Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polycythaemia vera (PV) and essential thrombocythaemia (ET) are classified as Philadelphia-negative chronic myeloproliferative diseases. Both PV and ET are rare diseases, but the prevalence is high. Patients who have not been treated for the diseases are at great risk of morbidity and mortality as a result of thrombohaemorrhagic events. However, if patients have been well treated, their prognosis is good and life-expectancy approaches normal. This article provides diagnostic tools and flowcharts for treatment of PV and ET. Treatment of PV and ET should be risk-adjusted and individualised. Low-dose aspirin is recommended as an antiaggregative drug in both diseases. For PV, phlebotomy to control a haematocrit at <0.45 is the cornerstone in treatment, and treatment with hydroxycarbamide (hydroxyurea) or interferon (IFN)-alpha is added to reduce hypermetabolic symptoms or splenomegaly becoming cytoreductive. In ET, hydroxycarbamide and anagrelide are the most used drugs, and anagrelide may also be added in PV to reduce thrombocytosis. IFNalpha is the only myelosuppressive treatment available during pregnancy. Current controversies regarding treatment illustrate the need for more randomised clinical trials. Demonstration of over expression of the PV-1 gene and in particular the JAK-2 mutation will be novel diagnostic criteria and may have an impact for future therapy of both PV and ET.
 ...
PMID:Polycythaemia vera and essential thrombocythaemia: current treatment strategies. 1713 2

Primary myelofibrosis is a clonal haematopoietic stem cell disease, characterised by marrow stromal fibrosis, extramedullary haematopoiesis, splenomegaly, hepatomegaly and progressive cytopenia. Therapeutic options once cytopenia has developed are limited to supportive care, such as erythrocyte transfusions and growth factors. The aetiology has become more clear, especially since JAK-2 mutations were found, resulting in increased production of cytokines. The immune-modulating drug thalidomide and its derivative lenalidomide have shown to be effective in reducing cytopenia, most probably by inhibiting the cytokine responses. In some patients the bone marrow fibrosis disappears. We describe the experience with these drugs in a cohort of 14 patients for thalidomide and seven for lenalidomide (in six patients lenalidomide was given after thalidomide and one patient received lenalidomide upfront). Thalidomide gave clinical improvement in 6/14 patients, but its use was limited mainly due to toxicity, especially the development of neuropathy. The drug could be given for a median period of 15.5 months in responding patients. Lenalidomide was effective in 4/7 of the patients, in some patients with no response on thalidomide. Due to the more favourable toxicity profile, the median duration of therapy was 19 months, with 3/4 patients on therapy longer than 19 months. These data are discussed in view of the clinical studies published. We conclude that lenalidomide is preferred in myelofibrosis, given a higher response rate and more favourable toxicity profile. If no response the addition of prednisone can be considered. In some patients it can normalise haemoglobin and make them transfusion independent.
 ...
PMID:Thalidomide and lenalidomide in primary myelofibrosis. 2073 25

Ruxolitinib, a Janus kinase (JAK)-1 and JAK-2 inhibitor, is the first-in-class drug to be licensed in the United States for the treatment of high- and intermediate-risk myelofibrosis (MF). Several other JAK inhibitors are in development with some currently undergoing phase-3 clinical trial testing. None of the currently available JAK inhibitors are specific to mutant JAK2; their mechanism of action involves attenuation of JAK-STAT signaling with downregulation of proinflammatory cytokines, rather than selective suppression of the disease clone. Accordingly, while ruxolitinib and other JAK inhibitors are effective in controlling splenomegaly and alleviating constitutional symptoms, their benefit in terms of reversing bone marrow fibrosis or inducing complete or partial remissions appears to be limited. The experience to date with ruxolitinib shows that despite its salutary effects on quality of life, over half of the patients discontinue treatment within 2-3 years. In the current perspective, we examine the incidence and causes of ruxolitinib 'treatment failure' in MF patients based on our personal experience as well as a review of the published literature. We also discuss the challenges in defining and classifying ruxolitinib failure, and within the context of several clinical scenarios, we provide recommendations for the post-ruxolitinib management of MF patients.
...
PMID:Definition and management of ruxolitinib treatment failure in myelofibrosis. 2550 Oct 25

We retrospectively studied 181 patients with polycythaemia vera (n=67), essential thrombocythaemia (n=67) or primary myelofibrosis (n=47), who presented a first episode of splanchnic vein thrombosis (SVT). Budd-Chiari syndrome (BCS) and portal vein thrombosis were diagnosed in 31 (17.1%) and 109 (60.3%) patients, respectively; isolated thrombosis of the mesenteric or splenic veins was detected in 18 and 23 cases, respectively. After this index event, the patients were followed for 735 patient years (pt-years) and experienced 31 recurrences corresponding to an incidence rate of 4.2 per 100 pt-years. Factors associated with a significantly higher risk of recurrence were BCS (hazard ratio (HR): 3.03), history of previous thrombosis (HR: 3.62), splenomegaly (HR: 2.66) and leukocytosis (HR: 2.8). Vitamin K-antagonists (VKA) were prescribed in 85% of patients and the recurrence rate was 3.9 per 100 pt-years, whereas in the small fraction (15%) not receiving VKA more recurrences (7.2 per 100 pt-years) were reported. Intracranial and extracranial major bleeding was recorded mainly in patients on VKA and the corresponding rate was 2.0 per 100 pt-years. In conclusion, despite anticoagulation treatment, the recurrence rate after SVT in myeloproliferative neoplasms is high and suggests the exploration of new avenues of secondary prophylaxis with new antithrombotic drugs and JAK-2 inhibitors.
 ...
PMID:Splanchnic vein thrombosis in myeloproliferative neoplasms: risk factors for recurrences in a cohort of 181 patients. 2781 34

