Abstract:
:Immune dysregulation, a hallmark of chronic lymphocytic leukemia (CLL), manifests itself in three autoimmune diseases: warm autoimmune hemolytic anemia (AIHA); idiopathic thrombocytopenia (ITP); and, pure red cell aplasia (PRCA). AIHA occurs in 11% of advanced stage CLL patients. Prednisone is the first treatment of choice, with 90% responses and 65% complete responses. More than 60% of patients relapse when treatment is stopped. Intravenous immunoglobulin, the next line of treatment, causes responses in 40% of patients. While the data are very limited, cyclosporine A is a reasonable choice for third-line therapy. Alkylating agents, danazol, plasma exchange, immunoabsorption, vincristine-loaded platelets, splenectomy, and splenic irradiation are also reported to cause responses. The data on mechanisms of AIHA are most consistent with immune dysregulation leading to loss of tolerance to a self antigen which in turn leads to the immune-based hemolytic anemia. PRCA is underrecognized in CLL with 6% of CLL patients having PRCA when tested for it. Unlike AIHA, PRCA often occurs in early stage disease. Anemia, reticulocytopenia, and a marrow virtually devoid of red blood cell precursors are hallmarks of PRCA. Corticosteroid therapy is the first line of treatment. If a response is not obtained in 4 weeks, cyclosporine A should be added. Although the data on pathophysiology are very limited, PRCA appears to be the result of an abnormal T cell that both fails in its normal function to support growth and inhibits the growth of erythroid progenitor cells. ITP occurs in 2-3% of CLL patients, occurs in early stage disease and may be a presenting manifestation. Initial therapy for ITP mirrors the guidelines for primary ITP. Initial therapy should consist of prednisone. Seventy percent of patients respond. Splenectomy is a reasonable second-line treatment. Autoimmune phenomena, largely related to blood cells, are based in the immune dysregulation of CLL. Longer survivals in CLL patients, more treatment regimens per patient, and more immunosuppression with modern treatments, allow us to predict an increasing incidence of autoimmune blood cell diseases in CLL.
journal_name
Semin Oncoljournal_title
Seminars in oncologyauthors
Diehl LF,Ketchum LHsubject
Has Abstractpub_date
1998-02-01 00:00:00pages
80-97issue
1eissn
0093-7754issn
1532-8708journal_volume
25pub_type
杂志文章,评审abstract::A large meta-analysis showed that chemotherapy results in significant prolongation of survival for patients with non-small cell lung cancer (NSCLC). Pemetrexed is a new multitargeted antifolate chemotherapeutic agent that has shown activity in NSCLC and appears to be similar to the third-generation antitumor agents cu...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/sonc.2002.37470
更新日期:2002-12-01 00:00:00
abstract::Autoimmune complications are common in chronic lymphocytic leukemia (CLL), occurring in up to a quarter of all patients during the course of the illness. By far the most common manifestation is autoimmune hemolytic anemia (AIHA), followed by immune thrombocytopenia (ITP). It is not true to say that autoimmunity is con...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2006.01.011
更新日期:2006-04-01 00:00:00
abstract::In recent years, several new cytotoxic agents have been investigated for the management of non-small cell lung cancer (NSCLC), including the antimetabolic gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN) and the new multitargeted antifolate pemetrexed (Alimta, Eli Lilly and Company), which are both among ...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1016/s0093-7754(03)00284-7
更新日期:2003-08-01 00:00:00
abstract::Early detection of response to neoadjuvant chemoradiation in esophageal cancer may allow individualization of treatment strategies and avoidance of unnecessary treatment. Although positron emission tomography (PET) with [(18)F]fluorodeoxyglucose (FDG) permits detection of changes in tumor proliferation before any chan...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:10.1053/j.seminoncol.2007.01.002
更新日期:2007-04-01 00:00:00
abstract::Inhibition of cellular DNA synthesis is the major action of gemcitabine. In cells, this drug is converted to its triphosphate (dFdCTP), which is incorporated into DNA and terminates DNA strand elongation. After incorporation of gemcitabine nucleotide into the DNA strand, one more deoxynucleotide is incorporated, and t...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:
更新日期:1995-08-01 00:00:00
abstract::Docetaxel (Taxotere, Rhône-Poulenc Rorer, Antony, France) is highly effective in the first-line treatment of metastatic breast cancer, achieving an objective response rate of 61% (95% confidence interval, 52% to 69%). This rate of response is seen in patients with poor prognostic factors such as liver metastases and m...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1999-06-01 00:00:00
abstract::Preclinical models in vitro and in vivo have shown that tumor hypoxia alters the malignant cell phenotype, selecting for p53 mutations, stimulating angiogenesis and metastasis, and markedly reducing the efficacy of both radiotherapy and chemotherapy. Similarly, clinical studies measuring pretreatment tumor oxygen stat...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/sonc.2002.31531
更新日期:2002-02-01 00:00:00
