Clinical Lymphoma and Myeloma最新文献_第6页

The Use of New and Better Antibiotics for Bacterial Infections in Patients With Leukemia 新型更好的抗生素治疗白血病患者细菌感染

Clinical Lymphoma and Myeloma Pub Date : 2009-09-01 Epub Date: 2012-09-20 DOI: 10.3816/CLM.2009.s.035

Kenneth V.I. Rolston

{"title":"The Use of New and Better Antibiotics for Bacterial Infections in Patients With Leukemia","authors":"Kenneth V.I. Rolston","doi":"10.3816/CLM.2009.s.035","DOIUrl":"10.3816/CLM.2009.s.035","url":null,"abstract":"<div><p>Bacterial infection is the most common complication of chemotherapy-induced neutropenia particularly in patients with hematologic malignancies. Bacterial infections predominate during the initial phases of neutropenic episodes. The spectrum of bacterial infection continues to evolve globally and locally at the institutional level, as do patterns of antimicrobial susceptibility/resistance. These trends are often associated with local treatment practices (eg, use of antimicrobial prophylaxis, open versus restricted formularies, clinical pathways and/or guidelines) and have a significant effect on the nature of empiric antimicrobial therapy. Increasing rates of resistance among gram-positive and gram-negative bacteria are posing new therapeutic challenges. These challenges can to some extent be overcome by new drug development. Many novel agents for the treatment of resistant gram-positive infections have been developed and are being evaluated in clinical trials. Newer agents for the treatment of <em>Clostridium difficile</em> associated diarrhea are also in the pipeline. Far fewer options to treat multi-drug resistant gram-negative infections exist, and new drug development is lagging behind. Consequently, the judicious use of currently available agents is essential. This is best achieved by the development of multidisciplinary antibiotic stewardship teams that gather baseline data, make recommendations for appropriate antimicrobial usage, and provide monitoring and feedback services to clinical care providers. Along with strict adherence to infection control policies, antimicrobial stewardship provides the best strategies for the management of infectious complications in patients with hematologic malignancies and other high-risk settings.</p></div>","PeriodicalId":100272,"journal":{"name":"Clinical Lymphoma and Myeloma","volume":"9 ","pages":"Pages S357-S363"},"PeriodicalIF":0.0,"publicationDate":"2009-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3816/CLM.2009.s.035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40034059","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}

引用次数: 10

What Are the Endpoints of Therapy for Acute Leukemias? Old Definitions and New Challenges 急性白血病治疗的终点是什么?旧的定义和新的挑战

Clinical Lymphoma and Myeloma Pub Date : 2009-09-01 Epub Date: 2012-09-20 DOI: 10.3816/CLM.2009.s.027

B. Douglas Smith , Judith E. Karp

{"title":"What Are the Endpoints of Therapy for Acute Leukemias? Old Definitions and New Challenges","authors":"B. Douglas Smith , Judith E. Karp","doi":"10.3816/CLM.2009.s.027","DOIUrl":"10.3816/CLM.2009.s.027","url":null,"abstract":"<div><p>Acute leukemias are complex diseases on multiple levels, and laboratory efforts over the past 3 decades have focused on better understanding of the molecular underpinnings and their stem cell biology. We now have a panoply of technologic advances that allow us to characterize individual leukemias by molecular profiles that relate directly to clinical behavior, to detect minimal residual disease, and to begin to develop “targeted” therapeutic strategies based on molecular considerations. There are a number of challenges surrounding this task: first, how to combine these agents with traditional chemotherapeutics and/or with each other to maximize leukemic cell kill and increase the cure rate; second, how to use these targeted agents in the minimal residual disease with potential curative intent; third, for patients unable to tolerate or unlikely to benefit from aggressive approaches, how to use one or more of these agents to reduce tumor bulk and either permit some restoration of normal marrow function or induce morphologic and functional differentiation of the leukemic clone to overcome the leukemia-associated bone marrow failure; and lastly, how to measure the effects of these agents on the molecular and cellular biologic levels in ways that correlate with and might even predict overall clinical outcome. These challenges are further complicated by the inherent heterogeneity in host biology; disease etiology and biology; and interactions among host, disease, and treatment that ultimately determine individual clinical outcomes. Toward this end, we will discuss selected issues surrounding new clinical trial designs and the development of clinically relevant molecular endpoints that might facilitate the development of new treatment approaches that will improve the outlook for adults with acute leukemias.</p></div>","PeriodicalId":100272,"journal":{"name":"Clinical Lymphoma and Myeloma","volume":"9 ","pages":"Pages S296-S301"},"PeriodicalIF":0.0,"publicationDate":"2009-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3816/CLM.2009.s.027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40033576","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}

