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)

The Italian Society of Hematology (SIE) and the two affiliated societies (SIES and GITMO) commissioned a project to develop clinical practice guidelines for the treatment of nodal indolent non-Hodgkin's lymphomas (NHL). Key questions clinically relevant to the management of patients with nodal indolent NHL were formulated by an Advisory Committee and approved by an Expert Panel composed of eight senior hematologists. After a comprehensive, systematic review of the literature, the Expert Panel formulated therapy recommendations and graded them according to the supporting evidence. An explicit approach to consensus methodologies was used for evidence interpretation and for providing recommendations based on poor evidence. The Expert Panel formulated recommendations on when to start a lymphoma-specific therapy, which first-line therapy to choose and which therapy to adopt for patients with relapsed, refractory and transformed disease. Treatment deferral was recommended for patients with stage III-IV disease without systemic symptoms, high tumor burden, extranodal disease, cytopenia due to marrow involvement, leukemic phase, serous effusion and high lactate dehydrogenase levels. Patients with stage I-II disease and a low tumor burden should receive frontline external involved-field radiotherapy, while patients with a high tumor burden or a severe prognostic score should receive front-line chemotherapy plus involved-field radiotherapy. Younger patients with stage III-IV disease should receive front-line therapy with anthracycline- or fludarabine-based regimens combined with rituximab, while older patients who are candidates for treatment should receive single-agent alkylating therapy. By using a systematic literature review and an explicit approach to consensus among experts, recommendations for the key therapeutic decisions in patients with nodal indolent NHL are provided.
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PMID:Management of nodal indolent (non marginal-zone) non-Hodgkin's lymphomas: practice guidelines from the Italian Society of Hematology, Italian Society of Experimental Hematology and Italian Group for Bone Marrow Transplantation. 1615 48

Central nervous system (CNS) involvement in non-Hodgkin lymphoma (NHL) is a well-recognised complication. There is no consensus regarding indications for prophylaxis or a standard CNS chemoprophylaxis regimen. Current UK practice was evaluated using a questionnaire. A total of 223 questionnaires were sent to clinicians who administered chemotherapy to patients with NHL; 158 (71%) evaluable questionnaires were returned. The overwhelming majority of respondents used prophylaxis in all cases of lymphoblastic lymphoma (97%) and Burkitt lymphoma (96%). Ninety-six per cent of respondents required risk factors to be present before prophylaxis was initiated in cases of diffuse large B-cell lymphoma. The commonest risk factor was site of involvement (paranasal sinus 88%, testicular 85%, orbital cavity 78%, bone marrow 65% and bone 28%). Other risk factors included stage IV, high International Prognostic Index score, >1 extranodal site and raised lactate dehydrogenase levels (34%, 21%, 16% and 10%). A total of 82% did not give prophylaxis in follicular lymphoma and 90% used intrathecal chemotherapy as their preferred method of prophylaxis. The most popular regimen was 12.5 mg methotrexate with each cycle of chemotherapy for six courses. Thirty-nine per cent used systemic chemotherapy for CNS prophylaxis either alone (4%) or as an adjunct to intrathecal prophylaxis (35%). These variations in the indications and methods of prophylaxis indicate that this subject deserves further review.
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PMID:Central nervous system chemoprophylaxis in non-Hodgkin lymphoma: current practice in the UK. 1619 49