abstract::Cancer cells that express excessive levels of Bcl-2 pose a major problem in the delivery of curative therapy. Most treatments for such cancer involve chemotherapy to induce the apoptotic process. While these therapies often result in disease control for periods of time, failure to initiate apoptosis as a result of acq...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2004.10.014
更新日期:2004-12-01 00:00:00
abstract::In spite of the chemosensitivity seen with the initial treatment of malignant lymphoid disorders, relapse is common and death most often occurs as a result of disease progression. This is related to a multitude of resistance mechanisms associated with the various lymphoproliferative disorders. As a result, therapies t...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:
更新日期:2000-04-01 00:00:00
abstract::High-dose interferon alfa (IFN alfa) therapy induces an overall response rate of 25% to 30% in unselected patients with acquired immunodeficiency syndrome (AIDS)-related Kaposi's sarcoma. Up to 50% of patients with relatively preserved immune reactivity respond to treatment. However, when dosages of 20 x 10(6) units o...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1990-02-01 00:00:00
abstract::Ifosfamide, an oxazaphosphorine analogue, is now commonly used in first-line anthracycline-containing regimens for advanced soft tissue sarcomas, based on its demonstrated single-agent activity in previously treated patients. At the Institut Gustave-Roussy, we performed a phase II study of high-dose ifosfamide without...
journal_title:Seminars in oncology
pub_type: 临床试验,杂志文章
doi:
更新日期:1996-06-01 00:00:00
abstract::MicroRNAs (miRNAs) are aiding our understanding of cancer biology, and are now coming close to therapeutic use as well. Here, we focus specifically on the interaction between miRNAs and genomic instability. MiRNA regulation is essential to many cellular processes, and escape from this regulatory network seems to be a ...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2011.08.003
更新日期:2011-12-01 00:00:00
abstract::Monoclonal antibodies (mAbs) and their directly derived cell-based application known as chimeric antigen receptors (CARs) ensue from the need to develop novel therapeutic strategies that retain high anti-tumor activity, but carry reduced toxicity compared to conventional chemo- and radiotherapies. In this concise revi...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2014.08.005
更新日期:2014-10-01 00:00:00
abstract::The treatment of locally advanced carcinoma of the cervix with radiation therapy as a single modality is inadequate, specifically for stage III and IVA disease. While chemotherapy as single-modality therapy is ineffective in advanced cervical cancer, there is some evidence of efficacy when used in combination with rad...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1996-08-01 00:00:00
abstract::The clinical development of the recombinant alpha interferons has provided a prototype for the clinical development of biological compounds. With over 5,000 patients now treated with these compounds, some general principles have emerged that have wider implications for phase I-II strategies for testing other biologica...
journal_title:Seminars in oncology
pub_type: 临床试验,杂志文章,评审
doi:
更新日期:1987-06-01 00:00:00
abstract::Non-platinum combination regimens have been developed for advanced non--small cell lung cancer using the novel and active agents docetaxel, gemcitabine, vinorelbine, and irinotecan. The aim of these combinations is to equal or exceed the survival benefits achieved with cisplatin doublets while minimizing toxicity. Of ...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:2001-06-01 00:00:00
abstract::COVID-19 has a clear sex disparity in clinical outcome. Globally, infection rates between men and women are similar; however, men are more likely to have more severe disease and are more likely to die. The causes for this disparity are currently under investigation and are most likely multifactorial. Sex hormones play...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2020.06.002
更新日期:2020-10-01 00:00:00
abstract::To evaluate the activity of thalidomide in Waldenstrom's macroglobulinemia (WM), 20 patients were treated on a dose schedule that escalated from 200 mg/d to 600 mg/d. On an intention-to-treat basis, five (25%) patients achieved a partial response, which was noted within 3 months of treatment. Adverse effects were comm...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/sonc.2003.50079
更新日期:2003-04-01 00:00:00
abstract::Recurrent and second primary tumors arising within a previously radiated head and neck volume represent a difficult clinical scenario to manage. For patients who have resectable disease, surgery is the standard treatment. Chemotherapy is the standard for patients with unresectable or metastatic disease but offers no c...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2008.03.010
更新日期:2008-06-01 00:00:00
abstract::Tamoxifen has been demonstrated to be hepatocarcinogenic in some but not all strains of the laboratory rat and is not a carcinogen in the mouse. To resolve the question of whether tamoxifen is genotoxic in humans, many laboratories have studied its interspecies metabolism and its propensity to form DNA adducts. This r...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1997-02-01 00:00:00
abstract::Although originally developed as an antitumor agent in the 1970s, dexrazoxane (DEX) is currently used as a cardioprotective agent in combination with doxorubicin (DOX). Due to concerns about anthracycline-induced cardiotoxicity at higher cumulative doses, many investigators have chosen to administer DOX by prolonged i...
