The treatment of multiple myeloma (MM) has changed dramatically in the past twenty years with the introduction of high-dose therapy plus autologous stem-cell transplantation (ASCT) in younger patients and, more recently, of three novel agents (thalidomide, bortezomib, and lenalidomide). When conventional chemotherapy was the only available possibility, complete responses (CR) were very rare and the objective of maintenance was to prolong remission duration by continuing the same type of treatment that induced the initial response. With recent therapeutic improvements, CR achievement becomes a realistic goal that, in most cases, is significantly correlated with the outcome (1). Therefore, both the nature and the impact of maintenance therapy have changed. Maintenance therapy is based currently on novel agents, and its objective is not only to control the clone but also to further decrease the tumor burden and improve the quality of response. A number of randomized studies show a benefit from maintenance therapy with novel agents (until now, mostly thalidomide), at least in terms of response rate and progression-free survival (PFS). However, there is still a debate as concerns the impact on overall survival (OS) and the optimal administration of maintenance therapy.
{"title":"Maintenance therapy in multiple myeloma","authors":"J. Harousseau","doi":"10.4081/hr.2009.e12","DOIUrl":"https://doi.org/10.4081/hr.2009.e12","url":null,"abstract":"The treatment of multiple myeloma (MM) has changed dramatically in the past twenty years with the introduction of high-dose therapy plus autologous stem-cell transplantation (ASCT) in younger patients and, more recently, of three novel agents (thalidomide, bortezomib, and lenalidomide). When conventional chemotherapy was the only available possibility, complete responses (CR) were very rare and the objective of maintenance was to prolong remission duration by continuing the same type of treatment that induced the initial response. With recent therapeutic improvements, CR achievement becomes a realistic goal that, in most cases, is significantly correlated with the outcome (1). Therefore, both the nature and the impact of maintenance therapy have changed. Maintenance therapy is based currently on novel agents, and its objective is not only to control the clone but also to further decrease the tumor burden and improve the quality of response. A number of randomized studies show a benefit from maintenance therapy with novel agents (until now, mostly thalidomide), at least in terms of response rate and progression-free survival (PFS). However, there is still a debate as concerns the impact on overall survival (OS) and the optimal administration of maintenance therapy.","PeriodicalId":12954,"journal":{"name":"Hematology Reviews","volume":"75 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2009-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86176712","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}
Prothrombin time (PT) is the leading test for monitoring oral anticoagulation therapy (OAT). According to the World Health Organization recommendation, International Normalized Ratio (INR) results obtained from the same patient samples with the major PT methods (Quick and Owren) should be the same when the therapeutic range is the same. In our study blood samples were obtained from 207 OAT patients. We analyzed the samples using two Quick and two Owren PT (combined thromboplastin) reagents for INR and assessed the sensitivity and true coagulation activity using a new-generation PT method. The INR values with the Quick PT and Owren PT methods were very similar around the normal range, while unacceptable differences were seen within the therapeutic range and at higher INR values. The Quick PT results as INR are clearly lower than those given by Owren PT and the difference increases toward higher INR. The new PT method functions well with both Owren PT reagents, and we can calculate the true active INR. The Quick PT methods show no sensitivity to coagulation inhibition measurement. The harmonization of the INR is an important goal for the safety of OAT patients. More accurate INR results reduce morbidity and mortality, and the therapeutic ranges should be similar worldwide. In this study we found unacceptable differences in INR results produced by the two PT methods. The new method showed a lack of sensitivity to Quick PT. For the global harmonization of OAT therapy and for INR accuracy only the more sensitive Owren PT method should be used.
