Biomedical subjects

E Thiel

Publications and source records attributed to E Thiel.

354 records · Page 20Linked to original sources

PubMedDate not supplied

CHOP and COPBLAM chemotherapy for diffuse large cell non-Hodgkin's lymphomas: a retrospective comparison.

Between 1979 and 1985 61 consecutive patients with non-Hodgkin's lymphomas of unfavourable histology (mostly diffuse large cell lymphomas subclassified according to Kiel nomenclature) were treated in our departments by either the CHOP- (n = 34) or the COPBLAM-regimen (n = 27). A retrospective analysis revealed that prognostic variables, excluding primary central nervous system (CNS)-involvement (n = 5), were equally distributed between both groups. Remission rates were significantly higher in the COPBLAM treated patients as compared with the CHOP treated group (85 per cent versus 38 per cent CR, P = 0.001) even when cases with primary CNS-disease were excluded. The survival curve did not reach a plateau in CHOP treated cases, whereas 85 per cent of the COPBLAM treated group reached a plateau by 15 months. The mean observation time, however, was shorter in the COPBLAM treated group (37 versus 30 months, respectively). It is concluded that the COPBLAM regimen is superior to the CHOP-protocol in inducing complete responses in aggressive non-Hodgkin's lymphomas. Longer follow-ups are needed to definitely show if this corresponds to an increased proportion of 'cures'.

Adolescent↗

PubMedDate not supplied

Highly fluorochrome labeled gene probes for quantitative tracing of RNA in individual cells by in situ hybridization.

A new method is presented for preparing highly fluorochrome labeled gene probes suitable for in situ hybridization. For this purpose fluorochromes were attached to a synthetic polypeptide, which was then coupled covalently to various gene probes. The advantage of the reported method is its high labeling efficiency and the easy coupling procedure. The method allows rapid and quantitative detection of homologous RNA at the single cell level. Optimal conditions for the hybridization of fluorochrome-labeled gene probes were established microfluorimetrically, and the specificity and sensitivity of the method were tested. Quantitation of the RNA with a fluorochrome-labeled gene probe in situ in individual cells allows determination of the degree of gene activation in individual cells and may thus provide a new tool for investigation of normal and malignant cells with respect to activation of genes controlling differentiation and proliferation.

Cells, Cultured↗

PubMedDate not supplied

[Membrane differentiation of acute lymphoblastic leukemia from cALL-type cells in diffusion chambers].

In order to explore their differentiation capacity peripheral blasts from 4 children with acute lymphoblastic leukemia of the common type (cALL) as well as cells of the Reh line were cultured in diffusion chambers implanted intraperitoneally into preirradiated CBA mice (8 gy). At various times after initiation of the culture, changes in the membrane marker profile were studied by investigation of surface antigens and rosetting phenomena. In the course of the culture, the cells of two patients, T. H. and I.G., developed surface immunoglobulin (sIg) in combination with the CALL antigen (cALLA). Simultaneously, the cells of I.G. containing cytoplasmic Ig prior to cultivation acquired a receptor for mouse erythrocytes (EM). Besides quite a few cells developing the T-cell antigen, the majority of the cell yield in patient V.M. expressed sIg alone or together with the cALLA. Comparable results together with an increasing portion of mouse rosette forming cells were obtained in the fourth patient, C.M. In case of the Reh-line the cells developed the T-cell antigen, and in one of two experiments they further acquired a receptor for sheep erythrocytes. conversely, in a second experiment and EM-receptor was detected. Our data suggest that leukemic blast cells carrying the cALLA are representative of an early developmental stage of lymphatic ontogeny.

Animals↗

PubMedDate not supplied

Phase 2 trial of vaccination with tyrosinase peptides and granulocyte-macrophage colony-stimulating factor in patients with metastatic melanoma.

