Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.5.1.1 (asparaginase)
2,695 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A randomized study was done in twenty newly diagnosed children with acute lymphoblastic leukemia. Ten children were treated with Escherichia coli L-asparaginase, and ten with Erwinia chrysanthemi L-asparaginase. L-asparaginase (ASP) treatment started halfway during ALL-induction treatment with vincristine, prednisone, daunorubicin and intrathecal methotrexate. The mean activated partial thromboplastin time (APTT) level in all children demonstrated a significant fall (P < 0.001) from 28.25 sec at diagnosis to 23.0 sec at the start of ASP treatment. In this same time interval, the mean fibrinogen level declined markedly from 3 g/l to 1.2 g/l (P < 0.001), probably due to prednisone therapy. The APTT stayed shortened during ASP therapy, whereas the hypofibrinogenemia recovered significantly faster in the Erwinia group (P < or = 0.01). Factors (F) II, V, VII and X stayed within the normal range, while F VIII and F IX were elevated. During the entire period of induction therapy, the ATIII activity remained within the normal range in both treatment groups. The protein C values, however, demonstrated a steady decline from 140% at start of ASP treatment to a mean of 81% and 93%, respectively, at the end of the ASP therapy in the E. coli and Erwinia group. Five of the ten children treated with E. coli ASP demonstrated protein C levels below 70% at the end of ASP therapy, opposed to none of the Erwinia treated patients (P = 0.03). We suggest that the effect of ASP resulting in decreased coagulation factor synthesis is in part counterbalanced by the effect of prednisone on the coagulation system, when ASP is administered at the end of ALL induction treatment. The overall effect of ASP either of E. coli or of Erwinia on the hemorrhagic system reveals a slight imbalance towards thrombosis, mainly because of a gradual decrease in protein C activity. This imbalance is less pronounced in the Erwinia group.
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PMID:Minimal effects of E. coli and Erwinia asparaginase on the coagulation system in childhood acute lymphoblastic leukemia: a randomized study. 805 4

The response to chemotherapy is determined essentially by two factors: first, pharmacokinetic factors, determining which concentration of drug reaches the malignant cells, and second, cellular drug resistance of these cells, determining how many of them will be killed by that concentration of drug. The study of cellular drug resistance has been stimulated by the development of short-term 'total cell kill' assays, such as the MTT assay, for use on patient samples. The drug resistance profiles differed markedly between ALL and ANLL, between immunophenotypic and karyotypic subgroups within ALL, and between initial and relapsed ALL. The results of the MTT assay showed a significant relation between the antileukemic activity of prednisolone in vitro and the clinical response to systemic monotherapy with that drug. At multivariate analysis including several well-known prognostic factors (WBC, age, immunophenotype) only the in vitro resistance to prednisolone, dexamethasone, L-asparaginase, and daunorubicin was significantly related to clinical outcome. At multiple regression analysis, combination of the results for prednisolone, L-asparaginase, and vincristine made it possible to distinguish between three patient groups with increasing levels of drug resistance and markedly different probabilities of 2-year disease-free survival: 100%, 83%, and 60%. These results show that in vitro drug resistance testing can give a correct prediction of prognosis, superior to that of currently used prognostic factors. Stratification of prognostic groups based on the results of drug resistance testing is feasible and should be introduced into new clinical trials. Many questions now remaining could be answered within carefully designed preclinical and clinical studies.
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PMID:Cellular drug resistance in childhood leukemia. 806 Nov 9

We reported the treatment outcome of Protocol 8704T, which included repeated L-asparaginase, for childhood T cell malignancies. Fifteen cases of acute lymphoblastic leukemia (T-ALL) and 11 cases of non-Hodgkin's lymphoma (T-NHL), aged 3 to 14 yrs (median 6 yrs), were enrolled. Twelve T-ALL had mediastinal mass. Murphy's stages of T-NHL were 6 with III and 5 with IV. Types of histology consisted of 8 lymphoblastic and 3 large cell. Treatment was performed for 2 years. Observation periods were from 14 months to 78 months (median 42 months). Twenty-three achieved remission and 6 of them were transplanted with bone marrow or peripheral stem cells in the first remission. The protocol was continued in 17 cases. Fourteen of them remain in first remission, but one died of measles and 2 died of relapse. The 5-year event-free survival was 76.1% for ALL and 65.5% for NHL. In terms of histology, it was 87.5% for lymphoblastic NHL and 33.3% for large cell NHL (p = 0.19). In terms of phenotypes in ALL, it was 88.7% for ALL positive to CD2, 5 and 7, while 2 ALL positive to CD7 alone both failed. Therefore, it was shown that this treatment protocol is very effective for T-lymphoblastic leukemia and lymphoma.
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PMID:[Outcome of treatment protocol 8704T for childhood T cell leukemia and lymphoma]. 806 18

