Acute lymphoblastic leukemia (ALL) comprises about 20% of leukemias in adult. Though the high complete remission (CR) rates after the first-line chemotherapy, only 30–40% of ALL patients may be cured. The prognosis of relapsed/refractory ALL remains poor. The 5-year overall survival (OS) rate is 7–10%. In recent years, new therapies utilizing monoclonal antibodies have been investigated. Inotuzumab ozogamycin is a humanized anti-CD22 antibody conjugated to an alkylating agent — calicheamicin. The drug was registered for relapsed/refractory ALL in adults based on INO-VATE trial, a phase III trial comparing efficacy of inotuzumab ozogamycin to chemotherapy. CR rates, progression-free survival, and OS were significantly higher in the inotuzumab group. In addition, significantly more patients from the inotuzumab group were treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). The most common adverse events were neutropenia and thrombocytopenia. Among the non-hematological adverse events the veno-occlusive disease (VOD) was the most dangerous. The frequency of VOD increased in patients who underwent allo-HSCT. This article presents the most important clinical trials with inotuzumab ozogamycin and the toxicity of the drug.
{"title":"Inotuzumab ozogamycyny w leczeniu chorych na ostrą białaczkę limfoblastyczną","authors":"A. Gołoś, J. Góra-Tybor","doi":"10.5603/HEM.2018.0036","DOIUrl":"https://doi.org/10.5603/HEM.2018.0036","url":null,"abstract":"Acute lymphoblastic leukemia (ALL) comprises about 20% of leukemias in adult. Though the high complete remission (CR) rates after the first-line chemotherapy, only 30–40% of ALL patients may be cured. The prognosis of relapsed/refractory ALL remains poor. The 5-year overall survival (OS) rate is 7–10%. In recent years, new therapies utilizing monoclonal antibodies have been investigated. Inotuzumab ozogamycin is a humanized anti-CD22 antibody conjugated to an alkylating agent — calicheamicin. The drug was registered for relapsed/refractory ALL in adults based on INO-VATE trial, a phase III trial comparing efficacy of inotuzumab ozogamycin to chemotherapy. CR rates, progression-free survival, and OS were significantly higher in the inotuzumab group. In addition, significantly more patients from the inotuzumab group were treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). The most common adverse events were neutropenia and thrombocytopenia. Among the non-hematological adverse events the veno-occlusive disease (VOD) was the most dangerous. The frequency of VOD increased in patients who underwent allo-HSCT. This article presents the most important clinical trials with inotuzumab ozogamycin and the toxicity of the drug.","PeriodicalId":38988,"journal":{"name":"Hematologia","volume":"53 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88375218","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}
Marzena Wątek, B. Durnas, Tomasz Wollny, Małgorzata Żendzian-Piotrowska, Marcin Pasiarski, S. Góźdź
One of the key obstacles in the progress of cancer treatment is the lack of balance between the uncontrolled proliferation and cell apoptosis. It is now known that sphingolipids are essential molecules regulating the processes of growth, differentiation and death of living cells. Depending on their chemical nature, sphingolipids may have a stimulatory (S1P, sphingosine-1-phosphate) or inhibitory (ceramide) effect on cellular proliferation. A number of different studies have shown that the generation of ceramide in response to cytotoxic therapy is an important element leading to cell death. Cancer cells use different methods limiting the production of ceramides that leads to their removal. The effect of oncogenic S1P results from its stimulating effect on DNA synthesis and chemotactic mobility of the vascular endothelial cells and angiogenesis. The use of monoclonal anti-S1P antibodies is potentially a valuable therapeutic option for inhibiting angiogenesis determining the growth of tumors. It was additionally demonstrated that S1P beyond the direct and indirect by stimulating the release of vascular endothelial growth factor and basic fibroblast growth factor angiogenic action has an effect on tumor growth and its metastatic potential. Among the sphingolipids, ceramide was identified first as inducing differentiation and the death of human HL-60 promyelocytic leukemia cells. Progress in understanding the role of sphingolipids was regarded until recently as the only structural component of cell membranes allowing the use in the treatment of complex properties of this group of signaling molecules. Thus, it has become important to clarify the role of sphingolipids in the regulation of the balance between proliferation signals/ /survival rate and death of cells in order to develop new therapies for neoplastic diseases of myeloid and lymphoid origin.
