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J Thaler

Publications and source records attributed to J Thaler.

At least 91 records · Page 5Linked to original sources
PubMed1993

[Value of interferon-alpha in treatment of chronic myeloid leukemia].

In 1983 Talpaz et al. (43) for the first time demonstrated the efficacy of interferon-alpha (IFN-alpha) for the treatment of patients with chronic myelogenous leukemia (CML). This observation has been confirmed by several study groups in the consecutive years. An overview over the 7 largest trials including more than 400 patients reveals response rates (partial and complete hematological remissions) of 55 to 91%. In contrast to conventional chemotherapy IFN-alpha treatment resulted in a decrease of Philadelphia-chromosome positive metaphases (cytogenetic remissions) in 19 to 47% of these patients. A complete disappearance of the Philadelphia chromosome was found in 5 to 10% of patients. The following factors influence the response to IFN-alpha in patients with CML: phase and duration of the disease, several well defined risk factors, and IFN-dose. Currently available data are strongly suggestive for a survival benefit of patients with cytogenetic remissions, although definitive prove by phase-III trials is lacking. Actual studies focus on combinations of IFN-alpha and cytostatics, e.g. low-dose cytosine arabinoside.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Surface immunoglobulin density in the differential diagnosis of B-cell chronic lymphocytic leukemia and leukemic immunocytoma.

Using flow cytometry peripheral blood samples of 37 consecutive patients with B-cell chronic lymphocytic leukemia (B-CLL) and 17 consecutive patients with leukemic immunocytoma (IC) were studied in order to determine quantitative differences in the surface immunoglobulin (slg) density. In 8/37 (21.6%) cases of B-CLL and 1/17 (5.9%) cases of IC slg staining remained in the control level. Analysis of slg-positive cases demonstrated a close association between the amount of slg and diagnosis: per case the mean calculated fluorescence intensity for IC lymphocytes was 209.7 arbitrary linear intensity units (IU) (median: 156.4, standard error of the mean (SEM): 53.7) and for B-CLL lymphocytes 10.8 IU (median: 7.3, SEM: 1.1; p less than 0.0001). Altogether, 94.6% of all B-CLL patients and 76.5% of all IC patients were correctly classified when a cut-off point was fixed at a mean fluorescence intensity value of 20.0 IU. The percentage of leukemic cells as characterized by CD19 and HLA-DR reactivity was significantly lower in cases of IC (p less than 0.03 and p less than 0.01, respectively). In both entities disease progression occurred more frequently in advanced stages (II-IV) according to the Rai classification (p less than 0.01). In progressive disease rather than in stable disease circulating T lymphocytes were shown to express decreased amounts of surface CD3 antigen (p less than 0.02). We conclude that the quantitative assessment of surface antigens in addition to their qualitative characterization provides accurate information. In particular, the diagnostic discrimination between B-CLL and IC may be improved by determining the lymphocytes' slg amount.

Antigens, CD↗
PubMed1992

Detection of activity of P-glycoprotein in human tumour samples using rhodamine 123.

Based on the fluorescent properties of the dye rhodamine 123 (Rh123), which is transported by the membrane efflux pump P-glycoprotein (P-gp), we developed a functional flow cytometric assay for the detection of multidrug-resistant (MDR) cells. Using drug sensitive cell lines (KB-3-1) and MDR mutants (KB-8-5, KB-C1) experimental conditions were established that enabled demonstration of significant differences in Rh123 efflux and accumulation. Subsequently we investigated the applicability of this functional assay for the prediction of MDR in human peripheral blood and bone marrow samples. Using two-colour flow cytometry, the leukaemic blast cells of six patients suffering from acute myeloid leukaemia (AML) were analysed. In three cases the blast cells showed a rapid and marked Rh123 efflux. In the presence of MDR inhibitors these cells retained Rh123. To determine whether the efflux of Rh123 was associated with P-gp expression, the leukaemic cells were stained with the monoclonal antibody MRK-16. In addition extracted RNA was analysed by polymerase chain reaction to evaluate the expression of mdr 1 mRNA. In all three Rh123+ cases mdr 1 mRNA was detectable whereas only one AML case expressed P-gp. In comparing Rh123 with daunorubicin, which also allows the detection of MDR cells, accumulation studies proved Rh123 to be the more sensitive drug for flow cytometric MDR screening. Additionally, two-colour flow cytometry was much easier to perform with Rh123 than with daunorubicin. Our results indicate that flow cytometric measurement of Rh123 accumulation/efflux proves applicable to detect MDR cells in heterogenous clinical samples.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

[Recombinant interferon alpha-2c in Ph-positive chronic myeloid leukemia. Results of a multicenter phase II study].

