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

{"title":"Relations between hemostatic variables, insulin resistance and inflammation.","authors":"Pierre E Morange, M C Alessi, I Juhan-Vague","doi":"10.1038/sj.thj.6200415","DOIUrl":"https://doi.org/10.1038/sj.thj.6200415","url":null,"abstract":"","PeriodicalId":22486,"journal":{"name":"The hematology journal : the official journal of the European Haematology Association","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24559895","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":"Phase II trial of arsenic trioxide and alpha interferon in patients with relapsed/refractory adult T-cell leukemia/lymphoma.","authors":"Olivier Hermine,&nbsp;Hervé Dombret,&nbsp;Joel Poupon,&nbsp;Bertrand Arnulf,&nbsp;Francois Lefrère,&nbsp;Phillippe Rousselot,&nbsp;Gandhi Damaj,&nbsp;Richard Delarue,&nbsp;Jean Paul Fermand,&nbsp;Jean Claude Brouet,&nbsp;Laurent Degos,&nbsp;Bruno Varet,&nbsp;Hugues de Thé,&nbsp;Ali Bazarbachi","doi":"10.1038/sj.thj.6200374","DOIUrl":"https://doi.org/10.1038/sj.thj.6200374","url":null,"abstract":"<p><p>Human T-cell lymphotropic virus type 1 associated adult T-cell leukemia/lymphoma carries a very poor prognosis due to its intrinsic resistance to chemotherapy. Although zidovudine (AZT) and alpha-interferon (IFN) yield some responses and improve ATL prognosis, alternative therapies are needed. Arsenic trioxide (As) dramatically synergizes with IFN to induce growth arrest and apoptosis of ATL leukemia cells in vitro. These results prompted us to initiate a phase II trial of As/IFN combination in seven patients with relapsed/refractory ATL (four acute and three lymphoma). Four patients exhibited a clear initial response (one complete remission and three partial remissions). Yet, the treatment was discontinued after a median of 22 days because of toxicity (three patients) or subsequent progression (four patients). Six patients eventually died from progressive disease (five patients) or infection (one patient), but the remaining patient is still alive and disease free at 32 months. Pharmacokinetic studies showed that maximum arsenic blood levels (median 0.46 microM) were slowly achieved (8-15 days). In conclusion, arsenic/IFN treatment is feasible and exhibits an anti-leukemia effect in very poor prognosis ATL patients despite a significant toxicity. Future studies should assess the best timing for arsenic therapy: frontline with IFN/AZT or as maintenance after induction.</p>","PeriodicalId":22486,"journal":{"name":"The hematology journal : the official journal of the European Haematology Association","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/sj.thj.6200374","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24438547","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":"Intravenous ribavirin for eradication of respiratory syncytial virus (RSV) and adenovirus isolates from the respiratory and/or gastrointestinal tract in recipients of allogeneic hematopoietic stem cell transplants.","authors":"Michael Schleuning,&nbsp;Harald Buxbaum-Conradi,&nbsp;Gundula Jäger,&nbsp;Hans-Jochem Kolb","doi":"10.1038/sj.thj.6200358","DOIUrl":"https://doi.org/10.1038/sj.thj.6200358","url":null,"abstract":"<p><p>In a retrospective analysis, we identified 38 evaluable patients who received intravenous ribavirin after adenovirus or RSV detection in the respiratory and/or gastrointestinal tract throughout the years 1998 and 2001. A total of 43 treatment cycles are analyzed. Intravenous ribavirin was combined with cidofovir in about half of the patients. In six out of eight patients treated because of RSV isolates from the respiratory tract, the virus was no longer detectable after treatment. In case of adenovirus isolates, the treatment was efficacious in eradicating the virus from the respiratory tract in more than 60% and from the gastrointestinal tract in 75% of treatment cycles. The addition of cidofovir was not beneficial in eradicating RSV isolates, but somewhat improved the virus clearance of adenovirus. Virus clearance was associated with a trend to a better median survival after virus detection. There were some episodes of suspected hemolysis and a trend towards lower leukocyte counts, reaching grade 3 toxicity in about 15% of treatment cycles. However, in general, intravenous ribavirin was well tolerated. In conclusion, the possible efficacy of intravenous Ribavirin in controlling RSV or adenovirus infections after allogeneic stem cell transplantations should be evaluated in prospective clinical trials.