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)

In diffuse large B-cell lymphoma (DLBCL), previous studies have suggested that, while concordant bone marrow (BM) involvement confers a poor prognosis, discordant BM involvement does not. Whether this correlation is independent of the non-Hodgkin lymphoma International Prognostic Index (IPI) was previously unknown. We reviewed all DLBCL case histories from 1986 to 1997 at our center with complete staging, IPI data, and follow-up. A total of 55 (11.2%) of 489 patients had BM involvement, including 29 with concordant involvement and 26 with discordant involvement. The 55 patients with BM involvement had a poor prognosis compared with the uninvolved BM group (5-year overall survival [OS], 34.5% versus 46.9%; log-rank P = .019). However, concordant involvement portended a very poor prognosis (5-year OS, 10.3%; P < .001), whereas discordant involvement did not (5-year OS, 61.5%, P value nonsignificant). Compared with the discordant subset, the concordant subset patients were older, had a higher serum lactate dehydrogenase level, and a significantly higher IPI. However, the poor survival associated with concordant BM involvement was independent of the IPI score (P = .002, Cox regression). We conclude that in patients with DLBCL, concordant but not discordant BM involvement confers a very poor clinical outcome. Furthermore, concordant BM involvement is an independent adverse prognostic factor.
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PMID:Concordant but not discordant bone marrow involvement in diffuse large B-cell lymphoma predicts a poor clinical outcome independent of the International Prognostic Index. 1747 10

We report our experience with high-dose chemotherapy (HDC) and autologous SCT (ASCT) in 66 patients with primary refractory Hodgkin's lymphoma (PR-HL) who received salvage chemotherapy followed by BEAM as HDC. Median age at ASCT was 23 years. Before salvage chemotherapy, stages I:II:III:IV were 2:21:14:29, bulky disease 27%, involvement of mediastinum 79%, spleen 26% and extranodal site 47%, 92% had ESHAP as salvage. Post-ASCT evaluation showed response in 50 patients (76%); complete response (CR) 37 (56%), partial response 14 (21%), no response or stable disease 3 (5%) and progressive disease in 10 (15%). Another five patients achieved CR after radiation therapy and one after surgery, making total CR 43 (65%). From diagnosis and HDC, median follow-up is 38.5 and 22.8 months and median overall survival (OS) 78 and 57 months, respectively. Event-free survival (EFS) and OS are 36 and 64%, respectively. In all, 47% patients are in CR. Twenty-two patients (33%) died due to disease. Multivariate analysis showed elevated lactate dehydrogenase (LDH) for EFS (P=0.041) and mediastinal involvement for OS (P=0.038) as negative prognostic factors. In conclusion, EFS and OS are only 36 and 64%, respectively. Elevated LDH and mediastinal involvement are poor prognostic factors.
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PMID:Primary refractory Hodgkin's lymphoma: outcome after high-dose chemotherapy and autologous SCT and impact of various prognostic factors on overall and event-free survival. A single institution result of 66 patients. 1766 Aug 37

