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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Hematology and cell therapy 38 (1997), S. 247-252 
    ISSN: 1279-8509
    Keywords: Acute myelogenous leukemia ; Clinical trials ; Bone-marrow transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Since the early 80s, the EORTC Leukemia Group has included 3947 patients in 8 consecutive phase III studies on acute myelogenous leukemia, with stratification according to the age groups. Some of these patients were included by other cooperative groups (GIMEMA, HOVON), within intergroup studies. The main hypotheses tested by randomization were intensive chemotherapy consolidation, allogeneic and autologous bone marrow transplantation in the younger patients. In patients aged 60 years or more, a wait and see policy followed by a palliative chemotherapy was compared to an immediate conventional induction treatment, mitoxantrone was compared to daunorubicin, and, during remission, a low dose Ara-C maintenance treatment to no maintenance. The main results can be summarized as follows: Allogeneic BMT, and, relatively, autologous BMT do better than intensive chemotherapy consolidation with regards to the disease-free survival, but not for the overall survival after remission. In the elderly, an immediate induction and a low-dose Ara-C maintenance treatment are preferable to the other options tested. Mainly in patients aged more than 45, the supplementary toxicity of more intensive chemotherapy consolidation, with high dose Ara-C, counter balanced the increased anti-leukemic effect. Finally the trials randomizing GM-CSF during induction yielded disappointing results. The EORTC LCG is currently studying the relative value of various intercalating agents during induction, and of the G-CSF as well, and, during remission the autologous peripheral stem cells compared to bone marrow transplantation.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 134 (1996), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 0165-4608
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Cancer Genetics and Cytogenetics 69 (1993), S. 156-157 
    ISSN: 0165-4608
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 0022-4731
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Cancer chemotherapy and pharmacology 24 (1989), S. 251-255 
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The main biochemical determinants involved in cytosine arabinoside (Ara-C) metabolism were studied in one lymphoblastic (Reh) and two myeloid (HL60 and K562) human leukemic cell lines exhibiting various sensitivities to Ara-C, Reh being the most and HL60 the least sensitive. The level of intracellular Ara-C accumulation and Ara-CTP formation was far more important in Reh cells than in myeloid cell lines but was not closely related to deoxycytidine kinase activity or to deoxycytidine triphosphate pool size. The level of Ara-C incorporated into DNA was similar in the three cell lines. Ara-CTP formation correlated better with the cytotoxicity to clonogenic cells than did Ara-C incorporation into DNA. DNA polymerase α was moderately inhibited to various degrees, depending on the cell line; this moderate inhibition does not seem sufficient to explain the inhibition of DNA synthesis. The activity of DNA ligase, the enzyme joining the Okazaki fragments, which was not detected in Reh cells, was strongly inhibited by Ara-C in HL60 and to a lesser degree, in K562 cells. The inhibition of DNA ligase probably also contributes to the inhibition of DNA synthesis and, thus, to the cytotoxic effect of Ara-C and may explain the smaller size of DNA fragments observed following Ara-C treatment. The variations in each critical determinant observed in these three cell lines increase the complexity and plurality of the mechanisms of Ara-C action.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-1335
    Keywords: Hodgkin's disease ; Chemotherapy ; Combination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A novel combination of epirubicin, bleomycin, vinblastine and prednisone (EBVP II) was scheduled to reduce the toxicity of chemotherapy and to improve its application in treatment of Hodgkin's disease. This combination followed a previous regimen given every 15 days (EBVP I) by the same cooperative group. EPVP II is given every 21 days with increased dosage and increased intensity of epirubicin. This regimen was given to 100 consecutive patients with favourable or unfavourable limited-stage disease (clinical stages I-IIIA) excluding very favourable stages I and II and stages IIIB and IV. Such patients first received three injections of EBVP II and were then radically irradiated; those with unfavourable prognosis factors received three subsequent injections of EBVP II. The present analysis reports the early results of such treatment and considers particularly toxicity and the obtention of complete remission, which is preeminent for a cure. EBVP II was given in full dosage in 99% of the primary set of three injections. The main toxicity was alopecia and to a lesser degree nausea and vomiting and veinitis. Complete remission was obtained in 76 patients before radiotherapy and in 20 others after radiotherapy. With a median follow-up of 30 months 1 patient died from Hodgkin's disease, 9 are alive after relapse and 90 with no evidence of disease. This treatment appears to be as efficient as previous chemotherapy, well tolerated and particularly easy to give. It deserves further comparison with other proved regimens taking into consideration the survival and quality of life of patients.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Annals of hematology 68 (1994), S. 55-60 
