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)

A 46-year-old woman was admitted to our hospital because of leukocytosis. A diagnosis of acute lymphoblastic leukemia (FAB: L2 type) was made by reviewing peripheral blood smear and bone marrow aspirate. Chromosome analysis showed the presence of Philadelphia chromosome. A combination chemotherapy with L-asparaginase, doxorubicin, vincristine, and prednisolone was started, but complete remission was not achieved. During a neutropenic period after combination chemotherapy with doxorubicin, vincristine, vinblastine, and VP-16, high fever and tender swelling of the right cheek were noticed. A diagnosis of maxillary sinusitis was made with tomography and CT scan of the maxillary sinus. Since culture of the aspirate from the maxillary sinus grew aspergillus, a diagnosis of aspergillosis of the maxillary sinus was made. Immediately after the intravenous administration of amphotericin B and the lavage of the sinus with amphotericin B was started, high fever subsided and clinical improvement was observed. Several regimens of chemotherapy failed to obtain hematological remission, she died of sepsis of Enterobactor cloacae without evidence or relapse of dissemination of aspergillosis after initial successful treatment. While a few cases with aspergillus maxillary sinusitis were reported in leukemic patients, the possible occurrence of this complication must be kept in mind in a severe neutropenic period after intensive chemotherapy. The combination of intravenous administration and local lavage of amphotericin B appeared to be an effective treatment in the Aspergillus maxillary sinusitis.
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PMID:[Aspergillosis of the maxillary sinus in a patient with Ph1 positive acute lymphoblastic leukemia: a case report]. 224 25

Forty-four previously untreated Chinese adult patients with acute lymphoblastic leukemia (ALL) were treated with vincristine, adriamycin and prednisone with or without L-asparaginase. The clinical features and prognostic factors were similar to those reported in Caucasian series. Overall complete remission (CR) rate was 52%. Duration of first remission and overall median survival were nine and 12 months respectively. The addition of L-asparaginase did not improve CR rate or duration of remission and was associated with clotting dysfunction and other adverse reactions. Factors associated with a higher CR rate include age less than 40 years, blast count less than 10 x 10(9)/l and CALLA + phenotype at presentation. Sex, platelet count and FAB morphology did not affect CR rate. Bone marrow relapse occurred in 11 patients and was associated with short survival after relapse (median two months; mean two months; range 0.5-7 months). Central nervous system relapse occurred in four patients and was compatible with relatively long survival after relapse (median 13 months; mean 12 months; range 6-12 + months). The poor CR rate and short median survival in this study could not be adequately explained by an increase in risk factors and is likely to be due to what is currently regarded as suboptimal chemotherapy.
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PMID:Acute lymphoblastic leukemia in Chinese adults in Hong Kong. 276 4

The Dutch Childhood Leukemia Study Group performed a phase III study (Study ALL V) to evaluate the effectiveness of addition of rubidomycin to induction treatment with vincristine, prednisone and L-asparaginase in children (0-15 years) with standard risk acute lymphoblastic leukemia: WBC less than 50.10(9)/l, absence of mediastinal mass and/or cerebromeningeal leukemia. Furthermore, the influence of some initial patient- en disease-characteristics on the outcome was analysed. Between May 1979 and December 1982 240 patients entered into the study and were randomized into 2 groups: group A (n = 122) received induction treatment with vincristine, prednisone and L-asparaginase; group B (n = 118) received induction treatment with vincristine, prednisone, L-asparaginase and rubidomycin. All patients received cranial irradiation (doses adjusted to age) and intrathecal methotrexate, followed by maintenance treatment with 6-mercaptopurine and methotrexate for 5 weeks, alternated with vincristine and prednisone for 2 weeks, up to 24 months. Complete remission rate was 94% in both groups. Event-free survival at 5 years after diagnosis was higher in group B (62% +/- 4.6%) than in group A (54.2% +/- 4.6%) but the difference was not significant. A higher initial WBC, age greater than or equal to 10 years and a positive acid phosphatase reaction of the leukemic cells were unfavorable prognostic factors (p less than 0.01). Sex, FAB-morphology, immunophenotype and place of treatment (center or general hospital) were not significant factors.
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PMID:[Results of treatment of children with acute lymphatic leukemia (ALL) according to the ALL V protocol of the Netherlands Working Group on Leukemia in Children]. 328 85

In a comparison of treatments for standard-risk acute lymphoblastic leukaemia in children (UKALL III), there were no differences in remission lengths between regimens with or without second-line drugs (cytosine arabinoside and asparaginase) and with continuous or discontinuous mercaptopurine. The number of infections was significantly lower when maintenance followed the less immunosuppressive modified induction period and when there were 1-week gaps each month in the administration of mercaptopurine. As in the previous trial, a higher rate of relapse in boys was found to be due partly to testicular and partly to bone marrow relapse. Cell-typing by the FAB system showed that the proportion of patients still in their first remission at 5 years was very much higher in L1 than in L2 cases.
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PMID:The treatment of acute lymphoblastic leukaemia (ALL) in childhood, UKALL III: the effects of added cytosine arabinoside and/or asparaginase, and a comparison of continuous or discontinuous mercaptopurine in regimens for standard risk ALL. 675 7

