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)

Improved survival of children with acute lymphoblastic leukaemia who relapse during therapy has been reported using the Capizzi maintenance regimen. We have treated ten such patients, without histocompatible donors, with this regimen, which consisted of fortnightly doses of vincristine (1.5 mg/m2) and an escalating dose of intravenous methotrexate (90-470 mg/m2) followed 24 hours later by asparaginase (15,000 units). Remission of disease had been successfully achieved in all patients using conventional therapy prior to the start of maintenance treatment. Cerebrospinal fluid concentrations of methotrexate were estimated serially in several patients but remained relatively low despite dose escalation. It appears that additional intrathecal chemotherapy is therefore necessary. Treatment was generally well tolerated but there is concern about the incidence of neurotoxicity in patients who had previously received cranial irradiation and intensive intrathecal therapy. The median duration of bone marrow remission was only 35 weeks (range 18-50). Two patients who had not been receiving IT therapy had early isolated CNS relapses. In conclusion, it appears that contrary to early expectations this treatment approach is unlikly to offer a significantly better outlook for these patients, in whom the chance of early marrow relapse remains high.
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PMID:Modified Capizzi maintenance regimen in children with relapsed acute lymphoblastic leukaemia. 345 98

Methotrexate (MTX) and L-asparaginase (ASP) are effective agents in the treatment of acute lymphoblastic leukemia (ALL). The effects of combining MTX and ASP are schedule dependent. To investigate this schedule dependency, the Cancer and Leukemia Group B (CALGB) employed vincristine and prednisone with progressive dose escalation of moderate-dose MTX (125 mg/m2) followed 24 h later with ASP (6,000 U/m2) in refractory adult ALL. We treated 38 patients with refractory or first relapse adult ALL. Most patients had received prior ASP (92%) and MTX (72%). A complete remission was achieved in 25% with a median duration of remission of 21 weeks. The median survival for the entire group was 7.4 months. Therapy was well tolerated and toxicity was acceptable. Our response rate was lower than other tandem MTX and ASP adult ALL trials. Therapy was similar with other series, with the exception of the dose of ASP employed. We conclude that tandem MTX and ASP, in the doses and schedule used here, has only modest activity in previously treated adult ALL. This regimen offers little advantage to other salvage regimens.
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PMID:Therapy of refractory adult acute lymphoblastic leukemia with vincristine and prednisone plus tandem methotrexate and L-asparaginase. Results of a Cancer and Leukemia Group B Study. 346 28

Between 1972 and 1982, 112 consecutive previously untreated adults (aged 15-69 years, median 26) commenced therapy for acute lymphoblastic leukaemia (ALL) at St Bartholomew's Hospital. The first 63 patients entered into the study received initial treatment which comprised four cycles of adriamycin and vincristine, prednisolone and L-asparaginase with the first cycle (OPAL). In 1978, six cycles were given, with escalating doses of adriamycin and cyclophosphamide from cycle 3 (HEAV'D). Central nervous system (CNS) prophylaxis incorporated intrathecal methotrexate and cytosine arabinoside with cranial irradiation. Maintenance chemotherapy consisted of 6-mercaptopurine, cyclophosphamide and methotrexate for 3 years. Results obtained with the OPAL and HEAV'D regimens were not significantly different. The overall complete remission (CR) rate was 66% (73/111), factors correlating unfavourably with achievement of CR being advanced age (P less than 0.001) and L3 morphology/B-ALL immunophenotype (P less than 0.01). Fifty-three patients have relapsed, the bone marrow being the primary site in 43. Extramedullary relapse alone occurred in 10 (seven CNS, two testicular and one skin). Only three of the 64 patients who had complete CNS prophylaxis subsequently relapsed in the CNS as an isolated site. One patient died in CR, 19 remain in continuous CR between 2.5 and 10.5 years. The median duration of remission of the 73 patients who achieved CR was 18.5 months, factors correlating favourably with duration of CR being low blast cell count at presentation (P less than 0.002) and common ALL immunophenotype (P less than 0.04). Twenty-four patients remain alive, with a median survival of all patients of 18 months. Long-term survival is possible for approximately 20% of adults with ALL treated relatively intensively.
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PMID:Treatment of acute lymphoblastic leukaemia in adults. 346 41