{"title":"A sensitivity comparison of the Quick and Owren prothrombin time methods in oral anticoagulant therapy","authors":"J. Horsti","doi":"10.4081/hr.2009.e15","DOIUrl":"https://doi.org/10.4081/hr.2009.e15","url":null,"abstract":"Prothrombin time (PT) is the leading test for monitoring oral anticoagulation therapy (OAT). According to the World Health Organization recommendation, International Normalized Ratio (INR) results obtained from the same patient samples with the major PT methods (Quick and Owren) should be the same when the therapeutic range is the same. In our study blood samples were obtained from 207 OAT patients. We analyzed the samples using two Quick and two Owren PT (combined thromboplastin) reagents for INR and assessed the sensitivity and true coagulation activity using a new-generation PT method. The INR values with the Quick PT and Owren PT methods were very similar around the normal range, while unacceptable differences were seen within the therapeutic range and at higher INR values. The Quick PT results as INR are clearly lower than those given by Owren PT and the difference increases toward higher INR. The new PT method functions well with both Owren PT reagents, and we can calculate the true active INR. The Quick PT methods show no sensitivity to coagulation inhibition measurement. The harmonization of the INR is an important goal for the safety of OAT patients. More accurate INR results reduce morbidity and mortality, and the therapeutic ranges should be similar worldwide. In this study we found unacceptable differences in INR results produced by the two PT methods. The new method showed a lack of sensitivity to Quick PT. For the global harmonization of OAT therapy and for INR accuracy only the more sensitive Owren PT method should be used.","PeriodicalId":12954,"journal":{"name":"Hematology Reviews","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2009-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86781456","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. Rice, M. Heidari, Ross H. Taplin, U. Kees, W. Greene
The homeoprotein TLX1, which is essential to spleen organogenesis and oncogenic when aberrantly expressed in immature T cells, functions as a bifunctional transcriptional regulator, being capable of activation or repression depending on cell type and/or promoter context. However, the detailed mechanisms by which it regulates the transcription of target genes such as ALDH1A1 remains to be elucidated. We therefore functionally assessed the ability of TLX1 to regulate ALDH1A1 expression in two hematopoietic cell lines, PER-117 T-leukemic cells and human erythroleukemic (HEL) cells, by use of luciferase reporter and mobility shift assays. We showed that TLX1 physically interacts with the general transcription factor TFIIB via its homeodomain, and identified two activities in respect to TLX1-mediated regulation of the CCAAT box-containing ALDH1A1 promoter. The first involved CCAAT-dependent transcriptional repression via perturbation of GATA factor-containing protein complexes assembled at a non-canonical TATA (GATA) box. A structurally intact homeodomain was essential for repression by TLX1 although direct DNA binding was not required. The second activity, which involved CCAAT-independent transcriptional activation did not require an intact homeodomain, indicating that the activation and repression functions of TLX1 are distinct. These findings confirm ALDH1A1 gene regulation by TLX1 and support an indirect model for TLX1 function, in which protein-protein interactions, rather than DNA binding at specific sites, are crucial for its transcriptional activity.
同源蛋白TLX1在未成熟T细胞中异常表达时对脾脏器官发生和肿瘤发生至关重要，它是一种双功能转录调节因子，能够根据细胞类型和/或启动子背景激活或抑制。然而，其调控靶基因(如ALDH1A1)转录的详细机制仍有待阐明。因此，我们通过荧光素酶报告细胞和迁移转移试验，从功能上评估了TLX1在两种造血细胞系(PER-117 t -白血病细胞和人红白血病(HEL)细胞)中调节ALDH1A1表达的能力。我们发现TLX1通过其同源结构域与一般转录因子TFIIB物理相互作用，并确定了TLX1介导的对含有ALDH1A1启动子的CCAAT盒的调节的两个活性。第一种方法涉及通过干扰组装在非规范TATA (GATA)盒中的含GATA因子的蛋白质复合物来抑制ccaat依赖性转录。虽然不需要直接的DNA结合，但结构完整的同源结构域是TLX1抑制所必需的。第二种活性涉及不依赖ccaat的转录激活，不需要完整的同源结构域，这表明TLX1的激活和抑制功能是不同的。这些发现证实了TLX1对ALDH1A1基因的调控，并支持TLX1功能的间接模型，其中蛋白质-蛋白质相互作用，而不是特定位点的DNA结合，对其转录活性至关重要。
{"title":"Transcriptional regulation of the human ALDH1A1 promoter by the oncogenic homeoprotein TLX1/HOX11","authors":"K. Rice, M. Heidari, Ross H. Taplin, U. Kees, W. Greene","doi":"10.4081/hr.2009.e13","DOIUrl":"https://doi.org/10.4081/hr.2009.e13","url":null,"abstract":"The homeoprotein TLX1, which is essential to spleen organogenesis and oncogenic when aberrantly expressed in immature T cells, functions as a bifunctional transcriptional regulator, being capable of activation or repression depending on cell type and/or promoter context. However, the detailed mechanisms by which it regulates the transcription of target genes such as ALDH1A1 remains to be elucidated. We therefore functionally assessed the ability of TLX1 to regulate ALDH1A1 expression in two hematopoietic cell lines, PER-117 T-leukemic cells and human erythroleukemic (HEL) cells, by use of luciferase reporter and mobility shift assays. We showed that TLX1 physically interacts with the general transcription factor TFIIB via its homeodomain, and identified two activities in respect to TLX1-mediated regulation of the CCAAT box-containing ALDH1A1 promoter. The first involved CCAAT-dependent transcriptional repression via perturbation of GATA factor-containing protein complexes assembled at a non-canonical TATA (GATA) box. A structurally intact homeodomain was essential for repression by TLX1 although direct DNA binding was not required. The second activity, which involved CCAAT-independent transcriptional activation did not require an intact homeodomain, indicating that the activation and repression functions of TLX1 are distinct. These findings confirm ALDH1A1 gene regulation by TLX1 and support an indirect model for TLX1 function, in which protein-protein interactions, rather than DNA binding at specific sites, are crucial for its transcriptional activity.","PeriodicalId":12954,"journal":{"name":"Hematology Reviews","volume":"54 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2009-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76994737","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}
