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Biomedical subjects

E Thiel

Publications and source records attributed to E Thiel.

At least 217 records · Page 12Linked to original sources
PubMed1990

Antigen receptor rearrangement and expression in acute leukemias.

Twenty-two leukemias, 11 of which were undifferentiated with respect to surface antigen markers, were investigated for their antigen receptor gene rearrangement, transcription products of these antigen receptor genes, and surface antigen pattern of the cells. Among the three less-differentiated groups rearrangement was observed in 2/10 cases for the TCR beta-chain and in 4/11 cases for the heavy-chain gene. TCR beta-mRNA, however, was expressed in seven out of eight cases and the mu heavy-chain mRNA in eight out of ten cases investigated. Also mRNA of TCR alpha, the rearrangement of which could not be detected with our probes, was expressed as frequently as TCR beta. Although rearrangement of the appropriate gene was found regularly in the more mature leukemias, transcription of these genes was lower or even lacking. These findings indicate that expression of antigen receptor mRNA in undifferentiated leukemias can be activated by events other than maturational rearrangement.

Acute Disease↗
PubMed1990

Rapid detection of chimeric bcr/abl mRNAs in acute lymphoblastic and chronic myeloid leukemia by the polymerase chain reaction.

We have developed a rapid method for the detection of bcr/abl mRNAs, the products of the BCR/ABL fusion genes. The method is based on the polymerase-chain-reaction (PCR). Through the use of additional internal primers it is possible to detect directly a single Ph1-positive cell among 10(5) unaffected cells thus omitting time-consuming blotting procedures. The whole analytical procedure starting from RNA isolation to agarose gel electrophoresis including two rounds of PCR can be performed in less than six hours.

Base Sequence↗
PubMed1990

Prognostic significance of glucocorticoid receptor determination in patients with chronic lymphocytic leukemia and immunocytoma--lack of a positive correlation between receptor levels and clinical responsiveness.

Glucocorticoid receptors (GR) have been suggested to have prognostic significance in patients with CLL treated with chemotherapy containing glucocorticoid. In this study, the GR levels in 65 patients with advanced CLL and immunocytoma (clinical stages III and IV according to Rai) were determined by means of a whole cell assay. The median GR-level was 1,920 bs/c with a range from 0 to 9591. The patients were subsequently treated according to a prospective, randomized trial with either a combination of chlorambucil and prednisolone, or with prednimustine. No significant difference in receptor levels was found between responders (median = 1940 bs/c; n = 47) and nonresponders (median = 1950 bs/c; n = 14). To assess the influence of receptor content on prognosis we have analyzed the relationship between GR content and survival time and duration of response. There was no significant difference in duration of response and in survival between those patients with high (greater than 1920 bs/c) and those with low GR levels (less than 1920 bs/c) (log-rank test). Our data suggest that determination of GR provides no reliable indicator for clinical response to regimens with glucocorticoid as a component in patients with CLL and immunocytoma.

Adult↗
PubMed1990

Recombinant IFN-alpha in lymphomas.

The effectiveness of interferon (IFN) therapy in malignant lymphoma is analyzed in this review. Although various treatment regimens including IFN at various dose levels have so far not proved to have curative potential, a substantial palliative effect has been noted in hairy-cell leukemia and in some non-Hodgkin lymphomas of low-grade malignancy. Early stages of lymphoma disease are more responsive to IFN therapy, and this holds true also for chronic lymphocytic leukemia, in which IFN treatment is usually not effective in progressed disease after chemotherapy. Concepts of early-phase treatment and of remission maintenance by using IFN therapy are discussed on the basis of the data from several studies.

Humans↗
PubMed1990

Possibilities and limitations of immunological marker analyses for the detection of minimal residual disease in childhood acute lymphoblastic leukemia.

