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Leukemia & Lymphoma Dec 2014Hydroxyurea (HU) has traditionally been the first-line treatment for patients with polycythemia vera (PV) or essential thrombocythemia (ET) at high risk for vascular... (Review)
Review
Hydroxyurea (HU) has traditionally been the first-line treatment for patients with polycythemia vera (PV) or essential thrombocythemia (ET) at high risk for vascular complications. However, approximately 20-25% of patients develop resistance or intolerance to HU and must be treated with second-line therapies. Resistance is associated with disease transformation and reduced survival. However, given the dearth of large-scale controlled clinical trials in this patient population, there is no clear consensus on how to best treat patients who develop resistance or intolerance to HU. Herein, we review current literature on treatment options for patients with HU-refractory/resistant PV or ET and provide recommendations for treating these patients.
Topics: Antineoplastic Agents; Busulfan; Disease Management; Drug Resistance; Histone Deacetylase Inhibitors; Humans; Hydroxyurea; Interferon-alpha; Janus Kinase 2; Pipobroman; Platelet Aggregation Inhibitors; Polycythemia Vera; Protein Kinase Inhibitors; Quinazolines; Thrombocythemia, Essential; Treatment Outcome
PubMed: 24524340
DOI: 10.3109/10428194.2014.893310 -
Indian Journal of Hematology & Blood... Sep 2013This presentation is a clinical narrative and long term follow up (6-16 years) of 21 prospectively studied patients with essential thrombocythaemia (ET) in Kuwait. The...
This presentation is a clinical narrative and long term follow up (6-16 years) of 21 prospectively studied patients with essential thrombocythaemia (ET) in Kuwait. The median age (55.9 years) is younger than reported by others. Two patients were below the age of 40 years with one of them presenting as post-polycytheamia ET at 16 years of age. Twelve patients (57.1 %) remained asymptomatic throughout the period of follow up. Four patients complained of erythromelalgia, three (19 %) suffered from thrombotic episodes and only one (4.3 %) had excessive bleeding. Four patients presented with splenomegaly. Intensity of thrombocytosis or duration of very high platelet count had no relationship with these complications. Two patients transformed to post-ET myelofibrosis and one patient developed chronic myeloid leukaemia (CML). None transitioned to acute leukaemia. All patients are still alive after follow up for 6-16 years. Janus kinase 2 mutation was positive in eight (38 %) patients. It had no bearing on transition of our ET patients to post-ET myelofibrosis or CML. Platelet aggregation tests were performed in 14 patients. Six (42.9 %) showed defective response to ADP. Only one of these patients suffered from bleeding. All patients were given aspirin (81 mg/day). Cyto-reductive therapy with hydroxyurea was taken by six (42.9 %) subjects. Two patients who were treated with anagrelide and one with alpha-interferon did not continue treatment for long.
PubMed: 24426359
DOI: 10.1007/s12288-012-0172-9 -
Romanian Journal of Morphology and... 2013Chronic myeloid leukemia is a clonal expansion of hematopoietic progenitor cells characterized by exaggerated proliferation of granulocytic lineage, with chronic phase,...
Chronic myeloid leukemia is a clonal expansion of hematopoietic progenitor cells characterized by exaggerated proliferation of granulocytic lineage, with chronic phase, accelerated phase and blast crisis. Accelerated phase and blast crisis may be associated with extramedulary disease. Extramedullary transformation of CML can be determined both in nodal and extranodal sites. Non-Hodgkin lymphoma is rare in chronic myeloid leukemia and may be misdiagnosed as an extramedullary lymphoid blast transformation; the majorities are T-cell lymphomas with an immature thymic phenotype, while peripheral B-cell lymphomas are rarer. We report the case of a 79-year-old woman carrier Ph+ chronic myeloid leukemia who developed at eight months of diagnosis an accelerated phase of CML associated simultaneous with a tumor of soft palate, which was initial considering an extramedullary disease. The patient was treated with specific chemotherapy for accelerated phase of CML (Cytosinarabinoside) + Anagrelide, and reversed to secondary chronic phase of CML, but soft palate tumor persists. The immunohistochemical findings of bone marrow trephine biopsy examination showed chronic phase of CML (negativity for immature cells such as CD34, Tdt) and the biopsy of soft palate tumor and immunohistochemical findings revealed a primitive non-Hodgkin lymphoma (NHL) with medium B-cells (CD20, CD79a positive) and excluding an extramedullary blast crisis (CD34 negative, Tdt negative). Cytogenetic analysis in tumor revealed absence of Philadelphia chromosome. The patient was treated with local radiotherapy for NHL, with a favorable evolution and Hydroxyurea 1 g/day for CML with hematological remission. A localized lymphoid neoplasm may be an extramedullary localized blast crisis of CML or a distinct malignancy, with distinguished therapy and prognosis. A correct diagnosis based on a complex investigation: immunohistochemistry, conventional cytogenetic analysis and fluorescence in situ hybridization (FISH), molecular analysis (Southern blot and RT-PCR) is necessary. Further studies are required to clarify the pathogenetic relationship between chronic myeloid leukemia and non-Hodgkin lymphomas.
