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S Kleiner

Publications and source records attributed to S Kleiner.

At least 19 recordsLinked to original sources
PubMed2001

ICE--an efficient drug combination for stem cell mobilization and high-dose treatment of malignant lymphoma.

Between 1989 and 1999 we studied the ICE regimen in sequential trials in 290 patients with malignant lymphoma and germ-cell tumours. For patients with relapsed or refractory lymphoma we could demonstrate a comparable efficacy of ICE to other high-dose chemotherapy (HDCT) regimens but with a toxicity profile in favour of ICE. From a retrospective comparative analysis of ICE as HDCT regimen in patients with malignant lymphoma and germ-cell tumours we conclude that the characteristic toxicity profile of ICE varies depending on prior drug exposure of individual patients. Further dose intensification of ICE may be achieved with acceptable toxicity by adding further drugs (e.g. anthracyclines) or by treatment with sequential cycles of ICE (Tandem-HDCT). More convenient drug formulations (e.g. etoposide phosphate) might further improve the therapeutic index of ICE.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

High-dose chemotherapy with carboplatin, etoposide and ifosfamide followed by autologous stem cell rescue in patients with relapsed or refractory malignant lymphomas: a phase I/II study.

Patients with relapsed or refractory non-Hodgkin's lymphomas (NHL) and Hodgkin's disease (HD) with recurrences after an anthracyclin-containing regimen only have a chance of cure of below 10% with conventional chemotherapy. In order to improve their prognosis, we started a phase I/II trial using high-dose therapy comprising carboplatin, together with etoposide and ifosfamide (CEI), followed by autologous stem cell rescue (ASCR) as consolidation after salvage treatment. Since September 1990, 40 patients with intensively pretreated advanced NHL (n = 24) or HD (n = 16) received one cycle of high-dose therapy (HDT) consisting of carboplatin 1500 mg/m2, ifosfamide 10 g/m2 and etoposide in escalating doses from 1200 mg/m2 to 2400 mg/m2 followed by ASCR. Thirty-nine patients were assessable for toxicity and response. The following doses appeared to be safe: carboplatin 1500 mg/m2, etoposide 2400 mg/m2 and ifosfamide 10 g/m2. All patients developed grade 3 nausea and grade 3 or 4 mucositis. Granulocytopenic fever occurred in 100% with grade 4 infections in 15%. Mild transient kidney toxicity was noted in 36% and liver toxicity in 20% of patients. One toxic death occurred (2.5%). Objective responses were obtained in 36 of 39 patients (92%) with complete remissions (CR) in 24 patients (61.5%) and partial remissions (PR) in 12 (30.7%). Median observation time for surviving patients was 23.3 months (range 3.4-52.3). The probabilities of overall, event-free and relapse-free survival at 2 years are 62, 39 and 55%, respectively. Patients with primary refractory disease or resistant relapse had a poor prognosis. High-dose carboplatin, etoposide and ifosfamide plus autologous stem cell rescue represents an effective, potentially curative salvage treatment with acceptable toxicities.

Adolescent↗
PubMed1996

Nucleus basalis magnocellularis and pedunculopontine tegmental nucleus: control of the slow EEG waves in rats.

Certain human disorders, which are characterized by learning and memory disturbances, are also accompanied by synchronizations of the cortical electroencephalogram (EEG). Although the EEG synchronization was casually related to the degeneration of the cholinergic basal forebrain, degenerations were found also in the cholinergic pontomesencephalic tegmentum. The present study was carried out to prove whether lesions of rat's pedunculopontine tegmental nucleus (PPTg) may cause EEG synchronizations like lesions of the basal forebrain. The effects of the unilateral ibotenic acid lesions of the nucleus basalis magnocellularis (NBM) and of the PPTg on the frontal and occipital EEG were compared in different behavioural states. The NBM lesion caused unilateral spectral power increases of all frequencies up to 20 Hz in the frontal EEG that were stronger with increased arousal level. Additionally, synchronized spike and wave discharges appeared in the frontal EEG. The NBM may suppress especially the delta EEG waves in the frontal motor cortex during motor active behaviours. The PPTg lesion caused unilateral suppressions of the occipital theta rhythm during exploratoring sniffing. During grooming the power of the frontal delta waves were elevated. Furthermore, the PPTg lesion caused a suppression of slow sleep waves. The results may indicate that a degeneration of both brain regions may change differently the power of the cortical slow EEG waves.

Acetylcholinesterase↗
PubMed1993

Immunotyping of blasts in refractory anaemia with excess of blasts.