journal_title:Seminars in oncology
pub_type: 临床试验,杂志文章
doi:
更新日期:1998-08-01 00:00:00
abstract::This article reviews the associations of cancer with rheumatic diseases. Recent epidemiologic data linking the autoimmune connective tissue diseases with malignancy will be emphasized. Reports linking the occurrence of malignancy with rheumatoid arthritis, systemic lupus erythematosus, idiopathic inflammatory myopathy...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1997-06-01 00:00:00
abstract::Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has demonstrated substantial single-agent activity against both minimally pretreated and resistant metastatic breast cancer. Evaluation of paclitaxel-based combinations has demonstrated appreciable activity, but also toxicity, for the paclitaxel/doxorubic...
journal_title:Seminars in oncology
pub_type: 临床试验,杂志文章
doi:
更新日期:1995-08-01 00:00:00
abstract::The treatment of diffuse malignant pleural mesothelioma (MPM) is currently less than satisfactory. Survival statistics are best for the epithelial subtype and for tumors that can be completely removed by surgery. Radiotherapy provides no survival benefit and is used only to palliate symptoms or to prevent growth along...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/sonc.2002.30765
更新日期:2002-04-01 00:00:00
abstract::Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has been shown to be an effective agent in the treatment of metastatic breast carcinoma. This multicenter randomized study compared paclitaxel 175 mg/m2 given as a 3-hour infusion every 3 weeks with mitomycin 12 mg/m2 given as an intravenous infusion ever...
journal_title:Seminars in oncology
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:
更新日期:1995-08-01 00:00:00
abstract::A phase II study was conducted to evaluate the efficacy and toxicity of lomustine, cytarabine, mitoxantrone and prednisone (CAMP) chemotherapy in doxorubicin-resistant intermediate- and high-grade malignant non-Hodgkin's lymphomas (NHL). Among 30 patients, the complete remission rate was 27% (duration: 10, 16, 22, 35,...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:
更新日期:1990-12-01 00:00:00
abstract::A wide variety of cytogenetic abnormalities and molecular pathways have been implicated in the pathogenesis of sarcoma, and significant progress has been made in the past decade toward identifying potential therapeutic targets. However, apart from gastrointestinal stromal tumors (GISTs) and dermatofibrosarcoma protube...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2011.09.003
更新日期:2011-10-01 00:00:00
abstract::The approval, in 2015, of the first poly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi; olaparib, Lynparza) for platinum-sensitive relapsed high-grade ovarian cancer with either germline or somatic BRCA1/2 deleterious mutations is changing the way that BRCA1/2 testing services are offered to patients with...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2017.08.004
更新日期:2017-06-01 00:00:00
abstract::Pancreatic cancer is one of the most lethal neoplasms. Incidence in the United States has remained fairly stable over the past 25 years, with about 25,000 cases annually. Almost 100% of cases are fatal. Incidence in the developed world parallels that in the United States. Incidence in undeveloped nations is lower but ...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1996-04-01 00:00:00
abstract::A phase II study was performed to investigate the tolerance and efficacy of the combination of docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) and gemcitabine in chemotherapy-naive patients with advanced non-small cell lung cancer (NSCLC). To date, 24 patients (five with stage IIIB and 19 with stage IV NSCLC...
journal_title:Seminars in oncology
pub_type: 临床试验,杂志文章,多中心研究
doi:
更新日期:1997-08-01 00:00:00