Non-Hodgkin's lymphomas are malignant lymphoproliferative disorders that originate from B or T-lymphocytes and rarely from NK cells. They represent an extremely heterogeneous group of diseases regarding histologic subtypes, clinical presentations, immunophenotypic profiles, cytogenetic and molecular features and suitable mode of treatment. A clinical indicator of prognosis, the International Prognostic Index, takes into account factors that are mostly linked to patient characteristics (age, performance status) and to disease extension and growth (disease stage, s.lactate dehydrogenase level and extent of extranodal involvement). However, it is clear that differences in clinical features and in treatment responses are a result of the marked genetic, immunophenotypic and molecular heterogeneity that underlie disease aggressiveness and tumour progresssion. We applied IPI (based on pretreatment clinical characteristics) in our group of 136 patients that identified a subgroup of clinical features that remained independently significant in multivariate analyses. In our results IPI turned out to be of prognostic significance for response rate and survival percentages. Based on their number of "poor risk" factors, patients were placed into four IPI risk groups: low (one or no risk factors), low-intermediate (two risk factors), intermediate-high (three risk factors), and high (four or five risk factors) with five years survival rates of 88%; 82%; 18% and 0% respectively. However, one limitation of this prediction strategy is that IPI does not encompass molecular abnormalities of tumour cells, which may play a critical role in determining profoundly different clinical outcomes in patients within the same group as defined by IPI. The aim of this study was to assess the clinical significance and potential prognostic value of the expression of the new immunologic prognostic markers including nuclear proliferating antigen, suppressor and oncogenic proteins, HLA-DR surface antigens, tumour infiltrating T-lymphocytes, lymphocyte homing receptor and angiogenic molecules. Immunohistochemistry was used to examine paraffin-embedded tumour tissues for determining the expression of immunologic prognostic markers. Survival analysis showed that serum-high lactate dehydrogenase level, poor performance status (ECOG 3, 4 and 5), high proliferative activity defined as nuclear Ki67 expression greater than 60% of malignant cells and high tumour invasive potential defined by discontinued or loss of Collagen IV were found as strong predictors of poor survival among these patients. These four prognostic parameters determined the New-PI with three risk groups: good (0-1 risk factors), intermediate (2 risk factors) and poor (3 and more risk factors), with predicted five-years survival rates of 88%, 64% and 0%. The New-PI more accurately predicts the outcome than the standard IPI (p < 0,001 vs. p < 0.0001). Based on a single institution series of 136 patients the IPI has proved to be a useful prognostic tool for NHL patients. Addition of new cellular markers into the standard IPI significantly improves risk stratification in NHL.
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PMID:Non-Hodgkin's lymphomas: immunologic prognostic studies. 1792 17

Regulatory T (Treg) cells contribute to immune evasion by malignancies. To investigate their importance in non-Hodgkin lymphoma (NHL), we enumerated Treg cells in peripheral blood mononuclear cells (PBMCs) and involved tissues from 30 patients. CD25(+)FoxP3(+)CD127(low)CD4(+) Treg cells were increased markedly in PBMCs (median = 20.4% CD4 T cells, n = 20) versus healthy controls (median = 3.2%, n = 13, P < .001) regardless of lymphoma subtype, and correlated with disease stage and serum lactate dehydrogenase (R(s) = 0.79, P < .001). T-cell hyporesponsiveness was reversed by depleting CD25(+) cells, or by adding anti-CTLA-4, supporting the view that Treg cells explain the systemic immunosuppression seen in NHL. A high proportion of Treg cells was also present in involved tissues (median = 38.8% CD4 T cells, n = 15) versus reactive nodes (median = 11.6%, n = 2, P = .02). When autologous CD25(-) PBMC fractions were incubated with tumor cells from patients (n = 6) in vitro, there was consistent strong induction and then expansion of cells with the CD4(+)CD25(+)FoxP3(+) phenotype of classic "natural" Treg cells. This population was confirmed to be suppressive in function. Direct cell-cell interaction of tumor cells with CD25(-) PBMCs was important in Treg induction, although there was heterogeneity in the mechanisms responsible. We conclude that NHL cells are powerful inducers of Treg cells, which may represent a new therapeutic target.
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PMID:Local and systemic induction of CD4+CD25+ regulatory T-cell population by non-Hodgkin lymphoma. 1830 20

Allogeneic stem cell transplantation (SCT) with reduced-intensity conditioning (RIC) has the potential to lead to long-term remissions for patients with lymphoma. However, the role of RIC SCT in the treatment of lymphoma is still unclear. Specifically, the relative benefit of RIC SCT across lymphoma histologies and the prognostic factors in this population are incompletely defined. We retrospectively analyzed the outcomes of 87 patients with advanced lymphoma who underwent RIC SCT at the Dana-Farber Cancer Institute over a 6-year period with a homogeneous conditioning regimen consisting of fludarabine and low-dose busulfan. Thirty-six patients had Hodgkin disease (HD) and 51 had non-Hodgkin lymphoma (NHL). Sixty-eight percent had undergone prior autologous transplantation. The 1-year cumulative incidence of nonrelapse mortality was 13%, and the 3-year cumulative incidence of progression was 49%. The incidence of grade 3-4 acute GVHD was 11%. The 2-year cumulative incidence of chronic GVHD was 68%, and its development was associated with a decreased risk of progression and an improved progression-free survival (PFS). Three-year overall survival (OS) was 56% for patients with HD, 81% for indolent NHL, 42% for aggressive NHL, and 40% for mantle cell lymphoma. The corresponding figures for 3-year PFS were 22%, 59%, 22%, and 30%, respectively. Multivariate analysis identified elevated pretransplantation lactate dehydrogenase (LDH) as an adverse factor for PFS, while indolent NHL histology was favorable. For OS, advanced age and elevated pretransplantation LDH were adverse factors, whereas indolent NHL histology was favorable. Low early donor chimerism was not predictive of poor outcome in univariate or multivariate analyses. Moreover, progression was not associated with loss of chimerism. These results emphasize the importance of lymphoma histology for patients undergoing RIC SCT, as well as the lack of relevance of donor chimerism for outcome in this patient population.
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PMID:Allogeneic transplantation with reduced-intensity conditioning for Hodgkin and non-Hodgkin lymphoma: importance of histology for outcome. 1834 84