A total of 125 children, who were diagnosed as having high-risk acute lymphoblastic leukemia (ALL), were treated with two consecutive protocols designated as AL851 (1985-1988) and ALHR88 (1988-1990). All patients received induction therapy consisting of vincristine (VCR), prednisolone (PSL), daunorubicin (DNR), and I-asparaginase (I-Asp). In the ALHR88 protocol, the patients whose blasts in the bone marrow (BM) were > or = 25% on day 14 of induction therapy and who were classified into T-cell type received additional cytosine arabinoside (AraC). After consolidation with intermediate-dose methotrexate (MTX), reinduction therapy including VCR, dexamethasone, and adriamycin followed by high-dose AraC was done for all patients. Intrathecal MTX and 24Gy of cranial irradiation were used to prevent central nervous system leukemia. A maintenance therapy consisting of 6-mercaptopurine, cyclophosphamide, MTX, DNR, VCR, and AraC was administered for 3 years after achieving a complete remission (CR). CR was achieved in 51/55 (92.7%) for AL851 and 68/70 (97.1%) for ALHR88. The 5-year event-free survival rates were 49.1 +/- 6.7% in AL851 and 62.5 +/- 6.1% in ALHR88. The factors related to a poor prognosis were a high initial leukocyte count of greater than 50 x 10(9)/L (P < 0.001), an L2 morphology of leukemic cells by FAB classification (P = 0.009), the chromosomal abnormality (P = 0.004) and high residual leukemic cells in BM (> or = 25%) on day 14 of induction therapy (P < 0.001). Taking these factors into consideration, more intensive protocols were started in 1990 for the patients with high-risk ALL.
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PMID:Treatment of high-risk acute lymphoblastic leukemia in children using the AL851 and ALHR88 protocols: a report from the Kyushu-Yamaguchi Children's Cancer Study Group in Japan. 749 7

This paper reported on a series of 49 elderly patients over 60 years of age affected by acute lymphoblastic leukemia (ALL), observed at our institution from 1969 to 1993. The biological characteristics considered, median WBC count, FAB classification, immunophenotype at onset of disease, were no different from those of our adult ALL series. Overall complete remission (CR) rate of these patients was 59%, 18% had resistant disease and 23% died during induction. Overall median survival was 9 months and overall median duration of CR was 7 months. All patients were divided according to treatment into two groups: group A (13 patients) received an intensive treatment including vincristine (VCR), prednisone (PDN), daunorubicin (DNR) and L-asparaginase (L-Asp), while in group B (36 patients) were included patients who received mild conventional induction with VCR and PDN. In group A, 77% of patients achieved CR and 23% died during induction. All patients were hospitalized during induction treatment. During follow-up, among 10 CRs, five (50%) died in CR because of hemorrhage (two), infections (two) and myocardial infarction (one); five (50%) relapsed. Median survival was 4 months and median duration of CR was 3.5 months. In group B, 53% of patients obtained CR, 25% had resistant disease and 22% died during induction. During induction, 44% of patients were hospitalized. During follow-up, among 19 CRs, 14 (74%) relapsed and three (15%) died in CR because of infection (two) and cardiorespiratory failure (one). Three patients (15%) are still alive: two in first CR and one in second CR. No statistical differences between the two groups in terms of CR rate or survival were noted. Standardized therapeutic trials are needed better to evaluate results in these patients, considering also the introduction of new therapeutic agents or supportive treatments, such as growth factors.
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PMID:Acute lymphoblastic leukemia in the elderly: results of two different treatment approaches in 49 patients during a 25-year period. 756 3

This 35-year-old housewife was initially treated with vincristine, prednisolone and L-asparaginase for acute lymphoblastic leukemia (ALL, L1 by FAB classification) in 1988 and entered into complete remission. Ten months later she underwent bone marrow transplantation (BMT) from her HLA-identical and MLC-negative sister. The conditioning regimens consisted of busulfan 4 mg/kg/day for 4 days orally and cyclophosphamide 60 mg/kg/day for 2 days intravenously followed by cyclosporine and prednisolone for graft-versus-host disease prophylaxis. Fifty days after BMT, she suffered interstitial pneumonitis and a gastric ulcer, and was treated with a high dose of methylprednisolone and cimetidine. She experienced transient improvement, but soon cough, dyspnea and epigastralgia became worse. The specimens obtained by transbronchial alveolar lavage (BAL) and endoscopic gastric biopsy showed many giant cells containing inclusion bodies which were identified as cytomegalovirus (CMV). This time ganciclovir was started in addition to prednisolone. Then she gradually improved and after repeated BAL and the gastric biopsy after treatment showed no inclusion body in the specimen. Although leukocytopenia was significant for this patient, ganciclovir is considered to be useful for controlling CMV infection in both the lungs and stomach.
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PMID:[Good response to ganciclovir in a patient of cytomegalovirus (CMV) interstitial pneumonitis and gastric ulcer following allogeneic bone marrow transplantation for acute lymphoblastic leukemia]. 774 99