Hematopoietic stem cell (HSC) chemotaxis, adhesion, proliferation, quiescence and differentiation are regulated by interactions with bone marrow (BM) niches. Two niches have been identified in the adult BM: the endosteal (close to the bone) and the perivascular niche (close to blood vessels). A vast body of literature has revealed the molecular basis for the interaction of HSCs with the two niches. However, the signals that regulate the communication between the two niches have not been well defined. Taking in consideration several clinical and experimental arguments this review highlights the molecular cues, involved in the communication between the BM niches, which regulate the basic properties of HSCs in physiological and malignant conditions. As such, it aims at clarifying the most important advances in basic and clinical research focusing on the role of different factors in the regulation of the BM microenvironment.
{"title":"Communication between bone marrow niches in normal bone marrow function and during hemopathies progression","authors":"S. Lamorte, Leonor Remédio, S. Dias","doi":"10.4081/hr.2009.e14","DOIUrl":"https://doi.org/10.4081/hr.2009.e14","url":null,"abstract":"Hematopoietic stem cell (HSC) chemotaxis, adhesion, proliferation, quiescence and differentiation are regulated by interactions with bone marrow (BM) niches. Two niches have been identified in the adult BM: the endosteal (close to the bone) and the perivascular niche (close to blood vessels). A vast body of literature has revealed the molecular basis for the interaction of HSCs with the two niches. However, the signals that regulate the communication between the two niches have not been well defined. Taking in consideration several clinical and experimental arguments this review highlights the molecular cues, involved in the communication between the BM niches, which regulate the basic properties of HSCs in physiological and malignant conditions. As such, it aims at clarifying the most important advances in basic and clinical research focusing on the role of different factors in the regulation of the BM microenvironment.","PeriodicalId":12954,"journal":{"name":"Hematology Reviews","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2009-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88329234","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}
T. Momah, Etwaru Dhanan, Phillip Xiao, Vasantha K Kondamudi
There are very few cases of clear cell renal cell carcinoma with metastases to the vagina and brain reported in the literature. Our case study highlights this rare clinical occurrence and its associated complications including pulmonary embolism. In addition we discuss current management guidelines for treating and diagnosing the disease, and how this management improves prognosis.
{"title":"Clear cell renal cell carcinoma with vaginal and brain metastases: a case report and literature review","authors":"T. Momah, Etwaru Dhanan, Phillip Xiao, Vasantha K Kondamudi","doi":"10.4081/hr.2009.e16","DOIUrl":"https://doi.org/10.4081/hr.2009.e16","url":null,"abstract":"There are very few cases of clear cell renal cell carcinoma with metastases to the vagina and brain reported in the literature. Our case study highlights this rare clinical occurrence and its associated complications including pulmonary embolism. In addition we discuss current management guidelines for treating and diagnosing the disease, and how this management improves prognosis.","PeriodicalId":12954,"journal":{"name":"Hematology Reviews","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2009-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85771947","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}
Warfarin is the most widely used medicine for oral anticoagulant therapy (OAT). It inhibits the synthesis of coagulation factors II, VII, IX, and X in the liver and results in the production of inactive or partially active versions of these factors. Inactive coagulation factors interfere with prothrombin time measurement (Quick and Owren PT) measuring the sum of coagulation activity and inhibition. The narrow therapeutic range here involves a danger of serious complications and the risk of bleeding or thrombosis. The new-generation PT method can measure coagulation activity and inhibition separately. This new technique promotes patient care and anticoagulant medication (warfarin, dicoumarol) based on coagulation activity in vivo. Both therapy and laboratory controls should be unquestionably accurate and based solely on in vivo coagulation activity. Inactive coagulation factors (inhibition) render measurement, calibration, and harmonization. The use of the new-generation PT method based on measurement of coagulation activity in vivo could develop vitamin K antagonist (VKA) therapy for the marked benefit of patients.
