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Leukemia Research Jul 2017Extreme thrombocytosis induces an acquired thrombotic-hemorrhagic diathesis, and left uncontrolled is a harbinger of potentially fatal vascular complications. Currently,... (Review)
Review
Extreme thrombocytosis induces an acquired thrombotic-hemorrhagic diathesis, and left uncontrolled is a harbinger of potentially fatal vascular complications. Currently, cytoreduction with medical therapy remains the mainstay of hyperthrombocytosis management. However, it offers a less-than-ideal option in situations where a rapid reduction in platelets is urgently needed, as in the presence of vital end-organ ischemia or to ameliorate of life-threatening hemorrhage. The role of thrombocytapheresis, or plateletpheresis, in hyperthrombocytosis has become increasingly obsolete given the proactive titration of cytoreductive therapies and early identification and correction of reversible causes of reactive thrombocytosis. Despite its narrowed indications, plateletpheresis continues to offer a valuable temporizing measure in platelet count reduction before cytoreductive agents exert their maximal effect. In this context, it is important for the treating physician to be aware of the symptoms and risks associated with hyperthrombocytosis to inform best clinical practices. In this review, we discuss the role of plateletpheresis in the modern-day management of hyperthrombocytosis in patients with myeloproliferative neoplasms through a case based review of the literature. It becomes apparent throughout the discussion that the decision to perform plateletpheresis should be individualized based upon the clinical scenario, degree of thrombocytosis, available infrastructure and every patient's risk profile.
Topics: Aged; Female; Humans; Male; Middle Aged; Myeloproliferative Disorders; Plateletpheresis; Thrombocytosis
PubMed: 28380402
DOI: 10.1016/j.leukres.2017.03.008 -
Clinical Pharmacology in Drug... Feb 2018Anagrelide is an established therapy for essential thrombocythemia. Common adverse effects have been linked to peak plasma concentrations of anagrelide and its 3OH... (Randomized Controlled Trial)
Randomized Controlled Trial
Anagrelide is an established therapy for essential thrombocythemia. Common adverse effects have been linked to peak plasma concentrations of anagrelide and its 3OH metabolite. Our study was performed to investigate the pharmacokinetics (PK) of a novel anagrelide extended-release (AER) formulation and its active metabolites. Thirty healthy volunteers were randomized to receive either 2 mg AER (under fasting and fed conditions) or 2 mg commercially available reference product (CARP) in an open-label, 3-way crossover trial with washout periods of 6 days. Plasma concentrations of anagrelide and its active metabolites were assessed by tandem mass spectrometry. The PK differed significantly between all treatment periods. Bioavailability of AER was 55% of the CARP under fasting conditions and 60% under fed conditions. C , AUCt, and AUC∞ were significantly higher and T and T were significantly shorter after the CARP compared with AER. Food had a significant impact on the PK of AER, increasing the C and AUC while reducing the T , plateau, and mean residence time. Both formulations were well tolerated, with a trend toward more frequently occurring adverse events after the CARP. The PK of AER and the CARP differed significantly in all parameters. Food enhanced the bioavailability of AER.
Topics: Administration, Oral; Adolescent; Adult; Cross-Over Studies; Delayed-Action Preparations; Fasting; Female; Fibrinolytic Agents; Food-Drug Interactions; Healthy Volunteers; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Quinazolines; Young Adult
PubMed: 28301098
DOI: 10.1002/cpdd.340 -
International Cancer Conference Journal Jan 2017Anagrelide is a cytoreductive agent for essential thrombocythemia and its common side effects are anemia, headache, palpitation, diarrhea, and fluid retention. However,...
Anagrelide is a cytoreductive agent for essential thrombocythemia and its common side effects are anemia, headache, palpitation, diarrhea, and fluid retention. However, severe pulmonary adverse effects are rare. A 66-year-old Japanese man with essential thrombocythemia presented with hemoptysis 2 months after starting anagrelide treatment. Interstitial pneumonia was diagnosed based on physical and radiographic findings. Discontinuation of anagrelide and institution of corticosteroids resulted in the improvement of interstitial pneumonia. Severe lung injury associated with anagrelide is a rare but an important adverse event that must be addressed when treating interstitial pneumonia.
PubMed: 31149463
DOI: 10.1007/s13691-016-0265-7 -
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 -
Current Hematologic Malignancy Reports Oct 2016Anagrelide (ANA) is a drug with specific platelet-lowering activity, used primarily in ET, registered as a second-line drug in essential thrombocythemia (ET) in Europe... (Review)
Review
Anagrelide (ANA) is a drug with specific platelet-lowering activity, used primarily in ET, registered as a second-line drug in essential thrombocythemia (ET) in Europe and in some countries as first-line therapy, in USA licensed by FDA for thrombocythemia in myeloproliferative neoplasms (MPN). The platelet-lowering efficacy is similar to that of hydroxycarbamide (HC), around 70 % complete response and 90 % partial response. Side effects are common, especially headache and tachycardia, but usually subside or disappear within a few weeks. Around 20 % of patients stop ANA therapy due to side effects or insufficient response. Studies of treatment patterns in Europe show that ANA is preferentially given to younger patients, probably because of the concern for a possible leukemogenic effect of the common first-line drug, HC. Only two randomized studies have compared the efficacy of ANA and HC in preventing thrombosis and haemorrhage, the larger of them showing a slightly better efficacy of HC, the other showing non-inferiority of ANA to HC. A recent observational 5-year study of 3600 patients shows a low and basically similar efficacy of ANA and other cytoreductive therapies in ET. ANA does not appear to inhibit fibrosis development, and probably due to its anticoagulation properties, the combination of ASA and ANA produces an increased rate of haemorrhage. Combination of ANA with HC or interferon (IFN) is feasible and effective in patients with insufficient platelet response to mono-therapy.
