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)

Neurological disorders, such as seizures, are not infrequently associated with anti-leukemic therapy. It has been hypothesized that a disrupted peptidergic transmission between neurons could be the cellular basis of the neurological dysfunction. Since endogenous opioids have been recently found to alter neuronal function and possess anticonvulsant properties, the cerebrospinal fluid (CSF) immunoreactive beta-endorphin levels in children with Acute Lymphoblastic Leukemia (ALL) during chemotherapy and cranial irradiation have been studied. Twenty-seven children, 2 at low, 20 at medium and 5 with high risk ALL, undergoing prophylactic treatment for meningeal leukemia, entered the study. Sequential lumbar punctures with introduction of MTX combined with oral prednisone therapy were performed; each lumbar puncture sample was collected and assayed for immunoreactive beta-endorphin. All the patients studied showed a biphasic profile of the peptide with the minimum levels reached during the induction (days 14-28) and the maximum levels detected at the end of the intensification chemotherapy (days 49-55). In the 3 groups the beta-endorphin decrease corresponded to the period of prednisone therapy; the increase was concomitant with the suspension of oral glucocorticoids. 3 patients showed tonic-clonic seizures which coincided with the lowest cerebrospinal fluid beta-endorphin levels and, in the follow-up, 13 out of 27 patients displayed EEG abnormalities. From these findings a relationship between cerebrospinal fluid beta-endorphin concentrations and neuronal excitability in patients with ALL can be suggested. It is also evidenced that oral glucocorticoid therapy has profound inhibitory effects on central beta-endorphin levels.
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PMID:Immunoreactive beta-endorphin levels in cerebrospinal fluid of children with acute lymphoblastic leukemia: relationship with glucocorticoid therapy and neurological complications. 253 Nov 80

Data from 634 patients who received HLA-identical bone-marrow transplants for acute lymphoblastic leukaemia in first or second remission were analysed to examine the influence of mode of prophylaxis against graft versus host disease on rate of relapse of leukaemia. Methotrexate was associated with a significantly lower risk of leukaemia recurrence than were other methods of GVHD prophylaxis (relative risk 0.2, p less than 0.0003, for first-remission transplants; relative risk 0.3, p less than 0.0001, for second remission transplants). The decreased risk of relapse did not seem to be mediated via an impact on incidence or severity of graft versus host disease. A direct antileukaemia effect of methotrexate is the most likely mechanism.
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PMID:Effect of methotrexate on relapse after bone-marrow transplantation for acute lymphoblastic leukaemia. International Bone Marrow Transplant Registry. 256 66

A group of 43 pediatric patients with standard-risk ALL were studied. Thirty-seven per cent of them presented with malnutrition at diagnosis. Malnourished children had a significantly worse outcome than well-nourished children. Five-year DFS was 83% for well-nourished children (WNC) and 26% for under-nourished children (UNC) (p less than 0.001). Relapses presented more frequently in the bone marrow in UNC than in WNC (56% vs 7%, p less than 0.0001). The doses of maintenance chemotherapy had to be reduced in 68% of UNC and 11% of WNC (p less than 0.005); the doses of maintenance myelosuppressive chemotherapy (6-MP, oral MTX and hydroxyldaunorubicin) received by UNC were approximately 50% of those received by WNC (p less than 0.01). The correlation between malnutrition and compromised treatment was 0.92. Malnutrition might be included as an adverse prognostic factor in acute lymphoblastic leukaemia (ALL).
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PMID:Leukaemia and nutrition. I: Malnutrition is an adverse prognostic factor in the outcome of treatment of patients with standard-risk acute lymphoblastic leukaemia. 258 44

Between January 1980 and March 1983, a study was conducted on the effects of intensification therapy in 20 adult acute leukemia patients who had achieved complete remission with induction therapy. Intensification therapy consisted of cyclic administration of six combination therapies given at gradually longer intervals, using daunorubicin, cytosine arabinoside, 6-mercaptopurine and prednisolone (DCMP), cyclocytidine (DCyMP), vincristine (DCVP), behenoyl-ara-c (BHAC-DMP), aclacinomycin (BHAC-AMP) and (ACM-MP). Six combinations were given sequentially at one-month intervals, at 2-, 3-, 4-, 5- and eventually 6-month intervals, until 5-year survival. The median remission duration was 38 months for AML, and 17 months for ALL. The median survival was 66 months for AML, and 37 months for ALL. The five year survival rate was 50%. Nine of the 20 patients are still alive. Methotrexate and prednisolone were administered intrathecally for prophylaxis of CNS leukemia on Day 4 for each intensification therapy. There was no CNS leukemia. This intensification protocol was shown to be effective in improving the prognosis of adults acute leukemia.
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PMID:[An intensification therapy of adults acute leukemia]. 264 96