{"title":"The progress of prothrombin time measurement","authors":"J. Horsti","doi":"10.4081/hr.2009.e19","DOIUrl":"https://doi.org/10.4081/hr.2009.e19","url":null,"abstract":"Warfarin is the most widely used medicine for oral anticoagulant therapy (OAT). It inhibits the synthesis of coagulation factors II, VII, IX, and X in the liver and results in the production of inactive or partially active versions of these factors. Inactive coagulation factors interfere with prothrombin time measurement (Quick and Owren PT) measuring the sum of coagulation activity and inhibition. The narrow therapeutic range here involves a danger of serious complications and the risk of bleeding or thrombosis. The new-generation PT method can measure coagulation activity and inhibition separately. This new technique promotes patient care and anticoagulant medication (warfarin, dicoumarol) based on coagulation activity in vivo. Both therapy and laboratory controls should be unquestionably accurate and based solely on in vivo coagulation activity. Inactive coagulation factors (inhibition) render measurement, calibration, and harmonization. The use of the new-generation PT method based on measurement of coagulation activity in vivo could develop vitamin K antagonist (VKA) therapy for the marked benefit of patients.","PeriodicalId":12954,"journal":{"name":"Hematology Reviews","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2009-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84082956","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}
H. Johnsen, L. Knudsen, A. Mylin, P. Gimsing, H. Gregersen, N. Abildgaard, N. F. Andersen, T. Plesner, A. Vangsted, T. Mourits‐Andersen
The impact of chemotherapy resistant B cells in multiple myeloma (MM) needs to be evaluated by in vivo targeted therapy. Here we report the conclusions from a phase II randomized, placebo controlled trial adding fludarabine to the induction with cyclophosphamide-dexamethasone. Based on an interim toxicity and safety analysis, the trial was stopped following inclusion of 34 of a planned 80 patients due to a reduced number of patients (4/17) actually harvested in the experimental arm compared to the control arm (11/17; p<0.05). In conclusion, the scheduled fludarabine dosage in 2 cycles combined with alkylating therapy impairs stem cell mobilization and standard therapy in young MM patients and should not be administrated up-front.
{"title":"Up-front fludarabine impairs stem cell harvest in multiple myeloma: report from an interim analysis of the NMSG 13/03 randomized placebo controlled phase II trial","authors":"H. Johnsen, L. Knudsen, A. Mylin, P. Gimsing, H. Gregersen, N. Abildgaard, N. F. Andersen, T. Plesner, A. Vangsted, T. Mourits‐Andersen","doi":"10.4081/hr.2009.e11","DOIUrl":"https://doi.org/10.4081/hr.2009.e11","url":null,"abstract":"The impact of chemotherapy resistant B cells in multiple myeloma (MM) needs to be evaluated by in vivo targeted therapy. Here we report the conclusions from a phase II randomized, placebo controlled trial adding fludarabine to the induction with cyclophosphamide-dexamethasone. Based on an interim toxicity and safety analysis, the trial was stopped following inclusion of 34 of a planned 80 patients due to a reduced number of patients (4/17) actually harvested in the experimental arm compared to the control arm (11/17; p<0.05). In conclusion, the scheduled fludarabine dosage in 2 cycles combined with alkylating therapy impairs stem cell mobilization and standard therapy in young MM patients and should not be administrated up-front.","PeriodicalId":12954,"journal":{"name":"Hematology Reviews","volume":"36 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2009-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78396875","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}
Progressive cardiotoxicity following treatment with doxorubicin-based chemotherapy in patients with non-Hodgkin's lymphoma (NHL) may lead to late onset cardiomyopathy. So, early prediction of toxicity can lead to prevention of heart failure in these patients. The aim of this work was to investigate the role of H-FABP as an early diagnostic marker of anthracycline-induced cardiac toxicity together with brain natriuretic peptide (BNP) as an indication of ventricular dysfunction in such patients. Our study was conducted on 40 NHL patients who received 6 cycles of a doxorubicin containing chemotherapy protocol (CHOP), not exceeding the total allowed dose of doxorubicin (500 mg/m2). Ten healthy controls were included in our study. Human heart-type fatty acid-binding protein (H-FABP) was assessed 24 hours after the first cycle of CHOP. Plasma levels of BNP were estimated both before starting chemotherapy and after the last cycle of CHOP. Resting echocardiography was also performed before and at the end of chemotherapy cycles. The ejection fraction (EF) of 8 of our patients decreased below 50% at the end of the sixth cycle. Elevated levels of both H-FABP and BNP were found in all patients wth EF below 50% and both markers showed a positive correlation with each other. We concluded that H-FABP may serve as a reliable early marker for prediction of cardiomyopathy induced by doxorubicin. Thus, in patients with elevated H-FABP, alternative treatment modalities with no cardiac toxicity may be considered in order to prevent subsequent heart failure in these patients.
