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Biomedical subjects

E Thiel

Publications and source records attributed to E Thiel.

At least 235 records · Page 13Linked to original sources
PubMed1989

Induction of lymphokine-activated killer cell against human leukemia cells in vitro.

The induction of lymphokine-activated killer (LAK) cells against fresh human leukemia cells was investigated. Two thirds of the 62 leukemias examined were susceptible to the lytic effect of allogeneic IL-2 induced LAK cells in vitro. No substantial differences could be detected between myeloid or lymphoid leukemias or with regard to the FAB subtype or the immunophenotype. Culturing mononuclear cells from peripheral blood or bone marrow of leukemia patients with IL-2 resulted in an expansion of residual large granular lymphocytes and development of cytotoxic activity. The combination of IL-2 with IFN-gamma or the presence of tumor cells during the activation process led to an enhancement of LAK cell cytotoxicity. These results suggest that LAK cells may be useful in the treatment of leukemia.

Cytotoxicity, Immunologic↗
PubMed1989

[Risk-adapted therapy of highly malignant non-Hodgkin's lymphomas with COP-BLAM/IMVP-16: a prospective multicenter study].

In a prospective multicenter therapy trial the remission-inducing potential of the COP-BLAM (5 courses) and the possibly not cross-resistant IMVP-16 (2 courses) regimen for advanced diffuse large cell lymphomas were investigated. Inadequately responding patients were switched early after 2-3 courses to the IMVP-16 protocol. Between January 1986 and August 1988 349 previously untreated patients were recruited who fulfilled the entry criteria: age 15-75 (mean 56 years), stage II-IV. A first restaging after 3 courses of chemotherapy was documented for 280 cases, a second restaging following 7 courses of chemotherapy or a final report was available for 221 patients, 130 of which where in CR (59%). These figures include 29 cases who died already during induction-chemotherapy of progressive disease (n = 17) as well as of therapy-related complications in CR (n = 12). Thirty-three patients were switched early to IMVP-16 due to incomplete response at the first restaging; 13 of those achieved CR by the new regimen (39%), 9 achieved a partial remission which was turned into CR by additional radiotherapy in 5 cases. Dose reductions and interval prolongations were necessary at increasing rates with subsequent chemotherapy courses (20-50% of the cycles). Relapses have occurred in 32 patients so far (14 early, 18 after stop of treatment). The median survival was 24 months (n = 309 patients). These data show that this treatment strategy is effective in a large unselected group of patients of relatively high age. However, patients showing only delayed response with this protocol probably need more aggressive regimens to obtain durable remissions.

Adolescent↗
PubMed1989

Prethymic phenotype and genotype of pre-T (CD7+/ER-)-cell leukemia and its clinical significance within adult acute lymphoblastic leukemia.

Pretreatment blast cells from 739 adults with acute lymphoblastic leukemia (ALL) were immunophenotyped as part of a prospective treatment protocol study. Among 192 patients (26%) with T lineage ALL, 47 (6%; 24% of T lineage ALL) had lymphoblasts without sheep erythrocyte rosette formation, but with pan-T antigen CD7 on the membrane and intracellular CD3 proteins mostly in perinuclear accumulation. The T-cell surface antigens CD5 and/or CD2 and focal acid phosphatase were additional markers of this subgroup traditionally called pre-T ALL, whereas thymocyte antigen CD1 as well as CD4 and CD8 antigens were not expressed. Hematopoietic progenitor cell markers, namely terminal deoxynucleotidyl transferase (TdT), and in part common ALL antigen (CD10), HLA-DR antigens, and/or My-10 (CD34), a unique antigen of marrow cells absent in thymus cells, further characterized this immature T-ALL form of putative prothymocytic phenotype (CD7+/intracellular CD3+/TdT+/My-10+/-/HLA-DR+/-/CD10+/-). The prethymic T cell character was supported by germ-line T-cell receptor beta genes found in 21 of 36 patients analyzed. In five cases only T gamma-chain genes were rearranged. Fifteen patients, however, had rearrangements of both T beta and T gamma genes. Immunoglobulin heavy chain genes were rearranged only in two cases. Pre-T ALL differed significantly from E-rosette+ T-ALL in some presenting clinical features, namely mediastinal mass, lymphoadenopathy, and platelet count, and independently of clinical factors in prognosis (P = .02, median remission duration: 15.7 v 33.5 months, and P = .02, median survival time: 24.6 v 50.7 months). We conclude that ALL classification based solely on T- or B-cell lineage affiliation is not sufficient but needs further subdivision according to relevant maturation stages as exemplified here within the T-cell axis. The putative prethymic T cell progenitor phenotype described might help elucidate the sequence of genetic events that commit normal hematopoietic cells to the T-cell lineage.

Adult↗
PubMed1989

T cell receptor alpha expression in B-type chronic lymphocytic leukemia.

Normal B lymphocytes are characterized by rearrangement and expression of immunoglobulin genes, but not of T cell receptor genes. These properties might assist in lineage assignment, but there are examples of fresh leukemic cells and of cell lines where exceptions to this rule have been noted. We have studied cell samples of patients with B-CLL for expression of TCR alpha and beta chain genes. Using in situ hybridization with fluorescein-labeled probes, TCR alpha mRNA was found to be expressed in 14 of 18 samples and TCR beta mRNA in 7 of 16 samples. Specificity of hybridization was demonstrated by near complete blockade of TCR alpha hybridization with unlabeled TCR alpha, but not with unlabeled TCR beta probe. Furthermore, in Northern blot analysis a truncated 1,4 kb message for TCR alpha was readily detectable. No significant cell surface staining with the anti-TCR alpha/beta monoclonal antibody WT31 was observed. A contribution of T cells within the leukemic sample could be excluded since only samples with leukemic cell counts of greater than 50,000 cells/mm3 and only samples with 5% or less CD2+ T lymphocytes were studied. Our data show that a large proportion of B-CLL samples may express a truncated version of the TCR alpha message, indicating that this gene can be activated in leukemic B cells frozen at a late stage of differentiation.

