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)

42 patients with ALL were treated according to the following protocol: induction with vincristine + prednisone (+/- L-asparaginase), CNS-prophylaxis with cranial irradiation (2400 rads) and intrathecal methotrexate, maintenance for 3 years with 6-MP 50 mg/m2/d p.o. + MTX 75-150 mg/m2/2 wk i.v. X 4, alternating in a cyclic fashion with 6-MP 50 mg/m2/d p.o. + cyclophophshamide 600 mg/m2/2 wk i.v. X 4. The observation time is 24-67 (median 49) months. The actuarial complete remission curve shows 40% continuous complete remissions at 36 months and 30% at 60 months.--The frequency and temporal distribution of typical infectious complications are presented. The incidence of varicella was comparable to that in a southgerman normal control group (5,7% per year). During treatment there were two zoster manifestations per one varicella case, the incidence of zoster being 1 case per 106 patient-months, viz 11,4% per year.
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PMID:[Treatment of ALL in children. Results and side effects with a modification of protocol memphis VII (author's transl)]. 27 17

From February 1986 to January 1991 the Pediatric Oncology Group (POG) treated 2404 children or adolescents with acute lymphoblastic leukemia (ALL) on immunophenotype (T-, B-, Pre-B, or Early pre-B-cell), age, and leukocyte count based treatment protocols (ALinC 14, T-cell 3, B-cell and infant leukemia studies). The immunophenotypic subgroups comprised 78.9% B-precursor cell, 15.1% T-cell, 2.0% B-cell, and 4% infant ALL. Patients with B-progenitor cell ALL were stratified by age and leukocyte count and randomized to receive induction therapy comprised of vincristine, prednisone, and asparaginase with triple intrathecal chemotherapy (methotrexate, hydrocortisone, cytarabine), followed by intensification with moderate-dose MTX (Regimen A), moderate-dose MTX plus asparaginase (Regimen B), moderate-dose MTX plus cytarabine given early (Regimen C), or moderate-dose MTX plus cytarabine given over the first 16 months of therapy (Regimen D). Continuation therapy comprised mercaptopurine and methotrexate with vincristine plus prednisone pulses. Central nervous system preventive treatment was continued for two years. Patients with T-cell or B-cell ALL or infants less than 1 yr old were treated on individual very intensive multiagent therapy protocols. The 4-year event-free survival for all patients was 66.4% +/- 2.4%; B-precursor ALL approximately 72%, T-ALL approximately 50%, B-ALL approximately 60%, and infants less than 1 yr old approximately 16.5%. We conclude that about two-thirds of newly diagnosed children with ALL can be cured with this approach which spares the majority of children exposure to alkylating agents, anthracyclines, epipodophylotoxins, and irradiation, diminishing the risks of serious acute and late effects.
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PMID:Current results of studies of immunophenotype-, age- and leukocyte-based therapy for children with acute lymphoblastic leukemia. The Pediatric Oncology Group. 157 22

Plasma homocysteine was determined in 12 children with acute lymphoblastic leukemia. The patients were investigated prior to chemotherapy (stage I), during seven weeks of induction chemotherapy (stage II), and thereafter during intermittent high-dose methotrexate (HD-MTX) therapy (stage III). The patients were followed for a period of three to 15 months, and the study included a total of 80 HD-MTX courses. Before start of chemotherapy (stage I), the average plasma homocysteine level in the children with leukemia was 13.18 +/- 6.23 (SD) mumol/liter, which is significantly (P less than 0.001) higher than the level in control children (6.52 +/- 1.21 mumol/liter). The plasma homocysteine level in the patients was positively correlated with the peripheral white blood cell count (P less than 0.01) and negatively correlated with serum folate (P less than 0.02). The serum folate was normal or subnormal in these patients. During induction therapy with cytotoxic drugs such as vincristine, asparaginase, and intrathecal MTX (stage II), there was a drastic change in plasma homocysteine as a function of time. A reciprocal alteration in serum folate was observed, suggesting fluctuating intracellular folate status at this stage of therapy. At the end of stage II (about seven weeks), there was a significant (P less than 0.01) reduction in total homocysteine (to 7.08 +/- 3.84 mumol/liter). HD-MTX (8 g/m2) therapy with 5-formyltetrahydrofolate "rescue" (stage III) was usually begun about seven weeks after start of chemotherapy, and the patients were followed for two to eight courses separated by three to eight weeks. Plasma homocysteine showed a transient increase (26-64%) following each MTX infusion. After three MTX infusions, basal total plasma homocysteine was reduced to 5.56 +/- 1.12 mumol/liter. During most MTX infusions, there was a variable reduction (17-56%) in plasma methionine followed by a rebound increase. It is concluded that plasma homocysteine in children with acute lymphoblastic leukemia is elevated prior to therapy, probably because of occasional folate deficiency and increased burden of proliferating cells. During induction therapy, monitoring plasma homocysteine and serum folate both suggest a labile folate homeostasis, usually a deficiency state. HD-MTX induced a temporary intracellular folate depletion before 5-formyl-tetrahydrofolate was administered, as judged by a transient homocysteinemia. The methionine depletion may interfere with the antileukemic effect of MTX.
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PMID:Plasma homocysteine in children with acute lymphoblastic leukemia: changes during a chemotherapeutic regimen including methotrexate. 198 22