{"title":"Human heart-type fatty acid-binding protein as an early diagnostic marker of doxorubicin cardiac toxicity","authors":"A. Elghandour, M. E. Sorady, S. Azab, M. Elrahman","doi":"10.4081/hr.2009.e6","DOIUrl":"https://doi.org/10.4081/hr.2009.e6","url":null,"abstract":"Progressive cardiotoxicity following treatment with doxorubicin-based chemotherapy in patients with non-Hodgkin's lymphoma (NHL) may lead to late onset cardiomyopathy. So, early prediction of toxicity can lead to prevention of heart failure in these patients. The aim of this work was to investigate the role of H-FABP as an early diagnostic marker of anthracycline-induced cardiac toxicity together with brain natriuretic peptide (BNP) as an indication of ventricular dysfunction in such patients. Our study was conducted on 40 NHL patients who received 6 cycles of a doxorubicin containing chemotherapy protocol (CHOP), not exceeding the total allowed dose of doxorubicin (500 mg/m2). Ten healthy controls were included in our study. Human heart-type fatty acid-binding protein (H-FABP) was assessed 24 hours after the first cycle of CHOP. Plasma levels of BNP were estimated both before starting chemotherapy and after the last cycle of CHOP. Resting echocardiography was also performed before and at the end of chemotherapy cycles. The ejection fraction (EF) of 8 of our patients decreased below 50% at the end of the sixth cycle. Elevated levels of both H-FABP and BNP were found in all patients wth EF below 50% and both markers showed a positive correlation with each other. We concluded that H-FABP may serve as a reliable early marker for prediction of cardiomyopathy induced by doxorubicin. Thus, in patients with elevated H-FABP, alternative treatment modalities with no cardiac toxicity may be considered in order to prevent subsequent heart failure in these patients.","PeriodicalId":12954,"journal":{"name":"Hematology Reviews","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2009-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76149083","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}
D. Védy, D. Robert, D. Gasparini, G. Canellini, S. Waldvogel, J. Tissot
Whereas the reduction of transfusion related viral transmission has been a priority during the last decade, bacterial infection transmitted by transfusion still remains associated to a high morbidity and mortality, and constitutes the most frequent infectious risk of transfusion. This problem especially concerns platelet concentrates because of their favorable bacterial growth conditions. This review gives an overview of platelet transfusion-related bacterial contamination as well as on the different strategies to reduce this problem by using either bacterial detection or inactivation methods.
