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)

Nonmyeloablative allogeneic stem cell transplantation (NMASCT) can be used to exploit the graft-versus-tumor (GVT) potential of allogeneic donor cells in the setting of reduced conditioning regimen toxicity. This approach is particularly attractive for patients who have received extensive prior therapy and are poor candidates for traditional allogeneic stem cell transplantation. However, toxicity in heavily pretreated patients remains uncertain. Additional immunosuppression in already immunocompromised patients may result in unexpected toxicity. We report a case of probable progressive multifocal leukoencephalopathy (PML) responsive to interleukin-2 (IL-2) following a NMASCT in a 29-year-old woman with relapsed Hodgkin's lymphoma. The patient developed severe neurological symptoms approximately 6 weeks following NMASCT associated with low CD4+ cell counts and magnetic resonance imaging (MRI) was consistent with PML. IL-2 therapy resulted in increasing CD4+ counts and progressive resolution of neurological symptoms. Disruption of IL-2 therapy led to neurological deterioration, which responded to reinstitution of IL-2 therapy. The patient's lymphoma initially progressed following NMASCT, but has responded to donor leukocyte infusions (DLI). This case reiterates the potent GVT potential of NMASCT in patients with Hodgkin's disease. However, it demonstrates the potential for severe complications related to immunosuppression, especially in heavily pretreated patients. The toxicity after NMASCT should not be understated and will need to be explored further.
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PMID:Nonmyeloablative allogeneic stem cell transplantation for refractory Hodgkin's lymphoma complicated by interleukin-2 responsive progressive multifocal leukoencephalopathy. 1218 17

DAB(389)IL-2 (ONTAK) is a fusion protein consisting of the ADP-ribosyltransferase and membrane translocating domains of native diphtheria toxin and the full-length sequence for interleukin-2 (IL-2) gene. In vitro data demonstrates that DAB(389)IL-2 is cytotoxic to cells expressing the high affinity IL-2 receptor (IL-2R). In Phases I and II clinical trials of patients whose tumor cells express a component of the IL-2R, the response rates were 18% for B-cell non-Hodgkin lymphoma (NHL) and 30% for cutaneous T-cell lymphoma (CTCL). In this study, we examined the effects of arginine butyrate on IL-2R expression and susceptibility of leukemia cells to intoxication by DAB(389)IL-2. We demonstrate that the p75 subunit of the IL-2R (IL-2Rbeta) is upregulated in the presence of low concentrations of arginine butyrate (0.06mM) which had no direct growth inhibitory effect on the cells. To explore mechanisms of this upregulation, we examined the effect of 0.06mM arginine butyrate on relevant transcriptional elements and on histone deacetylase and found activation of cAMP response element (CRE) but not NFAT or NFKB, as well as inhibition of histone deacetylase (HDAC). Our results suggest that the effects of physiologically achievable concentrations of butyrate on IL-2R expression could be exploited to enhance the susceptibility of intermediate and low-affinity IL-2R expressing leukemia cells to DAB(389)IL-2.
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PMID:Arginine butyrate increases the cytotoxicity of DAB(389)IL-2 in leukemia and lymphoma cells by upregulation of IL-2Rbeta gene. 1244 77

The pathogenesis of Hodgkin's disease (HD) is associated with the accumulation of functionally anergic T cells in the near vicinity of the malignant Hodgkin/Reed-Sternberg (H/RS) cell. To stimulate locally the anti-tumour immunity in Hodgkin's disease, we generated an anti-CD30-antibody-interleukin-2 fusion protein (HRS3-scFv-Fc-IL-2) that binds to CD30 constitutively expressed on H/RS cells. The fusion protein is composed of a CD30 binding domain (HRS3-scFv) that is linked via the human IgG hinge-CH2/CH3 domain to human IL-2. The HRS3-scFv-Fc-IL-2 fusion protein is expressed as a 140 kDa homodimer, has binding specificities to both the CD30 antigen and the IL-2 receptor and stimulates proliferation of preactivated T cells in vitro, demonstrating its IL-2 bioactivity. After binding to CD30+ Hodgkin lymphoma cells, HRS3-scFv-Fc-IL-2 moreover induces resting NK cells, but not T cells, to lyse the lymphoma cells with high efficiency. Recruitment of resting NK cells towards a cytolytic immune response against CD30+ lymphoma cells has the potential to build up an effective anti-tumour response despite of Hodgkin's disease associated T-cell anergy and makes the HRS3-scFv-Fc-IL-2 fusion protein suitable for the specific immunotherapy of Hodgkin's lymphoma.
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PMID:Anti-CD30-scFv-Fc-IL-2 antibody-cytokine fusion protein that induces resting NK cells to highly efficient cytolysis of Hodgkin's lymphoma derived tumour cells. 1509 4

