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Annals of Hematology Nov 2020Wider use of clozapine, one of the most effective antipshychotic drugs, is precluded by its propensity to cause agranulocytosis. Currently, clozapine is used for... (Review)
Review
Wider use of clozapine, one of the most effective antipshychotic drugs, is precluded by its propensity to cause agranulocytosis. Currently, clozapine is used for treatment-resistant schizophrenia, with mandatory blood count monitoring for the duration of treatment. Agranulocytosis occurs in up to 0.8% of patients and presents a significant medical challenge, despite decreasing mortality rates. In this paper, we review the epidemiology of clozapine-induced agranulocytosis (CLIA), advances in identifying genetic risk factors, and the preventive measures to reduce the risk of CLIA. We discuss the pathogenesis of CLIA, which, despite receiving considerable scientific attention, has not been fully elucidated. Finally, we address the clinical management and suggest the approach to clozapine re-challenge in patients with a previous episode of neutropenia. With a significant proportion of clozapine recipients in Western hemisphere being Black, we comment on the importance of recognizing benign ethnic neutropenia as a potential impediment to clozapine administration. This review aims to aid haematologists and psychiatrists to jointly manage neutropenia and agranulocytosis caused by clozapine.
Topics: Black People; Clozapine; Humans; Neutropenia; Risk Factors
PubMed: 32815018
DOI: 10.1007/s00277-020-04215-y -
Current Opinion in Hematology Jan 2016Neutropenia absolute neutrophil count (ANC) less than 1.5 × 10(9)/l is a common hematological finding, and severe neutropenia, that is, ANC less... (Review)
Review
PURPOSE OF REVIEW
Neutropenia absolute neutrophil count (ANC) less than 1.5 × 10(9)/l is a common hematological finding, and severe neutropenia, that is, ANC less than 0.5 × 10(9)/l is a well known risk factor for susceptibility to bacterial infections. This review provides a succinct clinical approach to the diagnosis and treatment of neutropenia with specific recommendations on the treatment of severe chronic neutropenia with the myeloid growth factor, granulocyte colony-stimulating factor (G-CSF).
RECENT FINDINGS
Experts agree that patients with acute febrile neutropenia should be treated with antibiotics and that patients at high risk of severe neutropenia (>20% risk) after myelosuppressive chemotherapy should be treated prophylactically with a myeloid growth factor, usually G-CSF. The diversity of causes and consequences of chronic neutropenia make the diagnosis and management of these patients more complicated.
SUMMARY
The review provides a stepwise approach to neutropenia focusing first on reaching a provisional diagnosis and treatment plan then steps to a final diagnosis. It also provides specific recommendations on the treatment of severe chronic neutropenia with G-CSF.
Topics: Humans; Neutropenia
PubMed: 26554885
DOI: 10.1097/MOH.0000000000000208 -
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 Immunology (Baltimore, Md. :... Aug 2015G-CSF and GM-CSF are used widely to promote the production of granulocytes or APCs. The U.S. Food and Drug Administration approved G-CSF (filgrastim) for the treatment... (Review)
Review
G-CSF and GM-CSF are used widely to promote the production of granulocytes or APCs. The U.S. Food and Drug Administration approved G-CSF (filgrastim) for the treatment of congenital and acquired neutropenias and for mobilization of peripheral hematopoietic progenitor cells for stem cell transplantation. A polyethylene glycol-modified form of G-CSF is approved for the treatment of neutropenias. Clinically significant neutropenia, rendering an individual immunocompromised, occurs when their number is <1500/μl. Current guidelines recommend their use when the risk for febrile neutropenia is >20%. GM-CSF (sargramostim) is approved for neutropenia associated with stem cell transplantation. Because of its promotion of APC function, GM-CSF is being evaluated as an immunostimulatory adjuvant in a number of clinical trials. More than 20 million persons have benefited worldwide, and >$5 billion in sales occur annually in the United States.
Topics: Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Neutropenia; Signal Transduction
PubMed: 26254266
DOI: 10.4049/jimmunol.1500861 -
Blood Reviews Sep 2019Benign ethnic neutropenia (BEN) is one of the most common causes of chronic neutropenia seen in individuals of African, Middle Eastern and West Indian descent, affecting... (Review)
Review
Benign ethnic neutropenia (BEN) is one of the most common causes of chronic neutropenia seen in individuals of African, Middle Eastern and West Indian descent, affecting many individuals worldwide. Despite its prevalence, many physicians are not familiar with this benign condition, resulting in unnecessary evaluation and testing for neutropenia in otherwise healthy individuals. Clinically, patients with BEN are at no increased risk of infection despite their neutropenia. Implications of this condition are highlighted in those patients receiving therapies that have a known side effect of neutropenia, most commonly chemotherapy agents. Studies have suggested that disparities in survival among those patients receiving chemotherapy between patients of European decent and African decent may be attributed to measured neutropenia in these populations, questioning whether BEN could be an influential factor. This review encompasses all aspects of benign ethnic neutropenia, providing information about this condition and helping to guide clinical decision-making as to when an aggressive work up and referral are indicated and when it is appropriate to monitor. Additionally, we review the role of genetic studies in identifying the genes related to BEN, summarize the theories that offer the most accepted mechanisms behind the condition, and address the importance of pursuing larger studies to assess the implication of BEN in oncology patients as well as patients taking neutropenia-causing medications.