{"title":"Bacterial contamination of platelet concentrates: pathogen detection and inactivation methods","authors":"D. Védy, D. Robert, D. Gasparini, G. Canellini, S. Waldvogel, J. Tissot","doi":"10.4081/hr.2009.e5","DOIUrl":"https://doi.org/10.4081/hr.2009.e5","url":null,"abstract":"Whereas the reduction of transfusion related viral transmission has been a priority during the last decade, bacterial infection transmitted by transfusion still remains associated to a high morbidity and mortality, and constitutes the most frequent infectious risk of transfusion. This problem especially concerns platelet concentrates because of their favorable bacterial growth conditions. This review gives an overview of platelet transfusion-related bacterial contamination as well as on the different strategies to reduce this problem by using either bacterial detection or inactivation methods.","PeriodicalId":12954,"journal":{"name":"Hematology Reviews","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2009-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81794777","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. Federico, G. Pagnucco, A. Russo, G. Cardinale, P. Guerrieri, F. Sciumé, Catherine E. Symonds, Letizia Cito, S. Siragusa, N. Gebbia, R. Lagalla, M. Midiri, A. Giordano, P. Montemaggi
Splenectomy and splenic irradiation (SI) are the sole treatment modalities to control drug resistant splenomegaly in patients with myelofibrosis (MF). SI has been used in poor surgical candidates but optimal total dose and fractionation are unclear. We retrospectively reviewed 14 MF patients with symptomatic splenomegaly. Patients received a median of 10 fractions in two weeks. Fraction size ranged from 0.2–1.4 Gy, and total dose varied from 2–10.8 Gy per RT course. Overall results indicate that 81.8% of radiation courses achieved a significant spleen reduction. Splenic pain relief and gastrointestinal symptoms reduction were obtained in 94% and 91% of courses, respectively. Severe cytopenias occurred in 13% of radiation courses. Furthermore patients were divided in three groups according to the radiation dose they received: 6 patients in the low-dose group (LDG) received a normalized dose of 1.67 Gy; 4 patients in the intermediate-dose group (IDG) received a normalized dose 4.37 Gy; the remaining 4 patients in the high-dose group (HDG) received a normalized dose of 9.2 Gy. Subgroup analysis showed that if no differences in terms of treatment efficacy were seen among dose groups, hematologic toxicity rates distributed differently. Severe cytopenias occurred in 50% of courses in the HDG, and in the 14.3% and in 0% of the IDG and LDG, respectively. Spleen reduction and pain relief lasted for a median of 5.5 months in all groups. Due to the efficacy and tolerability of the low-dose irradiation 4 patients from the LDG and IDG were retreated and received on the whole 12 RT courses. Multiple retreatments did not show decremental trends in terms of rates of response to radiation nor in terms of duration of clinical response. Moreover, retreatment courses did not cause an increased rate of adverse effects and none of the retreated patients experienced severe hematologic toxicities. The average time of clinical benefit in retreated patients was much longer (21 months, range 44–10) than patients who were not retreated (5.75 months, range 3–6).
{"title":"Palliative splenic irradiation in primary and post PV/ET myelofibrosis: outcomes and toxicity of three radiation schedules","authors":"M. Federico, G. Pagnucco, A. Russo, G. Cardinale, P. Guerrieri, F. Sciumé, Catherine E. Symonds, Letizia Cito, S. Siragusa, N. Gebbia, R. Lagalla, M. Midiri, A. Giordano, P. Montemaggi","doi":"10.4081/hr.2009.e7","DOIUrl":"https://doi.org/10.4081/hr.2009.e7","url":null,"abstract":"Splenectomy and splenic irradiation (SI) are the sole treatment modalities to control drug resistant splenomegaly in patients with myelofibrosis (MF). SI has been used in poor surgical candidates but optimal total dose and fractionation are unclear. We retrospectively reviewed 14 MF patients with symptomatic splenomegaly. Patients received a median of 10 fractions in two weeks. Fraction size ranged from 0.2–1.4 Gy, and total dose varied from 2–10.8 Gy per RT course. Overall results indicate that 81.8% of radiation courses achieved a significant spleen reduction. Splenic pain relief and gastrointestinal symptoms reduction were obtained in 94% and 91% of courses, respectively. Severe cytopenias occurred in 13% of radiation courses. Furthermore patients were divided in three groups according to the radiation dose they received: 6 patients in the low-dose group (LDG) received a normalized dose of 1.67 Gy; 4 patients in the intermediate-dose group (IDG) received a normalized dose 4.37 Gy; the remaining 4 patients in the high-dose group (HDG) received a normalized dose of 9.2 Gy. Subgroup analysis showed that if no differences in terms of treatment efficacy were seen among dose groups, hematologic toxicity rates distributed differently. Severe cytopenias occurred in 50% of courses in the HDG, and in the 14.3% and in 0% of the IDG and LDG, respectively. Spleen reduction and pain relief lasted for a median of 5.5 months in all groups. Due to the efficacy and tolerability of the low-dose irradiation 4 patients from the LDG and IDG were retreated and received on the whole 12 RT courses. Multiple retreatments did not show decremental trends in terms of rates of response to radiation nor in terms of duration of clinical response. Moreover, retreatment courses did not cause an increased rate of adverse effects and none of the retreated patients experienced severe hematologic toxicities. The average time of clinical benefit in retreated patients was much longer (21 months, range 44–10) than patients who were not retreated (5.75 months, range 3–6).","PeriodicalId":12954,"journal":{"name":"Hematology Reviews","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2009-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78234827","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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