{"title":"Rola i potencjał terapeutyczny sfingolipidowego szlaku sygnalizacyjnego w nowotworach hematologicznych","authors":"Marzena Wątek, B. Durnas, Tomasz Wollny, Małgorzata Żendzian-Piotrowska, Marcin Pasiarski, S. Góźdź","doi":"10.5603/HEM.2018.0038","DOIUrl":"https://doi.org/10.5603/HEM.2018.0038","url":null,"abstract":"One of the key obstacles in the progress of cancer treatment is the lack of balance between the uncontrolled proliferation and cell apoptosis. It is now known that sphingolipids are essential molecules regulating the processes of growth, differentiation and death of living cells. Depending on their chemical nature, sphingolipids may have a stimulatory (S1P, sphingosine-1-phosphate) or inhibitory (ceramide) effect on cellular proliferation. A number of different studies have shown that the generation of ceramide in response to cytotoxic therapy is an important element leading to cell death. Cancer cells use different methods limiting the production of ceramides that leads to their removal. The effect of oncogenic S1P results from its stimulating effect on DNA synthesis and chemotactic mobility of the vascular endothelial cells and angiogenesis. The use of monoclonal anti-S1P antibodies is potentially a valuable therapeutic option for inhibiting angiogenesis determining the growth of tumors. It was additionally demonstrated that S1P beyond the direct and indirect by stimulating the release of vascular endothelial growth factor and basic fibroblast growth factor angiogenic action has an effect on tumor growth and its metastatic potential. Among the sphingolipids, ceramide was identified first as inducing differentiation and the death of human HL-60 promyelocytic leukemia cells. Progress in understanding the role of sphingolipids was regarded until recently as the only structural component of cell membranes allowing the use in the treatment of complex properties of this group of signaling molecules. Thus, it has become important to clarify the role of sphingolipids in the regulation of the balance between proliferation signals/ /survival rate and death of cells in order to develop new therapies for neoplastic diseases of myeloid and lymphoid origin.","PeriodicalId":38988,"journal":{"name":"Hematologia","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78206409","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}
B. Pula, A. Giza, Monika Długosz-Danecka, J. Rybka, Edyta Subocz, Anna Waszczuk-Gajda, M. Piotrowska, Magdalena Rej, K. Jamroziak, W. Jurczak
Idelalisib is a selective inhibitor of phosphoinositide 3-kinase d , approved in relapsed/refractory (RR) chronic lymphocytic leukemia (CLL), first line CLL with del17p/TP53 mutation in patients unsuitable for immunochemotherapy and RR follicular lymphoma (FL) in whom at least two lines of therapy have failed. Despite good clinical efficacy, the development of this drug has been hampered due to its adverse events (i.e. autoimmune reactions and life-threatening opportunistic infections). In this retrospective study, we summarise the tolerability of idelalisib therapy in a Polish population, analysing 61 patients treated with idelalisib in monotherapy or idelalisib-based combination regimens. Idelalisib treatment was feasible for the majority of patients, with upper respiratory tract infections (N = 13.21%) being the most common adverse event (AE), and pneumonia (N = 11.18%) — the most prevalent grade 3 or higher non-hematological AE. We observed two cases of pneumonitis, one case of gastroenteritis, and no cases of liver transaminases elevation (all regarded as the AEs characteristic of idelalisib). Most of the patients were treated in haematology reference centres where physicians are more accustomed to dealing with opportunistic infections. Cotrimoxazole prophylaxis was given to 20 (32.8%) patients, whereas acyclovir prophylaxis was administered in 33 (54.1%) cases. This could explain the less frequent life-threatening infections and decreased mortality rate compared to the published registration studies. Our study confirms the high clinical efficacy of idelalisib in CLL and RR FL.