Patients with acute nonlymphoblastic leukemia (ANL) in first remission (n = 38) or chronic myelocytic leukemia (CML) (n = 55) were given cyclophosphamide and total body irradiation, followed by marrow infusion from HLA-identical siblings. To evaluate postgrafting prophylaxis for acute graft-versus-host disease (GVHD), the patients were randomized to receive either methotrexate and cyclosporine (n = 43) or cyclosporine alone (n = 50). Methotrexate/cyclosporine significantly reduced the incidence and severity of acute GVHD, and improved early survival. This report updates the results with a 3.0 to 4.5 year follow-up. Methotrexate/cyclosporine did not interfere with sustained hematopoietic engraftment, although granulocyte recovery to 1,000/microL was delayed by five days on the average. The incidence of chronic GVHD was identical in the two groups (26% v 24%). Disease-free 3-year survival was slightly better in the methotrexate/cyclosporine group (65% v 54%), but this benefit was restricted to patients with CML (73% v 54%), while no improvement was seen in patients with ANL (41% v 41%). In contrast to patients with CML (relapse rates 8% v 9%), the early survival benefit among patients with ANL given methotrexate/cyclosporine was offset by an increase in leukemic relapses (29% v 16%).
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PMID:Methotrexate and cyclosporine versus cyclosporine alone for prophylaxis of graft-versus-host disease in patients given HLA-identical marrow grafts for leukemia: long-term follow-up of a controlled trial. 265 61

Four antimicrobial and three antineoplastic drugs were screened for their effects on phagocytosis and killing of Candida albicans blastospores by human neutrophil polymorphonuclear leucocytes. Amphotericin B caused significant impairment of both phagocytosis and killing, but cefuroxime and ketoconazole had no effect. Tobramycin did not affect phagocytosis, but impaired killing. Methotrexate, prednisolone and vinblastine all caused significant impairment of phagocytosis, but did not affect killing. Combinations of these seven drugs, such as are used in the treatment of acute lymphoblastic leukaemia in childhood, were also shown to inhibit phagocytosis, although no additive effects were detected. None of the drug combinations tested affected killing.
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PMID:Effect of antimicrobial and antineoplastic drugs alone and in combination on the phagocytic and candidacidal function of human polymorphonuclear leucocytes. 266 8

We report a single center experience of 222 patients (pts) less than 18 years old transplanted from 1973 to 1987. The median age was 11 years (1-18). The donor was a monozygotic twin (9 pts), an HLA-id sibling (193 pts), an HLA-id, parent (9 pts), a mismatched related donor (9 pts) and a matched unrelated donor (1 pt). Ninety-six pts were transplanted for SAA. Conditioning varied with time but the majority (59 pts) received CY 150 mg/kg and 6 Gy TAI. The long term actuarial survival is 66% with a median follow-up of 3 years. The group who received CY 200 mg/kg and MTX had a 33% long term survival (LTS). GVH was the main complication with 40% acute and 37% chronic GVHD. Chronic GVHD tended to improve with time after 2 to 4 years of evolution. Ninety pts were transplanted for leukemia (35 AML, 45 ALL and 11 CGL), 20 pts were in relapse. Pts in CR had a LTS of 40%, in pts in relapse, it was 12%. The main causes of death were: interstitial pneumonitis (30%), relapse (27%), GVH (15%). Thirty-five pts were transplanted for constitutional disease: Fanconi anemia (FA) (26 pts), Dyskeratosis congenita (2 pts), Blackfan-Diamond erythroblastopenia (2 pts), Glanzmann thrombasthenia (1 pt), osteopetrosis (1 pt) and Gaucher's disease (1 pt). In FA, the LTS is 70% with a CY 20 mg/kg, 5 Gy TAI regimen. In all disease categories, we did not find any influence of donor's sex on GVH and survival.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pediatric bone marrow transplantation for leukemia and aplastic anemia. Report of 222 cases transplanted in a single center. 267 24