Specific application of immunological markers in acute lymphoblastic leukemia (ALL) for detection of inadequate blast cell reduction after induction therapy or early recognition of a relapse requires a precise characterization of the immunophenotype at the time of diagnosis and an understanding of the biology of the disease. Therefore, the ALL-BFM 83 study is first used to demonstrate the incidence, antigen expression and dynamics of relapse occurrence of immunological subtypes in childhood ALL. This is then followed by a discussion of the different immunological features hitherto applied for identification of residual leukemia cells in ALL (terminal deoxynucleotidyl transferase--TdT; common acute lymphoblastic leukemia-associated antigen--CALLA, CD10; various T-cell differentiation antigens; kappa/lambda labelling); these are, however, not leukemia-specific and are expressed to varying degrees by normal lymphoid progenitor cells. The sensitivity of these analyses is therefore largely determined by the markers applied and the type of investigational material. Finally, suitable markers are presented for detecting residual leukemia cells in the different immunological subtypes of ALL. Their clinical relevance still remains to be evaluated in prospective therapy studies.

Antibodies, Monoclonal↗
PubMed1990

Multiple myeloma in a patient at risk for AIDS.

An increased incidence of tumors and B-cell lymphomas development has been reported in persons with or at risk for acquired immunodeficiency syndrome (AIDS). This report focuses on a 50-year-old homosexual man with HIV antibodies who met the established criteria for the diagnosis of multiple myeloma: an IgG monoclonal spike greater than 2 g/dl and a plasma cell count greater than 20% in the bone marrow aspirate. Serum protein immunoelectrophoresis showed monoclonal IgG kappa, and in the urine no excess of kappa chains was found. Laboratory data revealed a total IgG of 38 g/l, IgA of 5.2 g/l, and IgM of 2.3 g/l; the calcium level was normal; ESR was 119/130, and no plasmocytoid cells were seen in the differential count. No lytic lesions were found in the skeletal survey. The helper/suppressor T-cell ratio was depleted with 0.1 and HLA-DR was highly elevated with 56% in the immunofluorescent analysis. The development of the most differentiated B-cell tumor broadens the spectrum of B-cell neoplasias in patients with a predominant helper T-cell defect and focuses on the role of disordered immunoregulation and chronic antigenic stimulation in predisposing to B-cell malignant transformation associated with AIDS.

Bone Marrow↗
PubMed1990

Sequential studies on the role of mitoxantrone, high-dose cytarabine, and recombinant human granulocyte-macrophage colony-stimulating factor in the treatment of refractory non-Hodgkin's lymphoma.

Mitoxantrone (Novantrone, American Cyanamid Company; NO) and high-dose cytarabine (Ara-C; AC) have each been shown to be active in non-Hodgkin's lymphomas (NHL) in various studies. The studies reported here are sequential. The first study (NOAC I) combined high-dose cytarabine (3 g/m2/12 h as a 3 h infusion on day 1) with mitoxantrone (10 mg/m2/d on days 2 and 3). Of 31 patients with relapsed and refractory NHL, 7 achieved complete remission (CR) and 7, partial remission (PR). Myelosuppression was the major toxicity of this regimen. In the second study (NOAC II), the dosage of cytarabine was escalated to 3 g/m2/12 h on days 1 and 2 (4 doses) while mitoxantrone remained 10 mg/m2/d on days 2 and 3. The effects of recombinant human (rh) granulocyte-macrophage colony-stimulating factor (GM-CSF) were simultaneously studied. Twenty-three patients from five centers were treated with NOAC plus rhGM-CSF while 14 patients from four centers received NOAC II alone. A CR was achieved in 9 of 23 patients who received the additional rhGM-CSF and in 2 of 14 patients treated with NOAC alone. With rhGM-CSF, the median duration of severe neutropenia (less than 0.5/nL) after chemotherapy was 8 days versus a median of 13 days without rhGM-CSF, while the duration of severe thrombocytopenia (less than 20/nL) was not significantly different. The rates of infection and mucositis were 25% and 17%, respectively, with rhGM-CSF compared to 53% and 60% without rhGM-CSF. Thus, this last nonrandomized pilot study indicates that administration of rhGM-CSF reduces the duration of chemotherapy-induced cytopenia and the rate of mucositis. This growth factor does not appear to result in stimulation of lymphoma cells. At present, a controlled randomized trial is being conducted using NOAC II with rhGM-CSF or placebo to establish the definitive role of this growth factor in the treatment of NHL.

