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)

A 41-yr-old man presented with jaundice, night sweats, and weight loss. The patient had been on phenytoin for seizure disorder. The drug was discontinued, and a diminution of bilirubin and transaminases occurred over several weeks. Percutaneous liver biopsy revaled cholestasis at the time of maximal hyperbilirubinemia. Recurrent jaundice ensued several weeks later, and an ERCP revealed a common bile duct lesion. Laparotomy revealed Hodgkin's disease involving the common bile duct and periportal node. This cause represents the first report of extrahepatic biliary obstruction from Hodgkin's disease.
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PMID:Obstructive jaundice secondary to primary biliary involvement with Hodgkin's disease. 151 80

Few cases of liver involvement have been reported in patients receiving treatment with CCNU. CCNU is an anti-tumoral agent used in the treatment of leukemia, Hodgkin's disease and bronchial or cerebral tumors. A single daily dose of 20 or 50 mg/kg CCNU in female Wistar rats induces an important increase of transaminases, reaching 10 times initial level between day 2 and day 6, followed by a second and moderate increase between day 21 and day 28. Three-fold increased alkaline phosphatases and conjugated hyperbilirubinemia were noted for the two doses, and was greater for the higher dose. Histological and ultrastructural studies showed two types of lesions: during the first phase of transaminase elevation, edema and inflammatory infiltration of the portal spaces; during the second phase of transaminases elevation, numerous bundles of pericanalicular microfilaments and severe dilation of the biliary tract. Hepatic cells had few alterations although some necrotic foci were observed, particularly at the higher dose. So CCNU induced an intrahepatic cholestasis with pericholangitis in the rat.
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PMID:[Hepatotoxicity of (chloro-2-ethyl)-1-cyclohexyl-3-nitroso-1-urea (CCNU) in the rat]. 351 69

Three cases of acute cholestatic viral hepatitis are presented. A discussion is made regarding the difficulties encountered and the methods used for certifying this not always easy diagnosis: one patient with virus A and two presumed cases of non-A, non-B virus. The most noteworthy laboratory findings are observed in the very slight transaminase changes or their abrupt descent over a short period whereas bilirubin and cholestatic parameters increase. Due to the particular characteristics observed in the first case, a doubt still exists regarding the possibility of an occult systemic disease existing even though 17 months have passed since the onset of symptoms. The possibility of Hodgkin's disease has been virtually ruled out since it seldom presents such long term hyperbilirubinemia and such high alkaline phosphatase levels.
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PMID:[Cholestatic viral hepatitis: is it an easy diagnosis?]. 393 59

A 25-year-old woman with apparently inactive Hodgkin's disease developed fulminant autoimmune hemolytic anemia in the 37th week of pregnancy. The baby required four exchange transfusions for hyperbilirubinemia. The same IgG antibody was found in mother and infant.
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PMID:Successful exchange transfusion of an infant for AIHA developing late in mother's pregnancy. 706 9

Autologous bone marrow transplantation (AuBMT) is an accepted treatment modality for patients with high-risk or relapsed hematological malignancies. Hepatotoxicity, in particular veno-occlusive disease (VOD), is a significant complication of this therapy. The purpose of this study was to determine the clinical relevance of abnormal liver function in the patients who received high-dose cytotoxic therapy and AuBMT for hematological malignancies at Memorial Sloan Kettering Cancer Center. Medical records of 180 consecutive patients between 1984 and 1991 treated with cytotoxic chemotherapy and AuBMT for acute myelogenous leukemia, non-Hodgkin's lymphoma, and Hodgkin's disease were reviewed. Forty-six patients (26%) developed jaundice with bilirubin > 4 mg/dl. These patients had a 43% toxic death rate compared to an 11% toxic death rate in patients with lower bilirubins (p < 0.001). The main etiology of hyperbilirubinemia was VOD of the liver noted in 22 of the 180 patients (12%). Other etiologies of jaundice included hepatitis, sepsis with multiorgan dysfunction, cholecystitis, and recurrent disease. Hyperbilirubinemia of various etiologies is a significant complication of AuBMT. Several new strategies are under investigation to decrease the toxicity of intensive therapy.
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PMID:Abnormal liver function in patients undergoing autologous bone marrow transplantation for hematological malignancies. 762 20

