Antibody-directed therapies allow greater selectivity in targeting of tumor associated antigens and spare normal cells. Brentuximab vedotin is an anti-CD30 antibody–drug conjugate. It has demonstrated impressive activity in the treatment of refractory and or relapsed Hodgkin's lymphoma, anaplastic large cell lymphoma and other CD30+ lymphoid malignancies. Several ongoing trials are testing the potential use of brentuximab vedotin for treatment of various CD30+ and CD30- malignancies in the setting of high-risk untreated disease. It is being tested in combination with chemotherapy, and testing in combination with immune therapy is also planned. CD30 plays a pivotal role in immune regulation and is also an attractive new target for intervention in the setting of select auto-immune diseases, as well as graft versus host disease.
{"title":"Brentuximab: a major advance in treatment of CD30-positive malignancies","authors":"P. Amarapurkar, J. Rosenblatt, D. Pereira","doi":"10.2217/IJH.15.27","DOIUrl":"https://doi.org/10.2217/IJH.15.27","url":null,"abstract":"Antibody-directed therapies allow greater selectivity in targeting of tumor associated antigens and spare normal cells. Brentuximab vedotin is an anti-CD30 antibody–drug conjugate. It has demonstrated impressive activity in the treatment of refractory and or relapsed Hodgkin's lymphoma, anaplastic large cell lymphoma and other CD30+ lymphoid malignancies. Several ongoing trials are testing the potential use of brentuximab vedotin for treatment of various CD30+ and CD30- malignancies in the setting of high-risk untreated disease. It is being tested in combination with chemotherapy, and testing in combination with immune therapy is also planned. CD30 plays a pivotal role in immune regulation and is also an attractive new target for intervention in the setting of select auto-immune diseases, as well as graft versus host disease.","PeriodicalId":14166,"journal":{"name":"International Journal of Hematologic Oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/IJH.15.27","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68221542","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}
David H Henry, MD, is a practicing hematologist/medical oncologist and Clinical Professor of Medicine at the Pennsylvania Hospital in Philadelphia (PA, USA), where he holds the title of Vice Chairman of the Department of Medicine. He is Editor in Chief of the Journal of Community and Supportive Oncology. For the past 25 years, he has had a special interest in supportive oncology and participated in clinical trials using growth factors to treat cancer-related anemia with or without intravenous iron, neutropenia, thrombocytopenia and bone metabolism due to bone metastases. He is also the Director of the HIV Malignancy Program and Director of the Austrian Medical Student Program at Pennsylvania Hospital.
David H Henry，医学博士，是费城宾夕法尼亚医院(Pennsylvania Hospital in Philadelphia, PA, USA)的执业血液学家/内科肿瘤学家和临床医学教授，在那里他拥有医学部副主席的头衔。他是《社区与支持肿瘤学杂志》的主编。在过去的25年里，他一直对支持肿瘤学有特殊的兴趣，并参与了使用生长因子治疗癌症相关贫血的临床试验，有或没有静脉注射铁，中性粒细胞减少症，血小板减少症和骨转移引起的骨代谢。他也是宾夕法尼亚医院HIV恶性项目主任和奥地利医科学生项目主任。
{"title":"An interview with David Henry: supportive oncology, anemia and cancer","authors":"D. Henry","doi":"10.2217/IJH.15.17","DOIUrl":"https://doi.org/10.2217/IJH.15.17","url":null,"abstract":"David H Henry, MD, is a practicing hematologist/medical oncologist and Clinical Professor of Medicine at the Pennsylvania Hospital in Philadelphia (PA, USA), where he holds the title of Vice Chairman of the Department of Medicine. He is Editor in Chief of the Journal of Community and Supportive Oncology. For the past 25 years, he has had a special interest in supportive oncology and participated in clinical trials using growth factors to treat cancer-related anemia with or without intravenous iron, neutropenia, thrombocytopenia and bone metabolism due to bone metastases. He is also the Director of the HIV Malignancy Program and Director of the Austrian Medical Student Program at Pennsylvania Hospital.","PeriodicalId":14166,"journal":{"name":"International Journal of Hematologic Oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/IJH.15.17","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68221368","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}
Cancer immunotherapy is evolving very fast. With understanding of tumor and immune system interactions, two pathways have been identified through which tumor cells evade and escape immune system. Blocking these pathways by monoclonal antibodies has shown promising results in wide variety of tumors. The treatment of lymphomas have been evolving with various new molecules ranging from monoclonal antibodies, antibody–drug conjugates to small molecule inhibitors. Here, we review the activity of immune checkpoint inhibitors in various lymphomas. These agents have shown very promising activity in Hodgkin lymphoma and other B-cell lymphomas in early-phase clinical trials.