Autoimmune haemolytic anaemia (AIHA) is an immune disorder caused by antibodies directed against unmodified autologous red cells. The disorder may be a primary (idiopathic) or a secondary disease. The diagnosis is based on the presence of anaemia, signs of haemolysis with reticulocytosis, low haptoglobin, increased lactate dehydrogenase, elevated indirect bilirubin, and a positive direct antiglobulin test (Coombs test). Sometimes, not all of these typical features are present. Most AIHA are caused by warm antibodies, whereas cold antibodies are less commonly detected. While half of the warm antibody-based AIHA are idiopathic anaemias, almost all cold antibody AIHA are secondary anaemias. Underlying diseases are Non Hodgkin's lymphomas and systemic autoimmune disorders, and less frequently organ transplantation, infections, or solid tumors. Moreover, AIHA is an important complication of treatment with nucleoside analogs. Most patients with AIHA require therapy. In warm antibody AIHA, standard first line therapy are glucocorticosteroids with or without high dose immunoglobulins, whereas splenectomy is considered second-line therapy. Response rates of primary AIHA to corticosteroid therapy are high. After initial remission, the dose should be tapered down slowly and with caution, and in some cases, low-dose maintenance therapy is required. The efficacy of standard therapy is low in secondary AIHA that develops in lymphoma patients, posttransplant patients, or tumor patients. Among other immunosuppressive treatments, rituximab (anti-CD20) appears to be highly effective in patients with warm antibody AIHA refractory to standard therapy. Mycophenolate mofetil is quite effective in AIHA patients with an underlying autoimmune or lymphoproliferative disease. Patients with cold agglutinins are refractory to steroids and splenectomy. Half of these patients may respond to rituximab, although responses usually are short-lived. Sometimes, AIHA that is associated with malignant lymphomas or tumors, disappears after successful anti-lymphoma or anti-tumor therapy.
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PMID:Diagnosis and treatment of autoimmune haemolytic anaemias in adults: a clinical review. 1836 53

Ofatumumab is a unique monoclonal antibody that targets a distinct small loop epitope on the CD20 molecule. Preclinical data show that ofatumumab is active against B-cell lymphoma/chronic lymphocytic leukemia cells with low CD20-antigen density and high expression of complement inhibitory molecules. In a phase 1/2 trial evaluating safety and efficacy of ofatumumab in relapsed or refractory follicular non-Hodgkin lymphoma (FL) grade 1 or 2, 4 dose groups of 10 patients received 4 weekly infusions of 300, 500, 700, or 1000 mg. Patients had a median of 2 prior FL therapies and 13% had elevated lactate dehydrogenase. No safety concerns or maximum tolerated dose was identified. A total of 274 adverse events were reported; 190 were judged related to ofatumumab, most occurring on the first infusion day with Common Terminology Criteria grade 1 or 2. Eight related events were grade 3. Treatment caused immediate and profound B-cell depletion, and 65% of patients reverted to negative BCL2 status. Clinical response rates ranged from 20% to 63%. Median time to progression for all patients/responders was 8.8/32.6 months, and median duration of response was 29.9 months at a median/maximum follow-up of 9.2/38.6 months. Ofatumumab is currently being evaluated in patients with rituximab-refractory FL. This trial was registered at www.clinicaltrials.gov as #NCT00092274.
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PMID:First clinical use of ofatumumab, a novel fully human anti-CD20 monoclonal antibody in relapsed or refractory follicular lymphoma: results of a phase 1/2 trial. 1877 7

