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)

Radioimmunotherapy (RIT) treatment for lymphoma is a novel targeted therapeutic approach. Several years of development of radioimmunotherapeutic compounds came to fruition in February of 2002 when the US Food and Drug Administration (FDA) approved yttrium 90 ((90)Y)-ibritumomab tiuxetan ((90)Y-IT) for the treatment of relapsed or refractory, low-grade, or transformed B-cell lymphoma. (90)Y-IT uses a monoclonal anti-CD20 antibody to deliver beta-emitting (90)Y to the malignant B cells. Clinical trials have demonstrated its efficacy, which is largely independent of the intrinsic activity of the anti-CD20 antibody. A similar anti-CD20 radiotherapeutic compound, iodine 131 ((131)I)-tositumomab ((131)I-T), is also under consideration for approval. The advantages of increased efficacy compared to the native antibody are gained at the expense of myelotoxicity, which is dose-limiting but reversible. Other radioimmunoconjugates (RIC), including products for Hodgkin's lymphoma, are in earlier stages of development. Studies exploring expanded applications of RIT are under way. RIT has been shown to be an effective and clinically relevant complementary therapeutic approach for patients with lymphoma.
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PMID:Radioimmunotherapy for non-Hodgkin's lymphoma. 1293 22

In order to increase the availability and affordability of radioimmunotherapy of refractory or relapsed non-Hodgkins lymphoma, we developed and evaluated radioiodinated rituximab in an ongoing physician-sponsored Phase II Clinical Trial. The chimeric 1gG(1) anti CD 20 monoclonal antibody rituximab was radiolabeled with iodine-131 using a modified Chloramine T method with high radiochemical purity (98% +/- 0.82) and preservation of immunoreactivity. All patients received therapeutic loading doses of unlabeled rituximab (375 mg/m(2)) immediately prior to administration of tracer (200 MBq (131)I) or therapy (1.7-4.3 GBq (131)I) activities of (131)I-rituximab to provide additive immunotherapy and enhance tumor uptake of the radiolabeled antibody. Objective response rate (ORR) was 71% in 35 patients with a median follow-up of 14 months (range 4-28 months). Complete remission (CR) was achieved in 54% of patients, with median duration 20 months. Toxicity evaluation included an additional 7 patients followed for at least 3 months. Tracer dosimetry studies were performed in each patient and the whole body radiation absorbed dose was limited to a mean prescribed dose (MPD) of 0.75 Gy. Myelosuppression was reversible and in only 2 of 42 patients was grade IV hematological toxicity observed. No hemopoietic support was required in any patient. There was no instance of hemorrhage or infection in this group of patients in each of whom individual prospective dosimetry was performed prior to (131)I rituximab radioimmunotherapy for relapsed or refractory non-Hodgkins lymphoma.
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PMID:131I-Anti CD20 radioimmunotherapy of relapsed or refractory non-Hodgkins lymphoma: a phase II clinical trial of a nonmyeloablative dose regimen of chimeric rituximab radiolabeled in a hospital. 1450 43

Waldenstrom's macroglobulinemia is an indolent B-cell malignancy that is characterized by high levels of IgM paraprotein production and is incurable with standard chemotherapy. Iodine 131I-Tositumomab (iodine-131-labeled murine anti-CD20 monoclonal antibody; Bexxar) is a novel radioimmunotherapeutic agent that has a high response rate in relapsed or chemotherapy refractory, CD20-positive, low grade or transformed B-cell non-Hodgkin's lymphomas. There are no data on the use of radioimmunotherapy in Waldenstrom's macroglobulinemia. We report a patient with Waldenstrom's macroglobulinemia with transformation to a large B-cell lymphoma, who was treated successfully with iodine 131I-tositumomab. The patient had a complete response to the treatment, including disappearance of any detectable IgM paraprotein. This case report demonstrates the potential for radioimmunotherapy in CD20 positive B-cell malignancies.
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PMID:Use of iodine 131I-tositumomab radioimmunotherapy in a patient with Waldenstrom's macroglobulinemia. 1516 Sep 23

