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Current Opinion in Hematology Jan 2022Myeloid diseases are often characterized by a disturbed regulation of myeloid cell proliferation, survival, and maturation. This may either result in a severe paucity of... (Review)
Review
PURPOSE OF REVIEW
Myeloid diseases are often characterized by a disturbed regulation of myeloid cell proliferation, survival, and maturation. This may either result in a severe paucity of functional neutrophils (neutropenia), an excess production of mature cells (myeloproliferative disorders) or in clonal expansions of dysplastic or immature myeloid cells (myelodysplasia and acute myeloid leukemia). Although these conditions can be regarded as separate entities, caused by the accumulation of distinct sets of somatic gene mutations, it becomes increasingly clear that they may also evolve as the prime consequence of a congenital defect resulting in severe neutropenia. Prominent examples of such conditions include the genetically heterogeneous forms of severe congenital neutropenia (SCN) and Shwachman-Diamond Syndrome. CSF3 treatment is a successful therapy to alleviate neutropenia in the majority of these patients but does not cure the disease nor does it prevent malignant transformation. Allogeneic stem cell transplantation is currently the only therapeutic option to cure SCN, but is relatively cumbersome, e.g., hampered by treatment-related mortality and donor availability. Hence, there is a need for new therapeutic approaches.
RECENT FINDINGS
Developments in disease modeling, amongst others based on induced pluripotent stem cell and CRISPR/Cas9 based gene-editing technologies, have created new insights in disease biology and possibilities for treatment. In addition, they are fueling expectations for advanced disease monitoring to prevent malignant transformation.
SUMMARY
This review highlights the recent progress made in SCN disease modeling and discusses the challenges that are still ahead of us to gain a better understanding of the biological heterogeneity of the disease and its consequences for patient care.
Topics: Congenital Bone Marrow Failure Syndromes; Humans; Mutation; Myelodysplastic Syndromes; Neutropenia
PubMed: 34854832
DOI: 10.1097/MOH.0000000000000696 -
International Journal of Clinical... Sep 2023To determine the safety of cabazitaxel and predictors of severe neutropenia caused by cabazitaxel in a patient population that includes those with comorbidities. (Observational Study)
Observational Study
OBJECTIVE
To determine the safety of cabazitaxel and predictors of severe neutropenia caused by cabazitaxel in a patient population that includes those with comorbidities.
MATERIALS AND METHODS
Of 42 prostate cancer patients treated with cabazitaxel at Osaka Medical and Pharmaceutical University Hospital between September 2014 and June 2022, 33 were included in this study, whereas 6 patients who were outpatients and 3 who were discharged early within 7 days upon patient request were excluded. Logistic regression analysis was used to examine predictors of severe neutropenia.
RESULTS
Of the 33 eligible patients, 24 had comorbidities, with hypertension being the most common (n = 19), followed by dyslipidemia (n = 14) and diabetes (n = 11). There was no statistically significant difference in the rate of severe neutropenia due to any of the comorbidities, depending on the presence or absence of the comorbidity. However, the rate of severe neutropenia was significantly higher in patients with baseline platelet levels < 22.4×10/μL and those receiving cabazitaxel doses > 34 mg/body. In the final model adjusted for age, body mass index, C-reactive protein, and monocyte count, lower baseline platelet levels and higher doses of cabazitaxel were also predictors of the development of severe neutropenia.
CONCLUSION
Comorbidities such as hypertension, dyslipidemia, diabetes mellitus, cerebrovascular disease, chronic kidney disease, liver dysfunction, and cardiac disease did not affect the incidence of severe neutropenia in patients receiving cabazitaxel. The baseline platelet count and the dose of cabazitaxel were also suggested to be markers for the development of severe neutropenia.
Topics: Male; Humans; Platelet Count; Treatment Outcome; Prostatic Neoplasms, Castration-Resistant; Neutropenia; Comorbidity; Hypertension
PubMed: 37439521
DOI: 10.5414/CP204393 -
Annals of Hematology Jan 2022Immune checkpoint blockade has demonstrated durable clinical benefits in a variety of malignancies. These immune checkpoint inhibitors (ICIs) produce unwanted autoimmune... (Review)
Review
Immune checkpoint blockade has demonstrated durable clinical benefits in a variety of malignancies. These immune checkpoint inhibitors (ICIs) produce unwanted autoimmune reactions due to an impaired self-tolerance. Hematologic immune-related adverse events (heme-irAEs) have been increasingly reported in the literature with a reported fatality rate of 12%. In this review, we illustrate 3 cases treated at Johns Hopkins Hospital for ICI-induced agranulocytosis, aplastic anemia, and thrombocytopenia. We then summarize the available evidence regarding the incidence and prevalence of heme-irAEs. We identified immune thrombocytopenia and hemolytic anemia as the most commonly reported heme-irAEs which are more commonly observed with nivolumab therapy. Median time to onset of heme-irAEs varies between patients but occurs earlier with CTLA-4 inhibitors than with anti-PD-L1/PD-1 agents. We also describe the current challenges regarding the recurrence of heme-irAEs despite immune checkpoint blockade termination. We provide the available evidence supporting a mixed T-cell and B-cell immune-mediated response. Finally, we review the treatment algorithm of these complications and provide treatment alternatives to steroid-refractory cases.