Topics: Aged; Antigens, CD20; Antigens, CD34; Biopsy; Bone Marrow; Female; Humans; Immunohistochemistry; Karyotyping; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Lymphoma, Non-Hodgkin; Mucous Membrane
PubMed: 24399014
DOI: No ID Found -
Haematologica Apr 2014Available information is limited regarding the use of cytoreductive combination therapy in high-risk patients with essential thrombocythemia. This analysis aims to...
Available information is limited regarding the use of cytoreductive combination therapy in high-risk patients with essential thrombocythemia. This analysis aims to evaluate the clinical relevance and patterns of cytoreductive combination treatment in European high-risk patients with essential thrombocythemia in the Evaluation of Xagrid(®) Efficacy and Long-term Safety study. Of 3643 patients, 347 (9.5%) received combination therapy. Data were recorded at each 6-month update. Of 347 patients who received combination therapy, 304 (87.6%) received hydroxycarbamide + anagrelide. Monotherapies received before this combination were hydroxycarbamide (n=167, 54.9%) and anagrelide (n=123, 40.5%). Median weekly doses of hydroxycarbamide and anagrelide were: 7000 and 10.5 mg when used as prior monotherapy; 3500 and 7.0 mg when used as add-on treatment. Overall, median platelet counts were 581 × 10(9)/L and 411 × 10(9)/L before and after starting hydroxycarbamide + anagrelide, respectively. In patients with paired data (n=153), the number of patients with platelet counts less than 400 × 10(9)/L increased from 33 (21.6%) to 74 (48.4%; P<0.0001), and with platelet counts less than 600 × 10(9)/L, from 82 (53.6%) to 132 (86.3%; P<0.0001). Hydroxycarbamide + anagrelide was discontinued in 158 patients: 76 (48.1%) stopped hydroxycarbamide, 59 (37.3%) stopped anagrelide, 19 (12.0%) stopped both and 4 (2.5%) had another therapy added. The most frequent reasons for discontinuation were intolerance/side-effects, lack of efficacy, and therapeutic strategy. Combination therapy, usually hydroxycarbamide + anagrelide, is used in approximately 10% of all high-risk patients with essential thrombocythemia and may be a useful approach in treating patients for whom monotherapy is unsatisfactory. (Clinicaltrials.gov identifier:NCT00567502).
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Cell Count; Drug Therapy, Combination; Female; Humans; Hydroxyurea; Interferons; Male; Middle Aged; Quinazolines; Thrombocythemia, Essential; Treatment Outcome; Young Adult
PubMed: 24334294
DOI: 10.3324/haematol.2012.083097 -
European Journal of Haematology Feb 2014To identify switch modalities used when initiating second- or third-line anagrelide for essential thrombocythemia (ET), assess whether anagrelide is initiated... (Clinical Trial)
Clinical Trial
Characterization of different regimens for initiating anagrelide in patients with essential thrombocythemia who are intolerant or refractory to their current cytoreductive therapy: results from the multicenter FOX study of 177 patients in France.
OBJECTIVES
To identify switch modalities used when initiating second- or third-line anagrelide for essential thrombocythemia (ET), assess whether anagrelide is initiated consistently with Summary of Product Characteristics (SPC) recommendations, and determine whether different observed switch regimens have any relationship with maintenance, platelet response, or tolerability.
