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Experimental and Clinical... Oct 2021Renal transplant is considered the best therapeutic option for suitable patients with end-stage kidney failure. Hematological complications that occur after kidney... (Review)
Review
Renal transplant is considered the best therapeutic option for suitable patients with end-stage kidney failure. Hematological complications that occur after kidney transplant include posttransplant anemia, leukopenia, neutropenia, and thrombocytopenia. Severely persistent leukopenia and neutropenia events predispose patients to infection, including opportunistic infections. The mainstay tactic for such complications is to reduce the burden of the immunosuppression by the offending agent, but this tactic is associated with increased risk of acute rejection. Given the absence of laboratory investigations to specifically identify the culprit, a complete withdrawal of these agents may be the ultimate diagnostic option. Future therapeutic strategies, however, should focus on reducing the immunosuppressive burden, the introduction of less myelotoxic agents, early recognition, and prompt treatment of infectious episodes. This will help in the optimization of the myelopoietic function and normalization of the hematological profile, resulting in better allograft and patient survival.
Topics: Anemia; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Neutropenia; Treatment Outcome
PubMed: 33736582
DOI: 10.6002/ect.2020.0100 -
Current Oncology Reports Jun 2022Pediatric oncology patients frequently experience episodes of prolonged neutropenia which puts them at high risk for infection with significant morbidity and mortality.... (Review)
Review
PURPOSE OF REVIEW
Pediatric oncology patients frequently experience episodes of prolonged neutropenia which puts them at high risk for infection with significant morbidity and mortality. Here, we review the data on infection prophylaxis with a focus on both pharmacologic and ancillary interventions. This review does not include patients receiving hematopoietic stem cell transplantation.
RECENT FINDINGS
Patients with hematologic malignancies are at highest risk for infection. Bacterial and fungal prophylaxis decrease the risk of infection in certain high-risk groups. Ancillary measures such as ethanol locks, chlorhexidine gluconate baths, GCSF, IVIG, and mandatory hospitalization do not have enough data to support routine use. There is limited data on risk of infection and role of prophylaxis in patients receiving immunotherapy and patients with solid tumors. Patients with Down syndrome and adolescent and young adult patients may benefit from additional supportive care measures and protocol modifications. Consider utilizing bacterial and fungal prophylaxis in patients with acute myeloid leukemia or relapsed acute lymphoblastic leukemia. More research is needed to evaluate other supportive care measures and the role of prophylaxis in patients receiving immunotherapy.
Topics: Adolescent; Antibiotic Prophylaxis; Antifungal Agents; Child; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Neutropenia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Young Adult
PubMed: 35230594
DOI: 10.1007/s11912-022-01192-5 -
Current Opinion in Hematology Jan 2013Neutropenia is a feature of several primary immunodeficiency diseases (PIDDs). Because of the diverse pathophysiologies of the PIDDs and the rarity of each disorder,... (Review)
Review
PURPOSE OF REVIEW
Neutropenia is a feature of several primary immunodeficiency diseases (PIDDs). Because of the diverse pathophysiologies of the PIDDs and the rarity of each disorder, data are often lacking, leading to the necessity of empiric treatment. Recent developments in the understanding of neutropenia in several of the PIDDs make a review of the data timely.
RECENT FINDINGS
The category of severe congenital neutropenia continues to expand. Mutations in G6PC3 have been identified as the cause of neutropenia in a minority of previously molecularly undefined cases. Recent advances have broadened our understanding of the pathophysiology and the clinical expression of this disorder. A possible function of the C16orf57 gene has been hypothesized that may explain the clinical overlap between Clerucuzio-type poikiloderma with neutropenia and other marrow diseases. Plerixafor has been shown to be a potentially useful treatment in the warts, hypogammaglobulinemia, infection, and myelokathexis syndrome. Investigations of patients with adenosine deaminase deficient severe combined immunodeficiency have identified neutropenia, and particularly susceptibility to myelotoxins, as a feature of this disorder. Granulocyte-colony stimulating factor is the treatment of choice for neutropenia in PIDD, whereas hematopoietic cell transplantation is the only curative option.
SUMMARY
The number of PIDDs associated with neutropenia has increased, as has our understanding of the range of phenotypes. Additional data and hypotheses have been generated helping to explain the diversity of presentations of neutropenia in PIDDs.