Topics: Aged; Agranulocytosis; Anemia, Aplastic; Anemia, Hemolytic; Disease Management; Female; Humans; Immune Checkpoint Inhibitors; Male; Middle Aged; Neoplasms; Purpura, Thrombocytopenic, Idiopathic
PubMed: 34962580
DOI: 10.1007/s00277-021-04690-x -
The Pharmacogenomics Journal Jul 2022Although clozapine is the most effective pharmacotherapy for treatment-resistant schizophrenia, it is under-utilized, and initiation is often delayed. One reason is the... (Meta-Analysis)
Meta-Analysis
Although clozapine is the most effective pharmacotherapy for treatment-resistant schizophrenia, it is under-utilized, and initiation is often delayed. One reason is the occurrence of a potentially fatal adverse reaction, clozapine-induced agranulocytosis (CIA). Identifying genetic variations contributing to CIA would help predict patient risk of developing CIA and personalize treatment. Here, we (1) review existing pharmacogenomic studies of CIA, and (2) conduct meta-analyses to identify targets for clinical implementation. A systematic literature search identified studies that included individuals receiving clozapine who developed CIA and controls who did not. Results showed that individuals carrying the HLA-DRB1*04:02 allele had nearly sixfold (95% CI 2.20-15.80, p = 0.03) higher odds of CIA with a negative predictive value of 99.3%. Previously unreplicated alleles, TNFb5, HLA-B*59:01, TNFb4, and TNFd3 showed significant associations with CIA after multiple-testing corrections. Our findings suggest that a predictive HLA-DRB1*04:02-based pharmacogenomic test may be promising for clinical implementation but requires further investigation.
Topics: Agranulocytosis; Alleles; Antipsychotic Agents; Clozapine; Humans; Pharmacogenetics; Pharmacogenomic Testing
PubMed: 35710824
DOI: 10.1038/s41397-022-00281-9 -
Supportive Care in Cancer : Official... Nov 2023Neutropenic ulcerations are characterized by mucosal ulcerations which occur in the presence of neutropenia, suggesting a direct link between neutropenia and mucosal... (Review)
Review
Neutropenic ulcerations are characterized by mucosal ulcerations which occur in the presence of neutropenia, suggesting a direct link between neutropenia and mucosal ulceration. An oral ulcer can be labeled as "neutropenic" only if the patients have primary (typically congenital) or secondary neutropenia, and neutropenia is the sole causative factor. Oral mucosal ulcers observed in patients undergoing oncologic therapy may also be termed as "neutropenic ulcers", but the pathogenesis of these oral ulcers more likely involves mucosal events related to trauma, microbial factors, and direct cytotoxicity. In cancer patients, the early appearance of oral ulcers is often attributed to oral mucositis which is a condition primarily caused by the direct mucosal cytotoxicity of chemotherapeutic agents and radiation therapy. Oral ulcers that develop later during or after active cancer therapy may result from intraoral trauma and typically manifest on non-keratinized areas of the oral mucosa which are more susceptible to mucosal damage. In patients undergoing chemotherapy, factors such as disturbances in mucosal barrier function as well as bone marrow suppression lead to reduced neutrophil count and function, and can contribute to the development of oral ulcers. While the etiology of oral ulcers in cancer therapy receiving patients can vary, it is important to emphasize that the host's response plays a crucial role in the progression and repair process of these lesions. This narrative review presents the etiopathogenesis, clinical presentation, and potential management approaches for oral ulcerations in neutropenic patients, with a particular focus on clarifying the usage of the term "neutropenic ulcer" since this term lacks diagnostic specificity and can be misleading in clinical practice regarding the underlying causes and treatment strategies.
Topics: Humans; Ulcer; Oral Ulcer; Medical Oncology; Neutropenia; Neoplasms
PubMed: 37991547
DOI: 10.1007/s00520-023-08187-3 -
Clinical Medicine (London, England) Jan 2023The general medical physician will often encounter patients who develop acute complications of their cancer diagnosis or anti-cancer treatment. Here we provide an...
The general medical physician will often encounter patients who develop acute complications of their cancer diagnosis or anti-cancer treatment. Here we provide an overview of emergency solid tumour oncology to guide the initial management of these patients.