From 1985 to 1989, we treated a total of 24 adult patients with acute lymphoblastic leukemia, 17 males and 7 females, median age 26 (range 16-70 yr), with a protocol consisting of remission induction with Adriamycin (ADR), vincristine (VCR), prednisolone (PDN) and 1-asparaginase (ASP), followed by two consolidation courses with ADR, VCR, cyclophosphamide, methotrexate and PDN (Ad-VEMP), combined with CNS-prophylaxis (intrathecal MTX and PDN). Cyclic chemotherapy with VMM (vindesine, 6-MP and MTX) and Ad-VEMP regimen or therapy with VMM regimen only was used to maintain remission. Twenty patients (83.3%) achieved complete remission. The median durations of overall survival and complete remission were 20 and 18 months respectively. The significant unfavorable prognostic factors associated with survival were old age (more than 50 yr), high WBC counts on admission (more than 20,000/microliters) and low nadir of WBC counts (less than 500/microliters). The responders who received ASP for a period of 10 days had longer survival durations than did other responders. Remission did not continue long enough with our protocol, although a high CR rate was achieved. We conclude that the design of consolidation and maintenance therapy must be improved in order to obtain a longer duration with our protocol.
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PMID:[Treatment of adult acute lymphoblastic leukemia with Ad-VP-L regimen]. 202 Jan 19

Thirty-three patients with ALL/AUL in first relapse were treated with an induction of prednisone, vindesine, daunorubicin, Erwinia asparaginase, i.t. MTX (phase I), high-dose cytarabine, and etoposide (phase II). Twenty-one (64%) achieved a complete remission, one a partial remission. Side effects of induction-phase I were predominantly hematological with subsequent infections and gastrointestinal toxicity. In phase II some patients had additional cutaneous, ocular, and hepatic toxicity. The treatment efficiently induced remissions with tolerable toxicity in relapsed ALL. The disease-free survival, however, needs to be improved.
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PMID:Treatment of relapsed acute lymphocytic leukemia in adults. 218 34

High-dose methotrexate (HDMTX, 1,000 mg/m2) and cranial irradiation/sequential chemotherapy (RTSC) were compared for ability to extend complete remission durations in children with acute lymphoblastic leukemia (ALL). Three hundred thirty patients were enrolled in the study, according to our criteria for standard-risk ALL: a leukocyte count less than 100 X 10(9)/L, no mediastinal mass, no leukemic involvement of the central nervous system (CNS), and blast cells lacking sheep erythrocyte receptors and surface immunoglobulin. Prednisone-vincristine-asparaginase induced complete remissions in 95% of the patients, who were then randomized to receive either HDMTX (n = 154) or RTSC (n = 155). HDMTX was administered with intrathecal MTX for the first 3 weeks following remission induction, and then every 6 weeks with daily mercaptopurine (MP) and weekly oral MTX for a total of 18 months. The RTSC regimen consisted of 1,800 cGy cranial irradiation and intrathecal MTX for 3 weeks, followed by MP/MTX, cyclophosphamide/doxorubicin, and teniposide/cytarabine administered sequentially over 18 months. The final 12 months of treatment for both groups was MP and oral MTX; all patients received intrathecal MTX every 12 weeks. With a median follow-up of 5 years, complete remission durations have been significantly longer among children treated with HDMTX, compared with RTSC (P = .049) or historical institutional control regimens (P = .002). Approximately 67% of the patients receiving HDMTX and 56% of those receiving RTSC are expected to be in continuous complete remission at 4 years. Overall, isolated CNS relapse rates were similar (P = .17) in the two treatment groups, although by newer risk criteria cranial irradiation could be expected to provide better protection in patients with an unfavorable prognosis. These findings indicate that addition of intermittent HDMTX infusions to conventional chemotherapy is an effective method for extending complete remissions in children with ALL.
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PMID:High-dose methotrexate improves clinical outcome in children with acute lymphoblastic leukemia: St. Jude Total Therapy Study X. 305 51

