Pub Date : 2007-10-01DOI: 10.1111/j.1600-0609.2007.00933.x
Radek Skoda, Tiziano Barbui, John T Reilly
{"title":"Myeloproliferative disorders: a time of new definitions. Outflow from New Horizons in Haematology Meeting, 9-10 March 2007.","authors":"Radek Skoda, Tiziano Barbui, John T Reilly","doi":"10.1111/j.1600-0609.2007.00933.x","DOIUrl":"https://doi.org/10.1111/j.1600-0609.2007.00933.x","url":null,"abstract":"","PeriodicalId":11926,"journal":{"name":"European journal of haematology. Supplementum","volume":" 68","pages":"1"},"PeriodicalIF":0.0,"publicationDate":"2007-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1600-0609.2007.00933.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26912736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2007-10-01DOI: 10.1111/j.1600-0609.2007.00940.x
Giovanni Barosi
In the treatment of essential thrombocythaemia (ET), cytoreductive agents are used to reduce the risk of thrombosis and other disease-related complications. Hydroxyurea (HU) is the cytoreductive agent most commonly used for the treatment of high-risk ET patients (1). Although the use of HU is supported by evidencebased guidelines (1) and the results of randomised studies (2), it is not an optimal treatment option for all ET patients. It is estimated that 10% of patients receiving it do not achieve the desired reduction in platelet count using recommended doses (clinical resistance) (3). Some patients also experience unacceptable side effects including leg ulcers, other muco-cutaneous manifestations and HU-related fever (clinical intolerance) (1, 2, 4, 5). In such cases, clinicians must decide whether it is appropriate to stop HU therapy and switch to an alternative agent. An important consideration in switching from HU to an alternative ET treatment option is the possible increased risk of leukaemic transformation that may apply if other cytostatic agents are used (6). The putative risk of leukaemia associated with HU therapy prompted the evaluation of other drugs thought to lack leukaemogenic potential such as interferon and anagrelide. In Europe, anagrelide has been approved for ‘at risk patients who are intolerant to their current therapy or whose elevated platelet counts are not reduced to an acceptable level by their current therapy’ (3). This indication highlights clinical intolerance or resistance as the basis for switching a patient’s current therapy to an alternative agent. It does not, however, specify precise criteria for how resistance and intolerance should be defined. The need for a unified definition of resistance and intolerance to hydroxyurea
{"title":"New consensus: a unified definition of clinical resistance and/or intolerance to hydroxyurea in essential thrombocythaemia.","authors":"Giovanni Barosi","doi":"10.1111/j.1600-0609.2007.00940.x","DOIUrl":"https://doi.org/10.1111/j.1600-0609.2007.00940.x","url":null,"abstract":"In the treatment of essential thrombocythaemia (ET), cytoreductive agents are used to reduce the risk of thrombosis and other disease-related complications. Hydroxyurea (HU) is the cytoreductive agent most commonly used for the treatment of high-risk ET patients (1). Although the use of HU is supported by evidencebased guidelines (1) and the results of randomised studies (2), it is not an optimal treatment option for all ET patients. It is estimated that 10% of patients receiving it do not achieve the desired reduction in platelet count using recommended doses (clinical resistance) (3). Some patients also experience unacceptable side effects including leg ulcers, other muco-cutaneous manifestations and HU-related fever (clinical intolerance) (1, 2, 4, 5). In such cases, clinicians must decide whether it is appropriate to stop HU therapy and switch to an alternative agent. An important consideration in switching from HU to an alternative ET treatment option is the possible increased risk of leukaemic transformation that may apply if other cytostatic agents are used (6). The putative risk of leukaemia associated with HU therapy prompted the evaluation of other drugs thought to lack leukaemogenic potential such as interferon and anagrelide. In Europe, anagrelide has been approved for ‘at risk patients who are intolerant to their current therapy or whose elevated platelet counts are not reduced to an acceptable level by their current therapy’ (3). This indication highlights clinical intolerance or resistance as the basis for switching a patient’s current therapy to an alternative agent. It does not, however, specify precise criteria for how resistance and intolerance should be defined. The need for a unified definition of resistance and intolerance to hydroxyurea","PeriodicalId":11926,"journal":{"name":"European journal of haematology. Supplementum","volume":" 68","pages":"24-6"},"PeriodicalIF":0.0,"publicationDate":"2007-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1600-0609.2007.00940.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26912743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2007-10-01DOI: 10.1111/j.1600-0609.2007.00937.x
Francisco Cervantes
Primary myelofibrosis (PMF), also known as idiopathic myelofibrosis or myelofibrosis with myeloid metaplasia, a chronic myeloproliferative disorder, is a rare disease mainly affecting older people, with a median survival of 3.5–5 yr (1), characterized by bone marrow fibrosis, extramedullary haemopoiesis, and the presence of tear drop red cells in the peripheral blood (2). Clinical manifestations of PMF include splenomegaly, progressive anaemia and constitutional symptoms. The pathogenesis of the disease is currently not understood. PMF is a clonal disorder of the haematopoietic stem cell in which the fibrosis is a reactive process involving the interaction of multiple cytokines, such as the platelet-derived growth factor (PDGF), transforming growth factor beta 1 (TGF-b1), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) (3–5) produced by the CD34+ cells, the megakaryocytes, and the monocytes.