Viral hepatitis is a common and important problem in immunocompromised cancer patients. The present study was conducted to investigate changes in some cellular and humoral immunological parameters as a consequence of HCV infection in non Hodgkin's lymphoma patients (NHL). The study included 40 NHL patients: 20 anti-HCV antibody positive (Gr. I ), and 20 anti-HCV antibody negative (Gr.II ). In addition, forty non-cancer controls (NCCs) were included: 20 of them were anti-HCV antibody positive (Gr. III) and 20 anti-HCV antibody negative (Gr. IV). The studied immunological parameters included serum levels of interleukin-1 (IL-1), interleukin-2 (IL-2), interleukin-6 (IL-6), and soluble tumor necrosis factor receptors (s-TNFr) measured by ELISA, as well as assessment of T and B lymphocyte subsets by PAP immunostaining method. Mean IL-1 level (pg/ml) was significantly higher in Gr. 1 (14 +/- 6) and Gr. III (20 +/- 12) as compared to those in Gr. II (7 +/- 5) and Gr. IV (9 +/- 6). Mean IL-2 level (pg/ml) was also significantly higher in Gr. I (132 +/- 101) and Gr. III (135 +/- 59) compared to those in Gr. II (36 +/- 29) and Gr. IV (31 +/- 48). On the other hand, level of IL-6 showed no significant difference between groups. The mean level of sTNF-r, (ng/ml) was only significantly higher in Gr. I (2.9 +/- 1.7) when compared to that in Gr. IV (1.9 +/- 2.2). In group IV, the average percentage of CD3 (70 +/- 4%) and CD4 (44 +/- 5%) were significantly higher than in those of Gr. I (CD3 = 51 +/- 11%, CD4 = 30 +/- 12%), Gr. II (CD3 = 52 +/- 7%, CD4 = 30 +/- 8%), and Gr. III (CD3 = 52 +/- 9%, CD4 = 26 +/- 8%). From all the above immunological and virological features two main tips could be inferred: (1) HCV leads a mild course of infection in NCCs evidenced by normal ALT level in all but 20% of subjects, normal IL-6, sTNF-r, lower counts of CD4+ T cells and hence a mild hepatocellular injury, and (2) In the immunocompromised NHL patients the virus leads potentially more aggressive course as evidenced by higher viremia, as well as significant elevation in sTNF-r, and CD8+ depression.
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PMID:Hepatitis C Virus and related changes in immunological parameters in non Hodgkin's lymphoma patients. 1572 87

Although autologous stem cell transplantation for Hodgkin's disease and non-Hodgkin's lymphoma has become a safe and effective therapy, relapses after transplant are common. Emerging data indicate that an increasing number of patients can be re-induced into durable complete remission. Conventional dose- salvage chemotherapy and single-agent monoclonal antibody treatment provided limited success, but combination chemotherapy-monoclonal antibody treatments, second autografts, and reduced-intensity conditioning allografts provide encouraging results. For some patients, the best strategy may consist of participation in phase I to II studies of novel agents. New strategies designed to prevent relapse after autograft include cytokine therapy such as interleukin-2 in combination with monoclonal antibodies and the use of autologous antilymphoma vaccines.
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PMID:Therapeutic options for patients with Hodgkin's disease and non-Hodgkin's lymphoma who relapse after autologous transplant. 1596 81