METHODS
This observational study was conducted across 43 centers in France. High-risk patients (>60 yr of age and/or history of thrombosis and/or platelet count >1000 × 10(9) /L) with ET starting second- or third-line anagrelide therapy were identified and monitored for 6 months.
RESULTS
A total of 177 patients were enrolled. The SPC-recommended starting dose (1 mg/d) was used in 52.6% of patients; 0.5 mg/d was used in 41.1%. 77.1% of patients underwent an anagrelide dose increase during the study. At 6-month follow-up, 84.7% of patients (n = 144/170) were still receiving anagrelide; 70.6% (n = 120/170) achieved a platelet response. A higher proportion of patients who discontinued previous cytoreductive therapy (CRT) after initiating anagrelide achieved a platelet response (n = 34/39, 87.2%) vs. patients who discontinued their previous CRT before anagrelide initiation (n = 77/115, 67.0%). Platelet response rates were higher in patients whose anagrelide initiation was consistent (n = 100/133, 75.2%) vs. inconsistent (n = 20/37, 54.1%) with the SPC. The incidence of adverse drug reactions was lower in patients whose anagrelide treatment was consistent (n = 52/133, 39.1%) vs. inconsistent (n = 25/37, 67.6%) with the SPC.
CONCLUSIONS
To our knowledge, the FOX study provides the first comprehensive real-world data on the modalities used when switching from previous CRT to anagrelide. Highest platelet responses were observed when previous CRT was discontinued after anagrelide initiation or when anagrelide was initiated consistently with the SPC. Safety data corresponded with the SPC.
Topics: Adult; Aged; Aged, 80 and over; Drug Substitution; Female; France; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Platelet Count; Quinazolines; Retreatment; Thrombocythemia, Essential; Time Factors; Treatment Outcome; Young Adult
PubMed: 24118452
DOI: 10.1111/ejh.12210 -
Journal of Cardiology Cases Nov 2013Essential thrombocythemia (ET), a chronic myeloproliferative disease, is characterized by an increased number of platelets and risk of vascular thrombosis. A case of a...
Essential thrombocythemia (ET), a chronic myeloproliferative disease, is characterized by an increased number of platelets and risk of vascular thrombosis. A case of a patient treated for ET who had acute myocardial infarction (MI) and reinfarction within a month is presented. A 55-year-old male patient was hospitalized because of subacute inferolateral non-ST-segment-elevation MI, without risk factors for cardiovascular diseases. The patient has been treated for ET for the past 8 years, received anagrelide for the past two years. The first coronary-angiography did not detect significant stenosis of epicardial vessels; the patient was discharged in stable condition with anagrelide therapy. Two weeks later, the patient had an acute anterolateral ST-segment-elevation MI. Primary percutaneous coronary intervention showed thrombus in the distal part of the left anterior descending coronary artery. Percutaneous transluminal coronary angioplasty was performed and eptifibatide was administered after the procedure. There was no residual stenosis, prescribed therapy included clopidogrel and low-molecular-weight heparin. Anagrelide therapy was replaced with hydroxyurea (HU) and acetylsalicylic acid (ASA). It is necessary to treat ET in line with the standard treatment protocol for coronary diseases. In the treatment of high-risk hematology patients anagrelide proved to be a worse option than the combination of HU and ASA. It is known that the myeloproliferative disorders carry the risk of vascular thrombosis and myocardial infarction. The occurrence of vascular events is usually the first sign of the disease. A case of a patient with history of hematological disease, who was receiving active treatment and was well-regulated with oral medication, is presented here. Various approaches to treatment of such patients are possible and treatment decision-making is important for clinicians. Therefore, this article presents both our view on this issue and an overview of the literature in this area.>.