A study of immunological markers was performed in 16 patients with newly diagnosed refractory anaemia with excess of blasts (RAEB) and RAEB in transformation (RAEB-T) and in 12 other patients with acute myeloid leukaemia evolving from RAEB or RAEB-T. Immunocytochemical investigation of bone marrow blasts was done using a modified indirect immunoperoxidase technique. This method permitted accurate morphological identification of blasts and other cells in bone marrow. The monoclonal antibodies used in RAEB and RAEB-T samples were anti-CD34, -c-kit, -HLA-DR and -CD13. The range of CD34 expression of blasts in RAEB samples was 1-14% (mean 6.2%) and in RAEB-T samples 29-48% (mean 35.5%). CD34 positivity was detected in 3-94% (mean 47.4%) of the bone marrow blasts in acute myeloid leukaemia evolving from RAEB and RAEB-T. Expression of c-kit was demonstrated only in a low percentage of blast cells in RAEB, RAEB-T and acute myeloid leukaemia following myelodysplasia. A high percentage (> 30%) of blasts in most patients with RAEB, RAEB-T and acute myeloid leukaemia was HLA-DR and CD13 positive. We observed the transformation from RAEB to acute myeloid leukaemia in three patients. The proportion of CD34 positive blasts increased to 25% and 32% in two patients. The third patient showed an unchanged percentage of CD34 positivity of blasts. These findings indicate that the CD34 positivity of blasts increases with the progression of myelodysplasia to RAEB-T and acute myeloid leukaemia demonstrating the instability of the clonal defect in myelodysplasia.

Acute Disease↗
PubMed1992

Analysis of chronic lymphoid leukaemias according to FAB.

We have studied the immunophenotypic features in patients with chronic lymphoid leukaemia and investigated the suitability of classification according to guidelines of the French-American-British (FAB) group. Immunophenotyping was carried out on cytocentrifuge preparations of mononuclear blood leukocytes using the alkaline phosphatase-antialkaline phosphatase (APAAP) method. The 114 leukaemias, including 58 cases of B-chronic lymphocytic leukaemia (B-CLL), 3 Waldenström's macroglobulinaemia, 6 prolymphocytic leukaemia (B-PL), 13 B-CLL/PL, 4 B-CLL of mixed cell type, 8 splenic lymphoma with villous lymphocytes (SLVL), 8 hairy cell leukaemia (HCL), two HCL variant, three leukaemic phase of follicular lymphoma, two leukaemic phase of intermediate lymphoma, two plasma cell leukaemia and two chronic T-cell leukaemia, were investigated. The 111 of 112 B-chronic lymphoid leukaemias (B-CLL + B-PL + B-CLL/PL + SLVL + HCL etc.) showed monotypic light chains. The antibody HML1 was highly specific for HCL. The antibodies CD11c and CD25 were positive in all HCL cases, but were not specific for this disease. CD5 positivity and CD22s negativity were found in most patients with B-CLL, B-CLL/PL and B-CLL of mixed type. This marker type has a limited value for differentiation from the other chronic lymphoid leukaemias. We also studied three patients with chronic lymphoid leukaemia which were not described by the FAB classification. We conclude that a study of the morphology of the leukaemic cells was the most useful basis for the diagnosis of these leukaemias, whereas immunotyping was apparently valuable only in individual cases.

Antigens, CD↗
PubMed1988

Effects of incremental infusions of atrial natriuretic factor on aldosterone, renin, and blood pressure in humans.

To evaluate the physiological effects of human atrial natriuretic factor-(99-126) (ANF), we infused ANF, 0.1, 0.3, and 1.0 micrograms/min, or placebo for 125 minutes on different days into six sodium-deprived normal men. During the last 45 minutes of infusion, angiotensin II, 6 ng/kg/min, was infused. Blood pressure, heart rate, plasma concentrations of ANF, aldosterone, and cortisol, and plasma renin activity (PRA) were measured before and during infusion. Steady state mean plasma ANF levels during infusion were 26.2 (placebo), 68.8 (0.1 micrograms ANF/min), 221 (0.3 micrograms ANF/min), and 648 pg/ml (1.0 microgram ANF/min). Systolic blood pressure fell significantly (with 1.0 microgram ANF/min), and diastolic pressure tended to rise in a dose-dependent manner, while heart rate was unchanged. PRA and plasma aldosterone fell during ANF infusion in a dose-dependent manner (significant with 0.3 and 1.0 microgram ANF/min infused). The blood pressure-raising and aldosterone-stimulating effects of angiotensin II were blunted by ANF (significant only with 1.0 microgram ANF/min). It is concluded that effects of ANF on blood pressure and the renin-aldosterone system occur with plasma ANF levels close to the physiological range, as well as with slightly elevated ANF levels, as observed in congestive heart failure and renal insufficiency.

Adult↗