{"title":"Ocena profilu korzyści i ryzyka leczenia idelalizybem u chorych na przewlekłą białaczkę limfocytową i chłoniaki nie-Hodgkina","authors":"B. Pula, A. Giza, Monika Długosz-Danecka, J. Rybka, Edyta Subocz, Anna Waszczuk-Gajda, M. Piotrowska, Magdalena Rej, K. Jamroziak, W. Jurczak","doi":"10.5603/HEM.A2019.0011","DOIUrl":"https://doi.org/10.5603/HEM.A2019.0011","url":null,"abstract":"Idelalisib is a selective inhibitor of phosphoinositide 3-kinase d , approved in relapsed/refractory (RR) chronic lymphocytic leukemia (CLL), first line CLL with del17p/TP53 mutation in patients unsuitable for immunochemotherapy and RR follicular lymphoma (FL) in whom at least two lines of therapy have failed. Despite good clinical efficacy, the development of this drug has been hampered due to its adverse events (i.e. autoimmune reactions and life-threatening opportunistic infections). In this retrospective study, we summarise the tolerability of idelalisib therapy in a Polish population, analysing 61 patients treated with idelalisib in monotherapy or idelalisib-based combination regimens. Idelalisib treatment was feasible for the majority of patients, with upper respiratory tract infections (N = 13.21%) being the most common adverse event (AE), and pneumonia (N = 11.18%) — the most prevalent grade 3 or higher non-hematological AE. We observed two cases of pneumonitis, one case of gastroenteritis, and no cases of liver transaminases elevation (all regarded as the AEs characteristic of idelalisib). Most of the patients were treated in haematology reference centres where physicians are more accustomed to dealing with opportunistic infections. Cotrimoxazole prophylaxis was given to 20 (32.8%) patients, whereas acyclovir prophylaxis was administered in 33 (54.1%) cases. This could explain the less frequent life-threatening infections and decreased mortality rate compared to the published registration studies. Our study confirms the high clinical efficacy of idelalisib in CLL and RR FL.","PeriodicalId":38988,"journal":{"name":"Hematologia","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89071986","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}
Aleksander Salomon-Perzyński, Agnieszka Końska, B. Pula, Justyna Łyczkowska-Piotrowska, K. Jamroziak
Treatment of patients with light chain amyloidosis (AL amyloidosis) is a challenge in routine clinical practice. Although deep and durable hematologic response is crucial for the success of the therapy, in this group of patients the proper conduct of supportive care becomes particularly important. Because AL amyloidosis is an interdisciplinary disease entity, the therapeutic process should be coordinated by an interdisciplinary team consisting of a hematologist, cardiologist, nephrologist, gastroenterologist, neurologist and clinical dietician. In this paper, we present a strategy for treating a patient with a newly diagnosed systemic intermediate-risk AL amyloidosis with cardiac involvement in the Department of Hematology of the Institute of Hematology and Transfusion Medicine in Warsaw, in which, apart of standard chemotherapy, doxycycline was used.
{"title":"Jak leczymy pacjenta z nowo rozpoznaną amyloidozą łańcuchów lekkich pośredniego ryzyka? Rola doksycykliny w terapii amyloidozy z zajęciem serca","authors":"Aleksander Salomon-Perzyński, Agnieszka Końska, B. Pula, Justyna Łyczkowska-Piotrowska, K. Jamroziak","doi":"10.5603/HEM.2018.0031","DOIUrl":"https://doi.org/10.5603/HEM.2018.0031","url":null,"abstract":"Treatment of patients with light chain amyloidosis (AL amyloidosis) is a challenge in routine clinical practice. Although deep and durable hematologic response is crucial for the success of the therapy, in this group of patients the proper conduct of supportive care becomes particularly important. \u0000Because AL amyloidosis is an interdisciplinary disease entity, the therapeutic process should be coordinated by an interdisciplinary team consisting of a hematologist, cardiologist, nephrologist, gastroenterologist, neurologist and clinical dietician. \u0000In this paper, we present a strategy for treating a patient with a newly diagnosed systemic intermediate-risk AL amyloidosis with cardiac involvement in the Department of Hematology of the Institute of Hematology and Transfusion Medicine in Warsaw, in which, apart of standard chemotherapy, doxycycline was used.","PeriodicalId":38988,"journal":{"name":"Hematologia","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75465787","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}
Wojciech Wołyniec, Agnieszka Perkowska-Ptasińska, A. Dębska-Ślizień, Tomasz Liberek, M. Durlik