Topics: Age Factors; Bone Marrow; Cardiovascular Diseases; Humans; Interferon-alpha; Myeloproliferative Disorders; Platelet Aggregation Inhibitors; Quinazolines; Tachycardia; Thrombocythemia, Essential
PubMed: 27497846
DOI: 10.1007/s11899-016-0335-0 -
Journal of Clinical and Experimental... 2016We hereby report a case of acute myeloid leukemia with translocation t(2;3) and involvement of the ectopic virus integration site-1 (EVI1) gene. Like most other...
We hereby report a case of acute myeloid leukemia with translocation t(2;3) and involvement of the ectopic virus integration site-1 (EVI1) gene. Like most other 3q26-related disorders reported thus far, we describe a phenotype with elevated platelet counts and dysmegakaryopoesis. The clinical course of our patient was complicated by symptomatic thrombophilia and chemoresistance. In addition, our case exhibited FLT3 (Fms-related tyrosine kinase 3) internal tandem duplication. Although anagrelide was successful in controlling elevated platelet counts, allogeneic stem cell transplantation failed to overcome chemoresistance due to simultaneous graft-versus-host-disease and relapse of acute myeloid leukemia. Given the dismal outcome of our case and previously reported cases, we propagate the implementation of targeted therapies to newly diagnosed patients with acute myeloid leukemia t(2;3). Preclinical models indicate drugs that plausibly target the EVI1-related molecular vulnerability as candidates for basket trials. Anagrelide exhibited a hopeful signal of activity in 3q26-related thrombocytosis and should be evaluated for implementation as supportive care.
Topics: Blood Platelets; DNA-Binding Proteins; Humans; Leukemia, Myeloid, Acute; MDS1 and EVI1 Complex Locus Protein; Male; Middle Aged; Platelet Aggregation Inhibitors; Platelet Count; Proto-Oncogenes; Quinazolines; Stem Cell Transplantation; Thrombophilia; Transcription Factors; Translocation, Genetic; fms-Like Tyrosine Kinase 3
PubMed: 27334861
DOI: 10.3960/jslrt.56.64 -
Srpski Arhiv Za Celokupno Lekarstvo 2016A high platelet count, or thrombocytosis, is either a reactive process or a result of a myeloproliferative disorder. Ankylosing spondylitis is a chronic inflammatory...
INTRODUCTION
A high platelet count, or thrombocytosis, is either a reactive process or a result of a myeloproliferative disorder. Ankylosing spondylitis is a chronic inflammatory rheumatic disease affecting the spine and sometimes peripheral joints in which reactive mild to moderate thrombocytosis is a common finding. There have been no previously reported cases of essential thrombocythemia associated with ankylosing spondylitis.
CASE OUTLINE
We report a case of a 32-year-old man with human leukocyte antigen B27-positive ankylosing spondylitis and Janus kinase 2-positive essential thrombocythemia who was treated first with a combination of anagrelide and disease-modifying antirheumatic drugs and, after liver toxicity, with a combination of anagrelide and etanercept (TNF-α antagonist). Both diseases were gradually brought under control.
CONCLUSION
Our case of ankylosing spondylitis and essential thrombocythemia suggests that concomitant etanercept and anagrelide therapy is safe, as well as effective.
Topics: Adult; Antirheumatic Agents; Etanercept; Humans; Male; Quinazolines; Spondylitis, Ankylosing; Thrombocythemia, Essential
PubMed: 27276864
DOI: 10.2298/sarh1602081z -
Turkish Journal of Haematology :... Sep 2016Myeloproliferative neoplasms (MPNs) share common clonal stem cells but show significant differences in their clinical courses. The aim of this retrospective study was to...
OBJECTIVE
Myeloproliferative neoplasms (MPNs) share common clonal stem cells but show significant differences in their clinical courses. The aim of this retrospective study was to evaluate thrombotic and hemorrhagic complications, JAK2 status, gastrointestinal and cardiac changes, treatment modalities, and survival in MPNs in Turkish patients.
MATERIALS AND METHODS
Medical files of 294 patients [112 essential thrombocythemia (ET), 117 polycythemia vera (PV), 46 primary myelofibrosis, and 19 unclassified MPN cases] from 2 different universities in Turkey were examined.
