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)

Combination of standard chemotherapy with rituximab led to improved disease control in patients with B cell lymphoma in clinical trials. We wanted to know if a similar benefit could be demonstrated in the routine data of a regional population-based cancer registry. We searched the registry of the Regensburg Tumor Center for B cell non-Hodgkin lymphomas diagnosed between 1998 and 2006 and compared overall survival of patients receiving any first-line chemotherapy with or without rituximab. Comparing registry data to death certificates, an 86% coverage within the registry was estimated. In the aggressive lymphoma group, 133 patients received rituximab-containing chemotherapy resulting in a 5-year survival of 69.6%, whereas 205 patients received chemotherapy alone with a significantly inferior 5-year survival of 56.8%. First-line chemotherapy with rituximab in 81 patients with indolent lymphoma also led to improved 5-year survival compared to 134 patients without rituximab (69.7% vs. 51.8%), primarily observed among patients with follicular lymphoma (84.7% vs. 52.0%). These data confirm the standard use of rituximab as first-line therapy in diffuse large B cell lymphomas as well as in indolent lymphoma. Furthermore, they support the collection of treatment data including detailed information on systemic therapy in cancer registries to be used for outcomes research.
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PMID:Treatment of B cell lymphoma with chemotherapy plus rituximab: a survival benefit can be demonstrated in the routine data of a regional cancer registry. 2220 Sep 72

Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) have traditionally been considered as two distinct entities. However, there are rare reports of patients that, over time, develop both diseases. It remains unresolved whether the origin of the two diseases is from the same clone. In this study, we attempted to retrospectively investigate the clinical and molecular aspects of patients who developed both lymphomas. The rearranged immunoglobulin heavy-chain variable region genes from both diagnoses were compared to each other. Twenty-six patients presented with both diagnoses. Twelve had HL as the primary disorder ("HL first" group) and the majority of these (75%) presented with aggressive lymphoma as the second lymphoma. In contrast, in the 11 patients for whom NHL was the primary disorder ("NHL first" group), this was usually (82%) of low-grade histology. Three patients were diagnosed concurrently with both diseases. Mean age at first diagnosis was higher (p = 0.037) in the NHL first group (56.1 years) than in the HL first group (40 years). Mean time between diagnoses was longer (p = 0.026) in the HL first group (9 years) than in the NHL first group (5 years). For 11 patients, diagnostic samples were available for molecular analyses from both diagnoses of HL and NHL. In 6 of these 11 patients, gene rearrangement studies were informative. No patient had the same gene rearrangement identified in both diseases. It seems that development of HL and NHL in one patient, at different time points, reflects, in many cases, separate biologic diseases.
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PMID:Separate diagnoses of Hodgkin lymphoma and non-Hodgkin lymphoma in an individual patient might not signify a common clonal origin. 2265 85

Mantle cell lymphoma (MCL) is a rare type of non-Hodgkin lymphoma that traditionally has been thought to possess the poor-risk features of both indolent lymphoma, with its incurability, and aggressive lymphoma, with its ability to proliferate rapidly. Although there is considerable debate as to whether MCL can be cured, a number of retrospective studies are beginning to suggest an improvement in overall survival over the past decade, likely coinciding with the introduction of rituximab, more intensive chemotherapy, and the increasing use of autologous stem cell transplant (ASCT) in first remission. At present, intensive induction chemotherapy regimens consistently produce a response rate of >90%, sometimes even 100% in the first-line setting, and consolidation with ASCT in first remission can improve the complete response rate to 90%. The emergence of a more sophisticated understanding of the underlying pathogenesis, coupled with a host of new agents and targets, has again created new opportunities to improve the care of our patients with MCL. Here, we discuss many of these developments and how they may potentially affect the natural history of this disease.
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PMID:New strategies in the treatment of mantle cell lymphoma. 2270 Aug 64