A single center, prospective clinical trial was conducted evaluating 2 cycles of induction high-dose chemotherapy for adults younger than 65 years of age with aggressive non-Hodgkin lymphoma (NHL) and 2 to 3 Age-Adjusted International Prognostic Index risk factors. Patients received one cycle of standard dose cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) followed by one cycle of dose-intensive cyclophosphamide 5.25 g/m(2), etoposide 1.05 g/m(2), cisplatin 105 mg/m(2) (DICEP), then underwent autologous blood stem cell collection, followed by one cycle of high-dose carmustine (BCNU) 300 mg/m(2), etoposide 800 mg/m(2), Ara-C 1600 mg/m(2), melphalan 140 mg/m(2) (BEAM), and autologous stem cell transplantation (ASCT) and radiotherapy to prior bulk. From June 1998 to August 2004, 55 patients aged 20 to 63 years (median 44 years) were accrued, 51 (92%) of whom had diffuse large B-cell NHL. Poor prognostic factors included stage 4 (n = 46), elevated lactate dehydrogenase (LDH; n = 47), Eastern Cooperative Oncology Group (ECOG) performance status 2 to 4 (n = 43), bulky mass more than 10 cm (n = 34), and marrow involvement (n = 16). Only one patient experienced nonrelapse mortality. With a median follow-up of 49 months, 4-year event-free survival (EFS) and overall survival (OS) rates for all 55 patients are 72% (95% confidence interval [CI] = 60%-84%) and 79% (95% CI = 69%-90%), respectively. In conclusion, CHOP-DICEP-BEAM is feasible and gave encouraging EFS and OS for patients with poor-prognosis aggressive NHL.
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PMID:Upfront double high-dose chemotherapy with DICEP followed by BEAM and autologous stem cell transplantation for poor-prognosis aggressive non-Hodgkin lymphoma. 1646 97

Patients treated with multicycle chemotherapy can exhibit large interindividual heterogeneity of haematotoxicity. We describe how a biomathematical model of human granulopoiesis can be used to design risk-adapted dose-dense chemotherapies, leading to more similar leucopoenias in the population. Calculations were performed on a large data set for cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP)-like chemotherapies for aggressive non-Hodgkin lymphoma. Age, gender, Eastern Cooperative Oncology Group performance status, lactate dehydrogenase and the degree of leucopoenia within the first therapy cycle were used to stratify patients into groups with different expected severity of leucopoenia. We estimated risk-specific bone marrow toxicities depending on the drug doses administered. These toxicities were used to derive risk-adapted therapy schedules. We determined different doses of cyclophosphamide and additional etoposide for patients treated with CHOP-14. Alternatively, the model predicted that further reductions of cycle duration were feasible in groups with low toxicity. We also used the model to identify appropriate granulocyte colony-stimulating factor (G-CSF) schedules. In conclusion, we present a method to estimate the potential of risk-specific dose adaptation of different cytotoxic drugs in order to design chemotherapy protocols that result in decreased diversity of leucopoenia between patients, to develop dose-escalation strategies in cases of low leucopoenic reaction and to determine optimal G-CSF support.
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PMID:Model-based design of chemotherapeutic regimens that account for heterogeneity in leucopoenia. 1648 72

The tissue inhibitor of metalloproteinase-1 (TIMP-1) is a stromal factor that promotes plasmablastic differentiation, and the survival of germinal center B-cells. The expression of TIMP-1 is known to be correlated with a subset of non-Hodgkin lymphoma at the mRNA level, and Epstein-Barr virus infection in vitro. To characterize TIMP-1(+) diffuse large B-cell lymphoma, TIMP-1 expression was investigated in tissue microarrays from 182 cases of de novo diffuse large B-cell lymphoma and compared with prognostic factors, immunophenotypes, and Epstein-Barr virus infection status. TIMP-1 was expressed not only in tumor cells themselves, in 14 of 182 cases (8%), designated as TIMP-1(+) diffuse large B-cell lymphoma, but also in stromal cells like fibroblasts and endothelial cells. In univariate analysis and hierarchical clustering, our findings suggest that TIMP-1 expression may represent a distinct subgroup. In multivariate analysis, TIMP-1(+) diffuse large B-cell lymphoma (n=14) was associated with unfavorable outcomes compared to TIMP-1(-) diffuse large B-cell lymphoma (n=168) (odds ratio=2.5, P=0.049). Together with TIMP-1 expression, age (greater than 60 years), the presence of B-symptoms, abnormal lactate dehydrogenase level, or more advanced stage (III/IV) was correlated with a poor overall survival. However, TIMP-1 expression in diffuse large B-cell lymphoma was not correlated with other prognostic factors including: clinical stage, international prognostic index score, and nongerminal center B-cell phenotype, as well as Epstein-Barr virus infection. Our results suggest that TIMP-1 expression may be an independent negative prognostic factor in patients with diffuse large B-cell lymphoma.
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PMID:Clinicopathologic implications of tissue inhibitor of metalloproteinase-1-positive diffuse large B-cell lymphoma. 1664 68

