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)

An analysis of dose and schedule dependence of calcium leucovorin rescue during high-dose methotrexate therapy of ascitic forms of l1210 leukemia and Sarcoma 180 is reported. Schedules with very delayed "low-dose" leucovorin rescue following lethal doses of methotrexate were highly effective in preventing toxicity and achieved a pronounced antitumor effect in both ascites tumor models. Best results were obtained on a schedule of methotrexate (400 mg/kg s.c.) followed 16 to 20 hr later by calcium leucovorin (12 mg/kg s.c.) given once every 2 hr for a total of 5 doses. Progressive increases in the calcium leucovorin dosage on any schedule reduced both toxicity and the antitumor effect of methotrexate in each model. Following a single course of therapy, essentially no toxicity was observed, and the antitumor effects were 2-fold (L1210 leukemia) and 4-fold (Sarcoma 180) greater than a single, maximally tolerated dose (24/kg s.c.) methotrexate alone. An increase in the methotrexate dosage to 800 mg/kg s.c. with or without an increase in calcium leucovorin dosages on the same schedule did not appreciably increase the antitumor effect observed. Two courses of high-dose methotrexate (400 mg/kg s.c.) with leucovorin rescue (24 mg/kg s.c. 16, 20, and 24 hr after drug) given with an 8-day interval between courses doubled the total antitumor effect in each model with no substantial increase in toxicity and gave long-term survivors with Sarcoma 180. The results, overall, are in close agreement with prior prediction for schedule and dose dependence made on the basis of related pharmacokinetic and biochemical studies in murine tumor models reported from this laboratory.
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PMID:Optimization of high-dose methotrexate with leucovorin rescue therapy in the L1210 leukemia and sarcoma 180 murine tumor models. 30 75

A combination of radiotherapy and cytostatic drugs was used in the treatment of 39 children with primary brain tumour between 1961 and 1974, and 40 children with acute lymphoid leukaemia between 1971 and 1974. Best results were obtained with medulloblastoma using cerebrospinal radiotherapy and cytostatic drugs: 10 of 17 children are still alive. Of 40 children with acute lymphoid leukaemia 18 are still alive after cerebrospinal or cranial radiotherapy. The side effects of the combined therapy were within justifiable limits.
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PMID:[Combined radiotherapy and chemotherapy of the central nervous system in malignant neoplasms of children (author's transl)]. 105 5

Childhood leukemia in Norway in the period 1963-1974 with special emphasis on own material. Acta Paediatr Scand, 65:529, 1976. -A nation wide up-to-date survey of childhood leukemia in Norway including 499 cases in the period 1963-1974 is presented. The median survival for all cases was about one year. Around 20% of the 499 cases were still alive in Novemeber 1974. Twenty-five of the children were off therapy without any signs of relapse. In our own material thirteen of 42 cases of acute lymphatic leukemia (ALL) were still in primary remission after 3-9 1/2 years. Twelve of them were still off therapy and none had relapsed. Best results were achieved in the 31 cases of ALL followed closely by us all the time. The number of cases in continuous complete remission and the median survival rate in this series compares favourably with the last two studies published by the St. Jude group.
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PMID:Childhood leukemia in Norway from 1963-1974 with special emphasis on own material. 106 55

We describe the results of treatment with 2'-deoxycoformycin (DCF) in 68 patients with post-thymic (mature) T-cell malignancies. These included: prolymphocytic leukaemia (T-PLL), 31, HTLV-1 + adult T-cell leukaemia/lymphoma (ATLL), 20, cutaneous T-cell lymphoma (CTCL), comprising mycosis fungoides and Sezary syndrome, 13, and large granular lymphocytic leukaemia, four. Two-thirds of patients were refractory to previous therapy, which included four drug combinations. DCF was given intravenously at 4 mg m-2 weekly for the first 4 weeks and then every 2 weeks until maximal response. Toxicity was very low with only one death resulting from prolonged neutropenia. Overall response rates, partial (PR) and complete. (CR), were 38%, with variations according to diagnosis. Best responses, 54%, were seen in CTCL but limited to Sezary patients, one CR, six PR, whilst none of the mycosis fungoides responded. Responses in T-PLL were recorded in 48% including three CR (of 8-12 months' duration unmaintained) and 12 PR. Fifteen per cent of responses were seen in ATLL. The only ATLL responders - two CR, one PR - were those patients who received combination chemotherapy prior to DCF, with reduction of tumour bulk but short of PR. When results were analysed according to membrane phenotypes it was apparent that responses were seen mainly in cases with CD4+, CD8- T cells -22 of 47 (47%) - contrasting with only three of 19 (16%) with other T-cell phenotypes. We conclude that DCF is a useful therapy for the treatment of T-cell leukaemias, in particular Sezary syndrome and T-PLL, and should play a part in strategies to improve the natural history of this group of lymphoid malignancies.
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PMID:Deoxycoformycin in the treatment of mature T-cell leukaemias. 193 13