{"title":"Amyloidoza nerek","authors":"Wojciech Wołyniec, Agnieszka Perkowska-Ptasińska, A. Dębska-Ślizień, Tomasz Liberek, M. Durlik","doi":"10.5603/hem.2018.0028","DOIUrl":"https://doi.org/10.5603/hem.2018.0028","url":null,"abstract":"","PeriodicalId":38988,"journal":{"name":"Hematologia","volume":"92 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73685983","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}
Amyloidosis is a heterogeneous group of diseases in which symptoms develop due to deposition of amyloid fibril proteins in the extracellular matrix of tissues and organs, as a result of protein misfolding. Because of the rareness, differential clinical manifestations and limited knowledge concerning the pathogenesis of amyloidoses of particular types, multiple medical terms developed in the professional literature to describe the same disease entity. However, with the increasing understanding of molecular basis of amyloidosis, it has become possible to standardize the terminology according to the structure of their chemical precursors. Currently recommended terminology of amyloid fibril proteins and amyloidosis is based on a regularly updated classification of the International Society of Amyloidosis (ISA). In accordance with the ISA definition, amyloid fibril protein deposits in the extracellular matrix in the form of amyloid, prone to Congo red staining and characterized by biofringence under polarized light. The current work presents the classification of so far identified amyloid fibril proteins and amyloidoses related to these proteins. General use of standardized amyloidosis terminology may be a significant facilitation in clinical practice, as well as in research.
{"title":"Zasady klasyfikacji i nazewnictwa amyloidoz","authors":"B. Pula, Sonia Dębek, K. Jamroziak","doi":"10.5603/Hem.2018.0022","DOIUrl":"https://doi.org/10.5603/Hem.2018.0022","url":null,"abstract":"Amyloidosis is a heterogeneous group of diseases in which symptoms develop due to deposition of amyloid fibril proteins in the extracellular matrix of tissues and organs, as a result of protein misfolding. Because of the rareness, differential clinical manifestations and limited knowledge concerning the pathogenesis of amyloidoses of particular types, multiple medical terms developed in the professional literature to describe the same disease entity. However, with the increasing understanding of molecular basis of amyloidosis, it has become possible to standardize the terminology according to the structure of their chemical precursors. Currently recommended terminology of amyloid fibril proteins and amyloidosis is based on a regularly updated classification of the International Society of Amyloidosis (ISA). In accordance with the ISA definition, amyloid fibril protein deposits in the extracellular matrix in the form of amyloid, prone to Congo red staining and characterized by biofringence under polarized light. The current work presents the classification of so far identified amyloid fibril proteins and amyloidoses related to these proteins. General use of standardized amyloidosis terminology may be a significant facilitation in clinical practice, as well as in research.","PeriodicalId":38988,"journal":{"name":"Hematologia","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77251296","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}
K. Jamroziak, P. Milani, B. Pula, Sonia Dębek, Giovanni Palladini
Light chain amyloidosis (AL amyloidosis) is a disease in which monoclonal immunoglobulin light chains, produced by clonal plasma cells are deposited extracellularly in the form of misfolded, insoluble protein complexes known as amyloid. This disease is a heterogeneous condition, due to the organ tropism, which varies among patients. Heart involvement prevails (80% of patients), whereas kidneys, liver and nervous system may be also involved. To diagnose AL amyloidosis, amyloid should be detected by staining tissue samples with Congo red, and the amyloid typing should reveal the immunoglobulin light chain character of the amyloid fibrils. The therapy usually focuses on the elimination of clonal plasma cells. Assigning the patient to the proper risk group (low, intermediate, high) is crucial. For younger patients of the low-risk group, high-dose melphalan with autologous hematopoietic stem cell transplantation (auto-HSCT) with optional bortezomib-based consolidation treatment should be considered. For the most numerous (70% of patients), intermediate-risk group, MDex (melphalan, dexamethasone), as well as bortezomib-based therapies should be given. Patients in the high-risk group should undergo a chemotherapy with reduced intensity. Refractory disease can be treated with IMIDs (immunomodulatory drugs), as well as new-generation proteasome inhibitors, bendamustine and monoclonal antibodies.