Intravascular lymphoma (IVL) is an extremely rare form of non-Hodgkin lymphoma characterized by almost exclusive growth of neoplastic lymphocytes within blood vessel lumen. IVL is morphologically characterized in most instances by large cells with B-cell lineage. IVL is an aggressive and usually disseminated disease that predominantly affects elderly patients, resulting in poor PS, B-symptoms, anemia, and high lactate dehydrogenase serum level. The brain and skin are the most commonly involved sites; nodal disease is rare. Survival after conventional chemotherapy is disappointing, with a relevant impact of diagnostic delay and lethal complications. Notwithstanding these results, IVL limited to the skin (cutaneous variant) is a favorable presentation with distinctive clinical characteristics. Moreover, differences in clinical presentation with Eastern Countries IVL cases, mostly associated with hemophagocytic syndrome, do exist. Intensive combinations containing drugs with higher central nervous system bioavailability are needed in cases with brain involvement; the role of high-dose chemotherapy with autologous stem cell transplantation should be investigated in younger patients with unfavorable features. The present review will discuss the most recent acquisitions related either to diagnosis and immunophenotypic/biologic characteristics as well as clinical/therapeutic issues of IVL.
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PMID:Intravascular lymphoma: a neoplasm of 'homeless' lymphocytes? 1672

B-lymphocyte stimulator/B-cell activating factor (BLyS/BAFF) and a proliferation-inducing ligand (APRIL), members of the tumor necrosis family of ligands, are expressed by monocytes, macrophages, and dendritic cells, and increased expression of these ligands is noted in lymphomas and plasma cell malignancies. BLyS and APRIL are essential for the survival of normal and malignant B lymphocytes, and altered expression of BLyS or APRIL or the receptors B-cell maturation, transmembrane activator and calcium-modulating cyclophilin ligand interactor, or BAFF-R have been reported in various B-cell malignancies, including B-cell non-Hodgkin's lymphoma, chronic lymphocytic leukemia, Hodgkin's lymphoma, multiple myeloma, and Waldenstrom's macroglobulinemia. Levels of BLyS (in the tumor and in the serum) increased with the transformation of the tumors to a more aggressive phenotype. A high BLyS level inversely correlated with a poor median overall survival, presence of constitutional symptoms, and increased levels of lactate dehydrogenase in patients with non-Hodgkin's lymphoma. Additionally, patients who responded to therapy had a lower BLyS level than those with progressive disease. Several agents targeting BLyS and APRIL are currently being pursued in phase I clinical studies in patients with B-cell malignancies.
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PMID:Targeting B-lymphocyte stimulator/B-cell activating factor and a proliferation-inducing ligand in hematologic malignancies. 1702 20

Histological transformation of low-grade non-Hodgkin lymphoma (NHL) to diffuse large cell NHL is well recognized and is associated with a poor prognosis. We sought to determine the overall outcome and the factors that affect survival in patients with histological transformation of low-grade NHL. Between November 1979 and September 2000, 93 patients who developed transformed lymphoma were identified. The median time to transformation was 4.2 years from the original diagnosis. The median age at transformation was 63 years. Seventy-eight percent had stage III or IV disease. Fifty-seven percent had extranodal involvement, including bone marrow; 33% had an elevated lactate dehydrogenase. The International Prognostic Index (IPI) at transformation was termed the transformation IPI (tIPI); 29% had a tIPI of 0-1, 59% had a tIPI of 2-3 and 8% had a tIPI of 4-5. At a median follow-up of 15 months from histological transformation, 20 of 93 patients (22%) were alive. The median survival from transformation was 15 months (4 months to 19.7 years). On univariate analysis, the following factors at the time of histological transformation were associated with an improved survival: low tIPI (P = 0.009), time to transformation > 4 years (P = 0.02), age < or = 60 years (P = 0.02) and stage I or II disease (P = 0.04). On multivariate analysis, factors that remained significant included a low tIPI (P = 0.0001) and a time to transformation > 4 years (P = 0.004). tIPI correlated with overall survival (OS); IPI 0-1, median OS 38 months; IPI 2-3, median OS 12 months; IPI 4-5, median OS 4 months. In conclusion, tIPI at the time of histological transformation is an important predictor of OS. A time to transformation > 4 years from diagnosis is associated with better OS.
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PMID:The International Prognostic Index predicts outcome after histological transformation of low-grade non-Hodgkin lymphoma. 1706 90