</p>","PeriodicalId":22486,"journal":{"name":"The hematology journal : the official journal of the European Haematology Association","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/sj.thj.6200358","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24438548","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":"Standardization and comparison of endogenous erythroid colony assays performed with bone marrow or blood progenitors for the diagnosis of polycythemia vera.","authors":"Irène Dobo,&nbsp;Magali Donnard,&nbsp;François Girodon,&nbsp;Pascal Mossuz,&nbsp;Nathalie Boiret,&nbsp;Rachida Boukhari,&nbsp;Annie Allégraud,&nbsp;Elisabeth Bascans,&nbsp;Lydia Campos,&nbsp;Danielle Pineau,&nbsp;Pascal Turlure,&nbsp;Vincent Praloran,&nbsp;Sylvie Hermouet","doi":"10.1038/sj.thj.6200344","DOIUrl":"https://doi.org/10.1038/sj.thj.6200344","url":null,"abstract":"<p><p>The reliability of the assay of endogenous erythroid colony (EEC) formation in serum-free, cytokine-free collagen-based media was investigated in a multicentric study including 140 patients with polyglobuly (80 polycythemia vera (PV), 54 secondary erythrocytosis (SE), six idiopathic erythrocytosis (IE)) and 10 healthy donors. In each center, EEC assays were performed in parallel with progenitor cells from bone marrow (BM) and peripheral blood (PB); two commercialized media and 'low' and 'high' cell plating densities were tested. Negativity of EEC assays was considered certain only when sufficient BFU-E growth was obtained in control cultures with cytokines. In the two media, EEC formation was specific - never observed in cultures of healthy donors or SE patients - and comparable. BM EEC assays were positive (presence of eythroid colonies) for 75% ('low' plating) to 100% ('high' plating) of PV patients; PB EEC assays were positive for 83.3% ('low' plating) to 93.7% ('high' plating) of PV patients (differences not significant). Depending on the medium, 86.2-93.7% of patients with a positive BM EEC assay had a positive PB EEC assay. Hence, a standardized collagen-based EEC assay can be performed with either BM or PB progenitors; the EEC assay described here is positive for at least 75% of PV patients when a single EEC assay is performed, and for at least 94% of PV patients when both BM and PB EEC assays are performed.</p>","PeriodicalId":22486,"journal":{"name":"The hematology journal : the official journal of the European Haematology Association","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24438551","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":"Role of fludarabine as monotherapy in the treatment of chronic lymphocytic leukemia.","authors":"Michel Leporrier","doi":"10.1038/sj.thj.6200387","DOIUrl":"https://doi.org/10.1038/sj.thj.6200387","url":null,"abstract":"<p><p>Fludarabine is a synthetic adenine nucleoside analog that is indicated for first- and second-line treatment of chronic lymphocytic leukemia (CLL). The recommended intravenous (i.v.) dosage regimen is 25 mg/m2 daily for 5 consecutive days, with treatment cycles repeated every 28 days. In treatment-naïve patients with Binet stage B and C CLL, i.v. fludarabine produces superior responses to established first-line chemotherapies. Fludarabine produces a higher overall remission rate (60-70%) and longer progression-free survival (median approximately 20-30 months) than standard therapy with chlorambucil+/-prednisone and CAP (cyclophosphamide/doxorubicin/prednisone), and a comparable overall remission rate to CHOP (cyclophosphamide/vincristine/prednisone/doxorubicin). Fludarabine demonstrates high efficacy in both intermediate-risk (Rai stage I or II) and high-risk (Rai stage III or IV) patients. Furthermore, fludarabine is equally effective in younger (< or =65 years) and older (>65 years) patients. Fludarabine has significant activity as monotherapy in previously treated CLL, producing objective response rates of up to 94% in typically small-scale, noncomparative studies, with the majority of studies yielding rates of 30-60%. In a phase III multicenter study, the overall remission rate was significantly higher with fludarabine than with CAP (48 versus 27%) among the subset of treatment-refractory patients (n=96). For those patients who are refractory to or have relapsed following conventional chemotherapy (chlorambucil, CAP and CHOP), fludarabine can be considered the treatment of choice for second-line therapy. Moreover, patients with relapsed CLL may benefit from retreatment with fludarabine if they have previously demonstrated sensitivity to the drug. Standard-dose i.v. fludarabine has an established safety profile and comparable tolerability to anthracycline-based regimens (CAP and CHOP) in terms of its myelosuppressive and immunosuppressive effects, and offers the advantage of a markedly lower incidence of gastrointestinal effects (nausea/vomiting) and alopecia.</p>","PeriodicalId":22486,"journal":{"name":"The hematology journal : the official journal of the European Haematology Association","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/sj.thj.6200387","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24464839","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":"Use of fludarabine in the treatment of mantle cell lymphoma, Waldenström's macroglobulinemia and other uncommon B- and T-cell lymphoid malignancies.","authors":"Stephen A Johnson","doi":"10.1038/sj.thj.6200391","DOIUrl":"https://doi.org/10.1038/sj.thj.6200391","url":null,"abstract":"<p><p>After initial efforts using fludarabine as a single agent in the treatment of acute leukemia, its activity at lower and safer doses was demonstrated in chronic lymphocytic leukemia (CLL) patients who were refractory or had relapsed from traditional chemotherapies, representing a highly effective therapy for this condition. Fludarabine was also rapidly shown to be beneficial as first-line therapy in CLL. There is now considerable evidence that fludarabine is an effective agent in non-Hodgkin's