Infection with the human immunodeficiency virus (HIV) is associated with an increased risk of systemic non-Hodgkin's lymphoma, Hodgkin's disease, and primary central nervous system lymphoma (PCNSL). Systemic lymphoma usually involves extranodal sites (80%-90%) and is usually of intermediate-grade (diffuse large-cell or immunoblastic( or high-grade (diffuse small noncleaved) histology. Approximately one third to one half of patients are cured with the cytotoxic treatment regimens that are used in immunocompetent patients with lymphoma. Careful attention must be paid to appropriate treatment of HIV infection and to primary and secondary infection prophylaxis. Colony-stimulating factors are commonly used in conjunction with cytotoxic therapy because of the high risk of febrile neutropenia. Patients with HIV-associated Hodgkin's disease also frequently have extranodal involvement and mixed cellularity histology, features associated with an adverse prognosis in immunocompetent patients. Treatment regimens used to treat Hodgkin's disease in immunocompetent patients have been used with some success, although the prognosis is not favorable in HIV-infected patients with PCNSL is generally poor because such patients typically present with advanced immunodeficiency (CD4 <50/microL), and the lymphoma often relapses after transient initial response to whole brain irradiation. There are anecdotal reports of responses to therapy directed against Epstein-Barr virus (ie, high-dose zidovudine, gancyclovir, and interleukin-2).
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PMID:Human immunodeficiency virus-associated lymphoma. 1622 26

Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of non-Hodgkin's lymphomas that manifest primarily in the skin. Mycosis fungoides is recognized as the most common type of CTCL. Patients with early-stage CTCL usually have a benign and chronic disease course. However, although there is a wide array of therapeutic options for early-stage CTCL, not all patients respond to these individual therapies, resulting in refractory cutaneous disease over time. Refractory early-stage CTCL poses an important therapeutic challenge, as one of the principal treatment goals is to keep the disease confined to the skin, thereby preventing disease progression. Much of the focus of current research has been on the evaluation of already available skin-directed therapies and biologic response modifiers and combination regimens thereof, such as the combination of psoralen and UVA (PUVA) with interferon-alpha or retinoids. Recent novel developments include oral bexarotene, a retinoid X receptor-selective retinoid that has activity in all stages of CTCL and has been shown to be effective in patients with refractory early-stage disease as well as advanced-stage disease. Likewise, the topical gel formulation of bexarotene has proved to be an important therapeutic option in patients with refractory or relapsed lesions. Oral bexarotene and topical bexarotene have been approved by the US FDA for the treatment of refractory CTCL. Systemic chemotherapy is typically reserved for advanced-stage CTCL and is usually not recommended for early-stage, skin-limited disease. However, recent exploratory studies indicate that low-dose methotrexate may represent an overall well tolerated therapy in a subset of patients with refractory early-stage CTCL, as may pegylated liposomal doxorubicin, which is currently being investigated in this specific clinical setting. Another recently FDA-approved therapy is the interleukin-2 fusion toxin denileukin diftitox, which is now well established to play a role in the treatment of refractory CTCL, including early-stage extensive plaque disease. The value of other agents, such as topical tazarotene, topical methotrexate, and topical imiquimod, and of novel immunomodulatory approaches including monoclonal antibodies, still needs to be assessed for refractory early-stage CTCL.
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PMID:Management of refractory early-stage cutaneous T-cell lymphoma. 1673 3

