Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

FDG-PET is both able to provide information of lymphomatous organ involvement not available by conventional imaging techniques (US, CT, MRI) and to give reliable data otherwise obtainable only by using invasive procedures. As a whole body-screening technique, PET reduces diagnostic requirements and potential complications. Nevertheless the conventional imaging techniques are essential for the exact localisation and correct interpretation of PET findings. A number of factors that may produce false-positive results have to be taken into consideration, including post-treatment inflammatory changes and the sensitivity of the method in the setting of minimal residual disease. Despite its potential of a screening method being performed prior to other imaging procedures, PET is not yet established as a routine element for the primary staging of Hodgkin's disease and non-Hodgkin's lymphoma. Its value for re-staging is less doubtful due to the frequency of stage migration and possible changes in therapy related to the use of PET. Detailed cost-effectiveness studies are needed to assess the economic implications of an expanded use of PET in lymphoma therapy.
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PMID:Positron emission tomography and lymphoma therapy. 1169 79

High relapse rates during the first year after autologous stem cell transplantation (ASCT) for multiple myeloma or non-Hodgkin lymphoma are due to the failure of high-dose chemotherapy to eradicate minimal residual disease. Post-ASCT immunorecovery studies have shown that quantities of natural killer (NK) cells return to normal within 1 month post-ASCT in contrast to the recovery of T and B cell populations (up to 1 year). Preclinical studies have demonstrated that NK cells have potent antitumor activity. IL-2 and IFN-alpha enhance NK-cell activity. We investigated the efficacy of IL-2 and IFN-alpha to up-regulate NK-cell cytotoxicity at 14 days post ASCT. Twenty patients undergoing ASCT had PBMCs collected pretransplantation and at 14 days post transplantation. PBMCs (effector cells) from each blood sample were incubated in vitro with IFN-alpha and IL-2 at 10000 IU/ml. NK cell activity was determined by sodium chromate (51)Cr release assay for lysis of K562 target cells. IL-2 and IFN-alpha each increased lysis of K562 cells compared with placebo (effector-to-target ratio, 50:1, P < 0.001). Increased NK cell activity occurred in samples from all patients. IL-2 and IFN-alpha up-regulated NK cell activity at 14 days post ASCT. They may be useful as immunomodulators as early as 14 days post ASCT to eradicate or control minimal residual disease.
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PMID:Immunomodulation of early engrafted natural killer cells with interleukin-2 and interferon-alpha in autologous stem cell transplantation. 1170 90

The primary gastric lymphomas are extranodal non-Hodgkin's lymphomas that likely originate from the mucosa-associated lymphoid tissue (MALT). Data suggest that chronic infection with Helicobacter pylori (H pylori) is significantly associated with the pathogenesis of low-grade gastric MALT lymphomas. This is in keeping with the observation that many patients with early low-grade MALT lymphomas have complete remissions after H pylori eradication therapy. However, the stability of these remissions remains unclear and relapses have been reported. It can be difficult to distinguish between early malignant and benign disorders of the gastric mucosa. A polymerase chain reaction (PCR) assay can detect rearrangements of the variable region of immunoglobulin heavy chains. This assay can be used to distinguish the clonality of B lymphocytes and has been investigated as a test for differential diagnosis of MALT lymphomas. Monoclonality is observed in the majority of MALT-lymphoma samples at diagnosis but has been found in gastritis samples as well. Whether the presence of monoclonal B cells is associated with the risk of lymphoma progression remains unclear. As many as 50% of patients who have complete histologic remissions of MALT lymphoma after H pylori eradication therapy have persisting monoclonal bands in follow-up PCR monitoring. Although it is unclear as to whether monoclonality indicates the presence of minimal residual disease, patients who have persistent monoclonal bands during follow-up should be considered at risk for relapse. The PCR assay for rearrangements of the variable region of the immunoglobulin heavy-chain gene appears to be of low value in the diagnosis of B-cell malignancies but could provide a useful tool in the follow-up of patients who achieve remissions after H pylori eradication.
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PMID:Molecular diagnostics in low-grade gastric marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type after Helicobacter pylori eradication therapy. 1170 50