Lymphoma is a rare cause of biliary obstruction and, on cholangiography, may mimic other causes of obstructive jaundice. The optimum treatment for these patients is unclear. The aim of this study is to evaluate the incidence, clinical and imaging findings, management, and outcome of biliary obstruction caused by lymphoma. Our database was searched retrospectively for patients with biliary obstruction due to lymphoma between 1999 and 2005. Biliary obstruction secondary to lymphoma was found in 7 (0.6%) of 1123 patients with malignant biliary obstruction. One patient had benign biliary obstruction related to lymphoma. Of the eight patients (five male, three female; mean age, 34.50 +/- 17.93 years), four had Hodgkin's disease and four had non-Hodgkin's lymphoma. Biliary obstruction occurred as part of the initial or early presentation of lymphoma in two patients. The most common cause of obstruction was compression of the biliary tract by enlarged lymph nodes (six patients). Cholangiographic appearances were diverse: narrowing of the common bile duct (six patients), splayed and narrowed common bile duct (one patient), and multiple strictures and dilatations of the intrahepatic bile ducts (one patient). Biliary drainage was performed in all patients including endoscopic stent placement in six patients, nasobiliary drainage in one, and choledochoduodenostomy in one. Hyperbilirubinemia resolved in all but one of the patients with a stent; however, none could be maintained in a stent-free condition. Five patients died within 1 year after onset of jaundice. One of the surviving patients developed a late benign stricture at the site of the earlier lymphoma. We conclude that lymphoma should be considered in the differential diagnosis of obstructive jaundice, particularly in younger patients. We suggest that biliary drainage by the endoscopic or percutaneous route is necessary for the treatment of these patients. Late benign strictures may develop. Biliary obstruction is a sign of poor prognosis in lymphoma.
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PMID:Biliary tract obstruction secondary to malignant lymphoma: experience at a referral center. 1740 15

Anthracycline-based chemotherapy is the cornerstone of modern curative regimens for aggressive lymphomas; however, these drugs cannot be safely administered in the setting of severe hepatic dysfunction. Alternative regimens for this setting are required. We describe 2 patients with newly diagnosed advanced aggressive lymphoma (diffuse large B-cell lymphoma [DLBCL] and classic Hodgkin lymphoma [HL]) presenting with severe hepatic dysfunction with hyperbilirubinemia (4.3-13.2 mg/dL). Because of the inability to safely administer unattenuated doses of anthracycline-based regimens, dexamethasone, high-dose cytarabine, and cisplatin (DHAP) was used at full doses (along with rituximab for the DLBCL patient) until hepatic function normalized (1-5 cycles). The treatment was then converted to R-CHOP (rituximab/cyclophosphamide/ doxorubicin/vincristine/prednisone) and ABVD (doxorubicin/bleomycin/vinblastine/dacarbazine) for the DLBCL and HL patient, respectively, to complete therapy. The patients had a partial remission and complete remission, respectively. These data suggest that DHAP is a safe and effective regimen that can be used without dose modification as part of initial therapy in the setting of aggressive lymphoma and hepatic failure. The literature on the use of treatment regimens for aggressive lymphoma in the setting of hepatic dysfunction is reviewed.
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PMID:Successful use of full-dose dexamethasone, high-dose cytarabine, and cisplatin as part of initial therapy in non-hodgkin and hodgkin lymphoma with severe hepatic dysfunction. 1940 29