RESULTS
Older age, higher leukocyte count at diagnosis, and JAK2 mutation positivity were risk factors for thrombosis. Platelet count over 1000x109/L was a risk factor for hemorrhagic episodes. Hydroxyurea treatment was not related to leukemic transformation. Median follow-up time was 50 months (quartiles: 22.2-81.75) in these patients. Patients with primary myelofibrosis had the shortest survival of 137 months when compared with 179 months for ET and 231 months for PV. Leukemic transformation, thromboembolic events, age over 60 years, and anemia were found to be the factors affecting survival.
CONCLUSION
Thromboembolic complications are the most important preventable risk factors for morbidity and mortality in MPNs. Drug management in MPNs is done according to hemoglobin and platelet counts. Based on the current study population our results support the idea that leukocytosis and JAK2 positivity are more important risk factors for thrombosis than hemoglobin and platelet values.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Chronic Disease; Female; Hemorrhage; Humans; Hydroxyurea; Janus Kinase 2; Male; Middle Aged; Mutation; Myeloproliferative Disorders; Quinazolines; Retrospective Studies; Risk Factors; Turkey; Venous Thromboembolism; Young Adult
PubMed: 27094255
DOI: 10.4274/tjh.2015.0041 -
Blood Cancer Journal Nov 2015Polycythemia vera (PV) and essential thrombocythemia (ET) constitute two of the three BCR-ABL1-negative myeloproliferative neoplasms and are characterized by relatively... (Review)
Review
Polycythemia vera (PV) and essential thrombocythemia (ET) constitute two of the three BCR-ABL1-negative myeloproliferative neoplasms and are characterized by relatively long median survivals (approximately 14 and 20 years, respectively). Potentially fatal disease complications in PV and ET include disease transformation into myelofibrosis (MF) or acute myeloid leukemia (AML). The range of reported frequencies for post-PV MF were 4.9-6% at 10 years and 6-14% at 15 years and for post-ET MF were 0.8-4.9% at 10 years and 4-11% at 15 years. The corresponding figures for post-PV AML were 2.3-14.4% at 10 years and 5.5-18.7% at 15 years and for post-ET AML were 0.7-3% at 10 years and 2.1-5.3% at 15 years. Risk factors cited for post-PV MF include advanced age, leukocytosis, reticulin fibrosis, splenomegaly and JAK2V617F allele burden and for post-ET MF include advanced age, leukocytosis, anemia, reticulin fibrosis, absence of JAK2V617F, use of anagrelide and presence of ASXL1 mutation. Risk factors for post-PV AML include advanced age, leukocytosis, reticulin fibrosis, splenomegaly, abnormal karyotype, TP53 or RUNX1 mutations as well as use of pipobroman, radiophosphorus (P(32)) and busulfan and for post-ET AML include advanced age, leukocytosis, anemia, extreme thrombocytosis, thrombosis, reticulin fibrosis, TP53 or RUNX1 mutations. It is important to note that some of the aforementioned incidence figures and risk factor determinations are probably inaccurate and at times conflicting because of the retrospective nature of studies and the inadvertent labeling, in some studies, of patients with prefibrotic primary MF or 'masked' PV, as ET. Ultimately, transformation of MPN leads to poor outcomes and management remains challenging. Further understanding of the molecular events leading to disease transformation is being investigated.
Topics: Fusion Proteins, bcr-abl; Humans; Leukemia, Myeloid, Acute; Lymphocyte Activation; Polycythemia Vera; Primary Myelofibrosis; Thrombocythemia, Essential
PubMed: 26565403
DOI: 10.1038/bcj.2015.95 -
Turkish Journal of Haematology :... Jun 2015Ruxolitinib, a JAK1 and JAK2 inhibitor drug, has recently been approved for the treatment of patients with high- or intermediate-risk myelofibrosis with symptomatic... (Review)
Review
Ruxolitinib, a JAK1 and JAK2 inhibitor drug, has recently been approved for the treatment of patients with high- or intermediate-risk myelofibrosis with symptomatic splenomegaly. Ruxolitinib is the first clinically useful targeted therapy in Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs). The aim of this paper is to indicate pharmacobiological aspects of ruxolitinib within the potential context of MPNs. Pharmacobiological assessments, in addition to knowledge of the risk profile for ruxolitinib in MPNs, are required. We propose hypotheses based on our experience in a splenectomized MPN patient with hyperproliferative bone marrow and moderate fibrosis receiving ruxolitinib. We believe that a true clinical development approach for this drug should include pharmacobiological assessments for ruxolitinib in addition to the disease risk profile of MPNs.
Topics: Bone Marrow; Combined Modality Therapy; Disease Progression; Female; Fibrosis; Humans; Hydroxyurea; Janus Kinase 2; Leukapheresis; Middle Aged; Myeloproliferative Disorders; Nitriles; Phlebotomy; Point Mutation; Polycythemia Vera; Protein Kinase Inhibitors; Pyrazoles; Pyrimidines; Quinazolines; Splenectomy; Splenomegaly
PubMed: 26316485
DOI: 10.4274/tjh.2013.0265