lymphoma and in combination therapy for acute myeloid leukemia. Further, good responses are achieved when fludarabine-based approaches are used as conditioning regimens prior to transplantation procedures. The actions of fludarabine are not restricted to these settings and its potential role in the treatment of a range of uncommon T- and B-cell lymphoid malignancies is slowly emerging. This review will focus on the characteristics and treatment options for two B-cell disorders, mantle cell lymphoma and Waldenström's macroglobulinemia, with emphasis on the clinical activity of fludarabine. Additionally, the advantages of using fludarabine-containing regimens for a range of other lymphoproliferative conditions will also be discussed. These include B-cell neoplasms such as the CLL variant prolymphocytic leukemia, hairy cell leukemia and mucosa-associated lymphoid tissue-derived lymphomas; the T-cell disorders cutaneous T-cell lymphoma, angioimmunoblastic lymphadenopathy and other rarer T-cell diseases; and aggressive variants of non-Hodgkin's lymphoma including Richter's syndrome.</p>","PeriodicalId":22486,"journal":{"name":"The hematology journal : the official journal of the European Haematology Association","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/sj.thj.6200391","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24464843","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":"Involvement of mitogen-activated protein kinase in the cytokine-regulated phosphorylation of transcription factor GATA-1.","authors":"Masayuki Towatari,&nbsp;Marco Ciro,&nbsp;Sergio Ottolenghi,&nbsp;Shinobu Tsuzuki,&nbsp;Tariq Enver","doi":"10.1038/sj.thj.6200345","DOIUrl":"https://doi.org/10.1038/sj.thj.6200345","url":null,"abstract":"<p><p>Gene-targeting experiments in transgenic mice have revealed an essential role for GATA-1 in the normal differentiation and development of erythroid cells. GATA-1 is phosphorylated in vivo on seven of its serine residues; the regulation and function of GATA-1 phosphorylation, however, is not understood. Here we demonstrate a role for MAP kinase (MAPK) signalling in the control of GATA-1 phosphorylation. We show that EGF-induced MAPK signalling results in the phosphorylation of ectopically expressed GATA-1 in COS cells. This phosphorylation can be positively or negatively regulated by genetic manipulation of the MAPK pathway through expression of constitutively activated, or dominant-negative, mutants of MAPK kinase (MAPKK), an upstream regulator of MAPK activity. In vitro phosphorylation experiments using purified MAPK and either recombinant GATA-1 or synthetic GATA-1 peptides suggest that GATA-1 is a MAPK substrate with MAPK phosphorylation occurring primarily on Ser26 and Ser178. We also show that GATA-1 is phosphorylated in factor-dependent haemopoietic progenitor cells in response to cytokine-induced signalling. Through the further use of a dominant-negative MAPKK mutant as well as chemical inhibitors of specific MAPKs, we identify ERK as an in vivo GATA-1 kinase. Finally, we demonstrate that mutation of serines 26 and 178 compromises the ability of GATA-1 to interact with the LIM-only protein LMO2 when both proteins are expressed in COS cells. These data implicate receptor-mediated signalling through the MAPK pathway as a control point in the regulation of transcription factor GATA-1.</p>","PeriodicalId":22486,"journal":{"name":"The hematology journal : the official journal of the European Haematology Association","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/sj.thj.6200345","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24540264","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":"Treatment of venous thromboembolism: duration and new options.","authors":"Menno V Huisman","doi":"10.1038/sj.thj.6200417","DOIUrl":"https://doi.org/10.1038/sj.thj.6200417","url":null,"abstract":"","PeriodicalId":22486,"journal":{"name":"The hematology journal : the official journal of the European Haematology Association","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/sj.thj.6200417","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24561604","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":"Immunotherapy with alloreactive T-cells?","authors":"Alejandro J Madrigal,&nbsp;Sylvie Rusakiewicz,&nbsp;Anthony I Dodi,&nbsp;Robert Rees","doi":"10.1038/sj.thj.6200430","DOIUrl":"https://doi.org/10.1038/sj.thj.6200430","url":null,"abstract":"","PeriodicalId":22486,"journal":{"name":"The hematology journal : the official journal of the European Haematology Association","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/sj.thj.6200430","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24561617","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":"Epoetin-induced autoimmune pure red cell aplasia.","authors":"Nicole Casadevall","doi":"10.1038/sj.thj.6200433","DOIUrl":"https://doi.org/10.1038/sj.thj.6200433","url":null,"abstract":"","PeriodicalId":22486,"journal":{"name":"The hematology journal : the official journal of the European Haematology Association","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/sj.thj.6200433","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24561620","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}