Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Seven hundred fifty-eight unselected children entered into the United Kingdom Medical Research Council acute lymphoblastic leukaemia UKALL VIII Study and Trial were studied for differences in early treatment-related toxicity according to the type of intramuscular L-asparaginase received. Two hundred seventy-five received a product obtained from Escherichia coli and 483 the enzyme from Erwinia chrysanthemi. The E. coli patients had a significantly higher incidence of neurotoxicity, pancreatitis, and life-threatening sepsis (4%, 2%, and 20%, respectively) when compared with the Erwinia group (2%, 0%, and 18%). Severe hypersensitivity was seen in one patient from both groups and the incidence of glucose intolerance was not significantly different. These findings indicate that E. coli asparaginase may be more toxic. With a minimum follow up of 4 1/2 years there is no evidence that either product has made a significantly different contribution to disease-free survival.
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PMID:Non-randomised study comparing toxicity of Escherichia coli and Erwinia asparaginase in children with leukaemia. 223 23

A 10-year-old boy with leukaemia-associated hypercalcaemia was treated with aminohydroxypropylidene biphosphonate (AHPrBP previously APD) in a total dosage of 60 mg over 5 days, when the condition failed to respond to rehydration and frusemide and no sustained effect was produced by haemodialysis with a calcium (Ca)-free dialysate. Bone films showed no lytic lesions, and AHPrBP, which is a potent inhibitor of osteoclast-mediated bone resorption was well tolerated and induced a rapid and sustained fall in plasma Ca (from 3.42 to 2.07 mM in 5 days). Plasma magnesium and alkaline phosphatase remained normal. The results could have been affected by other drugs [vincristine, cyclophosphamide, zorubicin (Rubidazone) L-asparaginase and prednisone] which were simultaneously administered. However, the observation that: (1) the response curve of plasma Ca was similar to that reported when AHPrBP was used alone, (2) there was complete inhibition of urinary Ca excretion and (3) hypocalcaemia occurred suggests that AHPrBP was the major cause of the reduction in plasma Ca. AHPrBP should be considered a potential therapy for hypercalcaemia in childhood malignancy.
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PMID:Leukaemia-associated hypercalcaemia in a 10-year-old boy: effectiveness of aminohydroxypropylidene biphosphonate. 224 18

The knowledge about drug resistance in childhood leukemias and acute lymphoblastic leukemia (ALL) in general is limited. This is because of the lack of a suitable in vitro drug sensitivity assay, which is in part due to low in vitro ALL cell survival. We recently adapted the highly efficient 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay to test cells from ALL patients and showed that its results were comparable with those of the DiSC assay, up to now the most valid but laborious assay. In this study, in vitro drug sensitivity was assessed in cells from 82 children with leukemia, 79 of whom had ALL, with the MTT assay. Dose response curves were obtained for 6-mercaptopurine, 6-thioguanine (6-TG), prednisolone (Pred), daunorubicin (DNR), vincristine (VCR), cytosine arabinoside (Ara-C), L-asparaginase (L-Asp), mafosfamide, and mustine. A cytotoxic effect of methotrexate could be detected in only a few cases. Large interindividual differences in drug sensitivity were detected. Compared with leukemia cells from newly diagnosed patients, leukemia cells from relapsed patients were significantly more in vitro resistant to 6-TG, Pred, Ara-C, mafosfamide and mustine but not to DNR, VCR, and L-Asp. Improvements of culture medium and methods to increase MTT reduction were studied. From 10 components tested, addition of insulin and bovine serum albumin to serum-containing medium improved ALL cell survival. Addition of succinate did not increase the amount of MTT reduction. We conclude that the in vitro MTT assay highly facilitates large-scale studies on drug resistance of ALL patients that can lead to rational improvements in existing treatment protocols.
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PMID:In vitro drug sensitivity of cells from children with leukemia using the MTT assay with improved culture conditions. 225 5

Treatment of acute lymphoblastic leukaemia (ALL) with L-asparaginase (L-asp) may be associated with thrombotic complications, but the pathogenetic mechanisms of thrombus formation and persistence remain unclear. We studied the procoagulant activity (PCA) of peripheral blood mononuclear cells and some components of the plasma fibrinolytic system in 10 children with ALL undergoing remission induction therapy which includes L-asp. Mononuclear cells obtained 14 days after starting L-asp treatment generated significantly higher amounts of PCA (identified as tissue factor) than cells isolated before the first dose of L-asp and 7 days after the cessation of L-asp administration (p less than 0.01). Augmented PCA coincided with an increase in the plasma D-dimer. The plasma levels of type 1 plasminogen activator inhibitor were found significantly elevated during L-asp therapy (p less than 0.05), whereas plasminogen levels were markedly decreased (p less than 0.05). These findings suggest that, during the course of L-asp treatment, the coagulation-fibrinolysis balance is shifted towards promotion of fibrin formation and deposition. Although it remains to be conclusively established whether L-asp per se or the concurrent administration of multiple chemotherapeutic agents is responsible for these changes, the latter could contribute to the thrombotic complications associated with remission induction therapy for ALL.
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PMID:Unbalanced coagulation-fibrinolysis potential during L-asparaginase therapy in children with acute lymphoblastic leukaemia. 227 27