Recombinant interleukin-2 (rIL-2) is a pleiotropic cytokine that activates select immune effector cell responses associated with antitumor activity, including antibody-dependent cellular cytotoxicity (ADCC). Rituximab is an anti-CD20 monoclonal antibody that activates ADCC in non-Hodgkin lymphoma (NHL). The ability of rIL-2 to augment rituximab-dependent tumor responses was investigated. The efficacy of rIL-2 in combination with rituximab was evaluated in 2 NHL tumor xenograft models: the CD20hi, rituximab-sensitive, low-grade Daudi model and the CD20lo, aggressive, rituximab-resistant Namalwa model. Combination of rIL-2 plus rituximab was synergistic in a rituximab-sensitive Daudi tumor model, as evidenced by significant tumor regressions and increased time to tumor progression, compared with rIL-2 and rituximab single agents. In contrast, rituximab-resistant Namalwa tumors were responsive to single-agent rIL-2 and showed an increased response when combined with rituximab. Using in vitro killing assays, rIL-2 was shown to enhance activity of rituximab by activating ADCC and lymphokine-activated killer activity. Additionally, the activity of rIL-2 plus rituximab F(ab')2 was similar to that of rIL-2 alone, indicating a critical role for immunoglobulin G1 Fc-FcgammaR-effector responses in mediating ADCC. Antiproliferative and apoptotic tumor responses, along with an influx of immune effector cells, were observed by immunohistochemistry. Collectively, the data suggest that rIL-2 mediates potent tumoricidal activity against NHL tumors, in part, through activation and trafficking of monocytes and natural killer cells to tumors. These data support the mechanistic and therapeutic rationale for combination of rIL-2 with rituximab in NHL clinical trials and for single-agent rIL-2 in rituximab-resistant NHL patients.
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PMID:Recombinant interleukin-2 significantly augments activity of rituximab in human tumor xenograft models of B-cell non-Hodgkin lymphoma. 1719 84

This phase II study evaluated the safety and efficacy of denileukin diftitox, an interleukin-2-diphtheria toxin fusion protein, in relapsed/refractory T-cell non-Hodgkin lymphoma (T-NHL), excluding cutaneous T-cell lymphoma. Eligible patients received denileukin diftitox 18 microg/kg/d x 5 d every 3 weeks for up to eight cycles. Tumour staging was performed every two cycles and the primary endpoint was the objective response rate [complete response (CR) + partial response (PR)]. For 27 patients enrolled, median age: 55 years (range 26-80 years), 70.4% male, and mean prior therapies: 2.5 (range 1-6). Objective responses (six CRs, seven PRs) were achieved in 13 patients (48.1%), stable disease in eight (29.6%) and six (22.2%) had progressive disease. An objective response was achieved in eight of 13 patients (61.5%) with CD25(+) tumours (four CR/four PR) and five of 11 patients (45.5%) with CD25(-) tumours (two CR/three PR). Median progression-free survival was 6 months (range, 1-38+ months). Most adverse reactions were grade 1/2 and transient. No grade 4-5 toxicities were reported. Denileukin diftitox had significant activity and was well tolerated in relapsed/refractory T-NHL, with responses observed in both CD25(+) and CD25(-) tumours. Further studies of denileukin diftitox in combination with other agents are warranted in previously untreated and relapsed/refractory T-NHL.
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PMID:Phase II trial of denileukin diftitox for relapsed/refractory T-cell non-Hodgkin lymphoma. 1723 46

Membrane-bound and soluble human leucocyte antigen-G (sHLA-G) molecules display immunotolerant properties favouring tumour cell escape from immune surveillance. sHLA-G molecules have been detected in several tumour pathologies; this study aimed to evaluate sHLA-G expression in lymphoproliferative disorders. sHLA-G plasma level was significantly increased in 110 of 178 newly diagnosed lymphoid proliferations cases i.e. 59% of chronic lymphocytic leukaemia, 65% of B non-Hodgkin lymphomas (NHL) and 58% of T-NHL. To assess the mechanisms involved in this secretion, the differential effect of cytokines was tested in in vitro cultures of NHL cells. A significant induction of sHLA-G level was shown in T-NHL in contrast with B-NHL and normal equivalent cells, after cytokine stimulation with (i) interferongamma (IFNgamma), interleukin-2 (IL-2) and granulocyte-macrophage colony-stimulating factor, (ii) IL-10 and (iii) transforming growth factor beta. An impact of microenvironment on sHLA-G expression was found in B-NHL as shown by the in vitro effect of addition of normal monocytes. Finally, a functional effect of sHLA-G molecules purified from pathologic plasma was demonstrated by their strong capacity to inhibit T-cell proliferation at concentrations currently observed during these disorders. These results suggest that functional sHLA-G molecules are upregulated in lymphoproliferative disorders which can support their potential immunomodulatory role during this pathology.
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PMID:Expression of functional soluble human leucocyte antigen-G molecules in lymphoproliferative disorders. 1759 27


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