Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inorganic arsenic trioxide (As(2)O(3)) induces a high proportion of complete remissions in relapsed patients with acute promyelocytic leukemia (APL). Previously, we have shown that both As(2)O(3 )and melarsoprol, an organic arsenical used for the treatment of trypanosomiasis, exhibit broad antileukemic activity against both chronic and acute myeloid and lymphoid leukemia cell lines. Given the breadth of this activity, we initiated a clinical study to evaluate the pharmacokinetics, safety, and potential efficacy of melarsoprol in patients with refractory or resistant leukemia. Using the antitrypanosomal dose and schedule, patients received escalating intravenous doses daily for 3 days, repeated weekly for 3 weeks. Doses were 1 mg/kg on day 1, 2 mg/kg on day 2, and 3.6 mg/kg on day 3 and on all days thereafter, up to a maximum daily dose of 200 mg. Eight patients [6 AML (2 morphologic APL), 1 CML, 1 CLL] were treated. Mean peak plasma concentrations of the parent drug were obtained immediately after injection, ranged from 1.2 microg/ml on day 1 to 2.4 microg/ml on day 3, were dose proportional, and decayed with a t(1/2) congruent with 15 min. A minor clinical response (regression of splenomegaly and lymphadenopathy) was observed in a patient with chronic lymphocytic leukemia. Central nervous system (CNS) toxicity proved limiting on this dose and schedule. Three patients experienced generalized grand mal seizures during the second week of therapy. We concluded that this dose and schedule of melarsoprol is associated with excessive CNS toxicity and that verification of the striking preclinical activity in patients with leukemia will require developing an alternative dose and schedule.
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PMID:Clinical study of an organic arsenical, melarsoprol, in patients with advanced leukemia. 1050 16

Case. A 34-year-old African-American female with a history of adult-onset Still's disease presented to an outside hospital with oligoarthritis. She experienced a generalized tonic-clonic seizure en route via ambulance, was intubated upon arrival, and transferred to the intensive care unit for treatment of suspected pneumonia and sepsis. She subsequently developed generalized cutaneous desquamation that progressed despite the cessation of antibiotics and other potential offending drugs which required transfer to our hospital's burn unit. She was suspected to have reactive hemophagocytic syndrome based on her clinical presentation of fever, rash, polyarthritis, elevated liver enzymes, coagulopathy, splenomegaly, normocytic anemia, thrombocytopenia, hypertriglyceridemia, hyperferritinemia, and hemophagocytosis visualized in bone marrow biopsy specimen. Magnetic resonance imaging demonstrated necrotic demyelination of the deep white matter and corona radiata. The patient developed multiorgan dysfunction and DIC without any other attributable etiology. Despite aggressive broad spectrum therapy and high dose of steroids she progressively deteriorated and eventually expired. Conclusion. Previous publications have highlighted the prevalence of necrotic leukoencephalopathy in children with familial hemophagocytic syndrome. Our patient demonstrated some uncommon features complicating her HLH including DIC and necrotic leukoencephalopathy, which are very rare entities in AOSD.
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PMID:An Unusual Case of Adult-Onset Still's Disease with Hemophagocytic Syndrome, Necrotic Leukoencephalopathy and Disseminated Intravascular Coagulation. 2470 28