Fifty two adults (aged 15 to 66 years) with newly diagnosed acute lymphoblastic leukemia (ALL, n = 47) or lymphoid blast phase chronic myelogenous leukemia (Ly-CML, n = 5) were managed with three distinct protocols containing idarubicin at a cumulative dose of 36, 20, and 10 mg/m2, respectively, plus vincristine, L-asparaginase, and prednisolone (IVAP-1, -2, -3). IVAP-1 was highly toxic and gave a low complete remission (CR) rate (7/17, 41%). Nine patients died of complications while severely neutropenic, and one had resistant disease. In contrast, 24 of 28 patients subsequently treated with IVAP-2 achieved a CR (86%, p 0.005), the rate of both hematological and extrahematological toxicity being significantly reduced compared with IVAP-1 (p < 0.05). With IVAP-3, 6/7 patients aged > 60 years achieved CR. IVAP-2 with total idarubicin 20 mg/m2 is a very effective and well tolerated regimen for the initial treatment of adults with ALL.
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PMID:Idarubicin in the initial treatment of adults with acute lymphoblastic leukemia: the effect of drug schedule on outcome. 822 Jan 42

We reported a case of ALL complicated with acute pancreatitis caused by L-asparaginase (L-Asp). The patient was a 42-year-old man, who showed eosinophilia in peripheral blood and an increase of lymphoblast in bone marrow. He was diagnosed as ALL (L2) and treated by JALSG '87 protocol. Remission induction chemotherapy including L-Asp was administered by 5,000 IU i.v. for 10 days. The day after giving all dose of L-Asp, slight epigastralgia developed and then became severe. After two days, s-amylase was markedly elevated, and the patient was diagnosed as acute pancreatitis caused by L-Asp. He was treated conservatively, but hyperglycemia occurred. The epigastrial tumor was palpable and gradually grew in size. CT-scan and abdominal ultrasonography revealed pancreatic pseudocyst, so he was treated by percutaneous cyst drainage. The patient died of a relapse of ALL. The prophylaxis and early diagnosis of the pancreatitis and hyperglycemia caused by L-Asp are very difficult. We have to examine more cases and pay greater attention to the chemotherapy, including L-Asp.
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PMID:[A case of ALL complicated with acute pancreatitis and pancreatic pseudocyst caused by L-asparaginase ]. 842 80

Blood coagulation abnormalities induced by administration of E. coli L-asparaginase were investigated in 25 patients with acute lymphoblastic leukemia treated according to the GIMEMA ALL 0288 trial. Dosage of L-asparaginase was relatively low (6,000 U/m2/day for 7 days total dose 42,000 U/m2) as compared to the conventional dosages (120,000-140,000 U/m2 over 10-14 days). A significant decrease in fibronogen, plasminogen, alpha2-antiplasmin and antithrombin III was observed from day IV of L-asparaginase and it was maximum on day VIII, with return to the baseline levels on day XV. Protein C levels had only a borderline reduction, while no modification of protein S or factor VII was observed. Two of the patients investigated developed thrombosis. The presence of a prothrombotic state induced even by this low dosage of E. coli L-asparaginase was suggested by a significant increase of sensitive markers of hypercoagulability such as fibrinopeptide A, thrombin-antithrombin complexes, and prothrombin fragment F1 + 2.
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PMID:Evidence of a hypercoagulable state in patients with acute lymphoblastic leukemia treated with low dose of E. coli L-asparaginase: a GIMEMA study. 844 31

A case of successful pregnancy after BMT in a 24-year-old woman with ALL, conditioned with CY, L-asparaginase, methylprednisolone and total body irradiation (TBI) is reported. A second case of two spontaneously aborted pregnancies in a woman transplanted for ALL at the age of 29 years using CY and TBI conditioning and a third case, this time a successful pregnancy in a woman transplanted for AML at age 27 years using CY and TBI conditioning are also described. There are now 6 successful live births after TBI reports of, versus 16 following regimens in which no TBI is used. This is the first report of a successful pregnancy reported in a female transplanted when older than 25 years using any TBI-containing regimen.
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PMID:Pregnancy after BMT: three case reports. 850 78

