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)

Over the last 5 years, a plethora of histone deacetylase inhibitors (HDACi) have been evaluated in clinical trials. These drugs have in common the ability to hyperacetylate both histone and nonhistone targets, resulting in a variety of effects on cancer cells, their microenvironment, and immune responses. To date, responses with single agent HDACi have been predominantly observed in advanced hematologic malignancies including T-cell lymphoma, Hodgkin lymphoma, and myeloid malignancies. Therefore, in this review we focus upon hematologic malignancies. Generally HDACi are well tolerated with the most common acute toxicities being fatigue, gastrointestinal, and transient cytopenias. Of note, few patients have been treated for prolonged periods of time and little is known about long-term toxicities. The use of the biomarker of histone hyperacetylation has been useful as a guide to target specificity, but generally does not predict for response and the search for more clinically relevant biomarkers must continue.
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PMID:Clinical studies of histone deacetylase inhibitors. 1950 72

A 10-year-old boy with unilateral ophthalmoplegia, ptosis, and proptosis underwent diagnostic examination. Symptoms of headache, nausea, dyspnea, fatigue, weakness, and loss of appetite began 14 days after the onset of ocular manifestations and 7 days before he was examined. Complete blood count showed an increased white blood cell count with 64% blast cells, anemia, and thrombocytopenia. The patient was transferred to a pediatric hematology unit, where he underwent bone marrow aspiration biopsy. Bilateral ocular inflammatory findings and left-sided mild proptosis became evident. He was diagnosed as having B-cell non-Hodgkin lymphoma infiltrating the bilateral cavernous and sphenoid sinuses.
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PMID:Cavernous sinus syndrome as the initial presentation of childhood non-hodgkin lymphoma. 1964 4

Hodgkin's disease (HD) affects younger and older adults and can disrupt developmental tasks and cause multiple medical sequelae. Since long-term survival is excellent, understanding issues related to all domains of health-related quality of life (HRQOL)-physical, psychological, social/functional, and spiritual-after completion of treatment is a critical step in designing and testing interventions to improve survivors' adjustment and return to their previous level of functioning. This article is an integrative review of empirical studies of HRQOL in HD survivors. Following Ganong's guidelines, 35 studies were identified and reviewed. Commonly reported physical consequences of HD include fatigue, anticipatory nausea and vomiting, and cognitive problems that lasted several years after treatment completion, as well as long-term life-threatening adverse effects including secondary cancers and cardiovascular and respiratory complications. Psychological consequences include emotional distress, especially depression and anxiety, and social/functional difficulty, including inability to return to work and adjustment to the workplace environment secondary to diminished capacity to complete work tasks. Within the spiritual domain, survivors reported that they had a greater appreciation for life after treatment. Development of appropriate theory-guided interventions to improve the HRQOL for HD survivors can be achieved through more rigorous study designs and standardization of HRQOL measurements.
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PMID:Health-related quality of life in adults with Hodgkin's disease: the state of the science. 1981 66

Certain malignant B cells rely on B-cell receptor (BCR)-mediated survival signals. Spleen tyrosine kinase (Syk) initiates and amplifies the BCR signal. In in vivo analyses of B-cell lymphoma cell lines and primary tumors, Syk inhibition induces apoptosis. These data prompted a phase 1/2 clinical trial of fostamatinib disodium, the first clinically available oral Syk inhibitor, in patients with recurrent B-cell non-Hodgkin lymphoma (B-NHL). Dose-limiting toxicity in the phase 1 portion was neutropenia, diarrhea, and thrombocytopenia, and 200 mg twice daily was chosen for phase 2 testing. Sixty-eight patients with recurrent B-NHL were then enrolled in 3 cohorts: (1) diffuse large B-cell lymphoma (DLBCL), (2) follicular lymphoma (FL), and (3) other NHL, including mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), mucosa-associated lymphoid tissue lymphoma, lymphoplasmacytic lymphomas, and small lymphocytic leukemia/chronic lymphocytic leukemia (SLL/CLL). Common toxicities included diarrhea, fatigue, cytopenias, hypertension, and nausea. Objective response rates were 22% (5 of 23) for DLBCL, 10% (2 of 21) for FL, 55% (6 of 11) for SLL/CLL, and 11% (1/9) for MCL. Median progression-free survival was 4.2 months. Disrupting BCR-induced signaling by inhibiting Syk represents a novel and active therapeutic approach for NHL and SLL/CLL. This trial was registered at www.clinicaltrials.gov as #NCT00446095.
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PMID:Inhibition of Syk with fostamatinib disodium has significant clinical activity in non-Hodgkin lymphoma and chronic lymphocytic leukemia. 2036 Apr 72