{"title":"Myelofibrosis: biology and treatment options.","authors":"Francisco Cervantes","doi":"10.1111/j.1600-0609.2007.00937.x","DOIUrl":"https://doi.org/10.1111/j.1600-0609.2007.00937.x","url":null,"abstract":"Primary myelofibrosis (PMF), also known as idiopathic myelofibrosis or myelofibrosis with myeloid metaplasia, a chronic myeloproliferative disorder, is a rare disease mainly affecting older people, with a median survival of 3.5–5 yr (1), characterized by bone marrow fibrosis, extramedullary haemopoiesis, and the presence of tear drop red cells in the peripheral blood (2). Clinical manifestations of PMF include splenomegaly, progressive anaemia and constitutional symptoms. The pathogenesis of the disease is currently not understood. PMF is a clonal disorder of the haematopoietic stem cell in which the fibrosis is a reactive process involving the interaction of multiple cytokines, such as the platelet-derived growth factor (PDGF), transforming growth factor beta 1 (TGF-b1), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) (3–5) produced by the CD34+ cells, the megakaryocytes, and the monocytes.","PeriodicalId":11926,"journal":{"name":"European journal of haematology. Supplementum","volume":" 68","pages":"13-7"},"PeriodicalIF":0.0,"publicationDate":"2007-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1600-0609.2007.00937.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26912740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2007-10-01DOI: 10.1111/j.1600-0609.2007.00939.x
Tiziano Barbui
The unified definition of clinical resistance and intolerance to hydroxyurea (HU) (1) is an important development in the management of essential thrombocythaemia (ET). In this article, the evolution of ET treatment will be reviewed in order to demonstrate why the consensus definition is necessary. More detailed discussions of the consensus process used to develop the definition and its implications for clinical practice are provided in the articles that follow.
{"title":"Evolving management of essential thrombocythaemia.","authors":"Tiziano Barbui","doi":"10.1111/j.1600-0609.2007.00939.x","DOIUrl":"https://doi.org/10.1111/j.1600-0609.2007.00939.x","url":null,"abstract":"The unified definition of clinical resistance and intolerance to hydroxyurea (HU) (1) is an important development in the management of essential thrombocythaemia (ET). In this article, the evolution of ET treatment will be reviewed in order to demonstrate why the consensus definition is necessary. More detailed discussions of the consensus process used to develop the definition and its implications for clinical practice are provided in the articles that follow.","PeriodicalId":11926,"journal":{"name":"European journal of haematology. Supplementum","volume":" 68","pages":"22-3"},"PeriodicalIF":0.0,"publicationDate":"2007-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1600-0609.2007.00939.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26912742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2007-10-01DOI: 10.1111/j.1600-0609.2007.00942.x
John T Reilly
The consensus-based definition for clinical resistance and intolerance to hydroxyurea (HU) (1) is intended to facilitate a more consistent approach to the management of essential thrombocythaemia (ET). In particular, the definition is designed to aid clinical decision-making regarding whether treatment with HU should be stopped or switched to an alternative agent such as anagrelide or a-interferon. However, incorporation of the definitions into clinical practice may vary between clinicians working in different countries, for example, due to differences in national treatment guidelines, patient populations, and the regulatory and reimbursement status of different medications. The implications of the consensus definition for clinical practice in different regions of the world were examined at the 2007 ‘New Horizons in Haematology’ meeting within country-based workshops. Discussions were framed around key topics including the importance of the definition in clinical practice, the use of platelet counts for defining treatment targets and HU resistance and the importance of muco-cutaneous side effects as a criterion for HU intolerance. The workshops were chaired by experts from each region who had been involved in the development of the consensus. The panel of experts then assessed the anticipated impact of the consensus definition on clinical practice and identified the areas of agreement and differences between countries. In this article, I will summarise the key issues identified during the country workshops as chairperson of the expert panel. Importance of the definition in clinical practice
