk patients where more aggressive hospital management is required. In children classified as low-risk, outpatient management may be considered initially or after 72 hours, whilst high-risk patients should be hospitalized and managed with parenteral antibiotics.
Topics: Age Factors; Anti-Bacterial Agents; Antineoplastic Agents; Chemotherapy-Induced Febrile Neutropenia; Disease Management; Emergency Service, Hospital; Humans; Neoplasms; Risk Assessment; Risk Factors; Time-to-Treatment
PubMed: 29652973
DOI: 10.4067/s0716-10182018000100062 -
Annals of Hematology May 2019Sepsis and septic shock are major causes of mortality during chemotherapy-induced neutropenia for malignancies requiring urgent treatment. Thus, awareness of the... (Review)
Review
Management of sepsis in neutropenic cancer patients: 2018 guidelines from the Infectious Diseases Working Party (AGIHO) and Intensive Care Working Party (iCHOP) of the German Society of Hematology and Medical Oncology (DGHO).
Sepsis and septic shock are major causes of mortality during chemotherapy-induced neutropenia for malignancies requiring urgent treatment. Thus, awareness of the presenting characteristics and prompt management is most important. Improved management of sepsis during neutropenia may reduce the mortality of cancer therapies. However, optimal management may differ between neutropenic and non-neutropenic patients. The aim of the current guideline is to give evidence-based recommendations for hematologists, oncologists, and intensive care physicians on how to manage adult patients with neutropenia and sepsis.
Topics: Adult; Chemotherapy-Induced Febrile Neutropenia; Critical Care; Female; Germany; Hematology; Humans; Male; Medical Oncology; Neoplasms; Practice Guidelines as Topic; Sepsis; Societies, Medical
PubMed: 30796468
DOI: 10.1007/s00277-019-03622-0 -
Leukemia May 2022The 9th web-based European Conference on Infections in Leukemia (ECIL-9), held September 16-17, 2021, reviewed the risk of infections and febrile neutropenia associated... (Review)
Review
Infectious complications of targeted drugs and biotherapies in acute leukemia. Clinical practice guidelines by the European Conference on Infections in Leukemia (ECIL), a joint venture of the European Group for Blood and Marrow Transplantation (EBMT), the European Organization for Research and...
The 9th web-based European Conference on Infections in Leukemia (ECIL-9), held September 16-17, 2021, reviewed the risk of infections and febrile neutropenia associated with more recently approved immunotherapeutic agents and molecular targeted drugs for the treatment of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Novel antibody based treatment approaches (inotuzumab ozogamicin, gemtuzumab ozogamicin, flotetuzumab), isocitrate dehydrogenases inhibitors (ivosidenib, enasidenib, olutasidenib), FLT3 kinase inhibitors (gilteritinib, midostaurin, quizartinib), a hedgehog inhibitor (glasdegib) as well as a BCL2 inhibitor (venetoclax) were reviewed with respect to their mode of action, their immunosuppressive potential, their current approval and the infectious complications and febrile neutropenia reported from clinical studies. Evidence-based recommendations for prevention and management of infectious complications and specific alerts regarding the potential for drug-drug interactions were developed and discussed in a plenary session with the panel of experts until consensus was reached. The set of recommendations was posted on the ECIL website for a month for comments from members of EBMT, EORTC, ICHS and ELN before final approval by the panelists. While a majority of these agents are not associated with a significantly increased risk when used as monotherapy, caution is required with combination therapy such as venetoclax plus hypomethylating agents, gemtuzumab ozogamicin plus cytotoxic drugs or midostaurin added to conventional AML chemotherapy.
Topics: Antibodies, Monoclonal; Biological Therapy; Febrile Neutropenia; Humans; Immunocompromised Host; Infections; Leukemia, Myeloid, Acute; Practice Guidelines as Topic; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 35368047
DOI: 10.1038/s41375-022-01556-7 -
Hematology. American Society of... Dec 2020Patients with hematologic malignancies are at increased risk of infection, with associated morbidity and mortality. Patients with acute myeloid leukemia (AML) have... (Review)
Review
Patients with hematologic malignancies are at increased risk of infection, with associated morbidity and mortality. Patients with acute myeloid leukemia (AML) have qualitative and quantitative deficits in granulocytes predisposing to bacterial and fungal infections. Acute lymphoblastic leukemia results in qualitative deficits in lymphocytes, resulting in hypogammaglobulinemia and reduced cell-mediated immunity predisposing to certain bacterial and viral as well as fungal infections. Chemotherapeutic regimens often compound these deficits, result in prolonged periods of severe neutropenia, and disrupt mucosal barriers, further elevating infection risk. Despite advances in antimicrobial therapies and prophylaxis, acute leukemia patients with disease- and treatment-related immunosuppression remain at risk for life-threatening infection, including with resistant organisms, antimicrobial-related adverse events, and higher treatment costs. Additionally, our knowledge of infection risk and drug-drug interactions with new immune-targeted cancer therapeutics is evolving. Here, we review 3 areas in which standard practice is evolving as challenges arise and new experience is gained, including antibiotic use in febrile neutropenia, fungal prophylaxis, and use of targeted therapies.