We investigated the addition of rituximab to an intensified salvage program followed by a myeloablative course with autologous stem cell transplantation (ASCT) in patients with relapsed or refractory aggressive non-Hodgkin lymphoma (NHL). Patients with relapsed or progressive aggressive NHL were treated with two cycles of conventional salvage chemotherapy (DHAP) followed by high-dose sequential chemotherapy (cyclophosphamide, methotrexate with vincristine and etoposide) and a final myeloablative course (BEAM) with ASCT. Rituximab (375 mg/m(2)) was administered at each treatment cycle. This cohort was compared with a historical control group of patients treated with the same chemotherapy but without rituximab. Patients from both groups were matched by duration of first remission and lactate dehydrogenase serum levels. Forty-five patients were treated with chemotherapy and 22 with immunochemotherapy. The overall response rates (ORR) at the final evaluation were 63% for the immunochemotherapy group and 42% for the chemotherapy group (p = 0.330). In the historical controlled analysis freedom from second failure (FF2F) at 2 years in the immunochemotherapy group was 57% and overall survival (OS) was 77%. FF2F in the chemotherapy group was 18% (p = 0.0051) and OS was 37% (p = 0.0051). In the matched-pair analysis, FF2F was 58% in the immunochemotherapy group compared to 16% in the chemotherapy group (p = 0.0517); OS was 74 vs 33%, respectively (p = 0.0424). The toxicity was tolerable and comparable in both groups. The addition of rituximab to an intensified salvage chemotherapy regimen seems to improve the prognosis. However, only prospective randomized trial can offer sufficient data of the value of rituximab in relapsed and refractory aggressive NHL.
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PMID:Rituximab added to an intensified salvage chemotherapy program followed by autologous stem cell transplantation improved the outcome in relapsed and refractory aggressive non-Hodgkin lymphoma. 1710 69

Primary central nervous system lymphoma (PCNSL) is a rare form of non-Hodgkin lymphoma that affects the brain, spinal cord, leptomeninges, and eyes. The clinical presentation and neuroimaging appearance of PCNSL differ in immunocompetent patients and in those with acquired immunodeficiency syndrome (AIDS). A magnetic resonance (MR) image of the brain in immunocompetent patients with PCNSL typically demonstrates one or more homogeneously enhancing lesions located in the periventricular white matter, characteristically spanning the corpus callosum. In patients with AIDS, multiple ring-enhancing lesions are more common. After neuroimages raising the suspicion of PCNSL are obtained, a definitive diagnosis should be established in both immunocompetent and AIDS patients by performing pathological analysis of cerebrospinal fluid (CSF), vitreous fluid, or a biopsy specimen. Brain biopsy sampling remains the gold standard for PCNSL diagnosis in all patients, although the possibility of establishing routine, minimally invasive diagnostic procedures in which Epstein-Barr virus polymerase chain reaction (PCR) analysis of the CSF and nuclear imaging are used is currently under investigation in the population of patients with AIDS. At the time of diagnosis, the patient should undergo further evaluation, which should include a physical examination, ophthalmic evaluation with a slit-lamp examination, serum lactate dehydrogenase levels, human immunodeficiency virus testing, computed tomography scans of the chest/abdomen/pelvis, bone marrow biopsy sampling, contrast-enhanced brain MR imaging, and lumbar puncture (LP). Testicular ultrasonography studies should be considered in men. In patients who cannot undergo LP or in those with evidence of spinal cord dysfunction, contrast-enhanced MR imaging of the entire spine should be considered.
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PMID:Primary central nervous system lymphoma: presentation, diagnosis and staging. 1713 17


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