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The Ulster Medical Journal May 2016(32)P has been available for the treatment of myeloproliferative neoplasms (MPNs) for over seventy years. It was first used in 1938 by John H Lawrence in the treatment...
UNLABELLED
(32)P has been available for the treatment of myeloproliferative neoplasms (MPNs) for over seventy years. It was first used in 1938 by John H Lawrence in the treatment of polycythaemia and chronic leukaemias. With the introduction of agents such as hydroxycarbamide, interferon and anagrelide the role of (32)P has been diminished. Today, Polycythaemia Rubra Vera (PRV) and Essential Thrombocythaemia (ET) remain the only myeloproliferative conditions in which (32)P is indicated.
MATERIALS AND METHODS
We carried out a retrospective review of all patients who had received 32P in Northern Ireland over a 24 year period. The time to successful response, duration of response, and associated complications were reviewed.
RESULTS
(32)P was successful in inducing remission in 90% of patients. This remission was sustained following one dose without the need for further therapy in 37% of cases. 47% required repeated doses. 26% required recommencement of alternative therapies. No cases of thrombosis, myelofibrosis or acute leukaemia were observed.
DISCUSSION
We conclude that (32)P is a well-tolerated and efficacious treatment option in the elderly. We discuss our results compared with previous work in this area. (32)P will continue to be offered to elderly patients in our practice.
Topics: Aged; Aged, 80 and over; Blood Cell Count; Female; Humans; Ireland; Male; Medical Records, Problem-Oriented; Myeloproliferative Disorders; Outcome and Process Assessment, Health Care; Phosphorus Radioisotopes; Retrospective Studies
PubMed: 27601760
DOI: No ID Found -
International Journal of Hematology Oct 2022In Japan, anagrelide has been approved for use in patients with essential thrombocythemia. Here, the safety and efficacy of anagrelide was assessed in clinical practice...
Safety and efficacy of anagrelide in Japanese post-marketing surveillance, with subgroup analyses on the effect of previous cytoreductive therapies, age, and starting dose.
BACKGROUND
In Japan, anagrelide has been approved for use in patients with essential thrombocythemia. Here, the safety and efficacy of anagrelide was assessed in clinical practice as post-marketing surveillance. Subgroup analyses were conducted to compare patients (1) with or without a history of cytoreductive therapy (CRT), (2) <60 or ≥60 years of age, and (3) with an anagrelide starting dose of ≤0.5 mg/day or 1.0 mg/day.
METHODS
Data were collected for all patients who received anagrelide, with an observation period of 12 months after treatment initiation.
RESULTS
Of the 648 patients, 54.3% experienced adverse drug reactions (ADRs). The most commonly reported ADRs were headaches, palpitations, and anemia. No significant difference was observed in overall ADRs across patient subgroups. A significantly higher incidence of headaches was observed in patients < 60 years versus those ≥ 60 years (P < 0.001). The incidence of anemia and serious ADRs were significantly higher in patients ≥ 60 years, and those with a history of CRT (P < 0.05). The discontinuation rate at 6 months was significantly lower in patients started at the lower anagrelide dose (P < 0.05). Platelet counts decreased in all analyzed groups.
CONCLUSIONS
This surveillance showed that anagrelide has a tolerable safety and efficacy profile.
Topics: Cytoreduction Surgical Procedures; Headache; Humans; Japan; Platelet Aggregation Inhibitors; Product Surveillance, Postmarketing; Quinazolines
PubMed: 35624199
DOI: 10.1007/s12185-022-03380-2 -
Journal of Biomolecular Structure &... May 2023Nowadays, a nanostructure-based drug delivery system is one of the most noticeable topics to be studied, and in this regard, boron nitride nanoclusters are promising...