The outcome of sixteen treatment programs for childhood acute lymphocytic leukemia reported by cooperative study groups were reviewed and analysed. The rate of disease-free survival for 3 years or more ranged from 34% to 75%, depending on each clinical trial. Remission induction therapy always consists of at least vincristine (V) and prednisone (P). L-asparaginase or daunorubicin is generally added to VP therapy. The following central nervous system (CNS) prophylaxis therapies were compared: craniospinal irradiation cranial irradiation (either 2400 rads or 1800 rads) plus intrathecal methotrexate, intrathecal drugs (either methotrexate alone or so-called triple therapy consisting of methotrexate, cytosine arabinoside and hydrocortisone) and intermediate- or high-dose methotrexate plus intrathecal methotrexate. These therapies have reduced the incidence of CNS leukemia to less than 10%. The intensification phase was the most variable component of treatment. In order to obtain maximum leukemic cell killing early in treatment, a number of protocols are investigating the use of an intensive consolidation course. An early consolidation study by the Berlin-Munster-Frankfurt group in West Germany achieved successful results. However, intensive therapy for low-risk patients failed to improve the disease-free survival. Further studies will be needed to assess the effectiveness of prolonged intensification for patients having any of the prognostic risk features. The standard duration of therapy varies between 2 and 3 years, but the minimum duration of effective chemotherapy is still unknown. It should be clarified whether a more intensive chemotherapy, can facilitate a shorter duration of treatment.
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PMID:[End results and comparative analysis of treatment programs for childhood acute lymphocytic leukemia]. 346 55

Childhood acute lymphoblastic leukemia with an initial leukocyte count greater than or equal to 100 X 10(9)/L responds poorly to conventional chemotherapy. To extend event-free survival (EFS) in this disease, we devised a protocol that specifies intensive 2-week courses of teniposide (VM-26, 165 mg/m2) plus cytarabine (ara-C, 300 mg/m2), before and immediately after standard 4-week remission induction therapy with prednisone, vincristine, and L-asparaginase. The VM-26 and ara-C combination was also administered intermittently for the first year of continuation treatment with oral 6-mercaptopurine and methotrexate. CNS prophylaxis consisted of periodic intrathecal (IT) injections of methotrexate and delayed cranial irradiation. At a median follow-up of 4 years, the estimated EFS rate for 57 consecutive patients with leukocyte counts of 100 to 1,000 X 10(9)/L was 44%, compared with 10% for matched controls (P less than .001). Remission induction rates in the two groups were similar (82% v 72%, P = .16). Twenty-five patients in the VM-26/ara-C group have survived without adverse events for 2.7 to 6.8 years, whereas only nine of the controls achieved more than a year of EFS. The most common complications during early treatment were acute hyperkalemia from rapid tumor cell lysis and infections due to prolonged marrow aplasia. Continuation chemotherapy was well tolerated. We conclude that VM-26 plus ara-C, added to each phase of an otherwise basic regimen of chemotherapy, will substantially improve prognosis in this high-risk form of childhood leukemia.
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PMID:Teniposide plus cytarabine improves outcome in childhood acute lymphoblastic leukemia presenting with a leukocyte count greater than or equal to 100 x 10(9)/L. 347 55

Forty-five patients with acute lymphoblastic leukemia of standard risk who were treated with the same protocol of therapy are presented. Induction therapy consisted of Vincristine (5 doses), L-asparaginase (10 doses) and prednisone. Complete remission was attained in 43 cases (95%). Two different methods of CNS prophylaxis were used; radiotherapy of the skull (18 Gy) associated with intrathecal methotrexate and intermediate dose intravenous methotrexate (1 g/M, 12 dose) with simultaneously intrathecal methotrexate. With a mean follow-up time of 28 months in group A and 35 Mo in group B, 82% and 75% respectively remain in continuous complete remission (p: NS). One case of meningeal leukemia was detected in each group. There patients in group A (13.6%) and four in group B (20%) suffered a bone marrow relapse. Actuarial survival rate at 36 months were 76 among the patients in group A and 83% in group B. Our results indicate that the two methods of CNS prophylaxis are both effective and in this series we have not observed any decrease in the bone marrow relapse rate when intermediate dose methotrexate was used.
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PMID:[Acute lymphoblastic leukemia of standard risk: preliminary results obtained with protocol LL-IV-81]. 348 21

By using a modification of the microtiter solid-phase radioimmunoassay, we have measured Escherichia coli L-asparaginase (L-ASP) specific IgG, IgG4, and IgE antibodies in children who received L-ASP as part of their chemotherapy for leukemia and lymphoma. In 13 children with acute lymphoblastic leukemia induced with vincristine, prednisone, and L-ASP (10,000 IU/M2 i.v. each week for 3 weeks), seven developed high titer specific IgG antibodies. Four of the seven relapsed at the time of their peaking IgG response (6-10 months). None of the six with low or absent L-ASP antibody response have relapsed (followed for 20-35 months). In six children with allergic reactions to L-ASP reinduction, all had high titers of L-ASP specific IgG4 (greater than or equal to 20 U/ml) at the time of their reaction. In 16 other children with low L-ASP IgG4 (less than 13 U/ml), none demonstrated allergic reactions to rechallenge. Specific IgE was not consistently detectable in either group. In 21 patients with leukemia or lymphoma on L-ASP with cyclophosphamide-containing regimens, none developed significant IgG antibody response, compared with seven of 13 not receiving cyclophosphamide (p less than 0.001). We conclude: (a) development of L-ASP antibodies may have prognostic significance; (b) the detection of specific IgG4 can predict L-ASP allergy; and (c) cyclophosphamide-containing regimens reduce antibody formation to L-ASP and may allow repetitive (without anaphylaxis) and more effective (avoiding neutralizing antibodies) use of L-ASP.
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PMID:Antibody response to Escherichia coli L-asparaginase. Prognostic significance and clinical utility of antibody measurement. 352 39