This phase II study was performed to determine the induction of a specific T-cell response, the clinical response rate, and toxicity of vaccination with different HLA class I-binding peptide epitopes derived from the melanocyte differentiation antigen tyrosinase in patients with stage IV melanoma. The study population consisted of 16 patients with metastatic disease and two patients who were macroscopically free of disease at study entry after resection of recurrent skin lesions. Patients received intradermal injections of 200 microgram [corrected] peptide corresponding to their HLA type on day 3, and 75 or 150 microg granulocyte-macrophage colony-stimulating factor on days 1 to 4. Vaccinations were repeated at weeks 2, 4, 6, 10, and 14. Monitoring of peptide-specific T-cell frequencies in the peripheral blood was performed using an interferon gamma ELISPOT assay. Eleven of the 16 patients with metastatic disease went off the protocol within the first 10 weeks because of tumor progression. Of the five patients with metastatic disease who received all six vaccinations, one patient showed a mixed response with regression of some lung metastases; two patients with progressive disease before vaccination had stable disease for 6 and 18+ months; and two patients had progression of their disease. The two patients who had all their metastases resected before vaccination did not have relapses for 6 and 12+ months after vaccination. Induction of tyrosinase-reactive T cells was found in these two patients and in two others with metastatic disease, including the one who achieved a mixed response and one with stable disease. This study shows limited clinical and immunologic activity of HLA class 1-peptide vaccination in combination with granulocyte-macrophage colony-stimulating factor in stage IV melanoma patients.

Bone Neoplasms↗

PubMedDate not supplied

Quantification of tumor-specific T lymphocytes with the ELISPOT assay.

The characterization of tumor-associated antigens and of human leukocyte antigen (HLA) class I molecule-binding peptide epitopes derived from these antigens has prompted the initiation of various vaccination trials aimed at inducing tumor-specific CD8+ T cells in persons with cancer. Sensitive and easy-to-perform T-cell assays that assess the frequency of tumor-reactive T cells are crucial for the evaluation and further development of vaccination approaches. This review focuses on a novel ELISPOT technique that allows quantification of tumor-specific T lymphocytes from peripheral blood by detecting antigen-induced cytokine secretion. Various ELISPOT methods using different antigen-presenting cells and different cytokines as read-out are described. T-cell analyses performed using the standard chromium release assay and the ELISPOT assay are also compared. Results from various clinical trials, including peptide and whole tumor cell vaccination and cytokine treatment, are now available and show the suitability of the ELISPOT assay for monitoring T-cell responses. To establish a basis for standardization and to further improve this technique, the first comparative quality assurance studies analyzing T-cell frequencies in different laboratories with the ELISPOT assay are being performed.

Antigens, Neoplasm↗

PubMedDate not supplied

Topical transforming growth factor-beta3 in the prevention or alleviation of chemotherapy-induced oral mucositis in patients with lymphomas or solid tumors.

Transforming growth factor (TGF)-beta3 has been hypothesized to prevent or alleviate oral mucositis (OM) in cancer patients receiving high-dose chemotherapy (CT). Two double-blind, placebo-controlled, multicenter, phase II studies of TGF-beta3 were initiated in the United States, Europe, and Argentina in patients with lymphomas or solid tumors who were receiving highly stomatotoxic CT regimens. Patients were to apply 10-mL mouthwash applications of TGF-beta3 (25 microg/mL) or placebo four times daily (or twice daily) 1 day before and all days during CT. The patients were subsequently evaluated for OM incidence, severity, and duration using National Institute of Cancer Common Toxicity Criteria (NCI-CTC) criteria and an objective scoring system (1). After the start of the trials, negative results from new preclinical studies suggesting suboptimal formulation and/or dosing led to an interim analysis of the ongoing clinical trials. One hundred fifty-two patients from the combined studies were included in the interim analysis, with 116 patients on the TGF-beta3 four times daily and placebo arms. Most (72%) patients had breast cancer, 22% had lymphomas, and 6% had other solid tumors. Although 98% (149 of 152) of patients experienced adverse events, only 14% (22 of 152) experienced events that were judged as possibly or probably related to the study drug (primarily gastrointestinal symptoms). No clinically relevant differences were seen between the treatment and placebo arms regarding safety, nor was there evidence for systemic absorption of TGF-beta3. Finally, there was no advantage of TGF-beta3 treatment regarding the incidence (TGF-beta3 four times daily versus placebo [46% versus 47%]), onset, or duration of NCI-CTC grade 3 or 4 OM. For this dose, formulation, regimen. and patient population, TGF-beta3 was not effective in the prevention or alleviation of CT-induced OM.

