NCCN Guidelines® Insights: Systemic Mastocytosis, Version 3.2024.

Mastocytosis is a heterogeneous group of disorders comprising cutaneous mastocytosis, systemic mastocytosis, and mast cell sarcoma. It is associated with a variety of symptoms related to the release of mast cell mediators and mast cell tissue infiltration. Referral to specialized centers with expertise in the management of mastocytosis and multidisciplinary collaboration with subspecialists (eg, allergists for the management of anaphylaxis and drug hypersensitivities, anesthesiologists for invasive procedures or surgery, high-risk obstetrician for pregnancy) is recommended.

A 35-Year-Old Man with Fever.

A 35-Year-Old Man with FeverA 35-year-old man presented for evaluation of fever for 2 weeks with left-sided abdominal pain. How do you approach the evaluation, and what is the diagnosis?

Cancer-Associated Thrombosis: Risk Assessment, Prevention, and Treatment.

The risk of developing venous thromboembolism (VTE) is four to seven times higher in patients with cancer than in those without. At JADPRO Live 2022, presenters discussed risk factors and assessing patients for VTE, as well as how to protect patients against VTE in both the inpatient and outpatient clinic settings. They reviewed selecting an appropriate anticoagulation treatment, including the choice of agent and duration of treatment for the patient with cancer, and finally the steps needed to assess and treat patients experiencing therapeutic anticoagulation failure.

PI3K Inhibition Restores and Amplifies Response to Ruxolitinib in Patients with Myelofibrosis.

Purpose: Treatment options are limited beyond JAK inhibitors for patients with primary myelofibrosis (MF) or secondary MF. Preclinical studies have revealed that PI3Kδ inhibition cooperates with ruxolitinib, a JAK1/2 inhibitor, to reduce proliferation and induce apoptosis of JAK2V617F-mutant cell lines.

Patients And Methods: In a phase I dose-escalation and -expansion study, we evaluated the safety and efficacy of a selective PI3Kδ inhibitor, umbralisib, in combination with ruxolitinib in patients with MF who had a suboptimal response or lost response to ruxolitinib.

Myeloproliferative Neoplasms, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology.

The classic Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) consist of myelofibrosis, polycythemia vera, and essential thrombocythemia and are a heterogeneous group of clonal blood disorders characterized by an overproduction of blood cells. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for MPN were developed as a result of meetings convened by a multidisciplinary panel with expertise in MPN, with the goal of providing recommendations for the management of MPN in adults. The Guidelines include recommendations for the diagnostic workup, risk stratification, treatment, and supportive care strategies for the management of myelofibrosis, polycythemia vera, and essential thrombocythemia.

Cancer-Associated Venous Thromboembolic Disease, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology.

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cancer-Associated Venous Thromboembolic Disease focus on the prevention, diagnosis, and treatment of patients with cancer who have developed or who are at risk for developing venous thromboembolism (VTE). VTE is a significant concern among cancer patients, who are at heightened risks for developing as well as dying from the disease. The management of patients with cancer with VTE often requires multidisciplinary efforts at treating institutions.

Myeloid/Lymphoid Neoplasms with Eosinophilia and TK Fusion Genes, Version 3.2021, NCCN Clinical Practice Guidelines in Oncology.

Eosinophilic disorders and related syndromes represent a heterogeneous group of neoplastic and nonneoplastic conditions, characterized by more eosinophils in the peripheral blood, and may involve eosinophil-induced organ damage. In the WHO classification of myeloid and lymphoid neoplasms, eosinophilic disorders characterized by dysregulated tyrosine kinase (TK) fusion genes are recognized as a new category termed, myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB or FGFR1 or with PCM1-JAK2. In addition to these aforementioned TK fusion genes, rearrangements involving FLT3 and ABL1 genes have also been described.

Safety and Outcomes of Permanent and Retrievable Inferior Vena Cava Filters in the Oncology Population.

Background: The role for inferior vena cava (IVC) filters in the oncology population is poorly defined.

Objectives: Our primary endpoint was to determine the rate of filter placement in cancer patients without an absolute contraindication to anticoagulation and the rate of recurrent VTE after filter placement in both retrievable and permanent filter groups. /.

TNF-α-driven inflammation and mitochondrial dysfunction define the platelet hyperreactivity of aging.

Aging and chronic inflammation are independent risk factors for the development of atherothrombosis and cardiovascular disease. We hypothesized that aging-associated inflammation promotes the development of platelet hyperreactivity and increases thrombotic risk during aging. Functional platelet studies in aged-frail adults and old mice demonstrated that their platelets are hyperreactive and form larger thrombi.

Systemic Mastocytosis, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology.

Mastocytosis is a group of heterogeneous disorders resulting from the clonal proliferation of abnormal mast cells and their accumulation in the skin and/or in various extracutaneous organs. Systemic mastocytosis is the most common form of mastocytosis diagnosed in adults, characterized by mast cell infiltration of one or more extracutaneous organs (with or without skin involvement). The identification of KIT D816V mutation and the emergence of novel targeted therapies have significantly improved the diagnosis and treatment of systemic mastocytosis.

NCCN Guidelines Insights: Cancer-Associated Venous Thromboembolic Disease, Version 2.2018.