引用次数: 5

Lenalidomide—A Transforming Therapeutic Agent in Myelodysplastic Syndromes 来那度胺:骨髓增生异常综合征的转化治疗剂

Clinical Lymphoma and Myeloma Pub Date : 2009-09-01 Epub Date: 2012-09-20 DOI: 10.3816/CLM.2009.s.028

Alan List

{"title":"Lenalidomide—A Transforming Therapeutic Agent in Myelodysplastic Syndromes","authors":"Alan List","doi":"10.3816/CLM.2009.s.028","DOIUrl":"10.3816/CLM.2009.s.028","url":null,"abstract":"<div><p>Lenalidomide is an immunomodulatory drug (IMiD™) with erythropoietic activity in myelodysplastic syndromes (MDS) that is karyotype dependent. The MDS-003 multicenter registration trial in deletion of chromosome 5q (del[5q]) showed that lenalidomide suppresses the del(5q) clone in patients who achieve transfusion independence and is a prerequisite for sustained restoration of effective erythropoiesis. Long-term outcome data indicate that cytogenetic response to lenalidomide might confer a survival advantage compared with cytogenetic nonresponders, with a corresponding reduced risk for acute myeloid leukemia (AML) progression. In lower-risk, transfusion-dependent patients with MDS without del(5q), lenalidomide has significant, albeit less erythropoietic, activity that could relate to dual effects on both the MDS clone and the bone marrow environment. The most common adverse effects are neutropenia and thrombocytopenia, which occur early and with greater frequency in patients with del(5q), consistent with the drug's action to suppress the MDS clone. Combination strategies are now in both MDS and AML that could further broaden the therapeutic potential of lenalidomide.</p></div>","PeriodicalId":100272,"journal":{"name":"Clinical Lymphoma and Myeloma","volume":"9 ","pages":"Pages S302-S304"},"PeriodicalIF":0.0,"publicationDate":"2009-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3816/CLM.2009.s.028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40033577","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}

引用次数: 8

Hairy Cell Leukemia 毛细胞白血病

Clinical Lymphoma and Myeloma Pub Date : 2009-09-01 Epub Date: 2012-09-20 DOI: 10.3816/CLM.2009.s.020

Farhad Ravandi

引用次数: 1

Red Bood Cell Transfusion Therapy and Iron Chelation in Patients With Myelodysplastic Syndromes 骨髓增生异常综合征患者的红细胞输血治疗和铁螯合

Clinical Lymphoma and Myeloma Pub Date : 2009-09-01 Epub Date: 2012-09-20 DOI: 10.3816/CLM.2009.s.029

Luca Malcovati

{"title":"Red Bood Cell Transfusion Therapy and Iron Chelation in Patients With Myelodysplastic Syndromes","authors":"Luca Malcovati","doi":"10.3816/CLM.2009.s.029","DOIUrl":"10.3816/CLM.2009.s.029","url":null,"abstract":"<div><p>Anemia is the most frequent peripheral cytopenia observed in myelodysplastic syndromes (MDS) and has been recognized among the most important factors affecting the outcome of patients with MDS. In patients who are not candidates for potentially curative approaches, therapeutic options for symptomatic anemia include red blood cell (RBC) transfusion and iron chelation, hematopoietic growth factors, immunosuppression, immune-modulatory drugs, and hypomethylating agents. In about 40% of patients, regular RBC transfusions are the only therapeutic option that can be offered. The onset of a regular transfusion requirement significantly worsens the survival of patients with MDS. Transfusion-dependent patients invariably develop secondary iron overload. Elevated serum ferritin was proven to be associated with worse survival in transfusion-dependent patients, and recent data obtained using magnetic resonance imaging show both hepatic and myocardial iron accumulation in heavily transfused patients. According to evidence-based guidelines, patients with sideroblastic anemia, 5q- syndrome, or other forms of refractory anemia, in whom long-term transfusion therapy is likely, are recognized as the best candidates to receive iron chelation therapy. In addition, patients who are candidates for allogeneic stem cell transplantation might also benefit from chelation therapy because iron overload is associated with increased transplantation-related mortality. RBC transfusions and iron chelation are the mainstay of therapy for many individuals with MDS. However, critical issues remain to be clarified in order to optimize treatment, including the identification of target hemoglobin levels to prevent anemia-related morbidity and more accurate information on the effect of iron-mediated organ damage on the outcome of patients with MDS.</p></div>","PeriodicalId":100272,"journal":{"name":"Clinical Lymphoma and Myeloma","volume":"9 ","pages":"Pages S305-S311"},"PeriodicalIF":0.0,"publicationDate":"2009-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3816/CLM.2009.s.029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40033578","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}