Nowadays, a nanostructure-based drug delivery system is one of the most noticeable topics to be studied, and in this regard, boron nitride nanoclusters are promising drug carriers for targeted drug delivery systems. In this article, the interaction mechanism of Anagrelide (AG) drug with B12N12 and Al- and Ga-doped B12N12 nanocages have been investigated using DFT with B3LYP/6-31 G (d, p) method in both gas and water media. All our studied complexes are thermodynamically stable, and doped nanocage complexes have higher negative adsorption energy (E and negative solvation energy than AG/B12N12 complexes which correspond to the stability of these systems in both media. The negative highest E value is 64.98 kcal/mol (63.17 kcal/mol) and 65.69 kcal/mol (65.11 kcal/mol) in gas (water) media for complex F (AG/AlB11N12) and complex I (AG/GaB11N12) respectively, which refers to the highest stability of these systems. The enhanced values of dipole moment (from 12.40 (12.65) Debye to 17.21 (17.69) Debye in complex F (complex I)) also confirm their stability. The QTAIM and RDG analysis endorse the strong adsorption nature of the AG drug onto the AlB11N12, and GaB11N12 nanocages, which is consistent with the adsorption energy as chemisorption occurs for these complexes. According to the electronic properties, doped nanocages show high sensitivity that infers their promising nature for drug delivery purposes. Thus, complex F and complex I are promising drug delivery systems, and doped nanocages (AlB11N12 and GaB11N12) are better carriers than pristine nanocages for the AG drug delivery system.Communicated by Ramaswamy H. Sarma.
Topics: Quinazolines; Boron Compounds; Nanostructures; Drug Carriers; Adsorption; Density Functional Theory; Quantum Theory
PubMed: 35272575
DOI: 10.1080/07391102.2022.2049369 -
[Rinsho Ketsueki] the Japanese Journal... Oct 2014
Review
Topics: Adrenal Cortex Hormones; Aspirin; Calreticulin; Carbamates; Clinical Trials as Topic; Drug Therapy, Combination; Hematopoietic Stem Cell Transplantation; Humans; Hydroxyurea; Immunosuppressive Agents; Janus Kinase 2; Molecular Targeted Therapy; Mutation; Nitriles; Platelet Aggregation Inhibitors; Polycythemia Vera; Primary Myelofibrosis; Prognosis; Pyrazoles; Pyrimidines; Quinazolines; Receptors, Thrombopoietin; Thalidomide; Thrombocythemia, Essential
PubMed: 25297748
DOI: No ID Found -
Turkish Journal of Haematology :... Dec 2021
Topics: Humans; Leg Ulcer; Quinazolines
PubMed: 34445859
DOI: 10.4274/tjh.galenos.2021.2021.0399 -
Annals of Hematology Dec 2014Patients with Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) like polycythemia vera and essential thrombocythemia are at increased risk of arterial...
Prophylaxis and management of venous thromboembolism in patients with myeloproliferative neoplasms: consensus statement of the Haemostasis Working Party of the German Society of Hematology and Oncology (DGHO), the Austrian Society of Hematology and Oncology (ÖGHO) and Society of Thrombosis and...
Patients with Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) like polycythemia vera and essential thrombocythemia are at increased risk of arterial and venous thrombosis. Strategies of prevention may consist of platelet aggregation inhibitors and/or cytoreductive agents depending on the underlying disease and the individual risk. Clinical evidence for management of acute venous thromboembolic events in MPN patients is limited. Modality and duration of therapeutic anticoagulation after venous thrombosis has to be evaluated critically with special regard to the increased risk for spontaneous bleeding events associated with the underlying diseases. Both for therapy of the acute event and for secondary prophylaxis, low-molecular-weight heparins should preferentially be used. A prolongation of the therapeutic anticoagulation beyond the usual 3 to 6 months can only be recommended in high-risk settings and after careful evaluation of potential risks and benefits for the individual patient. New direct oral anticoagulants (NOAC) should not preferentially be used due to lack of clinical experience in patients with MPN and potential drug interactions (e.g. with JAK inhibitors). Consequent treatment of the underlying myeloproliferative disease and periodical evaluation of the response to therapy is crucial for optimal secondary prophylaxis of thromboembolic events in those patients.
Topics: Anticoagulants; Disease Susceptibility; Drug Interactions; Female; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Hydroxyurea; Incidence; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Male; Myeloproliferative Disorders; Phlebotomy; Platelet Aggregation Inhibitors; Postoperative Complications; Pregnancy; Pregnancy Complications, Hematologic; Preoperative Care; Protein Kinase Inhibitors; Quinazolines; Secondary Prevention; Thrombophilia; Venous Thromboembolism; von Willebrand Diseases
PubMed: 25307456
DOI: 10.1007/s00277-014-2224-8 -
Case Reports in Hematology 2023VEXAS syndrome stands for vacuoles, E1 enzyme, -linked, autoinflammatory, somatic syndrome. The syndrome is a combined hematological and rheumatological condition caused...
