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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 -
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 -
Tidsskrift For Den Norske Laegeforening... Jun 2023Neutrophils are an important component of the innate immune system, and they prevent bacterial and fungal infections by phagocytosis and killing of pathogens....
Neutrophils are an important component of the innate immune system, and they prevent bacterial and fungal infections by phagocytosis and killing of pathogens. Neutropenia is defined as an abnormally low number of circulating neutrophils, and the term chronic neutropenia is used when it lasts more than three months. The objective of this clinical review is to raise awareness among doctors in Norway of chronic neutropenia and possible causes. A patient with severe neutropenia and fever requires immediate admission to hospital and initiation of empiric sepsis treatment before the cause of neutropenia has been determined, but patients with chronic neutropenia do not always require rapid and extensive workup.
Topics: Humans; Adult; Neutropenia; Cognition; Fever; Hospitalization; Hospitals
PubMed: 37341406
DOI: 10.4045/tidsskr.22.0491 -
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 -
Frontiers in Immunology 2021Severe congenital neutropenia (SCN) is a rare hematological condition with heterogenous genetic background. Neutrophil elastase (NE) encoded by gene is mutated in over... (Review)
Review
Severe congenital neutropenia (SCN) is a rare hematological condition with heterogenous genetic background. Neutrophil elastase (NE) encoded by gene is mutated in over half of the SCN cases. The role of NE defects in myelocytes maturation arrest in bone marrow is widely investigated; however, the mechanism underlying this phenomenon has still remained unclear. In this review, we sum up the studies exploring mechanisms of neutrophil deficiency, biological role of NE in neutrophil and the effects of mutation and neutropenia pathogenesis. We also explain the hypotheses presented so far and summarize options of neutropenia therapy.
Topics: Congenital Bone Marrow Failure Syndromes; Gene Expression Regulation; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Leukocyte Elastase; Mutation; Neutropenia; Neutrophils; Protein Processing, Post-Translational; Protein Transport; Signal Transduction; Structure-Activity Relationship
PubMed: 33968054
DOI: 10.3389/fimmu.2021.653932 -
The Journal of Antimicrobial... Nov 2022Most invasive fungal infections are opportunistic in nature but the epidemiology is constantly changing, with new risk groups being identified. Neutropenia is a...
Most invasive fungal infections are opportunistic in nature but the epidemiology is constantly changing, with new risk groups being identified. Neutropenia is a classical risk factor for fungal infections, while critically ill patients in the ICU are now increasingly at risk of yeast and mould infections. Factors to be considered when choosing antifungal treatment include the emergence of rarer fungal pathogens, the risk of resistance to azoles and echinocandins and the possibility of drug-drug interactions. Liposomal amphotericin B has retained its place in the therapeutic armamentarium based on its clinical profile: a broad spectrum of antifungal activity with a low risk of resistance, predictable pharmacokinetics with a rapid accumulation at the infection site (including biofilms), a low potential for drug-drug interactions and a low risk of acute and chronic treatment-limiting toxicities versus other formulations of amphotericin B. It is a suitable choice for the first-line empirical or pre-emptive treatment of suspected fungal infections in neutropenic haematology patients and is an excellent alternative for patients with documented fungal disease who can no longer tolerate or continue their first-line azole or echinocandin therapy, both in the haematology setting and in the ICU. Moreover, it is the first-line drug of choice for the treatment of invasive mucormycosis. Finally, liposomal amphotericin B is one of the few antifungal agents approved for use in children of all ages over 1 month and is included in paediatric-specific guidelines for the management of fungal disease.
Topics: Humans; Amphotericin B; Antifungal Agents; Azoles; Echinocandins; Neutropenia; Invasive Fungal Infections
PubMed: 36426672
DOI: 10.1093/jac/dkac352 -
Emerging Infectious Diseases Jan 2021Invasive fusariosis (IF) is associated with severe neutropenia in patients with concurrent hematologic conditions. We conducted a retrospective observational study to... (Review)
Review
Invasive fusariosis (IF) is associated with severe neutropenia in patients with concurrent hematologic conditions. We conducted a retrospective observational study to characterize the epidemiology of IF in 18 Spanish hospitals during 2000-2015. In that time, the frequency of IF in nonneutropenic patients increased from 0.08 cases per 100,000 admissions in 2000-2009 to 0.22 cases per 100,000 admissions in 2010-2015. Nonneutropenic IF patients often had nonhematologic conditions, such as chronic cardiac or lung disease, rheumatoid arthritis, history of solid organ transplantation, or localized fusariosis. The 90-day death rate among nonneutropenic patients (28.6%) and patients with resolved neutropenia (38.1%) was similar. However, the death rate among patients with persistent neutropenia (91.3%) was significantly higher. We used a multivariate Cox regression analysis to characterize risk factors for death: persistent neutropenia was the only risk factor for death, regardless of antifungal therapy.