Gilbert's syndrome is characterized by mild unconjugated nonhemolytic hyperbilirubinemia, without hepatic inflammation, fibrosis, chronic liver disease, or liver failure. It is readily diagnosed by genetic variants of the UGT1A1 gene, mainly UGT1A1*28, and is also associated with abnormalities of hepatobiliary transport and additional UGT1A gene variants. Apart from representing a potential risk factor in irinotecan and protease inhibitor therapy, it appears to exert protective effects in Hodgkin's lymphoma and cardiovascular disease. Gilbert's syndrome is part of a continuous spectrum of altered glucuronidation that extends to fatal Crigler-najjar disease. The complexity hidden behind this pharmacogenetic abnormality is of profound significance for drug development and therapy.
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PMID:Gilbert-Meulengracht's syndrome and pharmacogenetics: is jaundice just the tip of the iceberg? 2007 Feb 46

Although ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) therapy has been regarded as a standard of care for advanced-stage Hodgkin lymphoma (HL) since 1992, there has been no prospective data of ABVD therapy in Japan. To investigate the efficacy and safety of ABVd therapy with the lower dose of dacarbazine (250 mg/m(2)) in patients with newly diagnosed stage II-IV HL, Lymphoma Study Group of Japan Clinical Oncology Group conducted a phase II study. The primary endpoints were complete response rate (%CR) and progression-free survival (PFS). A total of 128 patients with age less than 70 years were enrolled and received 6-8 cycles of ABVd followed by radiation to initial bulky mass. The %CR in 118 eligible patients was 81.4% [95% confidence interval (CI) 73.1-87.9%]. Major toxicity was grade 4 neutropenia (45.3%). Grade 3 nausea/vomiting was the most frequent non-hematological toxicity (10.9%). Transient grade 4 constipation, infection (abscess), hypoxemia and hyperbilirubinemia were observed in 4 patients. No treatment-related death was observed. PFS and overall survival at 5 years were 78.4% (95% CI 70.9-85.9%) and 91.3% (95% CI 86.1-96.5%), respectively. In conclusion, ABVd is effective in Japanese patients with stage II-IV HL with acceptable toxicities (UMIN-CTR Number: C000000092).
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PMID:Phase II study of ABVd therapy for newly diagnosed clinical stage II-IV Hodgkin lymphoma: Japan Clinical Oncology Group study (JCOG 9305). 2107 95

Antibody-drug conjugates (ADC) are an attractive approach for the treatment of acute myeloid leukemia and non-Hodgkin lymphomas, which in most cases, are inherently sensitive to cytotoxic agents. CD33 and CD22 are specific markers of myeloid leukemias and B-cell malignancies, respectively. These endocytic receptors are ideal for an ADC strategy because they can effectively carry the cytotoxic payload into the cell. Gemtuzumab ozogamicin (GO, Mylotarg) and inotuzumab ozogamicin consist of a derivative of calicheamicin (a potent DNA-binding cytotoxic antibiotic) linked to a humanized monoclonal IgG4 antibody directed against CD33 or CD22, respectively. Both of these ADCs have a target-mediated pharmacokinetic disposition. GO was the first drug to prove the ADC concept in the clinic, specifically in phase II studies that included substantial proportions of older patients with relapsed acute myeloid leukemia. In contrast, in phase III studies, it has thus far failed to show clinical benefit in first-line treatment in combination with standard chemotherapy. Inotuzumab ozogamicin has shown remarkable clinical activity in relapsed/refractory B-cell non-Hodgkin lymphoma, and it has started phase III evaluation. The safety profile of these ADCs includes reversible myelosuppression (especially neutropenia and thrombocytopenia), elevated hepatic transaminases, and hyperbilirubinemia. There have been postmarketing reports of hepatotoxicity, especially veno-occlusive disease, associated with GO. The incidence is ~2%, but patients who undergo hematopoietic stem cell transplantation have an increased risk. As we steadily move toward the goal of personalized medicine, these kinds of agents will provide a unique opportunity to treat selected patient subpopulations based on the expression of their specific tumor targets.
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PMID:Antibody-drug conjugates of calicheamicin derivative: gemtuzumab ozogamicin and inotuzumab ozogamicin. 2200 69


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