    ISSN: 1432-0584
    Keywords: Chronic neutrophilic leukemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Chronic neutrophilic leukemia (CNL) is a very rare entity, which has to be included among the chronic myeloid leukemias. Once an underlying cause of neutrophilia is excluded, the diagnosis of CNL is based on exclusion of chronic granulocytic and other types of chronic myeloid leukemias. The classification proposed by Sheperd et al. has proven to be helpful, but it must be completed by cytogenetic analysis and the search for bcr rearrangement by molecular biology methods, in order to confirm the absence of Philadelphia chromosome and of bcr-abl hybrid gene. We report here four cases of CNL, with confirmed absence of bcr rearrangement in two cases. Two patients died, 12 and 8 years after diagnosis, the second one following transformation into myelofibrosis with myeloid metaplasia. The other two died of acute myelogenous leukemia, the first one, 25 years after diagnosis of CNL, following a 3-year phase of acceleration. The last patient presented combined features of CNL and refractory anemia with excess of blasts, and was characterized by both progressive leukocytosis and severe thrombocytopenia; acute transformation into acute myelogenous leukemia occurred 6 months after diagnosis and death 1 month later. Among the 30 cases reported so far, plus the four presented here, combined myelodysplastic features were observed in five cases and transformation into acute myelogenous leukemia in six. Chronic neutrophilic leukemias should be reported regularity, in view of the uncertain and low frequency of this hematological disease.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0584
    Keywords: Key words Acute myeloid leukemia ; Primary resistant ; Salvage regimen ; Cytosine arabinoside ; Idarubicin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Twenty-one patients with acute myeloid leukemia (AML) who failed to enter complete remission (CR) after first-line standard-dose remission-induction therapy with 7 days of cytarabine and 3 days of daunorubicin were treated with a salvage regimen containing intermediate-dose cytosine arabinoside (Ara-C) 2×500 mg/m2/day during 7 days in combination with continuous infusions of idarubicin 12 mg/m2/day on days 1, 3, and 5. Twenty patients were considered primary resistant, and one patient had a partial remission after two remission-induction courses. Overall, 11 patients (52%, 95% confidence interval: 30–74%) entered CR. Three patients died during hypoplasia and seven patients had resistant disease or a partial remission. The remission rate in this study compares favorably with the results obtained in similar patient categories. The toxicity of this salvage regimen was remarkably mild. No extramedullary toxicity was observed except for hepatic dysfunction in seven patients. The median duration of remission was 8.5 months, and ultimately, all complete remitters have relapsed except the patient who died from infectious complications after allogeneic bone marrow transplantation (BMT). This study shows that new intensive chemotherapy regimens may be effective after failure of primary treatment. Salvage regimens containing intermediate/high-dose Ara-C and/or alternative anthracyclines or anthracenes should be induced in the treatment of young patients with de novo AML.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0584
    Keywords: Granulocyte ; Macrophage colony ; Sti-mulating factor ; Myelodysplastic syndrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To assess the effects of GM-CSF in patients with myelodysplasia, a total of 101 patients with refractory anemia (RA), RA with ringed sideroblasts (RARS), and RA with an excess of blasts provided that the percentage of blasts in the bone marrow did not exceed 10% (RAEB) were enrolled in the EORTC Leukemia Cooperative Group study 06885. They were randomized to receive two daily subcutaneous injections of rhGM-CSF (mammalian, glycosylated, Sandoz/Schering-Plough) at a daily dose of either 108μg glycoprotein (group I) or 216μg glycoprotein (group II) for 8 weeks. Response was defined as an increase in Hb (〉 2.5 g%), neutrophil count (more than 100%), or platelet count (more than 100%) without progression of the disease. After exclusion of 19 patients who did not meet the entry criteria, 82 were evaluated. Fifty-four patients (66%) responded (27 of 42 patients in group I and 27 of 40 in group II). Progressive disease was seen in two patients of group I and in four of group II. Two of the latter developed leukemia. All responses were reflected in the granulocytic series. In two patients platelet numbers also increased. Cytogenetic analysis, successfully performed in 43 cases, showed that 14 of 16 patients with normal karyotypes responded, compared with 14 of 27 patients with abnormal karyotypes (p=0.008). In some cases GM-CSF was reduced in dose or discontinued prematurely due to side effects so that only 35% of all evaluable patients finished 8 weeks of treatment without a change of dose.
    Type of Medium: Electronic Resource
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