Topics: Antineoplastic Agents; Febrile Neutropenia; Humans; Immunosuppressive Agents; Infection Control; Infections; Leukemia, Myeloid, Acute; Male; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Risk Factors
PubMed: 33275701
DOI: 10.1182/hematology.2020000098 -
Antimicrobial Resistance and Infection... Mar 2022The 2011 4th European Conference on Infections in Leukemia (ECIL4) guidelines recommend antibiotics de-escalation/discontinuation in selected febrile neutropenia (FN)... (Observational Study)
Observational Study
BACKGROUND
The 2011 4th European Conference on Infections in Leukemia (ECIL4) guidelines recommend antibiotics de-escalation/discontinuation in selected febrile neutropenia (FN) patients. We aimed to assess the impact of an antimicrobial stewardship (AMS) program based on these guidelines on antibiotics use and clinical outcomes in high-risk FN patients.
METHODS
We conducted an observational study in the hematology department of Cochin University Hospital in Paris, France. An ECIL4-based antibiotics de-escalation and discontinuation strategy was implemented jointly by the hematologists and the AMS team. The pre-intervention (January-October 2018) and post-intervention (January-October 2019) periods were compared. We retrospectively collected clinical and microbiological data. We compiled antibiotics consumptions via hospital pharmacy data and standardized them by calculating defined daily doses per 1000 patient-days. We analyzed the two-monthly antibiotic consumption using an interrupted time series method and built a composite endpoint for clinical outcomes based on transfer to the intensive care unit (ICU) and/or hospital death.
RESULTS
Overall, 273 hospital stays (164 patients) in the pre-intervention and 217 (148 patients) in the post-intervention periods were analyzed. Patients were mainly hospitalized for intensive chemotherapy for acute leukemia or autologous stem-cell transplant for myeloma. Patients were slightly younger in the pre-intervention compared to the post-intervention period (median age 60.4 vs 65.2 years, p = 0.049), but otherwise comparable. After implementation of the AMS program, glycopeptide and carbapenem use decreased by 85% (p = 0.03) and 72% (p = 0.04), respectively. After adjustment on confounders, the risk of transfer to the ICU/death decreased significantly after implementation of the AMS program (post-intervention period: odds-ratio = 0.29, 95% Confidence Interval: 0.15-0.53, p < 0.001).
CONCLUSION
Implementation of a multidisciplinary AMS program for high-risk neutropenic patients was associated with lower carbapenem and glycopeptide use and improved clinical outcomes.
Topics: Anti-Bacterial Agents; Antimicrobial Stewardship; Carbapenems; Febrile Neutropenia; Humans; Middle Aged; Retrospective Studies
PubMed: 35346373
DOI: 10.1186/s13756-022-01084-0 -
Hematology. American Society of... Dec 2017Non-chemotherapy idiosyncratic drug-induced neutropenia (IDIN) is a relatively rare but potentially fatal disorder that occurs in susceptible individuals, with an... (Review)
Review
Non-chemotherapy idiosyncratic drug-induced neutropenia (IDIN) is a relatively rare but potentially fatal disorder that occurs in susceptible individuals, with an incidence of 2.4 to 15.4 cases per million population. Affected patients typically experience severe neutropenia within several weeks to several months after first exposure to a drug, and mortality is ∼5%. The drugs most frequently associated with IDIN include metamizole, clozapine, sulfasalazine, thiamazole, carbimazole, amoxicillin, cotrimoxazole, ticlopidine, and valganciclovir. The idiosyncratic nature of IDIN, the lack of mouse models and diagnostic testing, and its low overall incidence make rigorous studies to elucidate possible mechanisms exceptionally difficult. An immune mechanism for IDIN involving neutrophil destruction by hapten (drug)-specific antibodies and drug-induced autoantibodies is frequently suggested, but strong supporting evidence is lacking. Although laboratory testing for neutrophil drug-dependent antibodies is rarely performed because of the complexity and low sensitivity of tests currently in use, these assays could possibly be enhanced by using reactive drug metabolites in place of the parent drug. Patients typically experience acute, severe neutropenia, or agranulocytosis (<0.5 × 10 neutrophils/L) and symptoms of fever, chills, sore throat, and muscle and joint pain. Diagnosis can be difficult, but timely recognition is critical because if left untreated, there is an increase in mortality. Expanded studies of the production and mechanistic role of reactive drug metabolites, genetic associations, and improved animal models of IDIN are essential to further our understanding of this important disorder.
Topics: Animals; Chemotherapy-Induced Febrile Neutropenia; Humans; Incidence; Mice
PubMed: 29222255
DOI: 10.1182/asheducation-2017.1.187 -
The Oncologist Aug 2020This letter to the editor remarks on additional considerations for the management of febrile neutropenia during the COVID‐19 pandemic, in response to the letter by...
This letter to the editor remarks on additional considerations for the management of febrile neutropenia during the COVID‐19 pandemic, in response to the letter by Boutayeb et al.
Topics: Betacoronavirus; COVID-19; Coronavirus Infections; Febrile Neutropenia; Humans; Pandemics; Pneumonia, Viral; SARS-CoV-2
PubMed: 32378772
DOI: 10.1634/theoncologist.2020-0329