Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019209 (hepatomegaly)
 5,798 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gemtuzumab ozogamicin (Mylotarg) therapy may cause sinusoidal obstruction syndrome (SOS), the mechanism of which probably involves targeting of CD33+ cells in the sinusoids of the liver, activation of stellate cells, damage to sinusoidal endothelial cells, sinusoidal vasoconstriction, and ischemic hepatocyte necrosis. The clinical manifestations of this liver injury are hepatomegaly, weight gain, ascites, jaundice, and elevation of serum aminotransferase enzymes. An approach to patient management includes being certain that SOS is the correct diagnosis; ensuring that liver blood flow is optimized; and managing the accumulation of fluid in the peritoneal cavity, pleural spaces, and pulmonary interstitium. Currently, there is no specific therapy that is directed at the sinusoidal pathology caused by gemtuzumab ozogamicin. There are, however, several rational therapies that might be tried in patients who exhibit adverse prognostic signs early in the course of SOS. There is also considerable ongoing hepatology research dealing with stellate cell and sinusoidal endothelial cell biology and regulation of sinusoidal blood flow that can be brought to bear on this problem in the future.
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PMID:Management of hepatic sinusoidal obstruction syndrome following treatment with gemtuzumab ozogamicin (Mylotarg). 1197 Jul 69

Veno-occlusive disease (VOD) of the liver is characterized by jaundice, painful hepatomegaly, and retention of fluids. VOD is a severe complication in allogeneic stem cell or bone marrow transplantation. Additionally, the disease has been described in children suffering from nephroblastoma or rhabdomyosarcoma, treated with intense chemotherapy. Recently, VOD has been shown to be a complication in the treatment of myeloid leukemia with anti-CD33 linked to calicheamicin. We report the unusual case of a 21-year-old male patient with Marfan syndrome, diagnosed of acute lymphoblastic leukemia, who developed severe VOD during induction therapy after a single application of 2 mg vincristine. We speculate that coincidence of Marfan syndrome and application of induction chemotherapy might favor the disease in our patient.
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PMID:Veno-occlusive disease in a male patient with Marfan syndrome and common acute lymphoblastic leukemia during induction therapy. 1276 49

Gemtuzumab ozogamicin (GO) was approved for marketing in 2000 by the United States Food and Drug Administration (FDA) for older patients with relapsed acute myeloid leukemia (AML). Four months later, 14 phase II clinical trial participants who received novel GO-containing combination chemotherapy regimens developed an unexpected hepatic toxicity termed sinusoidal obstructive syndrome (SOS) or hepatic veno-occlusive disease (VOD). Investigators associated with the Research on Adverse Drug Events and Reports (RADAR) project reviewed safety reports for GO included in reports of clinical trials and observational studies, interim reports from an FDA mandated Prospective Observational Registry, and the Food and Drug Administration's Adverse Event Reporting System. Medline searches provided incidence estimates of GO-associated SOS and comparative rates of SOS without GO. SOS is characterized by hyperbilirubinemia, painful hepatomegaly, ascites, and sudden weight gain developing at a median of 10 days following GO administration for patients who did not undergo an allogeneic SCT procedure and 13 days following an allogeneic SCT for patients who had previously received GO. Among adult AML patients who received GO in clinical trials, SOS incidence was 3% at doses < or =6 mg/m(2) if administered as monotherapy or in combination with non-hepatotoxic agents versus 28% if administered with thioguanine and 15% when administered as monotherapy at a dose of 9 mg/m(2). Observational studies identified SOS rates between 15% and 40% if an SCT is performed within 3 months of GO administration. The FDA mandated Prospective Observational Registry of patients who receive care at 60 medical centers has identified GO-associated SOS rates of 14% if an SCT is performed and 9% otherwise. Caution is advised when administering GO in routine clinical practice, particularly if administered with other hepatotoxic agents, at doses and schedules more intensive than those approved by the FDA, or within 3 months of a SCT procedure.
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PMID:Gemtuzumab ozogamicin-associated sinusoidal obstructive syndrome (SOS): an overview from the research on adverse drug events and reports (RADAR) project. 1695 16