PubMed: 30546769
DOI: 10.1016/j.jccase.2013.08.001 -
British Journal of Haematology Nov 2013The incidence of essential thrombocythaemia (ET) in children (age ≤18 years) is extremely low. The natural course of the disorder in children has not been clarified.... (Review)
Review
The incidence of essential thrombocythaemia (ET) in children (age ≤18 years) is extremely low. The natural course of the disorder in children has not been clarified. The rarity of patients and the variability of tested parameters make it difficult to draw any definitive conclusion in pathogenesis and diagnosis of paediatric ET. What makes the onset of thrombocytosis earlier in children is still uncertain. A diagnostic algorithm for paediatric ET has not been established, and current risk stratification used to guide therapeutic decisions in adults has not been validated in children. Vascular complications and transformation to myelofibrosis and leukaemia in this special entity have been reported, suggesting that ET in children is not an entirely benign disease. The crucial question is how to identify patients who are at high risk of complications and need treatment. There are insufficient data to recommend a specific agent in children. The purpose of this review is to outline the most recent progress in paediatric ET and to help with understanding the clinical course, molecular features, diagnosis and treatment strategies in this special group.
Topics: Adolescent; Age of Onset; Anticoagulants; Child; Child, Preschool; Clone Cells; Disease Progression; GPI-Linked Proteins; Hemorrhage; Humans; Hydroxyurea; Incidence; Infant; Isoantigens; Janus Kinase 2; Leukemia, Myeloid, Acute; Platelet Aggregation Inhibitors; Point Mutation; Primary Myelofibrosis; Quinazolines; Receptors, Cell Surface; Risk Assessment; Symptom Assessment; Thrombocythemia, Essential; Thrombophilia
PubMed: 24032343
DOI: 10.1111/bjh.12530 -
Journal of Medical Case Reports Sep 2013The emergence of multiple myeloma as a second malignancy in patients with essential thrombocythemia is extremely rare. Several cases have been published so far, pointing...
INTRODUCTION
The emergence of multiple myeloma as a second malignancy in patients with essential thrombocythemia is extremely rare. Several cases have been published so far, pointing out the impact of a cytotoxic effect during treatment of essential thrombocythemia on the development of multiple myeloma.
CASE PRESENTATION
We report the case of a 52-year-old Caucasian man who presented to our hospital because of leukocytosis, a slightly decreased hemoglobin level and thrombocytosis. After a complete hematological work-up, essential thrombocythemia was diagnosed. The patient was included in a multicenter clinical study, treated with anagrelide and his platelet counts were maintained in the normal range for more than 3 years. A sudden drop in his hemoglobin level with normal leukocyte and platelet count occurred at the same time as a back pain. Magnetic resonance imaging of his spine revealed the existence of a pathological fracture of Th4, the collapse of the upper edge of Th7 and osteolytic lesions of multiple thoracic vertebrae. Repeated hematological examinations, including bone biopsy with immunohistochemistry, disclosed diagnosis of multiple myeloma of the non-secretory type.
CONCLUSIONS
To the best of our knowledge this is the first published case in which multiple myeloma developed during the treatment of essential thrombocythemia with the non-cytotoxic drug anagrelide. Our attempts to find a common origin for the coexistence of multiple myeloma and essential thrombocythemia have not confirmed the genetic basis of their appearance. Further studies are needed to determine the biological impact of this coexistence.
PubMed: 24025541
DOI: 10.1186/1752-1947-7-224 -
Blood Mar 2013High platelet counts in essential thrombocythemia (ET) can be effectively lowered by treatment with either anagrelide or hydroxyurea. In 259 previously untreated,... (Comparative Study)
Comparative Study Randomized Controlled Trial
High platelet counts in essential thrombocythemia (ET) can be effectively lowered by treatment with either anagrelide or hydroxyurea. In 259 previously untreated, high-risk patients with ET, diagnosed according to the World Health Organization classification system, the efficacy and tolerability of anagrelide compared with hydroxyurea were investigated in a prospective randomized noninferiority phase 3 study in an a priori-ordered hypothesis. Confirmatory proof of the noninferiority of anagrelide was achieved after 6 months using the primary end point criteria and was further confirmed after an observation time of 12 and 36 months for platelet counts, hemoglobin levels, leukocyte counts (P < .001), and ET-related events (HR, 1.19 [95% CI, 0.61-2.30], 1.03 [95% CI, 0.57-1.81], and 0.92 [95% CI, 0.57-1.46], respectively). During the total observation time of 730 patient-years, there was no significant difference between the anagrelide and hydroxyurea group regarding incidences of major arterial (7 vs 8) and venous (2 vs 6) thrombosis, severe bleeding events (5 vs 2), minor arterial (24 vs 20) and venous (3 vs 3) thrombosis and minor bleeding events (18 vs 15), or rates of discontinuation (adverse events 12 vs 15 or lack of response 5 vs 2). Disease transformation into myelofibrosis or secondary leukemia was not reported. Anagrelide as a selective platelet-lowering agent is not inferior compared with hydroxyurea in the prevention of thrombotic complications in patients with ET diagnosed according to the World Health Organization system. This trial was registered at http://www.clinicaltrials.gov as #NCT01065038.