The incidence of treatment-related myelodysplastic syndromes and acute myeloid leukemia (tMDSs/tAML) after tositumomab and iodine I(131) tositumomab administration to previously treated and untreated patients with non-Hodgkin lymphoma (NHL) was evaluated. A total of 1071 patients were enrolled in 7 studies: 995 with relapsed/refractory low-grade NHL, +/- transformation (median, 3 prior regimens [range, 1-13 regimens]) and 76 patients with previously untreated low-grade follicular NHL. A single dose of iodine tositumomab and I(131) tositumomab was administered. For tMDS/tAML patients, baseline and posttherapy peripheral blood and marrow specimens were reviewed in a blinded fashion. Median follow-up was 6 years from diagnosis and 2 years from radioimmunotherapy (RIT) for previously treated patients, and 4.6 years from radioimmunotherapy for previously untreated patients. tMDS/tAML was reported in 35 (3.5%) of 995 patients (annualized incidence, 1.6%/y [95% confidence interval, 1.0%-2.0%/y]), and 52% of the tMDS/tAML diagnoses of tMDS/tAML were confirmed in a blinded review (annualized incidence of 1.1%/y [95% confidence interval, 0.7%-1.6%/y]). Of the 25 cases, 10 patients (40%) were diagnosed with tMDS/tAML prior to receiving radioimmunotherapy; 2 (8%) had no pathologic or clinical evidence to support such a diagnosis; and 13 (52%) were confirmed to have developed tMDS/tAML following RIT. This incidence is consistent with that expected on the basis of patients' prior chemotherapy for NHL. With a median follow-up approaching 5 years, no case of tMDS/tAML has been reported in any of the 76 patients receiving iodine I(131) tositumomab as their initial therapy (P = .011 compared with previously treated patients).
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PMID:Assessment of treatment-related myelodysplastic syndromes and acute myeloid leukemia in patients with non-Hodgkin lymphoma treated with tositumomab and iodine I131 tositumomab. 1573 Nov 77

The CD20 antigen has become a major therapeutic target in the management of follicular and other B cell non-Hodgkin's lymphomas. The murine monoclonal antibody, tositumomab, on binding CD20, is able to induce antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity and apoptosis. In addition, when radioiodinated, the antibody exploits the tumour's sensitivity to ionising radiation by direct targeting of the malignant cell. Tositumomab and Iodine (I(131)) tositumomab (Bexxar, GlaxoSmithKline, Philadelphia, PA, USA) is administered in two steps. The dosimetric step determines individual patient pharmacokinetics, allowing a patient- specific dose to be calculated. This is followed by the therapeutic step, with administration of the therapeutic dose between 7 and 14 days after the dosimetric dose. Over a decade's worth of experience in clinical trials has determined the efficacy and safety of the regimen in a variety of clinical circumstances; establishment of exactly where the regimen fits amongst the algorithm for the management of follicular lymphoma continues.
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PMID:A review of tositumomab and I(131) tositumomab radioimmunotherapy for the treatment of follicular lymphoma. 1593 35

Many new treatment approaches have given promising results in experimental Hodgkin's lymphoma (HL) models. Early clinical trials evaluating antibody based compounds as immunotoxins (ITs), radioimmunotherapy (RIT), bispecific molecules (BSMs), and recently monoclonal antibodies (MAbs), have demonstrated some clinical efficacy in patients with advanced refractory or relapsed HL. In addition, cellular immunotherapy is evolving. Although it seems unlikely to cure chemotherapy resistant patients with larger tumor masses by either of these approaches alone, the combination with conventional chemotherapy might help to overcome resistance of Hodgkin-/ReedSternberg (H-RS) cells. Another rationale for the development of these immunotherapies is to eliminate residual disease and thereby to prevent relapses from the disease. Currently, several clinical studies are running. A murine MAb (Ki-4) based 131 Iodine conjugate has shown efficacy in refractory HL patients in a phase II study, but less toxic constructs using alternate MAbs or isotopes should be developed. A humanized as well as a fully human anti-CD30 MAb are being tested in clinical phase I/II studies. These MAbs could engage the human immune system against the H-RS cells. In addition, these MAbs could be then combined with conventional chemotherapy in order to improve the treatment of HL.
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PMID:Immunotherapy of Hodgkin's lymphoma. 1600 86

Irradiation of nanoabsorbers with pico- and nanosecond laser pulses could result in thermal effects with a spatial confinement of less than 50 nm. Therefore absorbing nanoparticles could be used to create controlled cellular effects. We describe a combination of laser irradiation with nanoparticles, which changes the plasma membrane permeability. We demonstrate that the system enables molecules to penetrate impermeable cell membranes. Laser light at 532 nm is used to irradiate conjugates of colloidal gold, which are delivered by antibodies to the plasma membrane of the Hodgkin's disease cell line L428 and/or the human large-cell anaplastic lymphoma cell line Karpas 299. After irradiation, membrane permeability is evaluated by fluorescence microscopy and flow cytometry using propidium iodide (PI) and fluorescein isothiocyanate (FITC) dextran. The fraction of transiently permeabilized and then resealed cells is affected by the laser parameter, the gold concentration, and the membrane protein of the different cell lines to which the nanoparticles are bound. Furthermore, a dependence on particle size is found for these interactions in the different cell lines. The results suggest that after optimization, this method could be used for gene transfection and gene therapy.
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PMID:Elevation of plasma membrane permeability by laser irradiation of selectively bound nanoparticles. 1640 77