Alpha interferon has proven efficacy in prolonging remissions in patients with follicular non-Hodgkin lymphoma (NHL) when given concurrently with or after conventional-dose anthracycline-based chemotherapy, but there are limited data on its use after myeloablative conditioning. We prospectively evaluated the toxicity and efficacy of interferon given thrice weekly for up to 5 years post-engraftment in patients with relapsed follicular NHL undergoing autologous stem cell transplant using busulfan-melphalan conditioning. Thirty-seven patients were enrolled in this Australasian Leukaemia & Lymphoma Group study and transplanted between 1995 and 1999. Only one patient had received prior rituximab. Two patients died of transplant-related toxicity; 28 of the remainder commenced interferon, but it was discontinued prematurely in most patients due to toxicity (mainly fatigue and depression) or relapse. While the majority of patients (29/36 evaluable: 81%) achieved a complete remission based on clinical and CT scan criteria post-transplant, most relapsed relatively early, with a median progression-free survival of 2.4 years. The overall survival at 7 years was 49%. Eight patients (22%), however, remain alive a median of 9.3 years post-transplant, having never relapsed, and another six patients (16%) remain alive in durable remission after salvage therapy. These results demonstrate that interferon is poorly tolerated post-autograft and hence is unlikely to positively contribute to patient outcome. Long-term follow-up demonstrates that autografting may result in durable remissions in a meaningful minority of patients with relapsed follicular NHL.
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PMID:Phase II study of autologous stem cell transplant using busulfan-melphalan chemotherapy-only conditioning followed by interferon for relapsed poor prognosis follicular non-Hodgkin lymphoma. 2021 9

Lymphoplasmacytic lymphoma (LPL) constitutes less than 5% of all non-Hodgkin lymphomas, and little is known about clinical features and treatment outcomes for patients with LPL in East Asia. In this study, we summarize our experiences managing patients diagnosed with LPL in Korea. A retrospective analysis was performed using data for 22 patients with LPL diagnosed at Samsung Medical Center. LPL was more common among males (77.3%), with a median age of diagnosis of 63 years (range 26-86). The most common presenting symptom was fatigue related to anemia (59.1%), and the bone marrow was commonly involved at diagnosis (90.9%). IgM paraproteinemia was found in 15 patients, and only one patient had anti-hepatitis C virus. Although some patients could be observed without treatment, the majority of patients required systemic treatment. Chlorambucil alone and cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) or CHOP-like combination chemotherapy was frequently used as a first-line treatment, and a fludarabine-based regimen was commonly used as salvage therapy. However, responses to those treatments were not satisfactory. Even patients who could be monitored without therapy became refractory to salvage therapies once their disease progressed. Eight patients died due to disease progression, and the median overall survival was 70.8 months (95% CI: 31.4-109.2 months). This study describes the clinical features and treatment outcome of LPL in Korea. The treatment approach was too heterogeneous to draw firm conclusions, however, and treatment recommendations in the future should utilize a uniform treatment strategy.
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PMID:Clinical features and treatment outcomes of lymphoplasmacytic lymphoma: a single center experience in Korea. 2044 47

Bendamustine is a cytotoxic agent with a novel mechanism of action. This phase I, dose-escalation study evaluated the safety, tolerability, efficacy, and pharmacokinetics of bendamustine in Japanese patients with relapsed/refractory indolent B-cell non-Hodgkin lymphoma (B-NHL) or mantle cell lymphoma (MCL) without major organ dysfunction. Bendamustine 90 or 120 mg/m(2) (dose escalation) was administered intravenously over 60 min on days 1 and 2 every 3 weeks for up to three cycles. Nine patients (eight indolent B-NHL and one MCL) received per-protocol treatment, three at 90 mg/m(2) and six at 120 mg/m(2) . No dose-limiting toxicities were observed; thus, the maximum-tolerated dose was not reached. Grade 3/4 hematologic toxicities were neutropenia (33%) and leukopenia (33%). Non-hematologic toxicities were grade 1/2 and included gastrointestinal events and fatigue. Peak plasma concentrations of bendamustine occurred near the end of infusion in both dose groups and were equivalent to therapeutic concentrations observed in vitro. Bendamustine was rapidly eliminated, with a mean elimination half-life (t(1/2) ) of 29 min. Plasma concentrations of active metabolites M3 and M4 were approximately 4 and <1% of the plasma concentration of the parent molecule, with t(1/2) of 42 and 33 min, respectively. Two unconfirmed complete responses and six partial responses were observed for an overall response rate (ORR) of 89%. The recommended dose for this schedule in phase II trials is 120 mg/m(2) . The acceptable safety profile and high ORR warrant further investigation of bendamustine in relapsed or refractory indolent B-NHL and MCL.
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PMID:Phase I and pharmacokinetic study of bendamustine hydrochloride in relapsed or refractory indolent B-cell non-Hodgkin lymphoma and mantle cell lymphoma. 2059 95