Venous thromboembolism (VTE) is common in patients with cancer and increases morbidity and mortality. VTE prevention and treatment are more complex in patients with cancer. The NCCN Guidelines for Cancer-Associated Venous Thromboembolic Disease outline strategies for treatment and prevention of VTE in adult patients diagnosed with cancer or in whom cancer is clinically suspected.

NCCN Guidelines Insights: Myeloproliferative Neoplasms, Version 2.2018.

Myeloproliferative neoplasms (MPNs) are a group of heterogeneous disorders of the hematopoietic system that include myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET). PV and ET are characterized by significant thrombohemorrhagic complications and a high risk of transformation to MF and acute myeloid leukemia. The diagnosis and management of PV and ET has evolved since the identification of mutations implicated in their pathogenesis.

Disease characteristics and prognosis of myelodysplastic syndrome presenting with isolated thrombocytopenia.

Patients with myelodysplastic syndrome (MDS) who present with isolated thrombocytopenia (TCP) constitute a poorly described subgroup. The aim of the present study was to retrospectively evaluate disease characteristics and prognosis in patients with MDS and isolated TCP at a tertiary care center. Fifty patients (12 %) had isolated thrombocytopenia as the first presentation of MDS.

Update on Anticoagulation: What the Interventional Radiologist Needs to Know.

The novel oral anticoagulants (NOACs) represent a major advance in the treatment of patients with nonvalvular atrial fibrillation and venous thromboembolism (VTE). They have several advantages over vitamin-K antagonists such as warfarin, including more predictable pharmacokinetics and improved safety, particularly with fatal bleeding and intracranial hemorrhage. However, several issues remain surrounding the use of NOACs in certain subpopulations and with the approach to reversal.

Survey of Provider Transfusion Practices for Oncology Patients in an Academic Medical Center.

Objectives: Hospitalized oncology patients receive care from a variety of professionals, each of whom plays a role in decisions related to blood transfusions. We sought to examine differences in transfusion practices based on professional role, years of experience, and patient clinical scenario.

Methods: We surveyed general medicine residents, hospitalists, and oncologists caring for inpatients at a large academic medical center between August 2013 and June 2014.

Evolving Therapeutic Strategies for the Classic Philadelphia-Negative Myeloproliferative Neoplasms.

Despite the emergence of JAK inhibitors, there is a need for disease-modifying treatments for Philadelphia-negative myeloproliferative neoplasms (MPNs). JAK inhibitors ameliorate symptoms and address splenomegaly, but because of the heterogeneous contributors to the disease process, JAK inhibitor monotherapy incompletely addresses the burden of disease. The ever-growing understanding of MPN pathogenesis has provided the rationale for testing novel and targeted therapeutic agents, as monotherapies or in combination, in preclinical and clinical settings.

Clinical Use of Anti-Xa Monitoring in Malignancy-Associated Thrombosis.

Introduction. Low molecular weight heparin (LMWH) is preferred for malignancy-associated venous thromboembolism (VTE). Many providers monitor LMWH with anti-Xa levels, despite little validation on correspondence with patient outcome.

Components of the Plasminogen-Plasmin System as Biologic Markers for Cancer.

Members of the plasminogen-plasmin (PP) system participate in many physiologic functions. In particular, uPA, its receptor (uPAR) and its inhibitor PAI-1 play an important role in cell migration, cell proliferation and tissue remodeling. Through a number of interactions, these components of the PP system are also involved in the pathogenesis of many diseases.

Bleeding complications in BCR-ABL negative myeloproliferative neoplasms: prevalence, type, and risk factors in a single-center cohort.

The BCR-ABL1-negative myeloproliferative neoplasms (MPN) share an increased risk of thrombotic and hemorrhagic complications. Risk factors for hemorrhage are less well defined than those for thrombosis. Because patients with CALR mutations have higher platelet counts compared to JAK2 V617F-mutated patients, bleeding rates may be increased in this group.

Rapid Aluminum Nanoparticle Production by Milling in NH₃ and CH₃NH₂ Atmospheres: An Experimental and Theoretical Study.

Ball milling of aluminum in gaseous atmospheres of ammonia and monomethylamine (MMA) was found to produce particles in the 100 nm size range with high efficiency. A combination of mass spectrometry, X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis with mass spectrometric product analysis (TGA-MS), scanning electron microscopy (SEM), infrared spectroscopy, and dynamic light scattering (DLS) was used to study the particles and the chemical interactions responsible for particle production. To help understand the nature of the surface chemistry, high level quantum chemical calculations were performed to predict the structures and energetics for binding and reactions of NH3 and MMA on aluminum surfaces.

Central role of ULK1 in type I interferon signaling.

We provide evidence that the Unc-51-like kinase 1 (ULK1) is activated during engagement of the type I interferon (IFN) receptor (IFNR). Our studies demonstrate that the function of ULK1 is required for gene transcription mediated via IFN-stimulated response elements (ISRE) and IFNγ activation site (GAS) elements and controls expression of key IFN-stimulated genes (ISGs). We identify ULK1 as an upstream regulator of p38α mitogen-activated protein kinase (MAPK) and establish that the regulatory effects of ULK1 on ISG expression are mediated possibly by engagement of the p38 MAPK pathway.