In a Phase II study, 82 patients with Philadelphia chromosome(Ph)-positive chronic myelogenous leukaemia were treated with 3.5 million I.U./d of recombinant interferon alpha-2c (rIFN). 73 patients have so far been evaluated (42 male, 31 female, mean age 50 [12-87] years). At the start of therapy, 10 were in the accelerated phase (group 1) and 63 in the chronic phase, of whom 19 had received previous treatment with cytotoxics (group 2), while the remainder (group 3, n = 44) had received primary treatment with rIFN. There was short-term stabilization in 7 of the 10 group 1 patients, but none had complete haematological or cytogenetic remission. In contrast, the remission rate (complete or partial haematological remission) was 63% in the previously treated (group 2) and 66% in the previously untreated chronic phase patients (group 3). There was a reduction in the proportion of Ph-positive metaphases in 7 group 2 patients (11%) and in 10 group 3 patients (23%). Complete cytogenetic remission has so far been seen in 2 patients. Cytogenetic improvement occurred after 3 months at the earliest, and in some patients only after 12 to 19 months treatment. Differences in response to treatment were related to stage (prognostic staging system of Kantarjian et al.) in group 3 patients: complete or partial haematological remission was seen in 22 out of 25 patients with stage 1 disease, in 4 out of 7 in stage 2, and in only 3 out of 12 in stages 3 and 4.

Adolescent↗
PubMed1991

Bone marrow diagnosis in lymphoproliferative disorders: comparison of results obtained from conventional histomorphology and immunohistology.

In this study we have investigated 313 bone marrow biopsies from 280 patients with lymphoproliferative disorders. Trephines were sectioned transversely to obtain one cylinder for cryostat sectioning and immunostaining and a second for histomorphological evaluation using a plastic-embedding technique. The results obtained by histomorphological and immunohistological evaluation were compared for their contribution to staging and classification. Using both techniques, bone marrow involvement was seen in 3/43 (7.0%) biopsies from patients with Hodgkin's disease and in 193/270 (71.5%) cases with non-Hodgkin's lymphoma, including multiple myeloma and acute lymphocytic leukaemia. Immunohistology proved superior in detecting minimal mainly interstitial bone marrow infiltration in 15 leukaemia/lymphoma cases. Biopsies showing infiltration with both methods (n = 157) were re-examined for classification of lymphomatous infiltrates. Whereas immunohistology did not provide additional information in cases with Hodgkin's disease and myeloma, this method was crucial for establishing the definitive diagnosis in a number of cases with acute lymphocytic leukaemia and non-Hodgkin's lymphoma. In all of six leukaemia cases, in which no or inadequate material was available for immunophenotyping of cell suspensions, immunohistology clearly defined the subtype. In the 140 cases of non-Hodgkin's lymphoma the majority of cases (76.4%) were identically classified. In some cases, with important prognostic and therapeutic implications, immunohistology alone provided the definitive diagnosis: T-cell lymphoma (n = 2), hairy cell leukaemia (n = 2) and centrocytic non-Hodgkin's lymphoma (n = 3). Bone marrow immunohistology is, therefore, an important supplement for classical lymphoma/leukaemia diagnosis. The differences observed between histomorphology and immunohistology emphasize the importance of lymph node biopsy in lymphoma classification.

Biomarkers↗
PubMed1990

Pentostatin in refractory chronic lymphocytic leukemia: a phase II trial of the European Organization for Research and Treatment of Cancer.

Pentostatin was used to treat 26 patients with advanced B-cell chronic lymphocytic leukemia resistant to conventional treatment. Twenty patients had progressive disease on previous regimens and six had had partial remission and then relapsed 3-34 months after previous chemotherapy. Eleven patients had previously been treated with three different regimens. 10 had been treated with two regimens, and five had been treated with one regimen. Pentostatin was administered at a dosage of 4 mg/m2 weekly for 3 weeks, then 4 mg/m2 every other week for 6 weeks and once a month for 6 months. Seven of 26 assessable patients (27%) achieved partial remission and five (19%) achieved clinical improvement. The median duration of partial remission until relapse or death was 210 days. Myelosuppression was minor and transient in responsive patients, indicating some degree of selective effect on lymphocytes. Except for one patient who died of cerebral hemorrhage during the first 6 weeks of treatment, no drug-related deaths were registered. Major toxic effects included nausea in 17 patients (mainly grade 1), infections in 15, and liver enzyme elevations in five. Thus, pentostatin is active, even in patients with advanced B-cell chronic lymphocytic leukemia that is refractory to multiple chemotherapy regimens. Response can be achieved with mild myelosuppression.

Adult↗
PubMed1990

Value of urinary neopterin in the differential diagnosis of bacterial and viral infections.

