-
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 -
Hematology/oncology Clinics of North... Apr 2022Evans syndrome (ES) is a rare immune disorder defined as the simultaneous or sequential occurrence in a single patient of immune thrombocytopenia (ITP) and warm... (Review)
Review
Evans syndrome (ES) is a rare immune disorder defined as the simultaneous or sequential occurrence in a single patient of immune thrombocytopenia (ITP) and warm autoimmune hemolytic anemia (wAIHA) ± autoimmune neutropenia (AIN). ES represents approximately 5% to 10% of all wAIHA and 2%-5% of all ITP cases in adults and its mortality rate is high. When ITP and wAIHA occurred concomitantly, other differential diagnoses must be ruled out. ES can be primary or secondary and isolated or associated with another underlying disorder and secondary ES. The management of ES is mostly empirical with a low level of evidence. This review reports some new insights on this rare disease and provides some practical tools for the diagnosis and management of adult ES.
Topics: Adult; Anemia, Hemolytic, Autoimmune; Humans; Neutropenia; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia
PubMed: 35282950
DOI: 10.1016/j.hoc.2021.12.004 -
International Journal of Laboratory... Jun 2020Neutropenia is a common laboratory finding in adults and children. Its underlying causes are extremely heterogeneous and include benign conditions, autoimmune disorders,... (Review)
Review
Neutropenia is a common laboratory finding in adults and children. Its underlying causes are extremely heterogeneous and include benign conditions, autoimmune disorders, infections, and malignancies. The clinical laboratory plays a central role in the diagnosis of these disorders, including data derived from hematology, microbiology, molecular biology/cytogenetics, and clinical chemistry. The purpose of this review is to (a) highlight the clinical, hematologic, and molecular genetic features of the major entities resulting in neutropenia and (b) outline an algorithm-based approach to permit the classification of neutropenias.
Topics: Algorithms; Autoimmune Diseases; Humans; Neutropenia
PubMed: 32543073
DOI: 10.1111/ijlh.13210 -
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 -
The Annals of Pharmacotherapy Aug 2021To review the incidence, management, and current understanding of the pathophysiology of β-lactam-induced neutropenia and to critically evaluate the practicality and... (Review)
Review
OBJECTIVE
To review the incidence, management, and current understanding of the pathophysiology of β-lactam-induced neutropenia and to critically evaluate the practicality and safety of direct substitution to an alternative β-lactam in the setting of this reaction.
DATA SOURCES
A literature analysis using the PubMed and Ovid search engines (July 1968 to October 2020) was performed using the search terms , and (granulocyte colony-stimulating factor).
STUDY SELECTION AND DATA EXTRACTION
The included English-language studies evaluated the incidence, mechanism, and/or management of β-lactam-induced neutropenia in pediatric or adult patients.
DATA SYNTHESIS
Drug-induced neutropenia is a well-documented adverse reaction of β-lactam antibiotics, with an incidence of approximately 10% following at least 2 weeks of intravenous therapy. However, multiple gaps in knowledge remain in the mechanism of pathophysiology and optimal management of this reaction. Both direct toxic and immune-mediated mechanisms have been implicated. Although the cornerstone of management includes cessation of the offending agent, controversy exists on the appropriateness of direct substitution or future use of an alternative β-lactam.
RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE
Given the frequency of use and superiority of β-lactams over alternative therapy for several infectious disease states, practical recommendations are needed on the management and safe use of β-lactams following β-lactam-induced neutropenia.
CONCLUSION
Future use of β-lactams with differing R1 side chains, particularly those from a separate class, should not be deemed contraindicated following β-lactam-induced neutropenia and may be considered when indicated, with close laboratory monitoring.
Topics: Adult; Anti-Bacterial Agents; Child; Humans; Neutropenia; beta-Lactams
PubMed: 33215507
DOI: 10.1177/1060028020975646 -
Expert Review of Anti-infective Therapy Dec 2019: Infections are among the most frequent complications in patients with hematological and oncological diseases. They might be classified as fever of unknown origin and... (Review)
Review
: Infections are among the most frequent complications in patients with hematological and oncological diseases. They might be classified as fever of unknown origin and microbiologically or clinically documented infections. Optimal duration of antimicrobial treatment is still unclear in these patients.: We provide an overview on the management of febrile neutropenia in the perspective of antimicrobial de-escalation and discontinuation.: Patients with febrile high-risk neutropenia should be treated empirically with an anti-pseudomonal agent such as piperacillin/tazobactam. Several clinical studies support the assumption that the primary antibiotic regimen might be safely discontinued prior to neutrophil reconstitution if the patient is afebrile for several days and all infection-related symptoms have been resolved. Primary empirical treatment with carbapenems or antibiotic combinations should commonly only be considered in selected patient subgroups, such as patients with severe neutropenic sepsis or colonization with multidrug-resistant bacteria. Preemptive antifungal treatment guided by lung imaging and other parameters (e.g. serial galactomannan antigen screening) might reduce the consumption of antifungals compared to the classical empirical approach.Multidrug-resistant pathogens are emerging, and novel anti-infective agents under development are scarce. Therefore, a rational use of antimicrobials based on the principles of antibiotic stewardship is crucial.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Antifungal Agents; Antimicrobial Stewardship; Drug Resistance, Microbial; Drug Resistance, Multiple; Drug Therapy, Combination; Febrile Neutropenia; Humans
PubMed: 30686067
DOI: 10.1080/14787210.2019.1573670 -
Expert Review of Anti-infective Therapy Mar 2021Febrile neutropenia represents one of the most common treatment-associated complications in the management of acute myeloid leukemia (AML) and is considered an oncologic... (Review)
Review
INTRODUCTION
Febrile neutropenia represents one of the most common treatment-associated complications in the management of acute myeloid leukemia (AML) and is considered an oncologic emergency. Rapid and detailed workup as well as the initiation of empiric broad-spectrum antibiotic therapy are critical to avoid sepsis and to reduce mortality. Although a definitive source of infection is frequently not identified, the severely immunosuppressed status of the AML patient undergoing cytotoxic therapy results in a high risk for a wide array of bacterial, fungal, and viral etiologies.
AREAS COVERED
The authors herein review the diagnostic and therapeutic approach to the neutropenic leukemia patient based on the current knowledge. Special consideration is given to the rapidly changing therapeutic landscape in AML, creating new challenges in the management of infectious complications.
EXPERT OPINION
Multidrug-resistant organisms pose a major challenge in the management of neutropenic fever patients with hematologic malignancies - including AML. Future directions to improve outcomes demand innovative treatment approaches as well as advances in biomarker research to facilitate diagnosis and disease monitoring. Recent achievements in AML-targeted therapy led to an increased incidence of differentiation syndrome, a potentially life-threatening side effect that frequently resembles clinical infection and requires prompt recognition and aggressive intervention.
Topics: Adult; Animals; Anti-Infective Agents; Chemotherapy-Induced Febrile Neutropenia; Drug Resistance, Microbial; Drug Resistance, Multiple; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute
PubMed: 32892669
DOI: 10.1080/14787210.2020.1820863