A randomized clinical trial of combination chemotherapy for adult acute lymphoblastic leukemia (ALL) with doxorubicin, vincristine and prednisolone with and without L-asparaginase (AdVP vs L-AdVP) was conducted, involving 58 institutions throughout Japan. After reaching complete remission (CR), patients were treated with the same regimen for more than 2 years. Among 166 evaluable cases of the 198 cases enrolled, CR rates were 63.1% (53/84) with AdVP and 64.6% (53/82) with L-AdVP (P = 0.837). Median survival times and 7-year survival rates were 12.7 months and 21.2% with AdVP, and 16.0 months and 22.3% with L-AdVP (P = 0.955 by generalized Wilcoxon test [GW], P = 0.952 by log-rank test [LR]). Median disease-free survival times and 7-year survival rates were 13.5 months and 23.8% with AdVP and 17.0 months and 30.6% with L-AdVP, showing some increments for L-AdVP but no statistical significance (P = 0.141 by GW, P = 0.300 by LR). Among the cases of extramurally confirmed FAB subtypes, CR rates were 75.9% (63/83) for the L1 subtype and 51.3% (39/76) for the L2 subtype (P = 0.001). As to adverse effects, pancreatitis was complicated more frequently in L-AdVP than in AdVP (P = 0.039). Other side effects such as hyperbilirubinemia, diabetes mellitus, diarrhea and hypofibrinogenemia were observed more frequently with L-AdVP, but with no statistical significance. Thus, addition of a single course of L-asparaginase in the induction phase of combination chemotherapy with doxorubicin, vincristine and prednisolone did not significantly enhance the effect of antileukemic treatment of adult ALL.
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PMID:Nation-wide randomized comparative study of doxorubicin, vincristine and prednisolone combination therapy with and without L-asparaginase for adult acute lymphoblastic leukemia. 830 8

Several clinical and cell biological features, such as sex, age, leukemic cell burden, morphologic FAB type, and immunophenotype, have prognostic value in childhood acute lymphoblastic leukemia (ALL). The explanation for their prognostic significance is unclear, but might be related to cellular drug resistance. We prospectively studied the relation between the above mentioned features with resistance to 13 drugs in 144 childhood ALL samples obtained at initial diagnosis. The MTT assay was used for drug resistance testing. The interindividual differences in drug resistance were very large and exceeded those between the several subgroups. There was generally no significant relation between sex, leukemic cell burden, and FAB type with drug resistance. However, subgroups with a worse prognosis as defined by age (< 18 months and > 120 months at diagnosis) or immunophenotype (pro-B ALL and T-ALL) did show relatively resistant drug resistance profiles as compared to the subgroups with a better prognosis (age 18-120 months, common and pre-B ALL). Within the group of common and pre-B ALL and compared to the intermediate age-group, samples of the younger children were significantly more resistant to daunorubicin, mitoxantrone and teniposide, and samples of the older children were significantly more resistant to prednisolone and mercaptopurine. Pro-B ALL samples were significantly more resistant to 1-asparaginase and thioguanine, and T-ALL samples were significantly more resistant to prednisolone, dexamethasone, 1-asparaginase, vincristine, vindesine, daunorubicin, doxorubicin, teniposide, and ifosfamide, than the group of common and pre-B ALL cases. We conclude that the prognostic significance of age and immunophenotype in particular may be explained, at least partly, by its relation with resistance to certain drugs. The results of this study may be useful for future rational improvements of chemotherapeutic regimens in childhood ALL.
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PMID:Clinical and cell biological features related to cellular drug resistance of childhood acute lymphoblastic leukemia cells. 859 Aug 40

We report a girl with type II Ehlers-Danlos syndrome who developed acute lymphoblastic leukemia. At the age of 5 years, she was referred to our hospital with mild hyperelasticity of skin and mild joint hypermobility, 'cigarette paper' wrinkled scarring of the forehead, and moderate ecchymoses. She was diagnosed with type II Ehlers-Danlos syndrome (mitis type). Ten months after referral, she developed acute lymphoblastic leukemia (FAB classification; L1). Her leukemia cells expressed both CD 10 and HLA-DR antigens. We treated her with L-asparaginase, prednisolone, vincristine, doxorubicin, methotrexate, and cytosine arabinoside and she has remained disease-free for 6 years since the first remission. To our knowledge, this is the first report of Ehlers-Danlos syndrome in a patient who developed acute lymphoblastic leukemia.
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PMID:Acute lymphoblastic leukemia in Ehlers-Danlos syndrome. 892 93


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