Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.1.1 (asparaginase)
 2,695 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fibrinolytic factors were assessed during L-asparaginase administration, to study whether their changes may predispose to a haemorrhagic or thrombotic diathesis. The total level of alpha 2-antiplasmin declined, as well as the ratio of the plasminogen-binding form of alpha 2-antiplasmin to the non-plasminogen-binding form. After cessation of L-asparaginase administration, the ratio increased to 1.6 times that of the pretreatment value. These data indicate that the plasminogen-binding form of alpha 2-antiplasmin is the form primarily synthesized in vivo. L-Asparaginase therapy reduced plasma levels of plasminogen and histidine-rich glycoprotein ( HRG ) and influenced the equilibrium between HRG , plasminogen and HRG -plasminogen complex, with a more pronounced decrease of plasminogen (62% +/- 8) and HRG (76% +/- 11) in comparison to the free-plasminogen levels (51% +/- 6). alpha 2-Macroglobulin was only slightly influenced by L-asparaginase and may consequently play a more pronounced role in inhibition. This is suggested by moderate declines in functional tests of plasmin, urokinase and tissue activator inhibition by patients plasma, and by the ratio of inhibition of these enzymes over alpha 2-antiplasmin. Thus the bleeding tendency described during L-asparaginase therapy can be ascribed not only to a temporary deficiency of coagulation factors but also to temporary alpha 2-antiplasmin deficiency.
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PMID:The influence of L-asparaginase therapy on the fibrinolytic system. 620 49

In the ongoing trial ALL-BFM 90 for the treatment of childhood non-B cell acute lymphoblastic leukemia (ALL) 1468 unselected patients (pts) were enrolled from 84 centers in Germany and Switzerland from 4/90 to 12/93. Based on the results of the previous trial ALL/NHL-BFM 86 this treatment program focused especially on therapy modifications for average (MRG) and high risk (HRG) pts, on the evaluation of therapy response for prognosis, and on the identification of high risk pts by molecular genetics. For average risk pts consolidation therapy was intensified by the addition of L-asparaginase (L-ASP) on a randomized basis. In HRG induction and consolidation therapy was modified by introduction of early intensification elements that had proved to be effective in relapsed pts. This patient group was randomized for the evaluation of the effects of G-CSF administered in the intervals between the intensification elements. Distribution of the 1376 eligible pts into the three treatment arms SRG (standard risk), MRG, and HRG was as expected (17 pts not yet assigned): 385 pts (28.0%), 834 pts (60.6%), and 140 pts (10.2%), respectively. Treatment consisted of the 8-drug induction (Protocol I), consolidation (Protocol M), reinduction (Protocol II), and maintenance therapy (total therapy duration 24 months). The drug doses and combinations were only slightly modified compared to the previous study ALL-BFM 86 with the exception of the randomized L-ASP containing arm MRG-2 (Protocol M-A) and group HRG. Preventive cranial irradiation was reduced to 12 Gy and applied to MRG and HRG pts only. As in study ALL-BFM 86, the initial response to a 7-day exposure to prednisone and to the first intrathecal injection of MTX at diagnosis was evaluated at day 8 of treatment with regard to blast count in peripheral blood (PB). In addition, pts were now investigated for the presence of blasts in the bone marrow (BM) at day 15 of treatment to compare the prognostic power of both response parameters. Identification of translocation t(9; 22) and/or BCR-ABL rearrangement characterized a small subgroup of pts that were not detected by poor initial therapy response. These pts were enrolled in HRG for more intensive treatment including allogeneic bone marrow transplantation (BMT). After a median observation time of 22 months, the overall probability for event-free survival (p-EFS) is 82 +/- 2%. 11 pts (0.8%) died before complete remission (CR) was achieved, 15 pts (1.1%) died while in CR for reasons other than relapse.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Concept and interim result of the ALL-BFM 90 therapy study in treatment of acute lymphoblastic leukemia in children and adolescents: the significance of initial therapy response in blood and bone marrow]. 752 27

Modern treatment strategies, consisting of intensive chemotherapy and cranial irradiation, have remarkably improved the prognosis for children with acute lymphoblastic leukemia. However, patients with a potential for cure are at risk of severe acute and late adverse effects of treatment. Furthermore, in 25-30% of patients treatment still fails. The objectives of the DCLSG study ALL 8 were to decrease the toxicity and to increase the effectivity of BFM-oriented treatment. Decrease of toxicity was aimed at by confirmation of the results of the previous DCLSG study ALL-7, showing that the majority (94%) of children with ALL can successfully be treated with BFM-oriented therapy without cranial irradiation, and by reduction of treatment for standard risk (SRG) patients. To increase the cure rate in medium risk (MRG) patients the efficacy of high doses of intravenous 6-mercaptopurine (HD-6MP) during protocol M and in SRG patients the efficacy of high doses of L-asparaginase (HD-L-ASP) during maintenance treatment was studied in randomized studies. Patient stratification and treatment were identical to protocol ALL-BFM90, with the following differences: no prophylactic cranial irradiation, SRG patients received only phase 1 of protocol I. Four hundred and sixty-seven patients entered the protocol: 170 SRG, 241 MRG and 56 HRG patients. The 5 years event-free survival rate for all patients was 73% (s.e. 2%); for SRG, MRG and HRG patients 85% (s.e. 3%), 73% (s.e. 3%) and 39% (s.e. 7%), respectively. In patients >1 year of age at diagnosis unfavorable prognostic factors were male sex, >25% blasts in the bone marrow at day 15 and initial white blood cell count (WBC) >50 x 10(9)/l. The cumulative risk of CNS relapse rate was 5% (s.e. 1%) at 5 years. These results confirm that the omission of cranial irradiation in BFM-oriented treatment does not jeopardize the overall good treatment results, nor does early reduction of chemotherapy in SRG patients. No benefit was observed from treatment intensification with HD-L-ASP in SRG patients, nor from HD-6MP in MRG patients.
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PMID:BFM-oriented treatment for children with acute lymphoblastic leukemia without cranial irradiation and treatment reduction for standard risk patients: results of DCLSG protocol ALL-8 (1991-1996). 1204 Apr 40