引用次数: 22

Flavopiridol in Chronic Lymphocytic Leukemia: A Concise Review 黄匹吡醇在慢性淋巴细胞白血病中的应用综述

Clinical Lymphoma and Myeloma Pub Date : 2009-09-01 Epub Date: 2012-09-20 DOI: 10.3816/CLM.2009.s.009

Beth A. Christian, Michael R. Grever, John C. Byrd, Thomas S. Lin

{"title":"Flavopiridol in Chronic Lymphocytic Leukemia: A Concise Review","authors":"Beth A. Christian, Michael R. Grever, John C. Byrd, Thomas S. Lin","doi":"10.3816/CLM.2009.s.009","DOIUrl":"10.3816/CLM.2009.s.009","url":null,"abstract":"<div><p>Patients with chronic lymphocytic leukemia (CLL) with high-risk cytogenetic features such as del(17p13) have limited treatment options and decreased overall survival. Dysfunction of p53 leads to resistance to fludarabine-based therapies. Cyclin-dependent kinase inhibitors (CDKi) are a novel class of agents that induce apoptosis in CLL cells independent of p53 mutational status. The synthetic flavone flavopiridol demonstrated promising in vitro activity in CLL. In initial phase I studies using a continuous infusion dosing schedule in a variety of malignancies, no clinical activity was observed. Detailed pharmacokinetic modeling led to the development of a novel dosing schedule designed to achieve target drug concentrations in vivo. In phase I testing, this dosing schedule resulted in acute tumor lysis syndrome (TLS) as the dose-limiting toxicity. With the implementation of a standardized protocol to prevent severe TLS, flavopiridol was administered safely, and responses were observed in heavily pretreated, fludarabine-refractory patients, cytogenetically high-risk patients, and patients with bulky lymphadenopathy. In a pharmacokinetic analysis, flavopiridol area under the plasma concentration-time curve (AUC) correlated with clinical response and cytokine release syndrome. Phase II studies are under way with encouraging preliminary results. Flavopiridol is currently under active investigation in combination with other agents and as a means to eradicate minimal residual disease in patients following cytoreductive chemotherapy. Several other investigational CDKi in preclinical and early clinical development are briefly discussed in this review.</p></div>","PeriodicalId":100272,"journal":{"name":"Clinical Lymphoma and Myeloma","volume":"9 ","pages":"Pages S179-S185"},"PeriodicalIF":0.0,"publicationDate":"2009-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3816/CLM.2009.s.009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40033749","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}

引用次数: 43

Familial Chronic Lymphocytic Leukemia: What Does it Mean to Me? 家族性慢性淋巴细胞白血病:对我意味着什么?