{"title":"Current status of checkpoint inhibitors in lymphoma","authors":"M. Jamil, Vipin Lohiya, A. Mehta","doi":"10.2217/IJH.15.18","DOIUrl":"https://doi.org/10.2217/IJH.15.18","url":null,"abstract":"Cancer immunotherapy is evolving very fast. With understanding of tumor and immune system interactions, two pathways have been identified through which tumor cells evade and escape immune system. Blocking these pathways by monoclonal antibodies has shown promising results in wide variety of tumors. The treatment of lymphomas have been evolving with various new molecules ranging from monoclonal antibodies, antibody–drug conjugates to small molecule inhibitors. Here, we review the activity of immune checkpoint inhibitors in various lymphomas. These agents have shown very promising activity in Hodgkin lymphoma and other B-cell lymphomas in early-phase clinical trials.","PeriodicalId":14166,"journal":{"name":"International Journal of Hematologic Oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/IJH.15.18","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68221407","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}
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the presence of an oncogenic fusion gene, BCR–ABL1. This fusion gene produces a cytoplasmic protein with tyrosine kinase activity that acts as a main driver of oncogenesis and abnormal proliferation of myeloid cells in CML. Targeted therapy with BCR–ABL1 tyrosine kinase inhibitors (TKIs) such as imatinib is followed by long-term responses in most patients. However, despite continuous treatment, relapses occur, suggesting the presence of TKI-resistant neoplastic stem cells in these patients. Here, we discuss potential mechanisms and signaling molecules involved in the prosurvival and self-renewal capacity of CML neoplastic stem cells as well as antigens expressed by these cells. Several of these signaling molecules and cell surface antigens may serve as potential targets of therapy and their use may overcome TKI resistance in CML in the future.
{"title":"Characterization and targeting of neoplastic stem cells in Ph+ chronic myeloid leukemia","authors":"M. Arock, F. Mahon, P. Valent","doi":"10.2217/IJH.15.16","DOIUrl":"https://doi.org/10.2217/IJH.15.16","url":null,"abstract":"Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the presence of an oncogenic fusion gene, BCR–ABL1. This fusion gene produces a cytoplasmic protein with tyrosine kinase activity that acts as a main driver of oncogenesis and abnormal proliferation of myeloid cells in CML. Targeted therapy with BCR–ABL1 tyrosine kinase inhibitors (TKIs) such as imatinib is followed by long-term responses in most patients. However, despite continuous treatment, relapses occur, suggesting the presence of TKI-resistant neoplastic stem cells in these patients. Here, we discuss potential mechanisms and signaling molecules involved in the prosurvival and self-renewal capacity of CML neoplastic stem cells as well as antigens expressed by these cells. Several of these signaling molecules and cell surface antigens may serve as potential targets of therapy and their use may overcome TKI resistance in CML in the future.","PeriodicalId":14166,"journal":{"name":"International Journal of Hematologic Oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/IJH.15.16","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68221360","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}
M. Braekeleer, M. L. Bris, A. Basinko, F. Morel, N. Douet-Guilbert
Aims & methods: We used interphase FISH to determine the incidence of chromosomal changes in 638 B-cell chronic lymphocytic leukemia patients. Results: Chromosomal abnormalities were found in some 75% of the patients. Del(13)(q14) was present in 57.3 and 57% of patients at diagnosis and during follow-up, respectively. It was followed by trisomy 12 (19 and 19.8% at diagnosis and during follow-up, respectively), del(11)(q22) (9.1 and 14.3% at diagnosis and during follow-up, respectively) and del(17)(p13) (2.8 and 12.4% at diagnosis and during follow-up, respectively). Discussion & conclusion: Our results correlate with those obtained in 55 studies reported in the literature. Trisomy 12 and del(13)(q14) are present in high proportions at diagnosis and are not enriched during progression, to the contrary of del(11)(q22) and del(17)(p13) that are markers of evolution.