Adult↗

PubMedDate not supplied

Dose intensity phase I/II trial with carboplatin, ifosfamide, etoposide and vincristine combined with filgrastim in patients with small-cell lung cancer.

BACKGROUND: The purpose of the study was to evaluate the feasibility of increasing dose intensity by a stepwise reduction of the time intervals between chemotherapy cycles in separate patient cohorts with small-cell lung cancer. Patients received up to 6 courses of combination chemotherapy with carboplatin, etoposide, ifosfamide and vincristine followed by support with filgrastim. Dose intensity, incidence, duration and severity of neutropenic fever and infections, objective response to chemotherapy, and safety of filgrastim were determined. PATIENTS AND METHODS: 29 patients with small-cell lung cancer (limited disease: 2, extensive disease: 27) were treated with a combination of carboplatin 250 mg/m2 i.v. day 1, ifosfamide 2 g/m2 and etoposide 120 mg/m2 i.v. days 1 and 2, etoposide 120 mg/m2 orally day 3, and vincristine 1.4 mg/m2 day 14. Initially, filgrastim (5 micrograms/kg) was administered subcutaneously from day 7 to 16. With shorter treatment intervals, filgrastim was administered on days 4-16 or 4-14. RESULTS: An overall increase in dose intensity by a factor of 1.44 was achieved after reducing the treatment interval from 27 to 17 days. Further reduction to 14 days was not feasible due to persistent thrombocytopenia. Six patients (21%) developed a total of 9 febrile episodes, and 14 patients (48%) had to be withdrawn from the study before the completion of six cycles of chemotherapy. The median duration of infectious episodes was 6 days. Overall, a total of 22 of 27 evaluable patients had an objective response. Longer treatment intervals resulted in a lower probability for objective response (> or = 23 days: 10/14 patients vs. < or = 17 days: 7/7 patients). CONCLUSION: Filgrastim allows for the reduction of treatment intervals in patients with small-cell lung cancer and increased dose intensity with acceptable hematologic and nonhematologic toxicities.

Adult↗

PubMedDate not supplied

Long-term results of a phase-II-pilot trial on preoperative high-dose chemotherapy with stem cell rescue in patients with cancer of the upper gastrointestinal tract.

We have tested the feasibility, tolerability, and efficacy of a multimodality treatment approach for patients with locally advanced cancer of the upper gastrointestinal tract including preoperative chemotherapy with the EAP-protocol as induction and a consecutive high-dose chemotherapy with MCVB and autologous stem cell rescue for responding patients. This first pilot trial in 16 patients shows that the approach is feasible with tolerable toxicity and can lead to prolonged disease-free survival in responding patients.

Adenocarcinoma↗

PubMedDate not supplied

Susceptibility of human leukemia to allogeneic and autologous lymphokine-activated killer cell activity: analysis of 252 samples.

The present study investigated the susceptibility of human leukemia cells to allogeneic lymphocytes with lymphokine-activated killer (LAK) activity from normal donors and autologous LAK activity from patients in complete remission. LAK activity was generated from peripheral-blood mononuclear cells cultured for 6 days with 1,000 U/ml recombinant interleukin-2 (IL-2). Cytotoxicity was evaluated using a standard 4-hour chromium release assay. Susceptibility of leukemic cells to LAK was defined on the basis of the mean Cr release in 52 samples of normal bone marrow cells. Using allogeneic LAK, we examined leukemic cells from bone marrow or peripheral blood of 252 patients [102 with acute myeloid leukemia (AML), 99 with acute lymphoblastic leukemia (ALL), 13 with chronic myelogenous leukemia in blast crisis (CML-BC) and 38 with chronic leukemias of various types]. A significant lysis could be detected in 62% of all leukemias tested (in 68% of AML, 60% ALL, 92% CML-BC, 39% chronic leukemias). The mean chromium release (effector-to-target cell ratio 50:1) was 28.8 +/- 13.5% for LAK-sensitive leukemias versus 5.2 +/- 3.2% for resistant leukemias. We observed a distinct susceptibility of various leukemia subtypes. LAK cytotoxicity against autologous leukemia cells was examined in 40 leukemia patients in complete remission (24 AML, 16 ALL). 63% of the patients developed a significant cytotoxicity against their autologous leukemia cells. Regarding mean Cr releases, the efficiency of allogeneic LAK activity of normal donors did not differ significantly from that of autologous LAK activity of patients in complete remission against the same leukemic target cells. Analysis of our data revealed that examinations with allogeneic LAK activity make it possible to predict whether patients will develop significant in vitro killing of their autologous leukemia cells during complete remission. These results may be of particular importance in determining which patients could benefit from immunologic therapy modalities and in scheduling immunotherapy. Further clinical studies are necessary to ascertain the clinical significance of therapeutic approaches with IL-2 or adoptive cellular immunotherapy combined with IL-2 for treatment of human leukemia.