Topics: Ethnicity; Humans; Neutropenia
PubMed: 31255364
DOI: 10.1016/j.blre.2019.06.003 -
British Journal of Haematology Aug 2017Neutropenia, usually defined as a blood neutrophil count <1·5 × 10 /l, is a common medical problem for children and adults. There are many causes for neutropenia,... (Review)
Review
Neutropenia, usually defined as a blood neutrophil count <1·5 × 10 /l, is a common medical problem for children and adults. There are many causes for neutropenia, and at each stage in life the clinical pattern of causes and consequences differs significantly. I recommend utilizing the age of the child and clinical observations for the preliminary diagnosis and primary management. In premature infants, neutropenia is quite common and contributes to the risk of sepsis with necrotizing enterocolitis. At birth and for the first few months of life, neutropenia is often attributable to isoimmune or alloimmune mechanisms and predisposes to the risk of severe bacterial infections. Thereafter when a child is discovered to have neutropenia, often associated with relatively minor symptoms, it is usually attributed to autoimmune disorder or viral infection. The congenital neutropenia syndromes are usually recognized when there are recurrent infections, the neutropenia is severe and there are congenital anomalies suggesting a genetic disorder. This review focuses on the key clinical finding and laboratory tests for diagnosis with commentaries on treatment, particularly the use of granulocyte colony-stimulating factor to treat childhood neutropenia.
Topics: Autoimmune Diseases; Child; Granulocyte Colony-Stimulating Factor; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Neutropenia
PubMed: 28419427
DOI: 10.1111/bjh.14677 -
Nature Reviews. Disease Primers Jun 2017Severe congenital neutropenias are a heterogeneous group of rare haematological diseases characterized by impaired maturation of neutrophil granulocytes. Patients with... (Review)
Review
Severe congenital neutropenias are a heterogeneous group of rare haematological diseases characterized by impaired maturation of neutrophil granulocytes. Patients with severe congenital neutropenia are prone to recurrent, often life-threatening infections beginning in their first months of life. The most frequent pathogenic defects are autosomal dominant mutations in ELANE, which encodes neutrophil elastase, and autosomal recessive mutations in HAX1, whose product contributes to the activation of the granulocyte colony-stimulating factor (G-CSF) signalling pathway. The pathophysiological mechanisms of these conditions are the object of extensive research and are not fully understood. Furthermore, severe congenital neutropenias may predispose to myelodysplastic syndromes or acute myeloid leukaemia. Molecular events in the malignant progression include acquired mutations in CSF3R (encoding G-CSF receptor) and subsequently in other leukaemia-associated genes (such as RUNX1) in a majority of patients. Diagnosis is based on clinical manifestations, blood neutrophil count, bone marrow examination and genetic and immunological analyses. Daily subcutaneous G-CSF administration is the treatment of choice and leads to a substantial increase in blood neutrophil count, reduction of infections and drastic improvement of quality of life. Haematopoietic stem cell transplantation is the alternative treatment. Regular clinical assessments (including yearly bone marrow examinations) to monitor treatment course and detect chromosomal abnormalities (for example, monosomy 7 and trisomy 21) as well as somatic pre-leukaemic mutations are recommended.
Topics: Adaptor Proteins, Signal Transducing; Blood Cell Count; Congenital Bone Marrow Failure Syndromes; Core Binding Factor Alpha 2 Subunit; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Leukocyte Elastase; Mutation; Myelodysplastic Syndromes; Neutropenia; Quality of Life; Receptors, Colony-Stimulating Factor
PubMed: 28593997
DOI: 10.1038/nrdp.2017.32 -
The Western Journal of Emergency... Mar 2019Oncologic emergencies may be seen in any emergency department and will become more frequent as our population ages and more patients receive chemotherapy. Life-saving... (Review)
Review
Oncologic emergencies may be seen in any emergency department and will become more frequent as our population ages and more patients receive chemotherapy. Life-saving interventions are available for certain oncologic emergencies if the diagnosis is made in a timely fashion. In this article we will cover neutropenic fever, tumor lysis syndrome, hypercalcemia of malignancy, and hyperviscosity syndrome. After reading this article the reader should be much more confident in the diagnosis, evaluation, and management of these oncologic emergencies.
Topics: Blood Viscosity; Emergencies; Emergency Treatment; Hematologic Diseases; Humans; Hypercalcemia; Neoplasms; Neutropenia; Tumor Lysis Syndrome
PubMed: 30881552
DOI: 10.5811/westjem.2018.12.37335 -
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