Topics: Animals; Hematopoietic Stem Cell Transplantation; Humans; Immunologic Deficiency Syndromes; Neutropenia
PubMed: 23196894
DOI: 10.1097/MOH.0b013e32835aef1c -
Current Opinion in Hematology Jan 2017Neutropenia lasting for at least for 3 months and not attributable to drugs or a specific genetic, infectious, inflammatory, autoimmune or malignant cause is called... (Review)
Review
PURPOSE OF REVIEW
Neutropenia lasting for at least for 3 months and not attributable to drugs or a specific genetic, infectious, inflammatory, autoimmune or malignant cause is called chronic idiopathic neutropenia (CIN). CIN and autoimmune neutropenia (AIN) are very similar and overlapping conditions. The clinical consequences depend upon the severity of neutropenia, but it is not considered a premalignant condition.
RECENT FINDINGS
Long-term observational studies in children indicate that the disease often lasts for 3-5 years in children, then spontaneously remits, but it rarely remits in adult cases. The value of antineutrophil antibody testing in both children and adults is uncertain. Most recent data suggest that CIN and AIN are immune-mediated diseases, but there are no new clinical or genetic tests to aid in diagnosis. Treatment with granulocyte colony stimulating factor (G-CSF) is effective to increase blood neutrophils in almost all cases; this treatment is reserved, however, for patients with both neutropenia and evidence of recurrent fevers, inflammatory symptoms and infections. There is little or no evidence to indicate that G-CSF treatment predisposes to myeloid malignancies in this population.
SUMMARY
It is important to recognize CIN and AIN, the most common causes of chronic neutropenia in both children and adults. If the neutropenia is not severe, that is more than 0.5 × 10/l, most patients can be observed and not treated prophylactically with antibiotics or a growth factor. When neutropenia is severe, treatment with G-CSF is often beneficial.
Topics: Chronic Disease; Combined Modality Therapy; Female; Genetic Testing; Granulocyte Colony-Stimulating Factor; Humans; Leukocyte Count; Neutropenia; Pregnancy; Prevalence; Risk Factors
PubMed: 27841775
DOI: 10.1097/MOH.0000000000000305 -
Acta Medica Portuguesa Nov 1998The authors reviewed the subject of neutropenia in what concern its definition, pathophysiology, clinical features, diagnosis and principles of treatment. A new... (Review)
Review
The authors reviewed the subject of neutropenia in what concern its definition, pathophysiology, clinical features, diagnosis and principles of treatment. A new pathophysiological classification of neutropenia and an evaluation of neutropenic patients are proposed. The extent of laboratory evaluation depends greatly on the duration and severity of the neutropenia. The hematopoietic growth factors controlling the growth, development, differentiation and activation of the hematopoietic progenitor cells have revolutionized the treatment of neutropenia.
Topics: Humans; Neutropenia
PubMed: 10021799
DOI: No ID Found -
Clinical Infectious Diseases : An... May 2022Standard testing fails to identify a pathogen in most patients with febrile neutropenia (FN). We evaluated the ability of the Karius microbial cell-free DNA sequencing...
BACKGROUND
Standard testing fails to identify a pathogen in most patients with febrile neutropenia (FN). We evaluated the ability of the Karius microbial cell-free DNA sequencing test (KT) to identify infectious etiologies of FN and its impact on antimicrobial management.
METHODS
This prospective study (ClinicalTrials.gov; NCT02912117) enrolled and analyzed 55 patients with FN. Up to 5 blood samples were collected per subject within 24 hours of fever onset (T1) and every 2 to 3 days. KT results were compared with blood culture (BC) and standard microbiological testing (SMT) results.
RESULTS
Positive agreement was defined as KT identification of ≥1 isolate also detected by BC. At T1, positive and negative agreement were 90% (9/10) and 31% (14/45), respectively; 61% of KT detections were polymicrobial. Clinical adjudication by 3 independent infectious diseases specialists categorized Karius results as: unlikely to cause FN (N = 0); definite (N = 12): KT identified ≥1 organism also found by SMT within 7 days; probable (N = 19): KT result was compatible with a clinical diagnosis; possible (N = 10): KT result was consistent with infection but not considered a common cause of FN. Definite, probable, and possible cases were deemed true positives. Following adjudication, KT sensitivity and specificity were 85% (41/48) and 100% (14/14), respectively. Calculated time to diagnosis was generally shorter with KT (87%). Adjudicators determined real-time KT results could have allowed early optimization of antimicrobials in 47% of patients, by addition of antibacterials (20%) (mostly against anaerobes [12.7%]), antivirals (14.5%), and/or antifungals (3.6%); and antimicrobial narrowing in 27.3% of cases.
CLINICAL TRIALS REGISTRATION
NCT02912117.
CONCLUSION
KT shows promise in the diagnosis and treatment optimization of FN.