Neopterin is released by stimulated macrophages. In this study we analyzed the diagnostic potential of urinary neopterin concentrations in patients with bacterial and viral infection. All but one of 17 patients with viral infection had increased urinary neopterin concentrations. Patients with bacterial urinary tract infection also showed increased neopterin concentrations, whereas patients with bacterial pneumonia had significantly lower neopterin levels. In addition, patients with acute bacterial pneumonia had lower neopterin levels than patients with protracted infection. A significant inverse correlation between urinary neopterin and hemoglobin concentrations was found. Neopterin concentrations could serve as a helpful additional marker of infectious diseases. Combined with other clinical and laboratory parameters it is a useful parameter for distinguishing between viral and bacterial origins of infection, as was shown by multivariate stepwise linear discriminant analysis.

Adult↗
PubMed1990

Correlation between neopterin, interferon-gamma and haemoglobin in patients with haematological disorders.

In this study, we further investigated a possible link between activation of cell-mediated immunity and anaemia in patients with haematological neoplasias. We compared serum concentrations of interferon-gamma and neopterin with haemoglobin levels. Significantly increased interferon-gamma and neopterin concentrations indicated persistent activation of cell-mediated immunity. Neopterin levels correlated significantly to interferon-gamma concentrations and inversely to haemoglobin levels. The data indicate an association between activated macrophages and the development of anaemia in patients with haematological neoplasias.

Adult↗
PubMed1990

Monoclonal antibody B-ly7: a sensitive marker for detection of minimal residual disease in hairy cell leukemia.

The new monoclonal antibody (MoAb) B-ly7 was tested for its value in bone marrow diagnosis in patients with hairy cell leukemia (HCL). Cryostat sections of bone marrow biopsies were examined by an indirect immunoperoxidase technique. Lymphoma cells from all of 26 HCL cases investigated displayed strong surface membrane staining with the MoAb B-ly7, whereas tumor cells from only one of 63 patients with other lymphoproliferative disorders of B cell type reacted with this antibody. The strong reactivity of hairy cells (HCs) with this marker was not altered after therapy as demonstrated on control biopsies taken from patients treated with interferon(IFN)-alpha-2 or 2'deoxycoformycin(DCF) six-64 weeks after start of treatment. This fact as well as the very low number of B-ly7 positive cells found in a series of 13 normal bone marrow biopsies (mean: 0.3% of bone marrow cells, range: 0.0%-1.0%), which could easily be distinguished from HCs by their lower staining intensity and their morphological appearance, provided the basis for the detection of even single HCs. In our hands, in terms of sensitivity the immunohistological detection of HCs using the MoAb B-ly7 was not only superior to classical morphological techniques but also to other immunohistological parameters usually applied for this purpose. Therefore, this MoAb provides a marker for the identification of HCs, hence monitoring disease activity in HCL, and particularly for a critical response evaluation in patients undergoing treatment with IFN-alpha or DCF.

Antibodies, Monoclonal↗
PubMed1989

Osteosclerotic myeloma with polyneuropathy and hypocalcemia.

A case is presented of a 46-year-old man with multifocal osteosclerotic bone lesions, peripheral polyneuropathy and hypocalcemia. Histologic examination of a bone marrow biopsy disclosed a multiple myeloma. Immunoelectrophoresis revealed a small M-component identified as IgG-lambda. Osteosclerotic myeloma lacking any osteolytic lesions seems to be very rare and shows several different features as compared with classical myeloma. A review of the current literature suggests that multiple myeloma is not a uniform disease but rather a group of clinical syndromes characterized by the special properties of their proliferating plasma cell clones.

Bone Marrow↗
PubMed1989

Immunohistological assessment of bone marrow biopsies from patients with hairy cell leukemia: changes following treatment with alpha-2-interferon and deoxycoformycin.

Forty-six bone marrow biopsies from twelve hairy cell leukemia (HCL) patients, treated with either interferon(IFN)-alpha-2 (n = 8) or 2'deoxycoformycin(DCF) (n = 4), were examined using cryostat sections and an immunoperoxidase technique. Using this sensitive method we were able to demonstrate residual hairy cell (HC) infiltration in five cases, in which evaluation with conventional staining techniques on plastic embedded biopsies revealed complete remission. The amount of HCs in these five samples ranged from 1 to 7% (mean: 3%) of bone marrow cells. Consecutive biopsies in individual HCL patients revealed no changes of the immunological phenotype (CD19, CD22, CD25, CD10, CD11c, FMC7, HLA-DR, surface immunoglobulins) during IFN and DCF treatment. Within the infiltrated bone marrow a considerable number of "reactive" T lymphocytes was identified with prevalence of the T-helper (CD4+) subtype in untreated cases, whereas T-suppressor/cytotoxic (CD8+) cells were within the normal range. IFN treatment resulted in a reduction of CD4+ T lymphocytes (p less than 0.02). Minor alterations of CD8+ T lymphocytes and NK cells (HNK-1 + lymphoid cells) were found in bone marrow during IFN treatment. In DCF-treated patients bone marrow T lymphocytes were markedly reduced below the values of normal bone marrow. This DCF-induced T-cell depression might be related to the clinical observation of persistent cellular immune dysfunctions in HCL patients despite a DCF-induced remission.

Adult↗