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  • 1
    ISSN: 1432-0584
    Keywords: Key words Acute myeloid leukemia ; Myelodysplastic syndrome ; Secondary leukemia ; Interleukin-2 ; G-CSF
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Intensive chemotherapy followed by treatment with interleukin-2 (IL-2) was evaluated in a prospective, randomized, multicenter trial including 18 patients with refractory anemia with excess of blasts in transformation (RAEB-T), 86 patients with acute myeloid leukemia (AML) evolving from myelodysplastic syndromes, and six patients with secondary AML after previous chemotherapy. Median age was 58 years (range: 18–76 years). Forty-nine patients (45%) achieved a complete remission (CR) after two induction cycles with idarubicin, ara-C, and etoposide, 52% of them aged ≤60 years and 35% aged 〉60 years (p=0.06). After two consolidation courses, patients were randomized to four cycles of either high- or low-dose IL-2. Patients aged up to 55 years with an HLA-identical sibling donor were eligible for allogeneic bone marrow transplantation. The median relapse-free survival was 12.5 months, with a probability of ongoing CR at 6.5 years of 19%. Overall survival of all patients was 8 months, and 21 months for the CR patients. Median survival was significantly longer among patients aged ≤60 years than among the older patients (16 vs 6 months, p〈0.001). Median duration of survival and relapse-free survival were not statistically different in the two IL-2 treatment arms.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0584
    Keywords: Key words PBPC mobilization ; CD34+ cells ; G-CSF ; Malignant lymphoma ; Multiple myeloma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We retrospectively analyzed factors influencing PBPC mobilization during steady-state hematopoiesis in 52 patients with malignant lymphoma (n=35) or multiple myeloma (n=17) who received 77 cycles of G-CSF (12.5–50 μg G-CSF/kg/day). For 15 of these patients, the first mobilization cycle (12.5 μg G-CSF/kg/day) was followed by a second course with an increased dose of G-CSF (25 or 50 μg/kg/day). Leukapheresis was started on day 4, about 2 h after s.c. G-CSF administration, and repeated on 2–5 consecutive days. CD34+ cells were determined by flow cytometry in each apheresis product and in the peripheral blood prior to G-CSF administration, beginning on day 4. Colony assays were performed on cryopreserved samples prior to autografting. In the 15 patients receiving two mobilization cycles the higher G-CSF dose was associated with higher levels of CD34+ cells, a higher mean yield of CD34+ cells per apheresis (p〈0.05), and a higher percentage of successful (〉2×106 CD34+ cells/kg) collections (p=0.058). Patients with limited previous cytotoxic therapy (n=19, up to six cycles of a standard regimen such as CHOP and/or less than 20% marrow irradiation) who received a daily dose of 12.5 μg G-CSF/kg had higher levels of circulating CD34+ cells, a higher mean yield of CD34+ cells per apheresis (p〈0.05), and a higher percentage of successful collections (p〈0.05) compared with patients previously treated with more intensive radiochemotherapy (n=15). Ten of 20 patients (50%) who failed during the first cycle were successful during subsequent cycles with escalated doses of G-CSF. Trough levels of circulating CD34+ cells on day 4 were predictive for success or failure to achieve 〉2×106 CD34+ cells/kg, especially in heavily pretreated patients. In conclusion, a daily dose of 12.5 μg G-CSF/kg seems sufficient to mobilize PBPC during steady-state hematopoiesis in the majority of patients who have received limited previous radiochemotherapy. Higher doses of G-CSF, up to 50 μg/kg/day, mobilize more PBPC and should be considered for patients previously treated with intensive radiochemotherapy or those failing to mobilize sufficient numbers of CD34+ cells with lower doses of G-CSF.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1076
    Keywords: Myopathy ; Convulsions ; Mitochondria ; Respiratory chain ; Coenzyme Q
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A patient is presented who had therapy-resistant epileptic seizures from the 7th day of life. Examination at the age of 17 months revealed a mentally retarded boy with epileptic seizures, generalised myoclonic contractions, and abnormal ocular movements. A cerebral CT scan showed central and cortical atrophy. Lactate levels in serum, cerebrospinal fluid and urine were elevated, the pyruvate level was raised in serum. A quadriceps muscle biopsy revealed aspecific morphologic signs of a myopathy. Biochemical analysis showed decreased substrate oxidation rates in the mitochondria associated with low rates of ATP production. Total and free carnitine levels were decreased. Investigation of the respiratory chain revealed a defect in the proximal part of respiratory chain revealed a defect in the proximal part of respiratory chain involving the region of coenzyme Q. Based on clinical and chemical data it is likely that the patient is suffering from a multi-system disorder.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1076
    Keywords: Myopathy ; Mitochondria ; Respiratory chain ; Succinate cytochrome c reductase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A boy presented suffering from generalised weakness, exercise intolerance and lactic acidosis. The weakness became evident at 2 years. A cerebral CT-scan showed cerebellar atrophy and central and peripheral atrophy of both hemispheres. With trichrome staining about 20% of the muscle fibres showed large areas containing redstaining granular material. Electron microscopic examination showed that this material consisted of areas of mitochondrial proliferation, most of the mitochondria having abnormal ultrastructural characteristics. Pyruvate dehydrogenase complex and citric acid cycle activities were determined by measuring 14CO2 production from various labelled substrates. Diminished oxidation rates were found with the patient's muscle homogenate for all substrates tested, indicating a defect in the respiratory chain. The cytochromes were present in normal quantities. Succinate cytochrome c reductase activity was very decreased. Carnitine concentration was decreased in serum and in muscle as well.
    Type of Medium: Electronic Resource
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