{"title":"Diagnostyka i leczenie amyloidozy AL","authors":"K. Jamroziak, P. Milani, B. Pula, Sonia Dębek, Giovanni Palladini","doi":"10.5603/HEM.2018.0024","DOIUrl":"https://doi.org/10.5603/HEM.2018.0024","url":null,"abstract":"Light chain amyloidosis (AL amyloidosis) is a disease in which monoclonal immunoglobulin light chains, produced by clonal plasma cells are deposited extracellularly in the form of misfolded, insoluble protein complexes known as amyloid. This disease is a heterogeneous condition, due to the organ tropism, which varies among patients. Heart involvement prevails (80% of patients), whereas kidneys, liver and nervous system may be also involved. To diagnose AL amyloidosis, amyloid should be detected by staining tissue samples with Congo red, and the amyloid typing should reveal the immunoglobulin light chain character of the amyloid fibrils. The therapy usually focuses on the elimination of clonal plasma cells. Assigning the patient to the proper risk group (low, intermediate, high) is crucial. For younger patients of the low-risk group, high-dose melphalan with autologous hematopoietic stem cell transplantation (auto-HSCT) with optional bortezomib-based consolidation treatment should be considered. For the most numerous (70% of patients), intermediate-risk group, MDex (melphalan, dexamethasone), as well as bortezomib-based therapies should be given. Patients in the high-risk group should undergo a chemotherapy with reduced intensity. Refractory disease can be treated with IMIDs (immunomodulatory drugs), as well as new-generation proteasome inhibitors, bendamustine and monoclonal antibodies.","PeriodicalId":38988,"journal":{"name":"Hematologia","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72819786","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}
AA amyloidosis is a complication of chronic diseases associated with the activation of acute phase reactants. The precursor of amyloid is the serum amyloid A. The kidneys are the most frequently involved, but amyloid can be deposited in any internal organ. AA amyloidosis often develops after many years of chronic illness, but its occurrence is a poor prognostic factor. Untreated leads to renal failure. For diagnosis of AA amyloidosis, histopathological confirmation is necessary. Staining with Congo red is a standard diagnostic test. Aspiration of abdominal fat is the preferred way to obtain the material for diagnostic testing. Normalization of inflammatory parameters and, as a consequence, the lack of the precursor of the deposited amyloid is a prerequisite for inhibiting the progression of the disease. In order to control inflammation, intensive treatment of the underlying disease is necessary. Initial data, in small groups of patients, indicate the benefits of interleukin 1 and 6 inhibitors.
{"title":"Amyloidoza AA — przyczyny, diagnostyka, opcje terapeutyczne","authors":"Ewa Więsik-Szewczyk","doi":"10.5603/HEM.2018.0023","DOIUrl":"https://doi.org/10.5603/HEM.2018.0023","url":null,"abstract":"AA amyloidosis is a complication of chronic diseases associated with the activation of acute phase reactants. The precursor of amyloid is the serum amyloid A. The kidneys are the most frequently involved, but amyloid can be deposited in any internal organ. AA amyloidosis often develops after many years of chronic illness, but its occurrence is a poor prognostic factor. Untreated leads to renal failure. For diagnosis of AA amyloidosis, histopathological confirmation is necessary. Staining with Congo red is a standard diagnostic test. Aspiration of abdominal fat is the preferred way to obtain the material for diagnostic testing. Normalization of inflammatory parameters and, as a consequence, the lack of the precursor of the deposited amyloid is a prerequisite for inhibiting the progression of the disease. In order to control inflammation, intensive treatment of the underlying disease is necessary. Initial data, in small groups of patients, indicate the benefits of interleukin 1 and 6 inhibitors.","PeriodicalId":38988,"journal":{"name":"Hematologia","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79028025","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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