Topics: Adult; Aged; Aged, 80 and over; Female; Follow-Up Studies; Humans; Hydroxyurea; Male; Maximum Tolerated Dose; Middle Aged; Nucleic Acid Synthesis Inhibitors; Platelet Aggregation Inhibitors; Prognosis; Prospective Studies; Quinazolines; Retrospective Studies; Single-Blind Method; Thrombocythemia, Essential; World Health Organization; Young Adult
PubMed: 23315161
DOI: 10.1182/blood-2012-07-443770 -
Clinical Drug Investigation Jan 2013The median age of patients diagnosed with essential thrombocythaemia (ET) is 65-70 years but the management of very elderly patients (aged >80 years) with ET has not...
BACKGROUND
The median age of patients diagnosed with essential thrombocythaemia (ET) is 65-70 years but the management of very elderly patients (aged >80 years) with ET has not been well characterized.
OBJECTIVE
This study aimed to document the treatment patterns of very elderly patients with ET in a multinational, real-world setting.
STUDY DESIGN
EXELS (Evaluation of Xagrid Efficacy and Long-term Safety) is a phase IV observational study, designed to monitor the efficacy and safety of cytoreductive therapies in clinical practice. In total, 3,598 high-risk patients with ET were recruited from May 2005 to April 2009, in 13 European countries. Data were collected at registration and every 6 months thereafter for 5 years. This analysis was performed on a data-cut taken approximately 2 years after the last patient was registered.
PATIENTS
In total, 395 patients aged >80 years at registration into EXELS were included in the analysis; of these, 42.2 % had experienced a previous thrombohaemorrhagic event.
RESULTS
At registration, the most frequently prescribed cytoreductive therapy for patients aged >80 years was hydroxycarbamide (HC), which accounted for 82.8 % of patients whereas anagrelide use was less frequent (8.6 %). Very elderly patients were more likely to be switched from anagrelide than from HC (47.1 vs. 17.4 %; 95 % confidence interval for difference in proportion 12.4-46.9; Chi-squared test p < 0.001). Median platelet count during treatment was ~430 × 10(9)/L. In patients aged >80 years, the main reason for switch was intolerance/side effects (34.1 %); 0/16 patients reported treatment with anagrelide was non-efficacious compared with 8/57 (14 %) patients receiving HC, and 7/16 (43.8 %) anagrelide patients switched because of intolerance versus 18/57 (31.6 %) patients receiving HC. At least one predefined clinical event (PDE) was experienced by 27.3 % of patients aged >80 years. The most common PDEs reported in the very elderly age group were death (non-PDE related; 11.1 %), other cardiovascular symptoms (5.8 %), haematological transformation (3.8 %), congestive heart failure (3.3 %), myocardial infarction and angina (2.8 %), and thromboembolic events (6.3 %).
CONCLUSION
Well-tolerated and effective cytoreductive therapy has been achieved in patients aged >80 years by following individual treatment modalities that appear in agreement with the recent European LeukemiaNet (ELN) guidelines.
Topics: Age Factors; Aged, 80 and over; Analysis of Variance; Chi-Square Distribution; Drug Substitution; Europe; Female; Hematologic Agents; Humans; Hydroxyurea; Kaplan-Meier Estimate; Male; Platelet Count; Prospective Studies; Quinazolines; Risk Factors; Thrombocythemia, Essential; Time Factors; Treatment Outcome
PubMed: 23184668
DOI: 10.1007/s40261-012-0042-0