The comparison of pharmacokinetics of DNR in mouse plasma, in the DNR naturally resistant B16 melanoma and in the DNR naturally sensitive P388 leukemia showed that there is no direct correlation between total concentrations of this drug in tumours and the sensitivity resistance of these tissues. A finding which demonstrates the inadequacy of distribution models to select new potential anticancer drugs. Cytotoxicity of DNR and its metabolites to B16 melanoma and P388 leukemia cell lines were determined in vitro. Calculated inhibitory concentrations 50 (IC50) were compared to maximal concentrations determined by pharmacokinetic studies. In all cases in vitro IC50 were lower than Cmax values. Moreover, resistant cells in vivo were found to be sensitive to DNR and metabolites when they are propagated in vitro. Tissue concentrations, as well as in vitro data, were fitted to appropriate models by an original program (FADHA) which uses the simplex method to minimize a non-linear cost function. Best fit models were chosen by statistical criteria.
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PMID:Pharmacokinetics of daunorubicin and daunorubicinol in plasma, P388 and B16 tumours. Comparison with in vitro cytotoxicity data. 193 71

In 117 patients with chronic myelogenous leukaemia (CML) treatment with a combination of high-dose chemoradiotherapy plus transplantation of allogeneic bone-marrow from HLA-identical, mixed-lymphocyte-culture-identical siblings resulted in an actuarial probability of 3-year survival of 63 +/- 16% (95% confidence interval) for 39 patients transplanted in chronic phases; 36 +/- 14% for 56 transplanted in accelerated phase; and 12 +/- 15% for 22 transplanted during blast crisis. Irrespective of disease status at the time of transplantation, and in contrast to chemotherapy, a plateau-effect was observed in the survival curves starting 14 to 19 months after transplantation. The actuarial probability of recurrent or persistent leukaemia at 3 years was 7 +/- 9% for patients transplanted in chronic phase, 41 +/- 19% for accelerated phase, and 41 +/- 39% for blastic phase. All relapses occurred within 18 months of transplantation. This study demonstrates that long-term disease-free survival in CML can be achieved with bone-marrow transplantation. Best results were obtained in patients transplanted during chronic phase of the disease.
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PMID:Allogeneic bone-marrow transplantation for chronic myelogenous leukaemia. 614 57

We evaluated (i) the stability of a mixture of the three anti-cancer agents used for the treatment of leukemia, namely etoposide, cytarabine and daunorubicine, in 5% glucose, and (ii) its compatibility towards various materials during an infusion protocol as performed for therapeutic purposes in hospital practice. Etoposide and cytarabine were assayed by high-performance liquid chromatography with a C18 type column and UV detection. Daunorubicine was assayed by visible spectrophotometry. The stability study showed all three anti-cancer drugs to be stable in 5% glucose solution, both alone and mixed. Best conservation was obtained by keeping bottles containing the mixture in the dark at room temperature. During the infusion protocol used in clinical practice, etoposide, cytarabine and daunorubicine were stable and compatible with the various materials present in the infusion sets and extension tubing (polyvinyl chloride, polyethylene) and catheters (silicone). Observed variations in concentration did not exceed 10% of initial concentrations of each drug, though we would advocate changing infusion sets and extension tubing daily.
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PMID:Stability and compatibility of a mixture of the anti-cancer drugs etoposide, cytarabine and daunorubicine for infusion. 765 71

Marrow transplant from an HLA-matched sibling donor can cure CML. Best results are observed when patients are transplanted early in chronic phase. T-lymphocyte depletion of donor marrow can effectively prevent chronic graft versus host disease, but is associated with a high incidence of relapse. Hematologic relapse after marrow transplantation can be treated successfully with alpha-interferon, donor buffy coat cells or second transplant. HLA phenotypically matched and, in some cases, 1 HLA antigen mismatched unrelated donors can also be used successfully for marrow transplantation therapy of CML. Complications include an increased incidence of graft failure and graft vs. host disease. Chronic phase patients transplanted early in the disease course have the best outcome. The development of the National Marrow Donor Program in the United States and a network of donor registries throughout the world as well as the establishment of new techniques for histocompatibility testing will increase the availability of unrelated donors and expedite the donor search process. Autologous marrow transplantation can induce complete hematologic and cytogenetic remissions and may prolong survival when compared with results expected from conventional therapy for CML. Strategies are being developed to obtain benign primitive progenitors suitable for autologous marrow transplantation by positive selection techniques and to develop further post-transplant anti-leukemia cell therapy to use as an adjunct to autologous marrow transplantation for CML.
Leukemia 1993 Jul
PMID:Unrelated donor and autologous marrow transplant therapy of chronic myelogenous leukemia (CML). 832 Oct 29