A prospective longitudinal study was conducted to determine whether single-donor fresh frozen plasma (FFP) substitution was able to influence L-asparaginase-associated hypoproteinemia. Within a 36-month period, 20 of 42 children with ALL received a total of 42 prophylactic FFP doses at a median of 10 (5-20) mliter/kg when fibrinogen levels decreased to < 60 mg/dL and thrombin time was lengthened. Laboratory monitoring before, during and after FFP substitution showed no short-term improvements and demonstrated only a minimal increase in fibrinogen and alpha 2-antiplasmin. Plasma levels of antithrombin and plasminogen remained unchanged. Furthermore, administration of FFP had no influence on thrombin generation, the plasmin/alpha 2-antiplasmin complex or enhanced D-dimer formation.
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PMID:Inefficacy of fresh frozen plasma in the treatment of L-asparaginase-induced coagulation factor deficiencies during ALL induction therapy. 864 57

In the last two decades complete remission [CR] rates for adults with acute leukemia has increased to 60 to 80%. In acute myelogenous leukemia [AML], this is due to the application of intensive induction therapies, comprising an anthracycline and a cytarabine. In acute lymphoblastic leukemia [ALL], the introduction of intensive early consolidation and CNS prophylaxis played an additional important role. These myeloablative treatments became feasible because of considerable improvements in the management of infectious and bleeding complications. The standard induction for AML further on remains the '3 + 7' schedule [daunorubicin 45 to 60 mg/m2/day x 3, I.V. and Ara-C 100 to 200 mg/m2/day x 7, 24-h infusion]. In ALL, prednisone, vincristine, L-asparaginase and an anthracyeline are the backbone of the induction therapy. Unfortunately, there has been less improvement for overall long-term survival, which is about 15 to 20% in AML and 20 to 35% in ALL beyond 5 years. More intensive post-remission regimens which include high-dose Ara-C in AML and intermediate-dose methotrexate and cyclophosphamide in ALL seem to improve these results to some extent. Allogeneic bone marrow transplantation has the most powerful anti-leukemic potential; however, because of the high peritransplant mortality [20 to 25%], its use in first CR tends to be restricted to patients with adverse prognostic features predicting early relapse, while good-risk patients are transplanted at the first signs of relapse or in second CR. In both AML and ALL, the optimal form of post-remission treatment needs to be defined.
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PMID:[Current status of therapy and prognosis in acute adult leukemia]. 862 60

The influence of two different E. coli asparaginase (ASP) preparations on fibrinolytic proteins in childhood ALL was recently reported, demonstrating a clearly significant association between ASP activity and haemostatic changes. Since the Bayer preparation is no longer available for treatment of large series of patients with ALL, the present study was designed to prospectively evaluate coagulation and fibrinolytic changes in leukaemic children receiving different doses of Medac ASP, which is now available for treatment of childhood ALL. Leukaemic children in whom ASP Medac was administered at 3 d intervals in a two-step dose reduction (5000 IU/m2, n = 10; 2500 IU/m2, n = 15) were compared with children who had received Bayer ASP 10,000 IU/m2 in the same time schedule in a former randomized trial; at the same venipuncture, blood samples for coagulation studies were obtained before each ASP administration together with serum samples for pharmacokinetic monitoring. Compared with Bayer ASP 10,000 IU/m2, patients receiving Medac ASP 5000 IU/m2 showed significantly decreased values of fibrinogen, plasminogen, and alpha 2-antiplasmin, along with significantly enhanced thrombin generation. Improvement occurred in children treated with 2500 IU/m2 Medac ASP; alpha 2-antiplasmin and D-dimer no longer differed from the Bayer group. Since both patient groups showed complete asparagine depletion during the course of ASP administration, the lower dosage of 2500 IU/m2 administered at 3 d intervals should guarantee the specific metabolic therapy for ALL, leading to depletion of the circulating pool of asparagine.
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PMID:Changes in coagulation and fibrinolysis in childhood ALL: a two-step dose reduction of one E. coli asparaginase preparation. 885 48


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