Clinical Lymphoma and Myeloma Pub Date : 2009-09-01 Epub Date: 2012-09-20 DOI: 10.3816/CLM.2009.s.011

Susan L. Slager , Neil E. Kay

{"title":"Familial Chronic Lymphocytic Leukemia: What Does it Mean to Me?","authors":"Susan L. Slager , Neil E. Kay","doi":"10.3816/CLM.2009.s.011","DOIUrl":"10.3816/CLM.2009.s.011","url":null,"abstract":"<div><p>Though B-chronic lymphocytic leukemia (CLL) is known to be a heterogeneous disease, only recently has the familial component of CLL been more thoroughly investigated. This entity is seen in approximately 5%–10% of all patients with CLL and can be associated with earlier age of diagnosis, higher female prevalence, and increased incidence of other lymphoproliferative disorders (LPDs), such as non-Hodgkin lymphoma and the more recently described monoclonal B-cell lymphocytosis CLL in family members. The prognostic parameters and clinical course of familial CLL is not clearly distinguishable from that of sporadic disease. In addition, it is not clear that the treatment responses for progressive disease has any discernible difference in familial versus sporadic CLL. The genetic etiology of CLL is unknown, and early work on familial CLL has not yet uncovered any obvious gene or group of genes that can be clearly related to the pathophysiology of CLL. However, the detailed genetic study of familial CLL is likely to be critical in uncovering relevant genes. At present it is best to indicate to concerned CLL patients that their relatives are at relatively low risk of developing CLL or other LPDs.</p></div>","PeriodicalId":100272,"journal":{"name":"Clinical Lymphoma and Myeloma","volume":"9 ","pages":"Pages S194-S197"},"PeriodicalIF":0.0,"publicationDate":"2009-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3816/CLM.2009.s.011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40033751","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}

引用次数: 12

New Thrombopoietic Growth Factors 新的血小板生成生长因子

Clinical Lymphoma and Myeloma Pub Date : 2009-09-01 Epub Date: 2012-09-20 DOI: 10.3816/CLM.2009.s.034

David J. Kuter

{"title":"New Thrombopoietic Growth Factors","authors":"David J. Kuter","doi":"10.3816/CLM.2009.s.034","DOIUrl":"10.3816/CLM.2009.s.034","url":null,"abstract":"<div><p>Thrombopoietin (TPO) is the physiologic regulator of platelet production and works by binding to its receptor on megakaryocyte precursor cells, thereby activating a large number of antiapoptotic and cell maturation pathways. “First-generation” recombinant forms of TPO were developed over a decade ago and were found to increase the platelet count in patients undergoing nonmyeloablative chemotherapy, in patients with immune thrombocytopenic purpura (ITP) and myelodysplasia, as well as in platelet apheresis donors. Thrombopoietin did not improve platelet counts in patients undergoing stem cell transplantation or acute leukemia induction. Further development ended when antibodies formed against one of the recombinant proteins. Subsequently, 2 “second-generation” TPO mimetics have been developed and are entering clinical practice: romiplostim and eltrombopag. Romiplostim is an injectable peptide TPO mimetic that activates the TPO receptor just like native TPO. Eltrombopag is an oral nonpeptide TPO mimetic that activates the TPO receptor by binding to a different region of the TPO receptor that does not compete with TPO binding. Both increased the platelet counts in healthy subjects and in over two thirds of patients with ITP both before and after splenectomy; responses were maintained for at least 1 year. Romiplostim and eltrombopag are now US Food and Drug Administration approved for the second-line treatment of patients with ITP. Adverse events have been few, but long-term assessment for reticulin formation, increased bone marrow blasts, and thromboembolism is ongoing. Studies are under way to assess the efficacy of these drugs in the treatment of other thrombocytopenic disorders associated with chemotherapy, myelodysplasia, and chronic hepatitis.</p></div>","PeriodicalId":100272,"journal":{"name":"Clinical Lymphoma and Myeloma","volume":"9 ","pages":"Pages S347-S356"},"PeriodicalIF":0.0,"publicationDate":"2009-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3816/CLM.2009.s.034","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40034058","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}

引用次数: 40

T-Cell Prolymphocytic Leukemia t细胞前淋巴细胞白血病

Clinical Lymphoma and Myeloma Pub Date : 2009-09-01 Epub Date: 2012-09-20 DOI: 10.3816/CLM.2009.s.018

Claire E. Dearden

引用次数: 23

Transplantation in Chronic Lymphocytic Leukemia: Timing and Expectations 慢性淋巴细胞白血病的移植:时机和期望

Clinical Lymphoma and Myeloma Pub Date : 2009-09-01 Epub Date: 2012-09-20 DOI: 10.3816/CLM.2009.s.010

Simon Hallam, John G. Gribben

引用次数: 1