In 79 children treated for acute lymphoblastic leukaemia according to protocol ALL-BFM 81, serial EEG examinations were performed before, during and after therapy. Diffuse changes of the background activity were observed in 64% of the children at the time of diagnosis. During induction and reinduction treatment with vincristine and L-asparaginase, and with some delay after CNS irradiation, a marked slowing developed in up to 65% of patients. Children who had not been irradiated showed transient disturbances during treatment with medium-dose-methotrexate. Reinduction induced more abnormal EEGs in the children who had been irradiated. At the end of maintenance therapy, only slight EEG changes were found. No differences between the irradiated and non-irradiated group were then seen. Children with CNS leukaemia or seizures differed from those with an uncomplicated treatment in that they more often showed focal and persistent disturbances. In 39 patients who stayed in first remission for at least 18 months after the termination of treatment, a follow up investigation was performed. From the EEG examination, including power spectral analysis, no differences were found between irradiated and non-irradiated patients. Slowing of the dominant frequency was seen in the patients with more severe leukaemia and in those whose EEG had been markedly abnormal at diagnosis. The visually evoked potentials were normal in all groups of patients. In the brainstem auditory evoked potential, a prolongation of the latency of wave I and a decrease of the I-V interval was found in irradiated patients. We conclude that the diffuse EEG changes frequently emerging during treatment are reversible. Persistent or lateralized changes can indicate a neurological complication.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prospective neurophysiological study in children treated for acute lymphoblastic leukaemia: serial EEG during treatment and long-term follow up with evoked potentials. 227 9

Eighty-five consecutive patients with acute lymphoblastic leukaemia (ALL), having a median age of 24 years (range 10-69 years), underwent induction and consolidation chemotherapy with weekly parenteral vincristine, Adriamycin, l-asparaginase and daily oral prednisone (VAAP), followed by standard (CNS) prophylaxis. Maintenance therapy was given for 3 years and consisted of daily 6-mercaptopurine, weekly methotrexate and monthly intrathecal therapy, with drug intensification comprising either vincristine, Adriamycin and l-asparaginase (VAA) or cyclophosphamide, vincristine, cytosine arabinoside and prednisone (COAP). Complete remission (CR) was obtained in 59 patients (69%) and only the French-American-British (FAB) L1 morphology was a significant predictive factor (P = 0.048). Twenty-three patients failed to achieve CR and of these 12 had primary drug resistance. Median follow-up is currently 260 weeks, median predicted survival of all patients is 58 weeks and for those who achieved CR it is 104 weeks. Median duration of CR is 70 weeks. Of the prognostic factors for survival, only FAB L1 subtype was significant. Bone marrow relapses occurred in 29 patients, and of these 9 (31%) achieved CR. There has been CNS relapse in two patients and both have died. Eleven patients continue in CR off therapy, with a median of 152 weeks. This regimen is effective, with acceptable toxicity, and a number of patients are potentially cured. The incidence of resistant and relapsing disease is an argument for further intensifying both induction and postinduction therapy.
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PMID:Treatment of adult acute lymphoblastic leukaemia. 232 50

The preliminary results of the LAL-86 protocol applied to 43 patients diagnosed of acute lymphoblastic leukaemia (ALL) or lymphoblastic lymphoma (LL) between May 1986 and April 1989 are reported. Induction treatment consisted of one or two courses of vincristine, daunorubicin, prednisone, cytosine arabinoside and 6-thioguanine combination therapy. This phase was followed by consolidation treatment, in which VM-26, cyclophosphamide, BCNU and L-asparaginase were added to the former agents. Central nervous system prophylaxis was done with intrathecal methotrexate. Patients under 45 years of age with HLA identical sibs were subjected to allogeneic bone marrow transplantation (BMT) in the first complete remission (CR); when no HLA-identical sibs were available patients were randomised into autologous BMT or maintenance therapy. The remaining patients received maintenance chemotherapy. CR was achieved in 34 ALL patients (79%), 5 were refractory to treatment and 4 died during remission induction. Allogeneic BMT was carried out in 6 cases, autologous BMT in 3, and the remainders received chemotherapy. When performing this review, 7 patients had relapsed and the actuarial probability of 2-year duration of CR was 70%. Sixteen patients have died with a two-year disease-free survival probability of 60%. The preliminary results of the LAL-86 protocol are encouraging, but greater number of patients is needed, as well as a longer follow-up, to assess the effect of chemotherapy and compare these findings to the results of autologous or allogeneic BMT in the first RC.
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PMID:[Adult acute lymphoblastic leukemia: preliminary results of the LAL-86 protocol]. 233 81