Bendamustine is a unique cytotoxic agent that has demonstrated efficacy in the treatment of indolent B-cell non-Hodgkin lymphomas (B-NHLs). In this multicenter phase II trial, the efficacy and safety of bendamustine were evaluated in Japanese patients with relapsed or refractory indolent B-NHL or mantle-cell lymphoma (MCL). Patients received bendamustine (120 mg/m(2) ) on days 1-2 of a 21-day cycle, for up to six cycles. The primary endpoint was the overall response rate (ORR) as assessed by an extramural committee according to International Workshop Response Criteria (IWRC). Secondary endpoints included complete response (CR) rate, ORR according to Revised Response Criteria (revised RC), progression-free survival (PFS), and safety. Fifty-eight patients with indolent B-NHL and 11 with MCL were enrolled. By IWRC, bendamustine produced an ORR of 91% (95% confidence interval [CI], 82-97%; 90% and 100% in patients with indolent B-NHL and MCL, respectively), with a CR rate of 67% (95% CI, 54-78%). ORR and CR rates according to revised RC were 93% (95% CI, 84-98%) and 57% (95% CI, 44-68%), respectively. After a median follow-up of 12.6 months, median PFS had not been reached. Estimated PFS rates at 1 year were 70% and 90% among indolent B-NHL and MCL patients, respectively. Bendamustine was generally well tolerated. Reversible myelosuppression, including grade 3/4 leukopenia (65%) and neutropenia (72%), was the most clinically significant toxicity observed. Common non-hematologic toxicities included mild gastrointestinal events and fatigue. These results demonstrate the high efficacy and tolerability of single-agent bendamustine in relapsed patients with indolent B-NHL or MCL histologies.
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PMID:Multicenter phase II study of bendamustine for relapsed or refractory indolent B-cell non-Hodgkin lymphoma and mantle cell lymphoma. 2062 54

Survival of mammalian cells is achieved by tight control of cell volume, while transmembrane potential has been known to control many cellular functions since the seminal work of Hodgkin and Huxley. Regulation of cell volume and transmembrane potential have a wide range of implications in physiology, from neurological and cardiac disorders to cancer and muscle fatigue. Therefore, understanding the relationship between transmembrane potential, ion fluxes, and cell volume regulation has become of great interest. In this paper we derive a system of differential equations that links transmembrane potential, ionic concentrations, and cell volume. In particular, we describe the dynamics of the cell within a few seconds after an osmotic stress, which cannot be done by the previous models in which either cell volume was constant or osmotic regulation instantaneous. This new model demonstrates that both membrane potential and cell volume stabilization occur within tens of seconds of changes in extracellular osmotic pressure. When the extracellular osmotic pressure is constant, the cell volume varies as a function of transmembrane potential and ion fluxes, thus providing an implicit link between transmembrane potential and cell volume. Experimental data provide results that corroborate the numerical simulations of the model in terms of time-related changes in cell volume and dynamics of the phenomena. This paper can be seen as a generalization of previous electrophysiological results, since under restrictive conditions they can be derived from our model.
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PMID:Ion fluxes, transmembrane potential, and osmotic stabilization: a new dynamic electrophysiological model for eukaryotic cells. 2107 46

Intravascular large B cell lymphoma (IVLBCL) is a rare type of extranodal large B cell lymphoma in the lumina of small vessels. Low high-density lipoprotein cholesterol (HDL-C) is associated with sepsis, malignancy, and death. Recent evidence suggests an inverse relationship between HDL-C and non-Hodgkin lymphoma. We report the case of a 71-year-old female who presented with decreasing HDL-C for years prior to diagnosis of IVLBCL. The patient developed nonspecific symptoms, including dizziness, gait instability, fatigue, tinnitus, and weight loss. Although malignancy was high on the differential, no diagnosis was made antemortem. The diagnosis of disseminated intravascular large B cell lymphoma was made postmortem in multiple organ systems. The presentation of IVLBCL is nonspecific and misleading. To our knowledge this is the second known case report of low HDL-C preceding diagnosis of IVLBCL, but the first case documenting low HDL-C years prior to diagnosis.
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PMID:Disseminated intravascular large B cell lymphoma with slowly decreasing high-density lipoprotein cholesterol. 2111 58


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