Luminol-dependent chemiluminescence of whole blood (whole blood CL) was developed to estimate the phagocytic function of granulocytes and the serum opsonin activity simultaneously. Whole blood (0.1 ml) was examined directly and results were obtained within 20 minutes. Phagocytic function of granulocytes can be estimated from the peak CL of whole blood and the number of granulocytes in a specimen, and the opsonin activity from the amount of time the peak CL is shown after the addition of nonopsonized CL inducer (nonopsonized zymosan). Subsequently, whole blood CL was measured to evaluate phagocytic functions in children with disease. Patients with chronic granulomatous disease showed no CL, and one of their mothers (1/3) showed low CL, suggesting she is a carrier. Two patients with hypocomplementemia (SLE and chronic nephritis) showed low serum opsonin activity, and phagocytic function of their granulocytes was enhanced. In cord blood and newborn infants serum opsonin activity was low, and phagocytic function of granulocytes was slightly decreased in cord blood but not in newborn infants. Patients with systemic bacterial infections showed an increased phagocytic function of granulocytes. Anti-cancer drugs decreased serum opsonin activity in children with leukemia or lymphoma. The children treated with L-asparaginase had very low opsonin activity, suggesting the drug inhibits complement synthesis. The measurement of whole blood CL was useful for monitering the phagocytic functions of blood after granulocyte transfusion.
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PMID:[Chemiluminescence of whole blood--analysis of the kinetics and application of clinical examination of phagocytic functions of whole blood from various type of diseases]. 355 74

The use of L-asparaginase during remission induction in patients with leukemia is associated with coagulation abnormalities, which may present either as thrombosis or hemorrhage. However, because of the multiple pharmacologic and hematologic variables present in these patients, the exact contribution of L-asparaginase to these coagulation abnormalities is unclear. We studied platelet function and plasma coagulation parameters in 12 pediatric patients with acute lymphoblastic leukemia (ALL) receiving daily L-asparaginase as a single agent when in complete remission. Changes in the prothrombin time (PT), partial thromboplastin time (PTT), and fibrinogen, while statistically significant, remained within or close to the normal range during the study. Platelet function also remained normal during the study. In contrast, levels of protein C antigen decreased to a mean of 42%, a significant change from pretreatment values. Levels of antithrombin III (AT III) were likewise depressed to 15 mg/dL (34% of pretreatment value). Despite these changes in the levels of physiologic inhibitors of coagulation, this schedule of L-asparaginase administration was associated with only rare clinical thrombosis, and this study suggests that the development of this complication may be dependent on the presence of additional factors.
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PMID:Effect of L-asparaginase administration on coagulation and platelet function in children with leukemia. 357 67

A 41-year-old male was diagnosed as acute lymphocytic leukemia (ALL) in November, 1982 and partial remission was obtained by a combination chemotherapy of LVP, DVP ABOP and VAMP. In January, 1983, peripheral blood showed an increasing number of leukemic cells and he was readmitted to our hospital. WBC count in the peripheral blood was 13,200/mm3 and an 82% ratio of leukemic cells was observed. Bone marrow aspiration showed a hypercellularity of 89.4% leukemic cells. High-dose Ara-C therapy was started at a dose of 3 g/m2 i.v. every 12 hours for 6 days. Leukemic cells in peripheral blood were rapidly decreased in number, and the nucleated cell count of bone marrow was also reduced after 3 weeks of treatment, however 95% of leukemic cells remained. Low-dose L-asparaginase was then supplemented at a dose of 2000 U for 3 days, and 2 months later complete remission was achieved. The side effects associated with this high-dose Ara-C therapy were nausea, vomiting, diarrhea, fever and conjunctivitis, although these were tolerable. These observations suggest that high-dose Ara-C combined with L-asparaginase should be added to the treatment of leukemia which is refractory to conventional chemotherapy.
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PMID:[Complete remission obtained in refractory acute lymphocytic leukemia using high-dose cytosine arabinoside combined with low-dose L-asparaginase]. 385 16


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