Topics: Humans; Sepsis; Neutropenia; Neoplasms
PubMed: 36697019
DOI: 10.7861/clinmed.2022-0561 -
The American Journal of Emergency... Dec 2021Care of pediatric cancer patients is increasingly being provided by physicians in community settings, including general emergency departments. Guidelines based on... (Review)
Review
INTRODUCTION
Care of pediatric cancer patients is increasingly being provided by physicians in community settings, including general emergency departments. Guidelines based on current evidence have standardized the care of children undergoing chemotherapy or hematopoietic stem cell transplantation (HSCT) presenting with fever and neutropenia (FN).
OBJECTIVE
This narrative review evaluates the management of pediatric patients with cancer and neutropenic fever and provides comparison with the care of the adult with neutropenic fever in the emergency department.
DISCUSSION
When children with cancer and FN first present for care, stratification of risk is based on a thorough history and physical examination, baseline laboratory and radiologic studies and the clinical condition of the patient, much like that for the adult patient. Prompt evaluation and initiation of intravenous broad-spectrum antibiotics after cultures are drawn but before other studies are resulted is critically important and may represent a practice difference for some emergency physicians when compared with standardized adult care. Unlike adults, all high-risk and most low-risk children with FN undergoing chemotherapy require admission for parenteral antibiotics and monitoring. Oral antibiotic therapy with close, structured outpatient monitoring may be considered only for certain low-risk patients at pediatric centers equipped to pursue this treatment strategy.
CONCLUSIONS
Although there are many similarities between the emergency approach to FN in children and adults with cancer, there are differences that every emergency physician should know. This review provides strategies to optimize the care of FN in children with cancer in all emergency practice settings.
Topics: Adolescent; Age Factors; Antineoplastic Agents; Child; Child, Preschool; Emergency Service, Hospital; Fever; Humans; Infant; Infant, Newborn; Neoplasms; Neutropenia
PubMed: 34879488
DOI: 10.1016/j.ajem.2021.09.055 -
Clinical Infectious Diseases : An... May 2022
Topics: Cell-Free Nucleic Acids; Febrile Neutropenia; High-Throughput Nucleotide Sequencing; Humans; Immunocompromised Host
PubMed: 33870419
DOI: 10.1093/cid/ciab326 -
BMJ Case Reports Jan 2021We present a case of a 75-year-old woman with Austrian syndrome: pneumonia, meningitis and endocarditis all due to Transoesophageal echocardiogram demonstrated a large...
We present a case of a 75-year-old woman with Austrian syndrome: pneumonia, meningitis and endocarditis all due to Transoesophageal echocardiogram demonstrated a large mitral valve vegetation with severe mitral regurgitation. She was treated with intravenous ceftriaxone and listed for surgical repair of her mitral valve. Preoperatively, she developed an idiosyncratic drug-induced agranulocytosis secondary to ceftriaxone, which resolved on cessation of the medication. However, while awaiting neutrophil recovery, she developed an acute deterioration, becoming critically unwell. This deterioration was multifactorial, with acute decompensated heart failure alongside COVID-19. After multidisciplinary discussion, she was considered too unwell for surgery and palliated.
Topics: Aged; Agranulocytosis; Anti-Bacterial Agents; COVID-19; Ceftriaxone; Comorbidity; Echocardiography, Transesophageal; Endocarditis, Bacterial; Female; Humans; Meningitis, Bacterial; Pandemics; Pneumococcal Infections; SARS-CoV-2; Streptococcus pneumoniae; Syndrome
PubMed: 33408111
DOI: 10.1136/bcr-2020-239355 -
Expert Review of Hematology Nov 2022Copper is increasingly being recognized as a vital mineral required by both animals and humans. It plays a vital role in many metabolic processes such as cellular... (Review)
Review
INTRODUCTION
Copper is increasingly being recognized as a vital mineral required by both animals and humans. It plays a vital role in many metabolic processes such as cellular respiration, iron oxidation, and hemoglobin synthesis. Copper deficiency, which can be hereditary or acquired, can lead to a wide spectrum of disease processes such as ringed sideroblastic anemia, myelodysplasia, and pancytopenia. Timely identification and management of copper deficiency is necessary to prevent irreversible complications.
AREAS COVERED
Our study focuses on prevalence, etiology, pathophysiology, complications, and treatment of copper deficiency.
EXPERT OPINION
Copper deficiency is frequently underrecognized as the cause of anemia, neutropenia, and bone marrow dysplasia. As it is potentially treatable, it should always be kept in the differentials when patients present with neurological and hematological abnormalities.
Topics: Animals; Humans; Pancytopenia; Copper; Anemia; Hematologic Diseases; Neutropenia; Myelodysplastic Syndromes
PubMed: 36314081
DOI: 10.1080/17474086.2022.2142113