The hematology journal : the official journal of the European Haematology Association最新文献

{"title":"A phase II study of intensive chemotherapy with fludarabine, cytarabine, and mitoxantrone in P glycoprotein-negative high-risk myelodysplastic syndromes.","authors":"Thomas Prébet,&nbsp;Sophie Ducastelle,&nbsp;Stephan Debotton,&nbsp;Aspasia Stamatoullas,&nbsp;Eric Deconinck,&nbsp;Christophe Fruchart,&nbsp;Nicole Gratecos,&nbsp;Norbert Ifrah,&nbsp;François Dreyfus,&nbsp;Pierre Fenaux,&nbsp;Eric Wattel","doi":"10.1038/sj.thj.6200363","DOIUrl":"https://doi.org/10.1038/sj.thj.6200363","url":null,"abstract":"<p><p>Since leukemic cells primed by exposure to fludarabine exhibit enhanced accumulation of cytarabine triphosphate (the cytotoxic nucleotide of cytarabine), especially with continuous cytarabine (AraC) infusion, a phase II trial was designed to explore the feasibility and efficacy of a combination chemotherapy associating fludarabine, mitoxantrone (MXN), and high-dose cytarabine (continuous infusion) for high-risk P glycoprotein (PGP)-negative myelodysplastic syndromes (MDS) (FAM protocol). The outcomes of FAM-treated patients were compared with those of 32 PGP-negative MDS patients fulfilling identical inclusion and response criteria treated with MXN+AraC (1 g/m(2)/12 h d(1-5), MA protocol). A total of 29 patients (median age 55 years) were included in the FAM group. Six (21%) died from the procedure, and 16 (55%) achieved complete remission (CR). Of these, nine received consolidation chemotherapy, five were autografted and two were allografted in first CR. Abnormal karyotype was the only factor associated with poor survival. The overall median follow-up was 10.9 months. There was no significant difference between FAM and MA protocols with respect to CR rate, treatment-related mortality, duration of leukopenia, neutropenia, autologous stem cell transplantation feasibility, relapse-free survival, or overall survival. The duration of thrombocytopenia was significantly longer in the FAM protocol. In conclusion, the present results suggest that the combination therapy of fludarabine, MXN, and high-dose AraC does not improve CR rate, survival, or disease-free survival in high-risk MDS.</p>","PeriodicalId":22486,"journal":{"name":"The hematology journal : the official journal of the European Haematology Association","volume":"5 3","pages":"209-15"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24540333","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":"Molecular basis for stem-cell self-renewal.","authors":"Jana K Krosl, Amelie Faubert, Guy Sauvageau","doi":"10.1038/sj.thj.6200436","DOIUrl":"10.1038/sj.thj.6200436","url":null,"abstract":"","PeriodicalId":22486,"journal":{"name":"The hematology journal : the official journal of the European Haematology Association","volume":"5 Suppl 3 ","pages":"S118-21"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/sj.thj.6200436","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24560356","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":"Management of the myeloproliferative disorders : distinguishing data from dogma.","authors":"Anthony R Green,&nbsp;George S Vassiliou,&nbsp;Natasha Curtin,&nbsp;Peter J Campbell","doi":"10.1038/sj.thj.6200438","DOIUrl":"https://doi.org/10.1038/sj.thj.6200438","url":null,"abstract":"","PeriodicalId":22486,"journal":{"name":"The hematology journal : the official journal of the European Haematology Association","volume":"5 Suppl 3 ","pages":"S126-32"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/sj.thj.6200438","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24560358","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":"Discovery of novel molecular classification schemes and genes predictive of outcome in leukemia.","authors":"Cheryl L Willman","doi":"10.1038/sj.thj.6200440","DOIUrl":"https://doi.org/10.1038/sj.thj.6200440","url":null,"abstract":"","PeriodicalId":22486,"journal":{"name":"The hematology journal : the official journal of the European Haematology Association","volume":"5 Suppl 3 ","pages":"S138-43"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/sj.thj.6200440","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24560359","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":"Measuring platelet function?","authors":"Paul