Radioimmunotherapy (RIT) is a new treatment modality that combines the benefits of radiotherapy and immunotherapy. In RIT, a radionuclide is coupled to a monoclonal antibody, directed against an antigen expressed on tumor cells. Recently, RIT has been introduced targeting the CD20 surface antigen, which is expressed on nearly all B-cell non-Hodgkin lymphomas (NHL). Clinical experience with RIT in the treatment of patients with indolent NHL is increasing. To date, two commercially available agents are used: yttrium-90 ((90)Y)-ibritumomab tiuxetan and iodine-131 ((131)I)-tositumomab. In general, there is no organ-specific non-hematologic toxicity when a standard dose of RIT is used. Bone marrow suppression is the dose-limiting RIT toxicity; therefore, bone marrow infiltration by NHL should be investigated before treatment. Treatment-related myelodysplastic syndromes and acute myeloid leukemia after RIT are being investigated but long-term data are needed for final evaluation. Results are quite encouraging with respect to complete remission and overall response, even in pretreated patients with unconjugated monoclonal antibodies. RIT induces high response rates and a significant subgroup of patients has achieved long-term durable responses. RIT is feasible in heavily pretreated patients and does not compromise future treatments in the event of progressive disease. Randomized phase III studies are in progress to evaluate the timing of RIT in the overall management of indolent NHLInvestigations of new emerging therapeutic strategies for patients with indolent NHL are underway, with research into the feasibility of RIT as first-line therapy and in advanced disease, RIT dose escalation and combined modality approaches with autologous stem cell transplantation. The encouraging results of RIT in indolent NHL have initiated studies focusing on its benefit for patients with aggressive NHL.
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PMID:Radioimmunotherapy for indolent B-cell non-Hodgkin lymphoma in relapsed, refractory and transformed disease. 1683 Oct 19

The accident that occurred at the Chernobyl Nuclear Power Plant in 1986, released large quantities of radionuclides--among them radioiodine--into the atmosphere, thereby raising public concerns about its influence on thyroid structure and function, especially the development of malignancy. There were even reports about 700 deaths due to thyroid carcinoma in Russian Federation, Ukraine and Belarus, resulting from the accident. In this review we discussed the incidence of thyroid cancer in different parts of the world, especially in heavily contaminated countries, as Ukraine and Belarus, and the possible link between radioisotope activity in the thyroid and the development of malignancy. The study carried out in Minsk showed 40-fold increase of the incidence of thyroid cancer in the years 1986-1994, in comparison to the period 1977-1985. An increase of the incidence of thyroid cancer has generally been observed in many countries after the Chernobyl accident. We focused on the factors that may have an influence on this phenomenon, especially diagnostic tests, health care, social and environmental factors, like iodine level in water and soil. The results of molecular biology studies, e.g. RET translocation in carcinoma type RET/PTC1 in elderly and RET/PTC3 in children, and expression Ax1 and Gas6 in children were reviewed as well. We also mentioned other thyroid diseases, like nodular goitre, cysts, the disturbance of thyroid function and autoimmunity, possibly linked to the radiation after Chernobyl accident. Data obtained from the regions near Chernobyl showed no increased risk of other types of malignancy (leukaemia, Hodgkin's and non Hodgkin's lymphoma) in 1986-1996. In this article the epidemiology of thyroid diseases in Poland was also reviewed.
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PMID:[The effect of Chernobyl accident on the development of malignant diseases--situation after 20 years]. 1683 89

Studies in radiation oncology are focusing on the optimal use of systemic targeted radionuclide therapy (STaRT) in the treatment of patients with cancer. The two approved radioimmunotherapy agents, yttrium-90 ibritumomab tiuxetan and iodine-131 tositumomab, are being studied in a range of lymphoid malignancies, from low-grade to aggressive B-cell non-Hodgkin's lymphomas. Studies of standard- and escalated-dose radioimmunotherapy with or without stem cell support are reviewed, as are radioimmunotherapy with other therapeutic modalities in these settings. The results of these trials have important implications for clinical practice, and it is hoped that they will further clarify the optimal timing and dosing of these agents.
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PMID:Ongoing investigations and new uses of radioimmunotherapy in the treatment of non-Hodgkin's lymphoma. 1697 35


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