Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tiazofurin, an investigational antimetabolite, is undergoing clinical evaluation in leukemia. We analyzed the data base of 198 patients entered in Phase I trials to characterize the incidence and severity of toxicities associated with tiazofurin according to dose and schedule. Severe myelosuppression occurred infrequently, and was not dose-dependent. A five day bolus schedule had a higher incidence of severe or life-threatening neutropenia than other schedules. Tiazofurin produced lymphopenia which was not dose-dependent in the range of 23-36% decrease from baseline, and the effect on lymphocyte count was generally greater than the decline in neutrophil count. Non-hematologic toxicity of a moderate or worse severity (greater than or equal to grade 2) included nausea and vomiting (18% of all courses), serum transaminase elevations (SGOT, 16%; SGPT, 9%), rash (9%), stomatitis (3%), conjunctivitis (3%), headache (10%), other signs of central nervous system toxicity (8%), and cardiac toxicity, primarily pleuropericarditis (4%). Dose-related cutaneous toxicity, headache, and nausea and vomiting were evident in the five day bolus schedule, and myalgia was more frequently reported at higher doses on the single dose schedule. The five day continuous infusion (CI) schedule had a higher incidence of neurotoxicity, cardiac toxicity, SGPT elevations and ocular toxicity than the daily for five days bolus schedule, but none of these differences attained statistical significance. Although the peak plasma concentrations of tiazofurin achieved with the five day bolus schedule were 3-fold higher than the steady-state plasma levels seen with an equal dose given by CI, the area under the concentration-time curve (AUC) was approximately 1.6-fold higher with CI. These observations suggest that both high peak plasma concentrations (above 400 microM) and prolonged exposure to plasma levels exceeding 50 microM may result in a higher incidence of serious non-hematologic toxicity.
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PMID:Clinical toxicity associated with tiazofurin. 220 Jul 59

A nineteen-year-old woman whose Hodgkin's disease had relapsed experienced acral erythema in association with a asymptomatic pericardial friction rub following autologous bone marrow transplantation. An echocardiogram revealed a large pericardial and right pleural effusion. Since blood cultures gave negative results, renal function was normal, and the patient had neither neutropenia nor elevated temperature, an infectious cause was deemed unlikely and invasive procedures were not performed. These effusions resolved spontaneously. We propose that this patient's acral erythema and associated pericardial and pleural inflammation represent cutaneous and serosal toxic reactions to high-dosage chemotherapy that occur with the onset of leukocyte recovery. If so, acral erythema may signal the beginning of a toxic drug reaction. The appearance of erythema associated with lymphocyte recovery is due to immune hypersensitivity secondary to immaturity of the reconstituting immune system. Thus, we recommend that patients with acral erythema be examined for pleuropericarditis, especially if they experience chest pain.
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PMID:Pericarditis associated with acral erythema of chemotherapy: a syndrome of cutaneous and serosal toxicities? 840 22