Harrison","doi":"10.1038/sj.thj.6200445","DOIUrl":"https://doi.org/10.1038/sj.thj.6200445","url":null,"abstract":"","PeriodicalId":22486,"journal":{"name":"The hematology journal : the official journal of the European Haematology Association","volume":"5 Suppl 3 ","pages":"S164-9"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24560365","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":"Antiplatelet agents.","authors":"Marco Cattaneo","doi":"10.1038/sj.thj.6200446","DOIUrl":"https://doi.org/10.1038/sj.thj.6200446","url":null,"abstract":"","PeriodicalId":22486,"journal":{"name":"The hematology journal : the official journal of the European Haematology Association","volume":"5 Suppl 3 ","pages":"S170-4"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/sj.thj.6200446","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24560366","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":"Cytogenetic abnormalities in de novo acute myeloid leukemia in adults: relation to morphology, age, sex and ethnicity - a single center study from Singapore.","authors":"Anoop Kumar Enjeti,&nbsp;Sim Leng Tien,&nbsp;Christina Rudduck Sivaswaren","doi":"10.1038/sj.thj.6200544","DOIUrl":"https://doi.org/10.1038/sj.thj.6200544","url":null,"abstract":"<p><strong>Background: </strong>Cytogenetic analysis performed at diagnosis is considered to be the most valuable prognostic factor in acute myeloid leukemia (AML). Large systematic studies of cytogenetic abnormalities in AML patients from Southeast Asia are not available. The karyotypic patterns in AML patients from a single center in Singapore were studied and compared with reports from other regions of the world to identify possible geographic heterogeneity.</p><p><strong>Methods: </strong>Analysis was performed on 501 consecutive de novo AML patients diagnosed according to the FAB criteria in the Singapore General Hospital. The cytogenetic findings were analyzed for possible associations between karyotypic pattern and the age, gender, ethnicity as well as morphological (FAB) subtypes.</p><p><strong>Results: </strong>A total of 454 patients were studied of which 275(61%) had abnormal cytogenetics(median age 48 years). The t(15;17) and trisomy 8 were the most frequent karyotypic abnormalities - seen in 52(11%) and 33(7.3%) cases, respectively. Inv(lf) and t(16;16) were uncommon, seen only in five (1.1%) cases. The abnormalities del 5/5q and del 7/7q were seen in 30(6.6%) and 32(7%) of the cases. Complex karyotypes were seen in 78(17%) of the cases.Recurrent cytogenetic abnormalities correlated with the FAB subtypes. In all, 21 novel cytogenetic abnormalities were observed.</p><p><strong>Conclusions: </strong>Certain differences such as the age at presentation and frequency of recurrent balanced translocations were noted in comparison to previous reports. These point to the need for extensive epidemiological studies to clarify the role of genetic as well as geographic heterogeneity in the pathogenesis of AML.</p>","PeriodicalId":22486,"journal":{"name":"The hematology journal : the official journal of the European Haematology Association","volume":"5 5","pages":"419-25"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/sj.thj.6200544","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24759835","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":"Anti-CD20 monoclonal antibody rituximab for the treatment of B-cell chronic lymphocytic leukemia-associated pure red cell aplasia.","authors":"Despina Pantelidou,&nbsp;Costas Tsatalas,&nbsp;Dimitris Margaritis,&nbsp;Vasiliki Kaloutsi,&nbsp;Emmanuel Spanoudakis,&nbsp;George Bourikas","doi":"10.1038/sj.thj.6200554","DOIUrl":"https://doi.org/10.1038/sj.thj.6200554","url":null,"abstract":"","PeriodicalId":22486,"journal":{"name":"The hematology journal : the official journal of the European Haematology Association","volume":"5 6","pages":"546-7"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/sj.thj.6200554","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24835537","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":"Effectiveness and safety of combined iron-chelation therapy with deferoxamine and deferiprone.","authors":"Vasiliki Alymara,&nbsp;Dimitrios Bourantas,&nbsp;Aristeidis Chaidos,&nbsp;Paraskevi Bouranta,&nbsp;Maria Gouva,&nbsp;Amalia Vassou,&nbsp;Evagelia Tzouvara,&nbsp;Konstantinos L Bourantas","doi":"10.1038/sj.thj.6200550","DOIUrl":"https://doi.org/10.1038/sj.thj.6200550","url":null,"abstract":"<p><strong>Introduction: </strong>The purpose of our study was to evaluate the effectiveness and safety of combined therapy with deferoxamine (DFO) and deferiprone (DFP) in patients with beta-thalassemia major and increased serum ferritin.