Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019829 (Hodgkin's disease)
30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

High dose chlorambucil has been shown to be an effective single-agent treatment in chronic lymphocytic leukemia (CLL), and to be useful as part of combination chemotherapy in low-grade non-Hodgkin's (NHL) and Hodgkin's disease (HD). In general, it is well tolerated and can be used in an outpatient setting. The optimum dose of chlorambucil has not been defined and there are numerous different dosing schedules available. Pharmacokinetic studies suggest decreased bioavailability with successive cycles, probably due to accelerated metabolism. There is good evidence that regimens which use higher doses of chlorambucil have a better outcome than standard dose therapy. Most of the trials which have compared chlorambucil with fludarabine have not used a higher dose regimen of chlorambucil and cannot truly be described as comparative. There is an increase in the incidence of grade 3 and 4 neutropenia and also of sepsis with fludarabine treatment, compared to chlorambucil. Fludarabine produces a higher initial response rate in CLL but no statistical difference has been shown in long term survival between fludarabine and high dose chlorambucil. In the treatment of lymphoma, single agent chlorambucil does not confer a durable remission. There have been good results with combination chemotherapy regimens such as CID and PECC. The oral route of administration of these combinations makes them particularly useful as part of palliative chemotherapy. A further point to consider is that chlorambucil is very much cheaper than fludarabine and other newer agents. Chlorambucil should not automatically be overlooked in favor of more recently developed drugs such as fludarabine. There is good evidence that the drug is an effective treatment at a suitable dose, and there is a need for randomized trials to compare it fully with other current treatments.
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PMID:High dose chlorambucil in the treatment of lymphoid malignancies. 1510 11

Chronic myeloid leukemia (CML) is characterized by the presence of a constitutively active Abl kinase, which is the product of a chimeric BCR-ABL gene, caused by the genetic translocation known as the Philadelphia chromosome. Imatinib, a selective inhibitor of the Bcr-Abl tyrosine kinase, has significantly improved the clinical outcome of patients with CML. However, subsets of patients lose their response to treatment through the emergence of imatinib-resistant cells, and imatinib treatment is less durable for patients with late stage CML. Although alternative Bcr-Abl tyrosine kinase inhibitors have been developed to overcome drug resistance, a cocktail therapy of different kinase inhibitors and additional chemotherapeutics may be needed for complete remission of CML in some cases. Chlorambucil has been used for treatment of B cell chronic lymphocytic leukemia, non-Hodgkin's and Hodgkin's disease. Here we report that a DNA sequence-specific pyrrole-imidazole polyamide-chlorambucil conjugate, 1R-Chl, causes growth arrest of cells harboring both unmutated BCR-ABL and three imatinib resistant strains. 1R-Chl also displays selective toxicities against activated lymphocytes and a high dose tolerance in a murine model.
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PMID:Growth arrest of BCR-ABL positive cells with a sequence-specific polyamide-chlorambucil conjugate. 1897 32

Elderly Hodgkin lymphoma (HL), commonly defined as occuring in patients over 60 to 65 years of age, is an uncommon disease. In population-based studies, the proportion of HL patients over age 60 years has rangedfrom 15% to 30%. However, the proportion of patients over age 60 years in clinical trials has been considerably lower, typically constituting < 5% to 10% of participants. Elderly HL patients commonly present with mixed cellularity histology, B symptoms, advanced stage, and Epstein-Barr virus-positive disease. Progression-free and overall survival rates for elderly HL patients are disproportionately inferior to those of younger patients. Generally, treatment of elderly HL for all disease stages should be given with curative intent, but more effective, tolerable therapeutic regimens are needed. No standard treatment recommendations exist for elderly HL Bleomycin-containing regimens including ABVD (doxorubicin [Adriamycin], bleomycin, vinblastine, dacarbazine) are associated with pulmonary toxicity, and intensive therapy such as BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine [Oncovin], procarbazine [Matulane], prednisone) is poorly tolerated, whereas less-intensive regimens such as CVP/CEB (chlorambucil [Leukeran], vinblastine, procarbazine, prednisone, cyclophosphamide, etoposide, bleomycin) and ChlVPP (chlorambucil, vinblastine, procarbazine, prednisolone) appear to be less effective than anthracycline-based regimens. Recent data using CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) in this population merit further investigation. In addition, further evaluation of the prognostic value of early PET in elderly HL is warranted. Continued multicenter collaborations with prospective clinical trials, including formal assessment of comorbidity and functional status, will be critical to the successful study of elderly HL.
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PMID:Hodgkin lymphoma in older patients: an uncommon disease in need of study. 1932 48

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


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