The EORTC Children Leukemia Group (CLG) is part of the offspring of the EORTC Hemopathies Working Party which in 1978 split into a paediatric and to an 'adult' branch. At that time, the Berlin-Frankfurt-Munster (BFM) designed by H. Riehm for acute lymphoblastic leukaemia (ALL) appeared much more efficacious than all others and the CLG decided to adapt that treatment strategy for its own clinical trials. The main results of these may be summarised as follows:for standard risk patients, the deletion of cyclophosphamide from consolidation and reconsolidation courses does not jeopardise the patient's outcomefor medium- and high-risk patients receiving high-dose methotrexate (MTX), cranial radiotherapy is superfluouswith the dose scheduling of the BFM regimen, E-Coli L-Asparaginase is more efficacious than Erwinia L-Asparaginasethe addition of monthly intravenous (i.v.) 6-mercaptopurine to conventional maintenance chemotherapy is detrimentalthe assessment by quantitative polymerase chain reaction (PCR) of minimal residual disease at completion of induction is feasible in a cooperative setting and can be used as a powerful and independent prognostic factor. The CLG also conducted clinical studies of acute myeloblastic leukaemia. Since 1989, lymphoblastic non-Hodgkin's lymphomas have been treated within the ALL trials. The CLG collaborates with other Groups within the I-BFM Study Group and participants in the meta-analytic studies conducted by the Oxford team by the Oxford Children ALL Collaborative Group.
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PMID:The Children Leukemia Group: 30 years of research and achievements. 1185 64

Non-Hodgkin's lymphomas are highly sensitive to treatment and complete clinical responses are often achieved. However, disease recurrence is common and is caused by the persistence of malignant lymphoma cells at a level below the limits of detection by conventional assessment such as clinical examination, bone marrow morphology and CT scans. This minimal residual disease can be detected using molecular techniques such as the polymerase chain reaction (PCR), and treatments capable of eliminating minimal residual disease are described as producing molecular remission. Molecular assessment is now commonly used as a measure of outcome in clinical trials of novel therapies for the treatment of lymphoma. The evidence for using molecular remission as a surrogate marker of clinical response in this setting is reviewed and the significance of minimal residual disease in determining prognosis and planning treatment strategies is addressed.
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PMID:Molecular remission and non-Hodgkin's lymphoma. 1246 5

A feasibility study was undertaken to identify patient-specific primers (PSPs) from childhood non-Hodgkin lymphoma (NHL) specimens to detect minimal residual disease (MRD). Eleven tumor specimens were amplified using immunoglobulin heavy chain and T-cell receptor primers to identify PSPs, which were then used to evaluate staging/follow-up specimens. Disease was detected in 19 of 21 staging and 16 of 17 follow-up specimens. Among seven patients in remission by 1 month, PSPs identified MRD in follow-up specimens. This study demonstrated the feasibility of PSPs to identify disease in staging and follow-up specimens, which could be used to develop strategies for MRD analysis in a larger setting.
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PMID:Assessment of minimal residual disease in childhood non-hodgkin lymphoma by polymerase chain reaction using patient-specific primers. 1257 60

A real-time quantitative-polymerase chain reaction (RQ-PCR) targeting the immunoglobulin heavy chain (IgH) gene has been used for the quantification of minimal residual disease (MRD) in B-cell hematological malignancies. In non-Hodgkin lymphoma (NHL), experimental costs are increased, as a large number of primer-probe sets are required because of diversity, due to somatic and ongoing mutations of the IgH gene. We developed an allele-specific oligonucleotide (ASO) combined with a germline consensus probe-based RQ-PCR assay and examined MRD in peripheral blood stem cells (PBSC). The IgH consensus probes were adapted in seven (50%) of 14 amplifiable cases. Patients with heavily contaminating tumor cells in PBSC relapsed after PBSC transplantation. Our strategy will contribute to the development of a cost-efficient, precisely quantitative and systemic detection assay for MRD in NHL.
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PMID:Quantitative assessment of contaminating tumor cells in autologous peripheral blood stem cells of B-cell non-Hodgkin lymphomas using immunoglobulin heavy chain gene allele-specific oligonucleotide real-time quantitative-polymerase chain reaction. 1286 13