Polycomb group (PcG) proteins are important for the regulation of hematopoiesis by regulating chromatin compaction and silencing genes related to differentiation and cell cycle. Overexpression of enhancer of zeste homologue 2 (Ezh2) and Bmi-1/PCGF4 has been implicated in solid organ cancers, while Mel-18/PCGF2 has been reported as a tumor suppressor. Detailed expression profiles of PcG proteins and their diagnostic significance in malignant lymphomas are still unknown. In this study, we analyzed the expression levels of Ezh2, Bmi-1, Mel-18, and Ki67 in 197 Hodgkin's and non-Hodgkin's lymphoma patient samples and in lymphoma cell lines using immunohistochemistry, fluorescent immunocytochemistry, and Western blotting. Immunohistochemical staining showed that Ezh2 expression was significantly increased in aggressive compared to indolent subtypes of B cell neoplasms (P = 0.000-0.030), while no significant differences in Bmi-1 expression were found between these subtypes. Compared to the normal counterpart, T cell lymphomas showed significant overexpression of Bmi-1 (P = 0.011) and Ezh2 (P = 0.000). The Ki67 labeling index showed a positive correlation with Ezh2 expression in B cell lymphomas (correlation coefficient (Co) = 0.983, P = 0.000) and T/NK cell lymphomas (Co = 0.629, P = 0.000). Fluorescent immunohistochemical staining showed coexpression of Ezh2 and Ki67 in the same tumor cells, indicating that Ezh2 expression correlates with cell proliferation. Both B and T/NK cell neoplasms showed low expression of Mel-18 and high expression of both Bmi-1 and Ezh2. In conclusion, in aggressive lymphoma variants, Ezh2 is strongly expressed and polycomb repressive complex PRC1.4 dominates over PRC1.2. Coexpression of Bmi-1 and Ezh2 is a characteristic of aggressive lymphomas. Ezh2 correlates with the proliferation and aggressive nature of non-Hodgkin's lymphomas.
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PMID:In aggressive variants of non-Hodgkin lymphomas, Ezh2 is strongly expressed and polycomb repressive complex PRC1.4 dominates over PRC1.2. 2394 56

Transformation of chronic lymphocytic leukemia (CLL) to aggressive lymphoma is known as Richter syndrome (RS). In the CLL population considered as a whole, the prevalence of RS development ranges from 2 to 7 %. The most common pathologic phenotype at the time of RS transformation is diffuse large B-cell lymphoma (DLBCL), while, in a small fraction of cases, the transformed phase shows pathologic features mimicking Hodgkin lymphoma. TP53 disruption and MYC activation cooperate as dual hits in driving DLBCL transformation. Two biomarkers (NOTCH1 mutations and usage of the immunoglobulin VH CDR3 subset 8) may help in identifying CLL patients at risk of DLBCL transformation to be considered for close monitoring and a careful biopsy policy. In the presence of clinical features suspicious of RS, diagnosis of transformation and choice of the site of biopsy may take advantage of (18)FDG PET/CT. The prognosis of RS transformation is generally highly unfavorable. However, the pattern of survival is not homogeneous and may be predicted on clinical and biological grounds. RS that are clonally unrelated to the paired CLL phase are biologically and clinically different from clonally related cases, and should be considered, and probably managed, as a de novo DLBCL arising in the context of CLL. Rituximab-containing polychemotherapy represents the backbone for induction treatment in patients with clonally related DLBCL transformation. Younger patients who respond to induction therapy should be offered stem cell transplant to prolong survival.
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PMID:Richter syndrome. 2401 97

The risk of CNS dissemination and CNS prophylaxis strategies in aggressive non-Hodgkin lymphoma (NHL) is still debated. CNS dissemination is a rare but fatal event. A CNS prophylaxis is common for Burkitt and B-cell lymphoblastic lymphoma; however, in other NHLs, prophylactic treatments are not systematically warranted. Current risk models showed low sensitivity in predicting CNS involvement, implying overtreatment in roughly 70% of high-risk patients. Risk models in the rituximab era were modulated for the detection of occult CNS disease at diagnosis using flow cytometry. The optimal regimen for CNS prophylaxis in aggressive lymphoma patients has not been established thus far and should be modulated at different levels of 'intensity' such as standard intrathecal chemotherapy, 'active' intrathecal chemotherapy with liposomal cytarabine or more aggressive systemic treatment with high doses of drugs having good CNS bioavailability reserved for patients who are truly at high risk of CNS dissemination.
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PMID:The risk of CNS involvement in aggressive lymphomas in the rituximab era. 2416 78

APO866 is an inhibitor of nicotinamide adenine dinucleotide (NAD) biosynthesis that exhibits potent anti-lymphoma activity. Rituximab (RTX), an anti-CD20 antibody, kills lymphoma cells by direct apoptosis and antibody- and complement-dependent cell-mediated cytotoxicities, and has clinical efficacy in non-Hodgkin cell lymphomas. In the present study, we evaluated whether RTX could potentiate APO866-induced human B-lymphoma cell death and shed light on death-mediated mechanisms associated with this drug combination. We found that RTX significantly increases APO866-induced death in lymphoma cells from patients and lines. Mechanisms include enhancement of autophagy-mediated cell death, activation of caspase 3 and exacerbation of mitochondrial depolarization, but not increase of reactive oxygen species (ROS) production, when compared with those induced by each drug alone. In vivo, combined administration of APO866 with RTX in a laboratory model of human aggressive lymphoma significantly decreased tumor burden and prolonged survival over single-agent treatment. Our study demonstrates that the combination of RTX and APO866 optimizes B-cell lymphoma apoptosis and therapeutic efficacy over both compounds administered separately.
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PMID:The anti-lymphoma activity of APO866, an inhibitor of nicotinamide adenine dinucleotide biosynthesis, is potentialized when used in combination with anti-CD20 antibody. 2428 53