The combined effect of cisplatin (CDDP) with various types of antitumor drugs was examined in P 388 leukemia in vivo. Three representative drugs were chosen from every group of alkylating agents, antitumor antibiotics, antimetabolites, and plant originated drugs. According to their dependency on administration schedules, the dose-dependent and time-dependent drugs were administered once, and daily 5 times, respectively, before and after the single administration of CDDP. In addition to these sequential combinations, simultaneous treatment with CDDP was examined for the drugs which were singly administered. The combined effect was assessed by comparing ILS (increase in life span) in a combined group with the sum of ILS's of each of the 2 single-treatment groups. Synergistic effect was observed in the combination of CDDP with all drugs except MMC. Among them CYC, CQ, ACNU, ADR, PEP, ET, VCR, and VDS produced synergistic effect in any treatment schedules, irrespective of the combination sequences. In the cases of the combination with antimetabolites, the combined effect was depended on the treatment sequences; prior treatment of 5-FU, and posterior treatment of Ara-C and MTX to CDDP administration exhibited a synergistic effect, but the combination in reverse sequence remained almost additive.
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PMID:[Combined effect of CDDP with various types of antitumor drugs against P 388 leukemia]. 273 70

Between January 1980 and March 1983, a study was conducted into the effects of postremission therapy on 20 patients with acute leukemia who had achieved complete remission through induction therapy. Postremission therapy consisted of cyclic administration of six combination therapies given at gradually longer intervals. Postremission therapy used DCMP (D, daunorubicin; C, cytosine arabinoside; M, 6-mercaptopurine; P, prednisolone), DCyMP (Cy, cyclocytidine), DCVP (V, vincristine), BHAC-DMP (BHAC, behenoyl-ara-c), BHAC-AMP (A, aclarubicin) and ACM-MP (ACM, aclacinomycin). Six combinations were given sequentially starting at one month interval, and then at 2, 3, 4, 5 and eventually 6 month intervals until 5 year survival was reached. The median remission duration was 38 months for acute myelogenous leukemia (AML), and 17 months for acute lymphoblastic leukemia (ALL). The median survival was 66 months for AML, and 33 months for ALL. The survival rate at 5 years was 60% for AML., 40% for ALL, and 50% in all 20 patients. Methotrexate and prednisolone were administered intrathecally for prophylaxis of CNS leukemia on Day 4 of each stage of postremission therapy. There was no CNS leukemia. This postremission therapy was shown to be effective in improving the prognosis of adults with acute leukemia.
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PMID:An eight year experience with gradually longer interval postremission therapy for adults with acute leukemia. 278 38

In the first part of this study the availability of folinic acid (FA) and its main active circulating metabolite, 5-methyltetrahydrofolate (5-MTHF), were studied in plasma and cerebrospinal fluid (CSF) from normal subjects after i.v. administration of 100 and 250 mg of FA. 5-MTHF rapidly appeared in plasma, the maximum value being reached at the first observation time point (1 h). FA was eliminated in plasma more slowly than 5-MTHF. Between the two doses, there was no evidence of modification in pharmacokinetic parameters (terminal half-life, clearance) for either FA or 5-MTHF in plasma and CSF; 5-MTHF was the only product detectable in CSF. Considering FA plus 5-MTHF together, the AUC (area under the curve) ratios between CSF and plasma were close to 1%. 5-MTHF was cleared very slowly from CSF (t 1/2 = 85 h). This finding suggested possible accumulation of 5-MTHF in CSF during repeated administration of FA combined with medium or high dose MTX. In the second part of the study, dealing with a group of eight children treated by such protocols, an increase in CSF 5-MTHF was detected from cycle to cycle in five (r = 0.91, P less than 0.01) with a maximum at 5 x 10(-8) M. This progressive accumulation of 5-MTHF in CSF may have a negative effect on the local action of MTX and should be taken into account for therapeutic strategies designed for the management of meningeal leukaemia.
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PMID:Evidence for CSF accumulation of 5-methyltetrahydrofolate during repeated courses of methotrexate plus folinic acid rescue. 280 57


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