Topics: Antifungal Agents; Fusariosis; Fusarium; Humans; Neutropenia; Observational Studies as Topic; Spain
PubMed: 33352085
DOI: 10.3201/eid2701.190782 -
Frontiers in Immunology 2022Although chimeric antigen receptor T (CAR-T) cell therapy has been indicated to be effective in treating relapsed or refractory multiple myeloma (R/R MM), severe... (Clinical Trial)
Clinical Trial
UNLABELLED
Although chimeric antigen receptor T (CAR-T) cell therapy has been indicated to be effective in treating relapsed or refractory multiple myeloma (R/R MM), severe hematological toxicity (HT) remains an intractable issue. This study enrolled 54 patients with R/R MM following combined infusion of anti-CD19 and anti-BCMA CAR-T cells. The results showed that the rates of severe cytopenia were high, including severe neutropenia (28/54, 52%), severe anemia (15/54, 28%), and severe thrombocytopenia (18/54, 33%). Moreover, the incidence of prolonged HT (PHT) on Day 28 post-infusion was 52% (28/54), including 46% for severe neutropenia, 30% for severe anemia, and 31% for severe thrombocytopenia. Patients with PHT had a poorer median progression-free survival (PFS) and overall survival (OS) than patients without PHT (=0.011; =0.007). Furthermore, Cox regression analyses showed that PHT was an independent risk factor for PFS and OS. Univariate analyses showed that IFNγ (OR: 1.046; 95% CI: 1.002-1.093, =0.042) and severe HT after lymphodepletion chemotherapy (OR: 0.082; 95% CI: 0.017-0.404; =0.002) were independent risk factors for PHT. In conclusion, these results indicated that PHT was associated with poor outcomes following CAR-T-cell therapy in MM patients. Early detection and management of PHT would be beneficial for the prevention of life-threatening complications and improvement in the survival of patients after CAR-T-cell therapy.
CLINICAL TRIAL REGISTRATION
This trial was registered on 1 May 2017 at http://www.chictr.org.cn as ChiCTR-OIC-17011272.
Topics: Humans; Anemia; Antigens, CD19; B-Cell Maturation Antigen; Cell- and Tissue-Based Therapy; Multiple Myeloma; Neutropenia; Receptors, Chimeric Antigen; Thrombocytopenia
PubMed: 36330523
DOI: 10.3389/fimmu.2022.1019548 -
BMJ Case Reports Dec 2019
Topics: Adult; Anti-Bacterial Agents; Female; Granulocyte Colony-Stimulating Factor; Humans; Multiple Sclerosis; Neutropenia; Rituximab
PubMed: 31888912
DOI: 10.1136/bcr-2019-233569 -
Molecular Genetics and Metabolism Aug 2022Because of the broad clinical spectrum, heritable autoinflammatory diseases present a management and therapeutic challenge. The most common genetic interferonopathy,...
BACKGROUND
Because of the broad clinical spectrum, heritable autoinflammatory diseases present a management and therapeutic challenge. The most common genetic interferonopathy, Aicardi Goutières Syndrome (AGS), is associated with early onset neurologic disability and systemic inflammation. The chronic inflammation of AGS is the result of dysregulation of interferon (IFN) expression by one of nine genes within converging pathways. While each AGS subtype shares common features, distinct patterns of severity and potential for systemic complications amongst the genotypes are emerging. Multilineage cytopenias are a potentially serious, but poorly understood, complication of AGS. As immunomodulatory treatment options are developed, it is important to characterize the role of the disease versus treatment in hematologic abnormalities. This will allow for better understanding and management of cytopenia.
METHODS
In total, 142 individuals with molecularly-confirmed AGS were included. Information on genotype, demographics, and all available hematologic laboratory values were collected from existing medical records. As part of a clinical trial, a subset of this cohort (n = 52) were treated with a janus kinase inhibitor (baricitinib), and both pre- and post-treatment values were included. Abnormal values were graded based on Common Terminology Criteria for Adverse Events (CTCAE v5.0), supplemented with grading definitions for thrombocytosis, and were compared across genotypes and baricitinib exposure.
RESULTS
In total, 11,184 laboratory values were collected over a median of 2.54 years per subject (range 0-22.68 years). To reduce bias from repeated sampling within a limited timeframe, laboratory results were restricted to the most abnormal value within a month (n = 8485). The most common abnormalities were anemia (noted in 24% of subjects prior to baricitinib exposure), thrombocytopenia (9%), and neutropenia (30%). Neutropenia was most common in the SAMHD1 cohort and increased with baricitinib exposure (38/69 measurements on baricitinib versus 14/121 while not on baricitinib). Having an abnormality prior to treatment was associated with having an abnormality on treatment for neutropenia and thrombocytopenia.
CONCLUSION
By collecting available laboratory data throughout the lifespan, we were able to identify novel patterns of hematologic abnormalities in AGS. We found that AGS results in multilineage cytopenias not limited to the neonatal period. Neutropenia, anemia, and thrombocytopenia were common. Moderate-severe graded events of neutropenia, anemia, and leukopenia were more common on baricitinib, but rarely of clinical consequence. Based on these results, we would recommend careful monitoring of hematologic parameters of children affected by AGS throughout the lifespan, especially while on therapy, and consideration of AGS as a potential differential diagnosis in children with neurologic impairment of unclear etiology with hematologic abnormalities. Trial registration ClinicalTrials.gov Identifier: NCT01724580 ClinicalTrials.gov Identifier: NCT03921554.
Topics: Anemia; Autoimmune Diseases of the Nervous System; Child; Humans; Infant, Newborn; Inflammation; Nervous System Malformations; Neutropenia; Thrombocytopenia
PubMed: 35786528
DOI: 10.1016/j.ymgme.2022.06.003