VEXAS syndrome stands for vacuoles, E1 enzyme, -linked, autoinflammatory, somatic syndrome. The syndrome is a combined hematological and rheumatological condition caused by a somatic mutation in the . There is an association between VEXAS and hematological conditions such as myelodysplastic syndrome (MDS), monoclonal gammopathies of uncertain conditions (MGUS), multiple myeloma (MM), and monoclonal B-cell lymphoproliferative conditions. There are not many descriptions of patients having VEXAS in combination with myeloproliferative neoplasm (MPN). With this article, we want to present a case history of a man in his sixties with a V617F mutated essential thrombocythemia (ET) developing VEXAS syndrome. The inflammatory symptoms occurred three and a half years after the ET diagnosis. He started to experience symptoms of autoinflammation and an overall worsening of his health, and blood work showed high inflammatory markers, leading to repeated hospitalizations. His major complaint was stiffness and pain, and high dosages of prednisolone were necessary to obtain pain relief. He subsequently developed anemia and significantly variable levels of thrombocytes, which previously were at a steady level. To evaluate his ET, we made a bone marrow smear demonstrating vacuolated myeloid and erythroid cells. Having VEXAS syndrome in mind, genetic testing identifying the gene mutation was performed, thus confirming our suspicion. The work-up with myeloid panel on his bone marrow identified genetic mutation in the too. After developing VEXAS syndrome, he experienced thromboembolic events with both cerebral infarction and pulmonary embolism. Thromboembolic events are also common in mutated patients, but in his case, they presented first after VEXAS had developed. Throughout the course of his condition, several attempts with prednisolone tapering and steroid sparing drugs were tried. He could not get pain relief unless the combination of medications included a relatively high dose of prednisolone. Currently, the patient uses prednisolone, anagrelide, and ruxolitinib, with partial remission and fewer hospitalizations and more stabilized hemoglobin and thrombocytes.
PubMed: 36879894
DOI: 10.1155/2023/6551544 -
Frontiers in Genetics 2022Glioma is the most malignant cancer of the central nervous system. There are various therapies for treating gliomas, but their outcomes are not satisfactory. Therefore,...
Glioma is the most malignant cancer of the central nervous system. There are various therapies for treating gliomas, but their outcomes are not satisfactory. Therefore, new targets for glioma treatment are needed. This study examined the cadherin-6 (CDH6) expression in gliomas using The Cancer Genome Atlas and Chinese Glioma Genome Atlas datasets. CDH6 expression positively correlated with the World Health Organization (WHO) tumor grade and negatively correlated with patient prognosis. A significant decrease in CDH6 promoter methylation was identified with an increase in the WHO grade severity. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses suggested that CDH6 might be involved in cell-cell interactions and immune processes in the glioma microenvironment. Weighted gene co-expression network analysis revealed a correlation between CDH6 and cell adhesion molecules, focal adhesions, phosphatidylinositol 3-kinase-protein kinase B signaling pathways, nuclear division, chromosome segregation, mitotic nuclear division, and immune-related pathways. CDH6 strongly correlated with immunosuppressive cells, including regulatory T cells, monocytes, macrophages, tumor-associated macrophages, and myeloid-derived suppressor cells. It also showed correlations with immune-active cells such as B cells, CD8 T cells, and dendritic cells. Single-cell analysis showed that CDH6 was expressed mainly in astrocyte (AC)-like malignant cells. Differentially expressed genes of AC-like malignant cells were found to be associated with stress response, membranous processes, viral infections, and several types of cancers. Potential drugs associated with high CDH6 expression were also predicted, including AMG-22, rutin, CCT128930, deforolimus, bis(maltolato)oxovanadium, anagrelide, vemurafenib, CHIR-98014, and AZD5582. Thus, this study showed that CDH6 correlates with glioma immune infiltration, it is expressed mainly in AC-like malignant cells, and it may act as a new target for glioma therapy.