This is the report of the clinical case of a patient who presents the association of a JAK-2 positive chronic myeloproliferative neoplasia to a subsequent 5q- myelodysplastic syndrome, developed after about 14 years from the first diagnosis. Patient's symptoms had rapidly worsened, and she became transfusion-dependent. Therapy with low-dose Lenalidomide quickly reduced the splenomegaly and completely brought white cells counts, haemoglobin, and platelets back to normal. After more than one year from the start, blood cell count is still normal. As far as we know, this is the first case of an effective treatment with Lenalidomide reported in this clinical setting.
 ...
PMID:Diagnosis of del(5q) MDS, 14 Years after JAK-2 Positive PV Appearance: Complete Remission of both Diseases with Lenalidomide Monotherapy. 2787 30

Primary myelofibrosis is characterized by bone marrow fibrosis, splenomegaly and presence of JAK-2 V617F mutation in more than 90% of patients. Ruxolitinib is a Janus kinase inhibitor used for the treatment of primary myelofibrosis. We describe herein a persistent foot ulcer development attributed to ruxolitinib therapy. We are unaware of any previous reports of this phenomenon in the scientific literature. A thorough examination of the lower extremities is perhaps necessary before initiating this oral agent. If ruxolitinib therapy cannot be safely discontinued, diligent wound care and a course of antibiotics are warranted.
 ...
PMID:Persistent foot ulcer due to ruxolitinib therapy for primary myelofibrosis. 2843 80

The aim of the studywas to determine the risk of thrombosis among patients with Essential thrombocythemia based on the modern criteria of diagnosis and to reveal the treatment accordingmethods of research in Georgia. We analyzed clinical manifestations of 25 cases of Essential thrombocythemia diagnosed in 2013-2017 y. at the Institute of Hematology and Transfusiology. Among 25 patients, female was 20 (80%), male - 5 (20%). Age varies from 28 to 75 years. Patients had the following clinical manifestations: The severity of the lower limbs, numbness, pain (erythromelalgia) in 13 (52%) of cases, headache in 7 (28%), dizziness in 5 (20%), splenomegaly in 6 (24%), bleeding in 1 (4%), several discontinued pregnancy in the first trimester in 1 (4%), thrombotic complication had been diagnosed in 8 (32%) of patients. In 8 (32%) patients with thrombosis in medical history, myocardial infarction had 2 patient, ischemic stroke - 2 patient, deep vein thrombosis - 2 patient, thrombosis of spleen artery - 1 patient, door vein thrombosis -1 patients. Laboratory indicators for patients at the moment of diagnosis were as follows: Hemoglobin level was 120-160g/L, Erythrocytes-3,7-5,2x1012/L, Leukocytes-10,2-35,5x109/L, Platelets - 860,0-4300,05x109/L. Cytological study ofbone marrow revealed hyper cellular bone marrowwith neutrophilic profile. There are a large number of megakaryocites and their large clusters. In bone marrow biopsy bone and bone marrow structure is mainly stored. There is a hyperplasia of myeloid tissue, a sharp or moderate hyperplasia of megakaryocite. Sometimes weak fibrosis is expresseds (4 patients). JAK-2 genes can only be studied in 3 (12%) cases: in 2 (8%) cases, gene mutations were 48% and 52%, while the gene mutation with 1 (4%) patient was only 12%. Based on international multi-center studies by WHO experts group, the risk of thrombosis development was predictable (WHO-ET-IPSET-thrombosis). Based on our data, we have identified thrombotic risk groups as well as the criteria that contributed to the increased risk: these are more likely to have thrombotic complications in medical history, existence ofJAK-2gene mutation, lesser than age >60years, risk factors from the cardiovascular system (Diabetes mellitus,Hypertension, smoking). From the patients who were studied, 10 (40%) were in the high risk group of thrombosis, 3 (12%) in the average risk group and 12 (48%) in thelow risk group. The goal of treatment of Essential thrombocythemia is to stop the progression of the disease and cure the symptoms of the disease.The methods of treatment for improving the quality of life of patients are multi-component and are divided into the following groups: 1) Prophylaxis of thrombotic complications; 2) cytoreductionalchemothrapy; 3) targeted therapy- JAK-2kinase activity inhibitors; 4) treatment of complications.
 ...
PMID:DETERMINING THE RISK OF THROMBOSIS AMONG THE PATIENTS WITH ESSENTIAL THROMBOCYTHEMIA. 3224 62