Treatment of malignant non-Hodgkin lymphomas (NHL) in the 21st century has been revolutionized by novel biological agents offering targeted approaches in addition to radio-chemotherapy. Monoclonal antibodies (MoAbs) against lymphatic surface antigens have been effective as monotherapeutic agents, and have already shown their superiority to conventional strategies when combined with chemotherapy. Radioimmunoconjugates are more effective than unlabelled antibodies. Specific inhibitors of neoangiogenesis as well as intracellular signal transduction pathways and antiapoptotic mechanisms have shown their efficacy in phase II studies. Long-term improvement in the setting of minimal residual disease has been observed after vaccination against surface antigens and non-myeloablative allogeneic stem cell transplantation is effective in controlling lymphoma growth. Novel specific antigens are currently identified using expression profiling of lymphomas. In the near future, combinations of biological agents will challenge conventional therapy. These exciting new strategies will improve the success rate in aggressive NHLs and may even challenge the paradigm of incurability of indolent lymphomas.
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PMID:Innovative strategies in lymphoma therapy. 1367 64

We have examined 72 patients with B-cell non-Hodgkin lymphoma (B-NHL) in order to search for consensus sequences of the immunoglobulin heavy chain (IgH) gene, and developed consensus fluorogenically labeled probes for use in an allele-specific oligonucleotide (ASO) real-time quantitative polymerase chain reaction (RQ-PCR) assay of minimal residual disease (MRD). We detected a clonal IgH variable region (VH) sequence in 51 (70.8%) of the 72 B-NHLs, the most frequent VH gene usages being VH3 and VH4 (45/51, 88.2%). It was possible to design three consensus fluorogenic probes for the VH3 gene and one for the VH4 gene avoiding these hypermutations. Our sequencing results suggested that consensus fluorogenic probes would be best based on the 5'-side of the framework region 3 (FR3) because the frequency of somatic hypermutations was significantly lower in the regions on which the probes were based than in the remaining parts of FR3 (P < 0.05). Nineteen (54.3%) of 35 B-NHLs with the VH3 gene and 5 (50%) of 10 with the VH4 gene had sequences identical to at least one of these probes. We found that probes containing one base substitution were still applicable for a MRD study, whereas those containing two or more were not. Therefore, our four probes were applicable for 37 (82.2%) of the 45 patients with VH3 or VH4. This limited number of probes makes a large-scale study of MRD in B-NHL more feasible.
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PMID:Development of consensus fluorogenically labeled probes of the immunoglobulin heavy-chain gene for detecting minimal residual disease in B-cell non-Hodgkin lymphomas. 1455 61

CD86 and CD80 costimulatory antigens are highly overexpressed on Hodgkin/Reed-Sternberg cells in patients with Hodgkin's disease (HD) and are candidate target antigens for immunotoxins in order to eliminate minimal residual disease. In this study we have evaluated the pharmacokinetics (and immunological) toxicity in rhesus monkeys of immunotoxins consisting of gelonin conjugated to anti-CD86 (alphaCD86-IT). Both alphaCD86-IT and alphaCD80-IT inhibited protein synthesis in B cell lines from rhesus monkeys and inhibited the mixed leukocyte reaction. Reactivity of the alphaCD86 antibody with rhesus monkey CD86 (RhCD86) was shown by cloning and transfecting RhCD86, which conferred reactivity of the alphaCD86 antibody used in this study. alphaCD86-IT was administered as single intravenous bolus injection in four rhesus monkeys, and achieved plasma concentration in 50-fold excess able to eliminate cultured Hodgkin/Reed-Sternberg cells up to 6 h. The animals were capable of generating primary immune responses to both gelonin and murine IgG within 9 days after infusion with alphaCD86-IT. No evidence could be found of significant (immunological) toxicity. The results of this study show that alphaCD86-IT can be applied safely in an effective dose.
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PMID:Preclinical evaluation of anti-CD86 immunotoxin in rhesus monkeys: analysis of systemic toxicity, pharmacokinetics, and effect on primary T-cell responses. 1462 29


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