{"title":"Incidence of chromosomal anomalies detected by interphase FISH in chronic lymphoid leukemia","authors":"M. Braekeleer, M. L. Bris, A. Basinko, F. Morel, N. Douet-Guilbert","doi":"10.2217/IJH.15.19","DOIUrl":"https://doi.org/10.2217/IJH.15.19","url":null,"abstract":"Aims & methods: We used interphase FISH to determine the incidence of chromosomal changes in 638 B-cell chronic lymphocytic leukemia patients. Results: Chromosomal abnormalities were found in some 75% of the patients. Del(13)(q14) was present in 57.3 and 57% of patients at diagnosis and during follow-up, respectively. It was followed by trisomy 12 (19 and 19.8% at diagnosis and during follow-up, respectively), del(11)(q22) (9.1 and 14.3% at diagnosis and during follow-up, respectively) and del(17)(p13) (2.8 and 12.4% at diagnosis and during follow-up, respectively). Discussion & conclusion: Our results correlate with those obtained in 55 studies reported in the literature. Trisomy 12 and del(13)(q14) are present in high proportions at diagnosis and are not enriched during progression, to the contrary of del(11)(q22) and del(17)(p13) that are markers of evolution.","PeriodicalId":14166,"journal":{"name":"International Journal of Hematologic Oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/IJH.15.19","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68221417","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}
Hairy cell leukemia (HCL) is a rare, indolent B-cell lymphoproliferative disorder that accounts for 2% of all cases of leukemia. Most patients present with pancytopenia and splenomegaly with variable number of ‘hairy’ lymphocytes in blood. BRAF V600E mutation can be detected in virtually 100% of HCL cases and is absent in other B-cell lymphomas. The mutated gene and its responding abnormal protein can be used as specific markers in the diagnosis of HCL. New therapeutic modalities targeting on mutated BRAF and its downstream pathways have shown encouraging results in clinical trials. The objective of this review article is to discuss the recent developments in the diagnosis and management of hairy cell leukemia.
{"title":"Recent advances in diagnosis and treatment of hairy cell leukemia","authors":"Asad Javed, Upasana Joneja, J. Gong, G. Uppal","doi":"10.2217/IJH.15.23","DOIUrl":"https://doi.org/10.2217/IJH.15.23","url":null,"abstract":"Hairy cell leukemia (HCL) is a rare, indolent B-cell lymphoproliferative disorder that accounts for 2% of all cases of leukemia. Most patients present with pancytopenia and splenomegaly with variable number of ‘hairy’ lymphocytes in blood. BRAF V600E mutation can be detected in virtually 100% of HCL cases and is absent in other B-cell lymphomas. The mutated gene and its responding abnormal protein can be used as specific markers in the diagnosis of HCL. New therapeutic modalities targeting on mutated BRAF and its downstream pathways have shown encouraging results in clinical trials. The objective of this review article is to discuss the recent developments in the diagnosis and management of hairy cell leukemia.","PeriodicalId":14166,"journal":{"name":"International Journal of Hematologic Oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/IJH.15.23","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68221522","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}
Recurrent chromosomal aberrations have long been recognized to influence prognosis in acute myeloid leukemia (AML), however, 50% of AML patients have a normal karyotype. The new millennium ushered in discoveries of gene mutations at the molecular level that predict outcome in patients with normal karyotype. Some recurrent mutations are already used in routine practice for AML risk stratification. With the development of high-throughput sequencing technologies, there has been a storm of new data, uncovering a complex genetic landscape in AML. In this review, we describe the significant progress in characterizing recurrent genetic abnormalities in AML in the last 5 years, focusing on prognostic significance and therapeutic implications.
{"title":"Update on recurrent genetic aberrations in acute myeloid leukemia","authors":"K. Jamani, C. Owen","doi":"10.2217/IJH.15.22","DOIUrl":"https://doi.org/10.2217/IJH.15.22","url":null,"abstract":"Recurrent chromosomal aberrations have long been recognized to influence prognosis in acute myeloid leukemia (AML), however, 50% of AML patients have a normal karyotype. The new millennium ushered in discoveries of gene mutations at the molecular level that predict outcome in patients with normal karyotype. Some recurrent mutations are already used in routine practice for AML risk stratification. With the development of high-throughput sequencing technologies, there has been a storm of new data, uncovering a complex genetic landscape in AML. In this review, we describe the significant progress in characterizing recurrent genetic abnormalities in AML in the last 5 years, focusing on prognostic significance and therapeutic implications.","PeriodicalId":14166,"journal":{"name":"International Journal of Hematologic Oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/IJH.15.22","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68221484","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}
Donor lymphocyte infusion, a rescue therapy after hematopoietic stem cell transplantation, has been increasingly adopted, as modalities of stem cell transplantation have widened. First described as donor lymphocyte transfusion or cell therapy, it consists of infusion of donor lymphocytes, collected in steady state or after growth factor enhancement. As in literature the most used name is donor lymphocyte infusion, we'll adopt it here. Its most striking efficacy is observed in patients with chronic myelogenous leukemia, who relapsed after allogeneic stem cells transplantation. However, graft-versus-host disease, its main complication, may still hamper its feasibility.