We performed analyses of electrolytes, amino acids, albumin, alpha 2-macroglobulin, gamma-globulin and LDH in the lumbar cerebrospinal fluid of children undergoing treatment for acute lymphoblastic leukemia, non-Hodgkin-lymphoma or acute myeloid leukemia. At the time of diagnosis signs of a disturbance of the blood-brain barrier were found in some patients. During induction treatment with L-asparaginase a rise of glutamic acid and a decrease of glutamine occurred. This finding correlated with slowing of the EEG. Treatment with vincristine was associated with a slight drop of sodium and chloride concentration in serum, but not in the cerebrospinal fluid. Central nervous system prophylaxis with cranial irradiation, and to a lesser degree with intravenous medium-dose methotrexate, gave rise to a further deterioration of the blood-brain barrier function as indicated by an increase in albumin, alpha 2-macroglobulin and LDH levels. During radiotherapy the concentration of several amino acids rose, probably due to a disturbance of active carrier mechanisms. Patients with elevated albumin at the end of radiotherapy more often suffered an early leukemia relapse while still on treatment. No other clinical or electroencephalographic correlations of altered barrier function could be found.
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PMID:Electrolytes, amino acids and proteins in lumbar CSF during the treatment of acute leukemia in childhood. 233 48

A national childhood acute lymphoblastic leukemia (ALL) study was initiated in Israel in 1984 with the aim of improving results in difficult aspects of treatment including: high-risk groups, the problems of late relapses, and the effect of cranial irradiation for CNS prophylaxis in leading to late neuropsychiatric sequelae and secondary tumors. Induction of chemotherapy with a combination of 6 drugs (vincristine, cyclophosphamide, cytosine arabinoside, adriamycin, prednisone and L-asparaginase), followed by intensification with methotrexate and L-asparaginase, was introduced in both the usual and the high-risk groups. In a selected group with better prognostic factors, therapy was reduced. In an attempt to minimize the sequelae of CNS prophylactic therapy, cranial irradiation was omitted in half the patients and intrathecal (IT) triple therapy was given instead. Following 2 years of unsatisfactory preliminary results in a very high-risk group (VHR; non-T- and T-cell leukemia with WBC counts of greater than 100,000 and greater than 20,000, respectively), treatment was modified and intensified. Between Nov. 1984 and Feb. 1989, 143 patients were enrolled from 10 hospitals. During follow-up of a median of 2.5 years, there were 32 failures (2 failed remissions, 27 relapsed and 3 died of bleeding and sepsis). 107 patients are alive in first remission and an additional 8 in second and third remissions. By Kaplan-Meier life table analysis, the rates of leukemia-free interval (LFI) and event-free interval (EFI) for 4 years were 60% and 57%, respectively. Improved LFI results of 71% for 4 years were achieved in a group with non-T-cell ALL with WBC less than 100,000 (the largest group, 65% of the patients). In the small "good risk" group (10% of patients), and the T-cell group with WBC less than 100,000, LFI for 4 years were 56% and 54%, respectively. In the VHR group, modification seemed to have improved results: LFI of 41% for 3 years. CNS prophylaxis with IT triple therapy was as effective as cranial irradiation in the standard risk group. In 1 out of 33 children on this protocol a single CNS relapse occurred, as compared to 2 out of 35 matched controls with cranial irradiation. These results warrant extension of IT triple therapy to higher risk groups of childhood ALL. As for systemic treatment, increased up-front high-dose intensive therapy is recommended for all groups with ALL, but with reduction of cumulative dose to minimize late effects.
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PMID:[Israel national childhood acute lymphoblastic leukemia study]. 235 44

Therapy of acute myelogenous leukemia (AML) with sequential high-dose ara-C and asparaginase (HiDAC----ASNase) on a day 1 and 8 schedule was designed to exploit potential recruitment of residual leukemia cells following initial cytoreduction from day 1 treatment. DNA flow cytometry was used to evaluate the proliferative index (%S + G2M) of bone marrow leukemia cells from pretreatment and day 8 marrow samples. The proliferative index on day 1, day 8, and incremental change (day 8 minus day 1) were analyzed for their correlation with bone marrow aplasia on day 15 and with the attainment of subsequent complete remission. Pretreatment (day 1) and the change in proliferative index did not correlate (p greater than 0.10) with day 15 marrow aplasia or with clinical outcome. However, the magnitude of the day 8 proliferative index did relate to the attainment of bone marrow aplasia on day 15 (p = 0.05) and the attainment of complete remission (p = 0.002). Recruitment of residual leukemia cells into the proliferative phases of the cell cycle may contribute to the unique efficacy of the day 1 and 8 schedule of HIDAC----ASNase. Additionally, the cytokinetics of residual leukemia after initial chemotherapy may be predictive of outcome and could be useful as a marker for the design of optimal therapeutic regimens.
Leukemia 1990 May
PMID:Correlation of the proliferative index of residual leukemia with outcome in patients treated with sequential high dose ara-C and asparaginase. 238 77


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