Twenty-three children with refractory or relapsed non-Hodgkin's lymphoma (NHL) received high-dose methotrexate (HD-MTX), and 9 received Ara-C by continuous intravenous infusion, as phase II studies. They all had previously received a protocol including vincristine, adriamycin, cyclophosphamide, IV push Ara-C, asparaginase, intrathecal MTX, and cranial irradiation, and had failed to respond or had relapsed. HD-MTX was given at the dose of 6 g/m2 or more with leucovorin rescue, Ara-C at the dose of 100 mg/m2/day by continuous infusion over 10 days. Among the 22 evaluable patients receiving HD-MTX, 10 responses (7 CR; 3 PR) were observed. Among the 9 patients receiving Ara-C, 4 responded (1 CR; 3 PR). Toxicity in those previously heavily treated patients was acceptable. These two drugs are now successfully included in childhood NHL treatment protocols.
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PMID:High-dose methotrexate and continuous infusion Ara-C in children's non-Hodgkin's lymphoma: phase II studies and their use in further protocols. 315 14

In order to reduce the toxicity of the otherwise very effective childhood ALL treatment protocol BFM 76/79 asparaginase was omitted from the 4-drug induction regimen and placed as single drug before the intensification phase. In addition the effect of 3-monthly intermediate dose methotrexate (ID-MTX) pulses versus conventional vincristine (VCR) pulses during maintenance therapy was studied. Of 145 evaluable patients 124 (85.5%) survive in continuous and complete remission (CCR) at a median observation time of 21 (1,5-47) months. The expected rate of patients in CCR at 4 years is 75% respectively 80% after exclusion of 4 patients with fatal complications and one remission failure. These relapse free survival data re equal to the BFM 76/79 and 79/81 results. There was very few therapy related morbidity and no mortality from the COALL-80 induction therapy modification. The intensification phase, however, which was adopted from the BFM study without modification was difficult to manage and was not free of life threatening mostly infectious complications which were fatal in 4 cases. ID-MTX pulses did not prove superior to conventional VCR pulses. The relapse rate in patients with the c-ALL subtype was markedly lower than in any other subtype, remarkably also than in the undifferentiated type.
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PMID:[COALL-80 therapy in the management of acute lymphoblastic leukemia in childhood--an interim report]. 657 3

Between 1972 and 1974, Childrens Cancer Study Group enrolled 724 children with newly diagnosed acute lymphoblastic leukemia on a single randomized clinical trial. Study CCG-101 was designed to test four types of presymptomatic central nervous system and sanctuary therapies consisting of (a) 2400-rad craniospinal radiation therapy (RT) plus 1200-rad extended-field RT, which included the liver, spleen, kidneys, lower abdomen, and gonads; (b) 2400-rad craniospinal RT; (c) 2400-rad cranial RT plus intrathecal methotrexate (i.t. MTX); and (d) i.t. MTX alone. Patients all received a 28-day induction course of vincristine, prednisone, and L-asparaginase and were maintained subsequently on a regimen consisting of daily 6-mercaptopurine, weekly MTX, and monthly pulses of vincristine and prednisone. Patients treated with six doses of i.t. MTX alone had a significantly higher incidence of central nervous system relapse than did patients treated with 2400-rad craniospinal RT plus 1200-rad abdominal RT, 2400-rad craniospinal RT, or 2400-rad cranial RT plus i.t. MTX. There was no significant differences in marrow remission duration or survival of the treatment groups. There appears to be a benefit with regard to length of bone marrow remission and survival for patients with initial white blood counts greater than or equal to 20,000/cu mm treated with cranial RT plus i.t. MTX. The majority of the patients remaining on study have now discontinued maintenance therapy. The 8-year overall estimated survival rate on this study is 56%, and the disease-free survival rate is 52%.
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PMID:Sanctuary therapy: a randomized trial of 724 children with previously untreated acute lymphoblastic leukemia: A Report from Children's Cancer Study Group. 703 27

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


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