Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0034065 (pulmonary embolism)
 14,979 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Among its multiple toxic effects, L-asparaginase induces allergic reactions that may reduce its biological effect. The impact of hypersensitivity reactions on the duration of leukemia-free survival (LFS) was assessed in adults with newly diagnosed acute lymphoblastic leukemia (ALL) receiving intensive multi-agent chemotherapy. In CALGB study 8811 (Blood 1995; 85: 2025-2037), 197 adults were scheduled to receive 14 doses of Escherichia coil L-asparaginase (6000 U/m2 SC) during 7 of the first 12 weeks of chemotherapy. No further L-asparaginase was given. Chemotherapy was given for 24 months. The median follow-up time has been 5.7 years. Of the 141 patients who remained on study after 12 weeks, 82 (58%) had received all 14 planned doses; 38 (27%) had 12-13 L-asparaginase doses documented in their treatment record; 21 (15%) patients had received < or =11 doses due to a variety of toxic effects. The mean number of doses received prior to experiencing any hypersensitivity reaction was seven (range 1-11). Seven patients had mild hypersensitivity reactions, but all seven eventually received 12-14 doses of E. coil L-asparaginase. Twenty-one other patients had severe hypersensitivity reactions that required discontinuation of E. coil L-asparaginase; 20 of these patients were switched to Erwinia L-asparaginase to complete their treatment. Ultimately, 12 of these 20 patients received 14 doses of L-asparaginase in total, and six received 12-13 doses. Thus, only three of the 21 patients who had severe hypersensitivity reactions received < or =11 total L-asparaginase doses. Other L-asparaginase-related complications included pancreatitis (15 patients), hypofibrinogenemia <100mg/dl (29 patients), and deep venous thrombosis or pulmonary embolism (eight patients); some of these patients had L-asparaginase discontinued after these complications. The estimates for LFS at 3 years were 55% (95% confidence interval, 44-65%) for the patients who received all 14 L-asparaginase doses (median LFS, 5.1 years), 47% (95% CI, 33-62%) for those who received 12-13 doses, and 48% (95% CI, 29-67%) for those who received < or =11 doses. There were no significant differences between these three groups in the length of LFS (P=0.68). LFS did not correlate with a history of severe hypersensitivity reaction (P=0.67). In general, E. coil L-asparaginase was well tolerated in these adult patients, and most patients received all of the planned therapy. Patients who had mild L-asparaginase hypersensitivity reactions and patients who switched to Erwinia L-asparaginase because of more severe allergic reactions did not have significantly shorter LFS than the remaining adults treated on this ALL protocol. The possibility that E. coli L-asparaginase is inactivated or destroyed in those individuals who have become hypersensitive to it becomes less important when allergic patients are secondarily treated with Erwinia L-asparaginase.
Leukemia 1998 May
PMID:Hypersensitivity reactions to L-asparaginase do not impact on the remission duration of adults with acute lymphoblastic leukemia. 959 62

We have conducted a phase II outpatient trial testing weekly oral administration of idarubicin (ZAVEDOS-ZVD) alone to determine the rate of objective response and toxicity in poor risk acute myeloid leukemia (AML) patients over 60 years of age. The treatment consisted of three phases: induction, with 20 mg/m2 of ZVD on days 1, 8, 15 and 22; consolidation with 20 mg/m2 of ZVD for 4 weeks; and maintenance with six cycles lasting 3 months and consisting of oral 6 mercapto-purine 2 mg/kg/day, 4 days a week for 2 months; subcutaneous cytarabine 1 mg/kg, once a week for 2 months; and oral ZVD 20 mg/m2 on day 1 and day 8 of the third month. In case of failure after induction course, patients received salvage treatment with 4 weekly oral doses of 40 mg/m2 ZVD. Fifty-one patients with a median age of 76 years were enrolled and could receive induction course. Of these 51 patients, 37 could receive subsequent courses, which consisted either of consolidation, or salvage. Only 11 patients underwent maintenance treatment. Sixty-three percent of patients had to be hospitalized during induction, for a median duration of 14.5 days, and 87% required hospitalization during salvage for a median duration of 17.5 days. Only five patients (38%) required hospitalization during consolidation. There were three toxic deaths (6%), two from hemorrhage and one from pulmonary embolism. The overall response rate was 29%, with 12 patients in complete response (25%) and two in partial response (4%). The median overall survival rate is 4 months for the whole population, and the median DFS is 9.6 months among the 14 responding patients. The results of this trial show that this new weekly schedule of oral ZVD chemotherapy is feasible and effective in poor risk elderly patients with AML. This regimen may be helpful for patients unable to tolerate intensive intravenous regimens, and is a real alternative to palliative treatments.
Leukemia 1999 Oct
PMID:A phase II trial of induction and consolidation therapy of acute myeloid leukemia with weekly oral idarubicin alone in poor risk elderly patients. 1051 47

The optimal duration of treatment with vitamin K antagonists (VKA) after venous thromboembolism (VTE) in patients with Philadelphia-negative myeloproliferative neoplasms (MPNs) is uncertain. To tackle this issue, we retrospectively studied 206 patients with MPN-related VTE (deep venous thrombosis of the legs and/or pulmonary embolism). After this index event, we recorded over 695 pt-years 45 recurrences, venous in 36 cases, with an incidence rate (IR) of 6.5 per 100 pt-years (95% confidence interval (CI): 4.9-8.6). One hundred fifty-five patients received VKA; the IR of recurrent thrombosis per 100 pt-years was 4.7 (95% CI: 2.8-7.3) on VKA and 8.9 (95% CI: 5.7-13.2) off VKA (P=0.03). In patients receiving VKA, the IR of recurrent thrombosis per 100 pt-years was 5.3 (95% CI: 3.2-8.4) among 108 patients on long-term VKA and 12.8 (95% CI: 7.3-20.7) after discontinuation among the 47 who ceased treatment (P=0.008), with a doubled risk of recurrence after stopping VKA (hazard ratio: 2.21, 95% CI: 1.19-5.30). The IR of major bleeding per 100 pt-years was 2.4 (95%: CI: 1.1-4.5) on VKA and 0.7 (95% CI: 0.08-2.5) off VKA (P=0.08). In conclusion, in MPN patients with VTE recurrent thrombosis is significantly reduced by VKA and caution should be adopted in discontinuation; however, the incidence of recurrence on treatment remains high, calling for clinical trials aimed to improve prophylaxis in this setting.
Leukemia 2016 10
PMID:High rate of recurrent venous thromboembolism in patients with myeloproliferative neoplasms and effect of prophylaxis with vitamin K antagonists. 2711 12