{"title":"Implications of the consensus definition of clinical resistance and intolerance to hydroxyurea for clinical practice.","authors":"John T Reilly","doi":"10.1111/j.1600-0609.2007.00942.x","DOIUrl":"https://doi.org/10.1111/j.1600-0609.2007.00942.x","url":null,"abstract":"The consensus-based definition for clinical resistance and intolerance to hydroxyurea (HU) (1) is intended to facilitate a more consistent approach to the management of essential thrombocythaemia (ET). In particular, the definition is designed to aid clinical decision-making regarding whether treatment with HU should be stopped or switched to an alternative agent such as anagrelide or a-interferon. However, incorporation of the definitions into clinical practice may vary between clinicians working in different countries, for example, due to differences in national treatment guidelines, patient populations, and the regulatory and reimbursement status of different medications. The implications of the consensus definition for clinical practice in different regions of the world were examined at the 2007 ‘New Horizons in Haematology’ meeting within country-based workshops. Discussions were framed around key topics including the importance of the definition in clinical practice, the use of platelet counts for defining treatment targets and HU resistance and the importance of muco-cutaneous side effects as a criterion for HU intolerance. The workshops were chaired by experts from each region who had been involved in the development of the consensus. The panel of experts then assessed the anticipated impact of the consensus definition on clinical practice and identified the areas of agreement and differences between countries. In this article, I will summarise the key issues identified during the country workshops as chairperson of the expert panel. Importance of the definition in clinical practice","PeriodicalId":11926,"journal":{"name":"European journal of haematology. Supplementum","volume":" 68","pages":"32-4"},"PeriodicalIF":0.0,"publicationDate":"2007-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1600-0609.2007.00942.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26912745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2007-10-01DOI: 10.1111/j.1600-0609.2007.00943.x
Martin Griesshammer
Essential thrombocythaemia (ET) is an acquired myeloproliferative disease (MPD) characterized by an elevated platelet count and an excessive proliferation of megakaryopoiesis in the bone marrow. As there are no curative options for ET, current treatment strategies aim to reduce the risks of disease-related complications including thrombosis and haemorrhages (1, 2). The benefits of treatment must be carefully considered against the risks of drug-related toxicity and disease transformation (1, 2). The purpose of this article is to discuss the importance of platelet counts and other risk factors for developing an optimal treatment plan for each individual patient.
{"title":"Options in the management of essential thrombocythaemia.","authors":"Martin Griesshammer","doi":"10.1111/j.1600-0609.2007.00943.x","DOIUrl":"https://doi.org/10.1111/j.1600-0609.2007.00943.x","url":null,"abstract":"Essential thrombocythaemia (ET) is an acquired myeloproliferative disease (MPD) characterized by an elevated platelet count and an excessive proliferation of megakaryopoiesis in the bone marrow. As there are no curative options for ET, current treatment strategies aim to reduce the risks of disease-related complications including thrombosis and haemorrhages (1, 2). The benefits of treatment must be carefully considered against the risks of drug-related toxicity and disease transformation (1, 2). The purpose of this article is to discuss the importance of platelet counts and other risk factors for developing an optimal treatment plan for each individual patient.","PeriodicalId":11926,"journal":{"name":"European journal of haematology. Supplementum","volume":" 68","pages":"35-9"},"PeriodicalIF":0.0,"publicationDate":"2007-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1600-0609.2007.00943.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26912746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2007-10-01DOI: 10.1111/j.1600-0609.2007.00941.x
Gunnar Birgegård
Essential thrombocythaemia (ET) is generally associated with a more favourable prognosis compared with other myeloproliferative disorders. Several studies have demonstrated that life expectancy is not significantly affected by the disease (1–3), although conflicting results have been reported (4–6). One study reported that life expectancy during the first decade of the disease is similar to control subjects, but worsens during the second and third decades (7). Therapeutic options for ET are generally targeted at reducing the risk of complications such as thromboses and haemorrhages (8). However, most current treatment options have limitations such as side effects. In seeking a treatment strategy that optimally balances the risks of disease-related complications against the risks of therapeutic intervention, it is important to individualise treatment plans according to the needs of each patient.