PubMed: 35938030
DOI: 10.3389/fgene.2022.949552 -
Orvosi Hetilap Feb 2016Essential thrombocythemia is a Philadelphia chromosome-negative chronic myeloproliferative neoplasia with a risk of bleeding and thromboembolic complications during the... (Observational Study)
Observational Study
INTRODUCTION
Essential thrombocythemia is a Philadelphia chromosome-negative chronic myeloproliferative neoplasia with a risk of bleeding and thromboembolic complications during the course of illness. Cytoreductive drugs, such as non-selective hydroxyurea or interferon as first-line and specific, megakaryocyte-thrombocyte reductive anagrelide chosen as second-line treatment in cases of adverse, intolerable effects of hydroxyurea can lower the incidence of bleeding/thrombotic episodes in patients with essential thrombocythemia.
AIM
In this observational survey the effect of anagrelide was investigated in patients with essential thrombocythemia, who were first treated with hydroxyurea but failed to have clinicopathologic reponse (resistant) or were intolerant (adverse effects).
METHOD
Between 2000 and 2014, 104 patients were diagnosed with essential thrombocythemia and treated first-line with hydroxyurea (weekly median dose of 7500 mg) in the haematologic outpatient department of the authors. Because of intolerance and/or resistance, hydroxyurea was changed to anagrelide (7.5 mg weekly median dose), the doses of hydroxyurea and anagrelide were adjusted to achieve clinicopathological response according to the updated criteria of the European LeukemiaNET. Effect of anagrelide as monotherapy (first- or second-line after hydroxyurea) or in combination with hydroxyurea was followed. Statistical analysis was performed using the Windows Statistical Package Program.
RESULTS
Of the 104 patients with essential thrombocythemia (according to the updated WHO-ET classifications 58 patients JAK2V617F mutation positive, 46 patients negative, 15 patients calreticulin mutation negative, 6 patients MPL-1 mutation negative) 87 patients received hydroxyurea in first line, 4 patients interferon, and 13 patients acetylsalycilic acid only. Seven patients who proved to be intolerant and 22 patients who were resistant to hydroxyurea received anagrelide in second line (in 18 patients monotherapy and in 11 patients in combination with hydroxyurea), while other 5 rather young patients in first line therapy (34/104, 32.6%). In the anagrelide first line group 5 patients (100%), in the second line anagrelide monotherapy group 16 patients (88,8%), and in the combined hydroxyurea plus anagrelide group 9 patients (82.1%) achieved complete remission. The 10-year overall survival was 82.1%. In 2 patients treated with anagrelide major bleeding and in one patient myocardial infarction occurred, other serious adverse events due to anagrelide treatment were not detected. Three elder patients died from non-hematologic diseases, but leukaemic transformation was not observed.
CONCLUSIONS
First or second line anagrelide therapy, combined with hydroxyurea if necessary, was able to reduce the platelet-count and the rate of complications, and to control the course of essential thrombocythemia with tolerable adverse effects.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Drug Resistance, Neoplasm; Female; Humans; Hungary; Hydroxyurea; Interferons; Male; Middle Aged; Platelet Aggregation Inhibitors; Quinazolines; Survival Analysis; Thrombocythemia, Essential; Treatment Failure; Treatment Outcome
PubMed: 26895801
DOI: 10.1556/650.2016.30323 -
Expert Review of Hematology Dec 2015Although hydroxyurea is considered the first-line cytoreductive therapy in high-risk patients with polycythemia vera or essential thrombocythemia, approximately 20-25%... (Review)
Review
Although hydroxyurea is considered the first-line cytoreductive therapy in high-risk patients with polycythemia vera or essential thrombocythemia, approximately 20-25% of patients develop resistance or intolerance and they need an alternative therapy. Anagrelide is the treatment of choice in patients with essential thrombocythemia intolerant or with resistance to hydroxyurea. Anagrelide is usually well tolerated. Although there is concern about the increased risk of cardiac side effects, in most cases these are mild, and easily manageable. In this paper, the available evidence about the management of patients with myeloproliferative neoplasms, with a special focus on the side effects of drug therapies is reviewed.
Topics: Female; Fibrinolytic Agents; Fusion Proteins, bcr-abl; Humans; Male; Myeloproliferative Disorders; Quinazolines
PubMed: 26368319
DOI: 10.1586/17474086.2015.1088779