This study reviews results of a radiation-free preparative regimen consisting of busulfan and cyclophosphamide in 65 unrelated allogeneic bone marrow transplant recipients. Thirty-eight patients had chronic myelogenous leukemia (17 patients chronic phase, 13 patients accelerated phase, eight patients blast phase), 19 patients had acute leukemia (second complete remission or relapse) and eight patients had myelodysplasia. The patients were transplanted at four different medical centers from July 1988 to November 1992. Ages ranged 4-48 years (median 32). Fifty-seven patients received busulfan 16 mg/kg and cyclophosphamide 120 mg/kg, and eight received busulfan at doses between 15 and 17 mg/kg and cyclophosphamide at doses 100-200 mg/kg as preparative regimens. All patients received cyclosporine for graft-versus-host disease prophylaxis; in addition 46 patients received corticosteroid, 38 methotrexate, six anti-CD5 ricin A-immunotoxin, and four T cell-depleted bone marrow. Median follow-up of survivors was 53 months (range 15-68 months). Four year actuarial survival was 24 +/- 12%. Four-year survival based on disease was 29 +/- 27% for chronic myelogenous leukemia (CML) in chronic phase, 20 +/- 9% for chronic myelogenous leukemia in accelerated phase, 0% for chronic myelogenous leukemia in blast phase, 32 +/- 40% for acute leukemia, and 38 +/- 34% for myelodysplasia. Actuarial survival was 66 +/- 40% in patients age < 20 years, vs 23 +/- 13% for patients ages 20 to 40, and 10 +/- 14% for patients age > 40 years. Fifty patients (88%) engrafted. Graft failure occurred in eight patients. Acute graft-versus-host disease grade II-IV occurred in 36 (72%). Two patients relapsed after engraftment with the donor cells and died of leukemia within a month of relapse. The most common causes of death were graft-versus-host disease (37%), and transplant-related toxicity (59%); relapse (4%) was a rare cause of death. Busulfan/cyclophosphamide is an effective preparative regimen in unrelated bone marrow transplantation permitting adequate engraftment and a low relapse rate. Best results are observed in patients less than 20 years old.
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PMID:Unrelated allogeneic bone marrow transplantation using high-dose busulfan and cyclophosphamide (BU-CY) for the preparative regimen. 873 82

Aplastic anemia is a disease that presents with a hypocellular marrow and peripheral blood pancytopenia. In Europe and the United States, it has an age-adjusted incidence per million population per year of 2.2 compared to 11.0 in Japan and Korea. Pathogenic mechanisms are varied and include intrinsic defects of hematopoietic stem cells, defects in the marrow microenvironment, and abnormal humoral or cellular immune control of hematopoiesis. In most patients, aplastic anemia is of unknown etiology, whereas in some, the disease can be related to infections, drugs and chemicals, and hereditary causes. Therapy for aplastic anemia includes blood component transfusions, antibiotics, androgenic steroids, and corticosteroids. With supportive care, most patients with aplastic anemia die within a year of diagnosis, and only approximately 20% of patients are surviving, although often with persisting hematologic abnormalities. The use of hematopoietic growth factors has shown, for the most part, only transient beneficial effects. More definitive therapy has been the use of immunosuppressive agents including antithymocyte globulin, cyclosporine, and cyclophosphamide. With immunosuppressive therapy, a variable proportion of patients respond to therapy, ranging from 20% to 80%. However, although responses may be frequent, long-term outlook is guarded because some patients may relapse with aplastic anemia, whereas others may go on to have a clonal disorder develop, including myelodysplasia, leukemia, or paroxysmal nocturnal hemoglobinuria. As a result, survival estimates at 15 to 18 years may be only on the order of 30%. More definitive therapy has been with transplants of hematopoietic stem cells from allogeneic donors. Transplants are carried out after high-dose immunosuppressive conditioning programs. Best current results show long-term, event-free survivals with successful allografts on the order of 90%.
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PMID:Aplastic anemia. 942 94


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