Adolescent↗
PubMed1989

Mitoxantrone and high-dose cytarabine as salvage therapy for refractory non-Hodgkin's lymphoma.

Mitoxantrone (Novantrone, NO) and high-dose cytarabine (Ara-C, AC) have each been shown in monotherapy trials to be active in non-Hodgkin's lymphoma (NHL). In the current study, a combination of the two drugs (NOAC) was administered to 31 patients with advanced NHL refractory to modern sequential chemotherapy regimens. Ara-C was administered at 3 g/m2 as a 3 hour infusion every 12 hours on day 1 (2 doses) and mitoxantrone at 10 mg/m2/day on days 2 and 3. Of the 18 patients with high-grade malignant NHL, six have attained a complete remission (CR) and two, a partial remission (PR). One CR and 5 PRs were achieved among the other 13 patients with intermediate or low-grade NHL. The median time to relapse (TTR) of patients achieving CR was 7 months with a range from 4 to 17 months. Myelosuppression with subsequent infections was the major toxicity of this regimen. The median duration of severe neutropenia (less than 0.5/nl) was 9 days with a range of 0 to 27 days and the median duration of severe thrombocytopenia (less than 20/nl), 5 days with a range of 0 to 35 days. Infectious complications during cytopenia was seen in 45.3% of the courses administered and fever of unidentified origin was seen in 42.3%. About 63% of the patients were hospitalized for intravenous antibiotic or antimycotic treatment. Other side effects were mild and included nausea, stomatitis, and transient tachycardia of greater than 100/min. Thus, this regimen was active in refractory NHL with poor prognosis, and the toxic side effects were not excessive. Evaluation of the activity of this regimen at higher dose levels of Ara-C is warranted.

Adolescent↗
PubMed1989

Quantitative tracing of mRNAs for T- and B-lymphocyte receptor genes in individual cells by in situ hybridization with fluorochrome-labeled gene probes. I. Expression in malignancies carrying B-lineage associated antigens.

Acute and chronic lymphatic leukemias were investigated on the single-cell level for the activity of genes coding for the IgM heavy chain and the alpha and beta chains of the T-cell antigen receptor (TCR). We used a new method for preparing highly fluorochrome-labeled gene probes for in situ hybridization, which allowed rapid and quantitative detection of mRNA at the individual cell level. Leukemic cell populations classified as belonging to the B lineage according to their surface antigenic patterns revealed increasing expression of mRNA for the IgM heavy chain (mu mRNA) in a maturation-dependent fashion, which was not correlated to rearrangement of the immunoglobulin mu chain gene--only 66% of the leukemias with rearranged mu gene also transcribed it. TCR mRNA was detected in B-antigen positive leukemic cells. High levels of both TCR and mu mRNA expression in all cells of some of these leukemias allowed the conclusion that these cells simultaneously transcribed the genes for T and B cell antigen receptors. TCR mRNA was also found in what are considered relatively mature B leukemias, lineage cross-over on the mRNA level being observed at a frequency of 23% (five of 22 cases), comparable with that of "inappropriate" receptor gene rearrangement. The quantitation of mRNA with fluorochrome-labeled gene probes in situ may allow determining the degree of gene activation in individual antigenically defined cells and may thus contribute a new tool for characterization of normal and malignant cells.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1989

Immunocytochemical identification of meningeal leukemia and lymphoma: poly-L-lysine-coated slides permit multimarker analysis even with minute cerebrospinal fluid cell specimens.

