Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034063 (pulmonary edema)
 10,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

High doses of cytosine arabinoside (ara-C) were administered by continuous infusion to 24 patients with acute leukemia in relapse or blast phase of chronic myelogenous leukemia (CML). Ara-C was infused at a dose rate of 250 mg/M2/hr for 36 to 72 hr. The major toxicities were myelosuppression, diarrhea, and abdominal pain. Other toxicities included pulmonary edema, neurotoxicity, and liver function abnormalities. The gastrointestinal toxicity was dose-limiting and a phase II dose was established at 250 mg/M2/hr for 60-72 hr. Four patients treated with this dose schedule had objective responses. Two patients with CML in blast phase returned to chronic phase and have remained stable without maintenance therapy for 12 and 18 months. Two patients with acute myelogenous leukemia in relapse entered complete remissions which continued unmaintained for 4 and 6 months. Steady-state plasma ara-C levels ranged between 7 and 24 x 10(-6) M, while ara-U levels were as high as 4.5 x 10(-4) M. There was no detectable accumulation of ara-C or ara-U during the infusion period. These findings would suggest that the continuous infusion of high dose ara-C may be useful in the treatment of acute leukemia and CML in blast crisis.
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PMID:Prolonged high dose ARA-C infusions in acute leukemia. 328 17

Ten pediatric patients with refractory leukemia received continuous infusion high-dose cytosine arabinoside (ara-C) according to one of two escalating dosage schedules: (1) a 500-mg/m2 rapid infusion loading dose followed by 3.5 g/m2 per day continuous infusion daily for four consecutive days, or (2) a 600-mg/m2 rapid infusion loading dose followed by 5.0 g/m2 per day continuous infusion daily for four consecutive days. Major toxicity at the lower dosage level was grade IV hematopoietic aplasia of three weeks' duration. At the higher dosage level, there was a prohibitive toxicity in multiple organ systems including transient noncardiogenic pulmonary edema, fungal infections, peritonitis, severe diarrhea, transaminase elevations, and one treatment-related death due to acute renal failure. In contrast to other methods of administration of high-dose ara-C, no CNS toxicity occurred. Oncolytic responses were seen in all patients and two achieved brief, partial remissions. Steady-state plasma ara-C concentrations were 13 to 40 mumol/L at the 3.5-g/m2 dosage level and 10 to 225 mumol/L at the 5-g/m2 dosage level; CSF concentrations at both dosages ranged from 2 to 5 mumol/L. Intracellular levels and ratios of 1-beta-D-arabinofuranosylcytidine-5' triphosphate and endogenous deoxycytidine 5' triphosphate in marrow blasts varied widely at steady state during infusion. No positive correlation existed between steady-state plasma ara-C levels, toxicity, oncolytic effect, or intracellular nucleotide concentration.
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PMID:Continuous infusion high-dose cytosine arabinoside in refractory childhood leukemia. 659 35

Twenty-five consecutive leukemia patients (21 AML, 4 ALL) with either primary resistance (n = 22) or resistant relapse (n = 3) of all FAB subtypes were treated with 1 or 2 cycles of ID-ara C (1 g/m2 i.v. q 12 h, days 1-6) and AMSA (120 mg/m2 i.v., days 5-7). Patients reaching CR received 1 cycle of intensive consolidation using ara C 3 g/m2 i.v. q 12 h, days 1-4 and AMSA 120 mg/m2 i.v., day 5. Two patients received an allograft thereafter and are still alive and in CCR. CR was achieved in 12/25 patients (48%), ten after 1 cycle of induction and two after 2 cycles; 10/22 patients with primary resistant disease reached CR, and 2/3 with resistant relapse. Nine patients remained refractory (36%) and four died during hypoplasia (16%). Median DFS of the 12 responders was 2.9 months, median survival from time of CR 8.9 months. Median overall survival of responders and nonresponders was 6 months from time of resistance. Survival advantage of responding patients (n = 12) as compared with nonresponders (n = 13) was 10.7 vs. 3.2 months (p = 0.002). Toxicity of chemotherapy was acceptable: one patient experienced pulmonary edema due to ara C; two patients developed life-threatening systemic fungal infections, one of whom died while in CR.
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PMID:Phase-II study of treatment of refractory acute leukemia with intermediate-dose cytosine arabinoside and amsacrine. 847 58

25 consecutive leukemia patients (21 AML, 4 ALL) with either primary resistance (n = 22) or resistant relapse (n = 3) of all FAB-subtypes were treated with 1 or 2 cycles of ID-ara C (1 g/m2 i.v. q 12h days 1-6) and AMSA (120 mg/m2 i.v. days 5-7). Patients reaching CR received 1 cycle of intensive consolidation using ara C 3 g/m2 i.v. q 12 h days 1-4 and AMSA 120 mgm2 day 5. Two patients received an allograft thereafter and are still alive and in CCR. CR was achieved in 12/25 patients (48%), in 10 after 1 cycle of induction and in 2 after 2 cycles. 10/22 patients with primary resistant disease reached CR, and 2/3 with resistant relapse. 9 patients remained refractory (36%) and 4 died during hypoplasia (16%) Median DFS of the 12 responders was 2.9 months and median survival from time of CR 8.9 mo. Median overall survival of responders and non-responders was 6 mo from time of resistance. The survival advantage of responding patients (n = 12) as compared to non-responders (n = 13) was 10.7 vs. 3.2 mo (p = 0.002). Toxicity of chemotherapy was acceptable. 1 patient experienced pulmonary edema due to ara C, 2 patients developed life threatening systemic fungal infections, one of whom died while in CR.
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PMID:Phase II-study for treatment of refractory acute leukemia with intermediate-dose cytosine arabinoside and amsacrine. 851 50

Preclinical data have shown that all-trans retinoic acid (ATRA) with interferon-alpha (IFN-alpha) can exert significant suppressive effects on Philadelphia-chromosome (Ph)-positive cells. The aim of this study combining IFN-alpha, low-dose cytosine arabinoside (ara-C) and ATRA was to increase the proportion of patients achieving a major cytogenetic response, in comparison with a group of 140 patients previously treated with IFN-alpha plus low-dose ara-C. Forty three patients with Ph-positive CML in early chronic phase were treated with IFN-alpha 5 MU/m2 s.c. daily, low-dose ara-C 10 mg s.c. daily and ATRA 45 mg/m2 orally daily, for 7 consecutive days every other week. Overall, 76% of patients achieved a complete hematologic response (CHR). A cytogenetic response was in observed 59% (major in 38% and complete in 17%). Compared with patients treated with IFN-alpha and low-dose ara-C, those receiving additional ATRA had a lower CHR rate (p. 014), but other response rates were similar. Severe toxicities were common with the triple regimen (64%), mostly related to ATRA therapy. Two patients experienced pseudotumor cerebri; two patients had leukocytosis during the week on ATRA treatment, decreasing during the week off (one suffered a severe asthma-like reaction followed by pulmonary edema, resembling ATRA syndrome). Six patients had other unusual side-effects: aseptic necrosis of the hip (1 patient), ataxic syndrome (1 patient), paranoid syndrome (2 patients), syncopal episodes (1 patient), pure red cell aplasia (1 patient). In conclusion the results of IFN-alpha and low-dose ara-C combined with ATRA in patients with early CML-chronic phase were disappointing, due to excessive toxicity. Whether different ATRA dose schedules may result in fewer side-effects and improve hematologic and cytogenetic response remains to be determined.
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PMID:Unexpected high incidence of severe toxicities associated with alpha interferon, low-dose cytosine arabinoside and all-trans retinoic acid in patients with chronic myelogenous leukemia. 1060 85