{"title":"Donor lymphocyte infusion after allogeneic hematopoietic stem cell transplantation","authors":"T. Pereira, R. Danby, V. Rocha","doi":"10.2217/IJH.15.20","DOIUrl":"https://doi.org/10.2217/IJH.15.20","url":null,"abstract":"Donor lymphocyte infusion, a rescue therapy after hematopoietic stem cell transplantation, has been increasingly adopted, as modalities of stem cell transplantation have widened. First described as donor lymphocyte transfusion or cell therapy, it consists of infusion of donor lymphocytes, collected in steady state or after growth factor enhancement. As in literature the most used name is donor lymphocyte infusion, we'll adopt it here. Its most striking efficacy is observed in patients with chronic myelogenous leukemia, who relapsed after allogeneic stem cells transplantation. However, graft-versus-host disease, its main complication, may still hamper its feasibility.","PeriodicalId":14166,"journal":{"name":"International Journal of Hematologic Oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/IJH.15.20","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68221474","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}
Chronic lymphocytic leukemia is a mature B-cell neoplasm in which the interactions between the malignant B cells and tumor microenvironment play a key role in cell survival and growth. B-cell receptor (BCR) is a key survival pathway in chronic lymphocytic leukemia. Following BCR signal trigger, several kinase pathways are activated that promote signal transduction. Ibrutinib is a first-in-class, potent, orally administered covalently binding inhibitor of Bruton's tyrosine kinase that is US FDA approved. Inhibition of Bruton's tyrosine kinase blocks downstream BCR signaling pathways (AKT, ERK) and thus prevents B-cell proliferation. Ibrutinib impairs microenvironment-induced survival of the malignant B cells. Ibrutinib is currently under investigation for both hematologic and solid tumor malignancies.
{"title":"Ibrutinib in chronic lymphocytic leukemia","authors":"N. Reddy, Tarsheen K Sethi","doi":"10.2217/IJH.15.15","DOIUrl":"https://doi.org/10.2217/IJH.15.15","url":null,"abstract":"Chronic lymphocytic leukemia is a mature B-cell neoplasm in which the interactions between the malignant B cells and tumor microenvironment play a key role in cell survival and growth. B-cell receptor (BCR) is a key survival pathway in chronic lymphocytic leukemia. Following BCR signal trigger, several kinase pathways are activated that promote signal transduction. Ibrutinib is a first-in-class, potent, orally administered covalently binding inhibitor of Bruton's tyrosine kinase that is US FDA approved. Inhibition of Bruton's tyrosine kinase blocks downstream BCR signaling pathways (AKT, ERK) and thus prevents B-cell proliferation. Ibrutinib impairs microenvironment-induced survival of the malignant B cells. Ibrutinib is currently under investigation for both hematologic and solid tumor malignancies.","PeriodicalId":14166,"journal":{"name":"International Journal of Hematologic Oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/IJH.15.15","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68221695","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}
“...the already excellent results of treatment can be optimized, but optimization aiming at a sustainable extension of the treatment worldwide, at a more cost-effective use of the available drugs and at more attention to the quality of life, requires a long and a demanding learning curve.”
{"title":"Treatment of chronic myeloid leukemia, which drugs? How long? How much?","authors":"M. Baccarani","doi":"10.2217/IJH.15.14","DOIUrl":"https://doi.org/10.2217/IJH.15.14","url":null,"abstract":"“...the already excellent results of treatment can be optimized, but optimization aiming at a sustainable extension of the treatment worldwide, at a more cost-effective use of the available drugs and at more attention to the quality of life, requires a long and a demanding learning curve.”","PeriodicalId":14166,"journal":{"name":"International Journal of Hematologic Oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/IJH.15.14","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68221451","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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