Use of immunocytology for accurate identification of malignant cells in cerebrospinal fluid (CSF) has so far been hampered by high cell requirements of the immunologic methods hitherto used. In an attempt to minimize cell loss in cytopreparation, electrostatic binding of cells to poly-L-lysine (PLL)-coated multispot slides, followed by immunocytochemistry, was investigated. Using optimized conditions of cell attachment and fixation and performing all washing procedures on the slide made multimarker analysis possible even in paucicellular specimens, while preserving excellent cell morphology and yielding high sensitivity in the detection of antigens. In a study of 26 CSF specimens with inconclusive cytomorphology, comprising 335 single marker determinations, we were able to discriminate reliably between resting or activated benign cells and a wide range of types of malignant lymphoid cell. A definitive diagnosis was reached in all cases by one tap only. Malignant meningitis was ruled out in ten specimens and proved in 16, including five in which the type of malignancy could only be determined by immunophenotyping. We conclude that immunocytochemistry on PLL-coated slides constitutes the method of choice for immunologic cell differentiation in CSF, which allows equivocal morphologic findings to be clarified.

Adult↗
PubMed1989

Favorable response of early stage B CLL patients to treatment with IFN-alpha 2.

Since interferon (IFN-alpha) treatment has proven effective in hairy cell leukemia, its evaluation in chronic lymphocytic leukemia (CLL), a cytologically related disease, appeared reasonable. In our study, we have focused on previously untreated, early stage patients who are less than 60 years of age. All patients had less than 50,000 lymphocytes/microL and immunologic analysis revealed a CD20+, IgM+, IgD- phenotype for leukemic B cells in eight of nine patients. Recombinant interferon alpha 2b (IFN-alpha 2) at 5 x 10(6) U was given subcutaneously three times per week for 8 to 16 months. Consistent with earlier reports, side effects were minor with this low-dose protocol. All patients responded with a decrease of WBC count and lymphocyte count; in one patient, splenomegaly resolved such that he moved from Rai stage II to Rai stage I. On the average CD20+ B cells decreased from 14,312 to 3,995 cells/microL, indicating that no complete eradication of the leukemic cells was possible. A partial response, based on a greater than 50% reduction of CD20+ B cells was obtained in five of seven patients analyzed. The increased numbers of CD2+ T lymphocytes decreased in response to interferon treatment in six of seven patients. Furthermore, in a portion of the patients class II antigen expression was enhanced on LeuM3+ monocytes suggesting an in vivo activation of the monocytes by IFN-alpha 2. Immunoglobulin levels were substantially improved in that serum IgG increased by more than 3 g/L in three of seven patients. In one patient, lymphocyte counts increased in spite of continued therapy, whereas all others exhibited no increase of lymphocyte numbers while on therapy. Our study clearly demonstrates effects of IFN-alpha 2 treatment on both the leukemic cells and on the nonleukemic components of the immune system in peripheral blood. Whether IFN-alpha treatment will result in long-term beneficial effects in early stage CLL needs to be evaluated in a larger study.

Antigens, Differentiation↗
PubMed1989

Spontaneous Epstein-Barr virus transformed B-cell line sharing the identical immunoglobulin gene rearrangement with acute myeloid leukemia.

Mononuclear cells from a 44-year-old patient with acute myeloid leukemia (AML) gave rise to a spontaneous permanent cell line cultured in suspension. The cell line was shown to be positive for Epstein-Barr virus nuclear antigen (EBNA). As expected, its composite phenotype was of B-cell type with B-cell antigens (CD 20, CD 21) and with monoclonal surface IgM of kappa type, but without detectable IgM secretion. Surprisingly, identical monoclonal rearrangements of the immunoglobulin heavy chain (JH) sequences could be demonstrated in the uncultured bone marrow AML cells and in the cell line that also had kappa light chain gene rearrangement. This is the first case to our knowledge of an EBNA positive B-cell line with identical monoclonal Ig heavy chain rearrangement as detected in myeloblastic leukemia cells.

Adult↗