{"title":"Essential thrombocythaemia treatment options: addressing patient-specific needs.","authors":"Gunnar Birgegård","doi":"10.1111/j.1600-0609.2007.00941.x","DOIUrl":"https://doi.org/10.1111/j.1600-0609.2007.00941.x","url":null,"abstract":"Essential thrombocythaemia (ET) is generally associated with a more favourable prognosis compared with other myeloproliferative disorders. Several studies have demonstrated that life expectancy is not significantly affected by the disease (1–3), although conflicting results have been reported (4–6). One study reported that life expectancy during the first decade of the disease is similar to control subjects, but worsens during the second and third decades (7). Therapeutic options for ET are generally targeted at reducing the risk of complications such as thromboses and haemorrhages (8). However, most current treatment options have limitations such as side effects. In seeking a treatment strategy that optimally balances the risks of disease-related complications against the risks of therapeutic intervention, it is important to individualise treatment plans according to the needs of each patient.","PeriodicalId":11926,"journal":{"name":"European journal of haematology. Supplementum","volume":" 68","pages":"27-31"},"PeriodicalIF":0.0,"publicationDate":"2007-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1600-0609.2007.00941.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26912744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2007-10-01DOI: 10.1111/j.1600-0609.2007.00944.x
John T Reilly
A key challenge in the management of essential thrombocythaemia (ET) is to develop an individualised treatment plan that accounts for variability in the clinical course of the disease and patients’ response to specific therapies. Initiatives designed to help clinicians to meet this challenge, which have been described in the preceding articles, include: (i) the consensus definition of hydroxyurea (HU) resistance and intolerance (1) and (ii) treatment algorithms based on risk stratification (2, 3). In seeking to optimise ET management approaches, it is useful to consider case studies that highlight some of the practical challenges encountered in clinical practice. This article summarises key aspects of four ET cases presented to an expert panel at the 2007 New Horizons in Haematology meeting.
{"title":"Practical approach to treating essential thrombocythaemia: case studies.","authors":"John T Reilly","doi":"10.1111/j.1600-0609.2007.00944.x","DOIUrl":"https://doi.org/10.1111/j.1600-0609.2007.00944.x","url":null,"abstract":"A key challenge in the management of essential thrombocythaemia (ET) is to develop an individualised treatment plan that accounts for variability in the clinical course of the disease and patients’ response to specific therapies. Initiatives designed to help clinicians to meet this challenge, which have been described in the preceding articles, include: (i) the consensus definition of hydroxyurea (HU) resistance and intolerance (1) and (ii) treatment algorithms based on risk stratification (2, 3). In seeking to optimise ET management approaches, it is useful to consider case studies that highlight some of the practical challenges encountered in clinical practice. This article summarises key aspects of four ET cases presented to an expert panel at the 2007 New Horizons in Haematology meeting.","PeriodicalId":11926,"journal":{"name":"European journal of haematology. Supplementum","volume":" 68","pages":"40-2"},"PeriodicalIF":0.0,"publicationDate":"2007-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1600-0609.2007.00944.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26912747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2007-10-01DOI: 10.1111/j.1600-0609.2007.00935.x
Radek Skoda
In 2005, several groups discovered an acquired mutation affecting the gene for janus kinase 2 (JAK2 V617F) in a high proportion of patients with polycythaemia vera (PV), primary myelofibrosis (PMF) and essential thrombocythaemia (ET) (1–4). The discovery of this mutation represents a major breakthrough in molecular understanding of the myeloproliferative disorders (MPDs) that may have significant implications for diagnosis and treatment. This article will review the role of the JAKs and impact of the JAK2 mutation on the signalling pathways that underlie MPDs.
{"title":"Update on the impact of the JAK2 mutation on signalling pathways in myeloproliferative disorders.","authors":"Radek Skoda","doi":"10.1111/j.1600-0609.2007.00935.x","DOIUrl":"https://doi.org/10.1111/j.1600-0609.2007.00935.x","url":null,"abstract":"In 2005, several groups discovered an acquired mutation affecting the gene for janus kinase 2 (JAK2 V617F) in a high proportion of patients with polycythaemia vera (PV), primary myelofibrosis (PMF) and essential thrombocythaemia (ET) (1–4). The discovery of this mutation represents a major breakthrough in molecular understanding of the myeloproliferative disorders (MPDs) that may have significant implications for diagnosis and treatment. This article will review the role of the JAKs and impact of the JAK2 mutation on the signalling pathways that underlie MPDs.","PeriodicalId":11926,"journal":{"name":"European journal of haematology. Supplementum","volume":" 68","pages":"5-8"},"PeriodicalIF":0.0,"publicationDate":"2007-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1600-0609.2007.00935.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26912738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Proceedings from the New Horizons in Haematology Meeting, 9-10 March 2007.","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":11926,"journal":{"name":"European journal of haematology. Supplementum","volume":" 68","pages":"1-42"},"PeriodicalIF":0.0,"publicationDate":"2007-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27206333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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