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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 -
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 -
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 -
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 -
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 -
Annals of Allergy, Asthma & Immunology... Jun 2023Rituximab is a chimeric anti-CD20 monoclonal antibody that targets CD20-expressing B lymphocytes, has a well-defined efficacy and safety profile, and is broadly used to... (Review)
Review
Rituximab is a chimeric anti-CD20 monoclonal antibody that targets CD20-expressing B lymphocytes, has a well-defined efficacy and safety profile, and is broadly used to treat a wide array of diseases. In this review, we cover the mechanism of action of rituximab and focus on hypogammaglobulinemia and late-onset neutropenia-2 immune effects secondary to rituximab-and subsequent infection. We review risk factors and highlight key considerations for immunologic monitoring and clinical management of rituximab-induced secondary immune deficiencies. In patients treated with rituximab, monitoring for hypogammaglobulinemia and infections may help to identify the subset of patients at high risk for developing poor B cell reconstitution, subsequent infections, and adverse complications. These patients may benefit from early interventions such as vaccination, antibacterial prophylaxis, and immunoglobulin replacement therapy. Systematic evaluation of immunoglobulin levels and peripheral B cell counts by flow cytometry, both at baseline and periodically after therapy, is recommended for monitoring. In addition, in those patients with prolonged hypogammaglobulinemia and increased infections after rituximab use, immunologic evaluation for inborn errors of immunity may be warranted to further risk stratification, increase monitoring, and assist in therapeutic decision-making. As the immunologic effects of rituximab are further elucidated, personalized approaches to minimize the risk of adverse reactions while maximizing benefit will allow for improved care of patients with decreased morbidity and mortality.
Topics: Humans; Rituximab; Agammaglobulinemia; Antineoplastic Agents; Antibodies, Monoclonal; Neutropenia
PubMed: 36706910
DOI: 10.1016/j.anai.2023.01.018 -
BMJ Case Reports Nov 2021Idiosyncratic drug-induced agranulocytosis is a rare life-threatening adverse reaction characterised by an absolute neutrophil count <500 cells/μL of blood....
Idiosyncratic drug-induced agranulocytosis is a rare life-threatening adverse reaction characterised by an absolute neutrophil count <500 cells/μL of blood. Nitrofurantoin has been associated with haematological adverse events, but few agranulocytosis cases worldwide have been reported. We present a case of a 68-year-old woman who presented with fever and agranulocytosis following treatment with nitrofurantoin. Extensive workup for agranulocytosis, including a bone marrow aspirate, was unremarkable. Treatment with nitrofurantoin was discontinued, which led to a complete recovery of the complete blood count. This case stresses the importance of monitoring treatments, given that widely used drugs are not free from severe adverse reactions.
Topics: Aged; Blood Cell Count; Female; Humans; Leukocyte Count; Neutropenia; Neutrophils; Nitrofurantoin
PubMed: 34764131
DOI: 10.1136/bcr-2021-246788 -
International Journal of Environmental... Mar 2022Premature loss of primary teeth can occur as a consequence of dental trauma, neonatal tooth extraction, early childhood caries, or periodontal problems, or it can be a... (Review)
Review
BACKGROUND
Premature loss of primary teeth can occur as a consequence of dental trauma, neonatal tooth extraction, early childhood caries, or periodontal problems, or it can be a manifestation of systemic disease. This review aims to present systemic disorders that can lead to premature loss of deciduous teeth in children and to provide a comprehensive resource for clinical practice for both physicians and dentists.
METHODS
This study is a narrative review of original studies and case reports published in English and Polish between 1957 and 2021 that was conducted by searching electronic scientific resources: PubMed, Google Scholar, Web of Science, and Science Direct. The schema of the qualification process is represented by a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). In total, 196 articles were identified; after provisional assessment of the titles and abstracts by two reviewers, 46 were found to be relevant to the topic, including 1 review, 16 original papers, and 27 case reports regarding systemic disease resulting in premature tooth loss.
RESULTS
In this study, 16 systemic diseases were linked to premature primary tooth loss in children: Papillon-Lefèvre syndrome, mucocutaneous dyskeratosis, Coffin-Lowry syndrome, congenital adrenal hyperplasia, Langerhans cell histiocytosis, cherubism, hypophosphatasia, acatalasia, Chediak-Higashi syndrome, cyclic neutropenia, erythromelalgia, Down syndrome, Hajdu-Cheney syndrome, short bowel syndrome, leukocyte adhesion deficiency type 1 (LAD-1), and Wiedemann-Steiner syndrome (WSS).
Topics: Child; Child, Preschool; Humans; Infant, Newborn; Leukocyte-Adhesion Deficiency Syndrome; Neutropenia; Papillon-Lefevre Disease; Tooth Loss; Tooth, Deciduous
PubMed: 35329073
DOI: 10.3390/ijerph19063386 -
Cancer Treatment Reviews Sep 2022
Review
Topics: Antineoplastic Agents; Granulocyte Colony-Stimulating Factor; Humans; Neutropenia
PubMed: 35785754
DOI: 10.1016/j.ctrv.2022.102427 -
CMAJ : Canadian Medical Association... Dec 2022
Topics: Humans; Neutropenia
PubMed: 36535676
DOI: 10.1503/cmaj.220499