Topics: Anti-Bacterial Agents; Cell-Free Nucleic Acids; Febrile Neutropenia; Fever; High-Throughput Nucleotide Sequencing; Humans; Prospective Studies
PubMed: 33870413
DOI: 10.1093/cid/ciab324 -
Cells Oct 2021Large granular lymphocyte leukemia (LGLL) is a rare lymphoproliferative disorder characterized by the clonal expansion of cytotoxic T-LGL or NK cells. Chronic isolated... (Review)
Review
Large granular lymphocyte leukemia (LGLL) is a rare lymphoproliferative disorder characterized by the clonal expansion of cytotoxic T-LGL or NK cells. Chronic isolated neutropenia represents the clinical hallmark of the disease, being present in up to 80% of cases. New advances were made in the biological characterization of neutropenia in these patients, in particular mutations and a discrete immunophenotype are now recognized as relevant features. Nevertheless, the etiology of LGLL-related neutropenia is not completely elucidated and several mechanisms, including humoral abnormalities, bone marrow infiltration/substitution and cell-mediated cytotoxicity might cooperate to its pathogenesis. As a consequence of the multifactorial nature of LGLL-related neutropenia, a targeted therapeutic approach for neutropenic patients has not been developed yet; moreover, specific guidelines based on prospective trials are still lacking, thus making the treatment of this disorder a complex and challenging task. Immunosuppressive therapy represents the current, although poorly effective, therapeutic strategy. The recent identification of a STAT3-mediated miR-146b down-regulation in neutropenic T-LGLL patients emphasized the pathogenetic role of STAT3 activation in neutropenia development. Accordingly, JAK/STAT3 axis inhibition and miR-146b restoration might represent tempting strategies and should be prospectively evaluated for the treatment of neutropenic LGLL patients.
Topics: Diagnosis, Differential; Fas Ligand Protein; Humans; Immunophenotyping; Leukemia, Large Granular Lymphocytic; Neutropenia; Prognosis
PubMed: 34685780
DOI: 10.3390/cells10102800 -
Biochimica Et Biophysica Acta.... Oct 2023HAX1 is a relatively small, ubiquitously expressed, predominantly mitochondrial, intrinsically disordered protein. It has been implicated in the regulation of apoptosis,... (Review)
Review
HAX1 is a relatively small, ubiquitously expressed, predominantly mitochondrial, intrinsically disordered protein. It has been implicated in the regulation of apoptosis, cell migration, calcium cycling, proteostasis, angiogenesis, autophagy and translation. A wide spectrum of functions, numerous interactions and still elusive molecular mechanisms of action make HAX1 an intriguing subject of research. Moreover, HAX1 is involved in the pathogenesis of diseases; its deficiency leads to neutropenia and its overexpression is associated with cancer. In this review we aim to describe the characteristics of HAX1 gene and protein, and comprehensively discuss its multiple functions, highlighting the emerging role of HAX1 in protection from stress and apoptosis through maintaining cellular proteostasis and homeostasis.
Topics: Humans; Adaptor Proteins, Signal Transducing; Mitochondria; Transcription Factors; Neutropenia
PubMed: 37454914
DOI: 10.1016/j.bbamcr.2023.119538 -
BMJ Case Reports Jan 2020Neutropaenia is defined as an absolute neutrophil count (ANC) of less than 1500 cells/µL and is often divided into mild (ANC: 1000 to 1500 cells/µL), moderate...
Neutropaenia is defined as an absolute neutrophil count (ANC) of less than 1500 cells/µL and is often divided into mild (ANC: 1000 to 1500 cells/µL), moderate (ANC: 500 to 1000 cells/µL) and severe (ANC: >500 cells/µL) neutropaenia. Autoimmune neutropaenia is arguably one of the most clinically relevant forms of neutropaenia and is defined by an ANC of <500 cells/µL alongside the confirmed presence of anti-neutrophil antibodies. It is a rare subset of neutropaenia boasting an incidence of just 1 in 100 000 infants and is thought to be caused as a result of a 'surveillance escape event' of the immune system. This case report identifies key issues in the diagnosis and monitoring of paediatric patients with recurrent neutropaenia and reviews current literature relating to its management in hospital and community settings.
Topics: Autoimmune Diseases; Delayed Diagnosis; Female; Humans; Infant; Neutropenia
PubMed: 31969396
DOI: 10.1136/bcr-2019-229979 -
Internal Medicine (Tokyo, Japan) Feb 2003
Topics: Autoantibodies; Autoimmune Diseases; Combined Modality Therapy; Drug Therapy, Combination; Female; Humans; Male; Multiple Sclerosis; Neutropenia; Prognosis; Risk Assessment; Splenectomy
PubMed: 12636227
DOI: 10.2169/internalmedicine.42.133