</p><p><strong>Patients and methods: </strong>Our study was performed in 36 patients with beta-thalassemia major. DFP was administered orally in a total daily dose of 60 mg/kg for 6 days per week and DFO was administered subcutaneously in a total daily dose of 40-50 mg/kg for 4-6 days per week. The efficacy of combined treatment was assessed by measurements of serum ferritin and 24-h urine iron excretion levels.</p><p><strong>Results: </strong>Out of the 36 patients, 11 discontinued DFO after a mean of 4 months; however, 25 patients, who continued to receive the combined therapy showed a very satisfactory compliance. After a mean of 13.5 months, their mean serum ferritin levels reduced from 2637 + 1292 to 1580 + 1024 ng/ml (P = 0.002) and their mean urinary iron excretion elevated from 0.41 + 0.27 to 0.76 +0.49 mg/24h (P = 0.003). The observed side effects were gastrointestinal disorders,elevations in liver enzymes, mild neutropenia, joint symptoms, taste disorders, dizziness and fatigue.</p><p><strong>Conclusions: </strong>The results of this study show that combined iron-chelation therapy with DFO and DFP results in satisfactory reduction of serum ferritin with no significant toxicity.</p>","PeriodicalId":22486,"journal":{"name":"The hematology journal : the official journal of the European Haematology Association","volume":"5 6","pages":"475-9"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/sj.thj.6200550","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24837241","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":"In vitro effects of interferon-gamma and tumor necrosis factor-alpha on CD34+ bone marrow progenitor cells from aplastic anemia patients and normal donors.","authors":"Jonathan P Welsh,&nbsp;Timothy R Rutherford,&nbsp;Julie Flynn,&nbsp;Theodora Foukaneli,&nbsp;Edward C Gordon-Smith,&nbsp;Frances M Gibson","doi":"10.1038/sj.thj.6200340","DOIUrl":"https://doi.org/10.1038/sj.thj.6200340","url":null,"abstract":"<p><p>Acquired aplastic anemia is characterized by loss or dysfunction of hematopoietic stem and progenitor cells. The proinflammatory cytokines Tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) may be responsible for the immune-mediated pathology observed in some patients. The CD34+ population of bone marrow mononuclear cells contains primitive cells responsible for hemopoiesis. We investigated the response of CD34+ cells from aplastic anemia patients to a combination of IFN-gamma and TNF-alpha, and compared them to cells from normal volunteer donors. This was to determine whether aplastic CD34+ cells are more sensitive than normal cells to IFN-gamma/TNF-alpha-mediated effects, and whether cytokine-induced CD95 expression can explain the high levels of apoptosis observed in CD34+ cells from aplastic patients. CD34+38- cells were most affected by overnight incubation with these cytokines, their proportion and numbers being reduced in both normal donors and patients. There was no evidence for increased apoptosis, suggesting that this effect may be due to differentiation. IFN-gamma/TNF-alpha induced upregulation of CD95 on both normal and aplastic CD34+ cells, although the basal level of CD95 expression was increased in aplastic cells. However, CD95 induction did not make cells from normal donors or aplastic anemia patients susceptible to induction of apoptosis by agonistic anti-CD95 antibodies, soluble CD95 ligand, or membrane-bound CD95L. In vivo CD95L is required for CD95 induced apoptosis. No forms of this protein were detectable in lymphocytes from aplastic patients. We conclude that increased apoptosis in aplastic CD34+ cells is not due to increased sensitivity to IFN-gamma/TNF-alpha. We further show that normal and aplastic CD34+ cells are resistant to CD95 apoptosis, even in the presence of mCD95L.</p>","PeriodicalId":22486,"journal":{"name":"The hematology journal : the official journal of the European Haematology Association","volume":"5 1","pages":"39-46"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/sj.thj.6200340","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24181853","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}