Richter syndrome describes the development of high-grade non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Richter transformation occurs in 3.3 to 10.6% of patients with CLL. The large cell lymphoma clone occurs by transformation of the original CLL clone in the majority of patients, and as a separate and independent neoplasm in fewer cases. Richter transformation may be triggered by viral infections, such as Epstein-Barr virus infection, which are common in immunosuppressed patients. Trisomy 12 and chromosome 11 abnormalities, as well as multiple genetic defects, have been described in patients with Richter syndrome. These abnormalities may cause CLL cells to proliferate and, by facilitating the acquisition of new genetic abnormalities, to transform into Richter syndrome cells. Presenting features typically include a rapid clinical deterioration with fever in the absence of infection, progressive lymph node enlargement, and an elevation in serum lactate dehydrogenase. Extranodal Richter syndrome has also been reported to occur in the central nervous system, eye, gastrointestinal system, nose, skin, face, bone and bronchus. The therapeutic options include cytoreductive therapy consisting of chemotherapy and immunotherapy, followed by allogeneic stem cell transplantation as postremission therapy.
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PMID:Richter syndrome: a review of clinical, ocular, neurological and other manifestations. 1901 18

The recurrence of non-Hodgkin lymphoma (NHL) in the central nervous system (CNS) is rapidly fatal in most cases. Highly aggressive lymphomas, such as lymphoblastic and Burkitt lymphomas, carry a high risk of CNS relapse. CNS relapse in intermediately aggressive subtypes, such as diffuse large B-cell lymphoma, is uncommon, but not rare. The risk of CNS relapse in indolent lymphomas is low. Prognostic markers of CNS relapse include elevated serum lactate dehydrogenase levels, the presence of B symptoms, and extranodal involvement at more than one site. Most centers give prophylactic CNS chemotherapy to patients considered at high risk of CNS recurrence. However, definitions of risk factors vary, and there is a lack of consensus regarding prophylaxis indications. More research is needed to define which patients might benefit from CNS prophylaxis at initial treatment and to find the optimal regimen for prophylaxis. A variety of treatments have been used to treat CNS relapse, but current regimens have had little success in extending survival after CNS relapse. Although long-term survival has been reported in a minority of patients with isolated CNS recurrence after treatment with methotrexate, more effective regimens are needed if survival times after relapse are to be prolonged.
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PMID:Secondary lymphomas of the central nervous system: risk, prophylaxis and treatment. 1882 33

The expression of lactate dehydrogenase 5 (LDH5), the major LDH isoenzyme sustaining the anaerobic transformation glycolysis was examined in B-cell non-Hodgkin lymphomas. Multi-tissue slides obtained from patients with diffuse large B-cell lymphomas (DLBCL; 95 cases), follicular lymphomas (FL; 49 cases) and from non-neoplastic lymph nodes (48 cases) were used for immuhistochemical analysis. High LDH5 expression (cytoplasmic and nuclear) was noted in 79/95 and 29/49 cases of DLBCL and FL, respectively (p = 0.002). No expression was noted in non-neoplastic lymphocytes. In DLBCL, LDH5 expression was significantly related to hypoxia inducible factor HIF1alpha, HIF2alpha, vascular endothelial growth factor (VEGF) and phosphorylated vascular endothelial growth factor receptor 2 (VEGFR2/KDR) expression. In FL, however, a significant relation was confirmed with pVEGFR2/KDR and HIF2alpha. FL cases with the highest microvessel density were those, which lacked both LDH5 and VEGF expression. It is concluded that LDH5 is highly upregulated in B-cell non-Hodgkin lymphomas and is in direct relation to HIFs expression. LDH5 expression is linked with activated VEGFR2/KDR expression in both lymphoid lesions.
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PMID:Lactate dehydrogenase 5 expression in non-Hodgkin B-cell lymphomas is associated with hypoxia regulated proteins. 1902 Oct 62


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