Acute Disease↗

PubMedDate not supplied

Molecular diagnosis of the Philadelphia chromosome in chronic myelogenous and acute lymphoblastic leukemias by PCR.

We have developed a very rapid method for the detection of the Philadelphia chromosome based on the polymerase chain reaction. This chromosomal translocation generates bcr/abl fusion mRNAs, which were transcribed in cDNAs and subsequently amplified with two sets of primers. Through the use of an additional internal primer set the method reaches the sensitivity to detect a single Ph1-positive cell among 10(5) unaffected cells without any blotting procedures. The whole analytical procedure starting from RNA isolation up to agarose gel electrophoresis can be performed in about 5 h. First results indicate that the frequency of the Ph1 translocation exceeds 40 per cent in certain immunologic subtypes of adult acute leukemia.

Base Sequence↗

PubMedDate not supplied

Prolymphocytic leukemia with suppressor T-cell phenotype: report of two cases.

The clinical course of two patients with prolymphocytic leukemia of the suppressor T-cell phenotype is presented. Diagnosis was established by specific monoclonal antibody tests, cytochemical, ultrastructural and cytogenetic studies. The bone marrow showed a diffuse infiltration with medium sized lymphocytes displaying a prominent nucleolus. Both patients presented with pronounced splenomegaly, diffuse lymphnode involvement, leukocytosis, thrombocytopenia and anemia. One of them was refractory to chemotherapy using CHOP, Asparaginase, IMVP16, and irradiation to the spleen. He benefited from prednimustin and repeated leukaphereses, without reaching complete remission (C.R.). The second patient achieved a C.R. of 4 months duration with CHOP-Bleomycin. Survival was 16 and 11 months respectively.

Female↗

PubMedDate not supplied

Expression of the stem cell factor receptor C-KIT (CD117) in acute leukemias.

BACKGROUND AND OBJECTIVE: The receptor for stem cell factor (CD117) is the gene product of the c-kit proto-ontogene. Together with its ligand, the stem cell factor (SCF), it plays an important role in hematopoiesis. In this study, we review the cellular distribution of CD117 in normal hematopoiesis and in hematopoietic malignancies focusing on the differential expression in subtypes of acute leukemias. EVIDENCE AND INFORMATION SOURCES: This review is based on a literature search in the Medline database, personal publications and results obtained as a reference laboratory of the German AML-BFM, AMLCG and ALL multi-center therapy studies. STATE OF THE ART AND PERSPECTIVES: Membrane expression of CD117 can be found on leukemic blasts from approximately 60% of adult and childhood AML patients, often associated with an immature immunophenotype (CD34). Moreover, AML with t(8;21) are frequently CD117 positive. Despite earlier reports, most recent studies have not been able to demonstrate any significant prognostic impact of CD117 expression in either childhood or adult AML. A small proportion of T-lineage ALL (9%), mainly consisting of immature pro-T/pre-T-ALL, is CD117 positive. CD117 expression is rare in B-cell-precursor-ALL and occurs in less than 3% of cases. CD117 in combination with other antigens might facilitate the immunologic characterization of acute leukemias, especially those of myeloid and early T-cell origin.

Acute Disease↗