Due to disease rarity, there is limited information regarding the optimal therapy and outcome for patients with advanced-stage nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). Forty-two patients with NLPHL by the Revised European-American Lymphoma/World Health Organization classification with advanced-stage disease were identified and paired 1:2 with a matched control with classical Hodgkin lymphoma (CHL) matched by age, gender, stage, decade of diagnosis, and treatment received. The median follow-up was 11.3 years (range, 1.9 to 35.5 years) for NLPHL patients and 10.7 years (range, 1.6 to 26.3 years) for CHL patients. The majority received doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD)-like chemotherapy. Although the 10-year overall survival (OS) (P = .579) and HL freedom from treatment failure (HL-FFTF) were similar between NLPHL and CHL patients (75% vs 73%; P = .610), the time to progression (TTP), which also includes the development of secondary aggressive lymphoma, was inferior in NLPHL (10-year, 63% vs 73%; P = .040). Splenic involvement was associated with an inferior 10-year TTP in patients treated with ABVD (48% vs 71%; P = .049) and an increased cumulative incidence of secondary aggressive lymphoma (P = .014) providing a rationale for further evaluation of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with rituximab in NLPHL.
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PMID:Advanced-stage nodular lymphocyte predominant Hodgkin lymphoma compared with classical Hodgkin lymphoma: a matched pair outcome analysis. 2471 29

Recently, bendamustine has become an important agent in the treatment for patients with lymphoid malignancies. Although the drug has received approval for second-line therapy in indolent lymphoma, a growing body of evidence suggests its efficacy and safety in first-line use. The results of randomised and observational studies with bendamustine as front-line therapy in non-Hodgkin lymphoma (NHL) with emphasis on efficacy and toxicity are presented. Furthermore, completed and ongoing clinical trials evaluating upfront bendamustine effectiveness in combination with other agents are discussed. The review refers mainly to indolent lymphoma, mantle cell lymphoma and aggressive lymphoma, as the most commonly diagnosed NHL types. Finally, we elaborated on the safety profile of bendamustine and the perspectives of using the drug as a first-line therapy.
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PMID:Bendamustine-based therapy as first-line treatment for non-Hodgkin lymphoma. 2475 17

Plasmablastic lymphoma (PBL) is a rare B-cell non-Hodgkin lymphoma often associated with Epstein-Barr virus (EBV) infection. To gain insight in this aggressive lymphoma subtype, the clinicopathologic characteristics of 25 unpublished single-center PBLs (2 in acquired immunodeficiency syndrome patients, 11 in immunocompetent individuals [IC-PBL], 12 in transplant recipients [PT-PBL]) and of 277 reported PBLs were summarized. In the reported series, PBL patients were predominantly male (77%) with a median age at diagnosis of 46 years (range, 1.2 to 87 y). The majority of the biopsies (66%) was EBV positive. Extranodal presentation was most frequent (88%, of which 35% were oral, 18% gastrointestinal, 12% cutaneous). PBL was diagnosed in acquired immunodeficiency syndrome patients (50%), immunocompetent individuals (35%), and transplant recipients (14%). These subgroups differed in age at diagnosis (median: 41, 64, 47 y, respectively), primary localization (oral, oral, cutaneous, respectively), EBV positivity (75%, 50%, 67%, respectively), CD45 expression (31%, 33%, 70%, respectively), and C-MYC aberrations (78%, 44%, 38%, respectively). Ann Arbor stage I, EBV positivity, CD45 expression, and lack of C-MYC aberrations were associated with better outcome (P<0.05). Our series of IC-PBL and PT-PBL cases revealed differential expression of CD10 (0% vs. 42%, respectively), CD56 (22% vs. 42%, respectively), TP53 (67% vs. 8%, respectively), and BCL2 (88% vs. 25%, respectively). Gene expression analysis of 5 of our PT-PBLs revealed upregulation of DNMT3B, PTP4A3, and CD320 in EBV-positive PT-PBL and suggested a role for cancer/testis antigens. The results of this retrospective study suggest different pathogenic mechanisms of PBL in different immunologic settings and a potentially important impact of EBV and CD45 on prognosis.
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PMID:Clinicopathologic comparison of plasmablastic lymphoma in HIV-positive, immunocompetent, and posttransplant patients: single-center series of 25 cases and meta-analysis of 277 reported cases. 2483 64


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