B-Lymphocytes↗
PubMed1989

Rearrangement of T cell receptor beta, gamma, and delta gene loci in human pre-T cell acute lymphoblastic leukemia.

Configuration of the T cell receptor (TCR) beta, gamma, and delta chain genes, as well as immunoglobulin (Ig) heavy and light chain genes, was studied in 29 cases of E rosette-negative (pre-T cell) acute lymphoblastic leukemias that lack early B cell (CD19), myeloid (CD33), as well as most T cell associated membrane antigens such as CD1, C4, and CD8, but express CD7, cytoplasmic CD3 (cCD3), and TdT strongly, as well as CD5 and/or CD2 heterogeneously. Hematopoietic progenitor cell markers, namely HLA-DR, J5 (CD10), and My10 (CD34), further characterized this immature T ALL of putative prothymocytic phenotype. Eleven ALLs showed a germline configuration of TCR as well as Ig genes. In three cases, only TCR delta sequences were rearranged, and four additional cases were characterized by recombination of both, TCR gamma as well as TCR delta sequences. Eleven patients showed concurrent rearrangements of TCR beta, gamma, and delta chain genes. An Ig heavy chain rearrangement was observed in one case. These data support the hypothesis that, analogous to pre-B development, a cascade of TCR rearrangements occurs in pre-T cells. Moreover, findings reported here suggest that CD7, as well as CD2 and CD5, antigens appear on precursor cells prior to entry into the thymus and support a model for the developmental hierarchy of TCR genes during early T cell ontogeny.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1988

Establishment of a human cell line (Mono Mac 6) with characteristics of mature monocytes.

A monocytic cell line, termed Mono Mac, was established from peripheral blood of a patient with monoblastic leukemia. Two clones, designated Mono Mac I and Mono Mac 6, were isolated and both were assigned to the monocyte lineage on the basis of morphological, cytochemical and immunological criteria. Most importantly, the clones express NaF-sensitive non-specific-esterase, produce reactive oxygen and stain with MAb My4. Mono Mac 6, in addition, constitutively exhibits phagocytosis of antibody-coated erythrocytes in 80% of the cells and reacts with a panel of MAbs that are specific for mature monocytes, i.e., M42, LeuM3, 63D3, Mo2 and UCHMI. By contrast, the monoblastic cell lines U937 and THP-I are negative for all these markers. Only expression of My4 could be detected after differentiation induced by interferon-gamma (IFN-gamma). Similar treatment of Mono Mac I, however, resulted in staining with all the monocyte-specific MAbs mentioned above, while IFN-gamma treatment of Mono Mac 6 enhanced antigen expression. In addition, the cells showed an increased frequency of multinucleated cells with a rise from 4.8% to 21.9%. Mono Mac 6 appears to be the only one of the cell lines studied to constitutively express phenotypic and functional features of mature monocytes.

Cell Line↗
PubMed1988

Blast crisis of Philadelphia chromosome-positive chronic myelocytic leukemia (CML). Treatment results of 69 patients.

We have studied the clinical courses of 69 patients with blastic crises of Philadelphia chromosome positive CML to identify parameters that were associated with an increased response rate or survival. Cytogenetic analysis at the time of blastic transformation revealed additional chromosome changes in 70% of the patients tested. Bone marrow fibrosis was detected in 58% of evaluable patients. Lymphoblastic transformation was seen in 28% of the patients tested with cell surface marker analysis. The value of 5'-nucleotidase as a marker for distinguishing lymphoid from non-lymphoid blast crisis was confirmed. Of 57 evaluable patients, 23 (40%) responded to therapy (CR/PR longer than 14 days). Median survival was 75 days. Longer survival was related to the following factors: Ph1-chromosome as the only detectable cytogenetic abnormality; lymphoblastic transformation; no bone marrow fibrosis; high percentage of blasts and promyelocytes in the bone marrow, and response to therapy. No prognostic significance was associated with age, sex, Tdt, LDH, spleen size, duration of the chronic phase of the disease, white blood cell count, Hb, platelet count and percentages of basophils, eosinophils, erythroblasts and blasts and promyelocytes in the peripheral blood. These data confirm the poor prognosis of patients with blastic crisis of CML treated by conventional chemotherapy.

Adult↗
PubMed1988

Quantitation of mu mRNA by in situ hybridization reveals a correlation between B-maturation associated antigens and IgM gene activation in acute lymphatic leukemias.

Acute lymphatic leukemias, expressing the common acute leukemia antigen were investigated for expression of early T- and B-cell associated markers and the activation of the gene for the heavy chain of the immunoglobulin M. The gene activation as determined by quantification of the mu mRNA with a fluorochrome labeled gene probe in situ in individual cells showed a wide spectrum of positivity which was correlated to increasing expression of B-maturation markers. There was also a correlation between the amount of cellular immunoglobulin as determined by immunofluorimetry. Quantitation of mRNA in individual cells may allow to determine the degree of gene activation in antigenically defined individual cells and may thus contribute a new tool for classification of normal and malignant cells.

Antigens, Differentiation↗
PubMed1988

[Intensive combined therapy for high-risk ALL patients].

In the risk-adapted multicenter trial (02/84) for adult ALL the effectiveness of a consolidation therapy consisting of VM26 and Ara-C for high-risk patients was tested. Out of a total of 442 patients in the study, 79.2% achieved a complete remission. For the 182 high-risk patients the median remission duration is 17 months and the probability of being in continuous complete remission (CCR) is 34%. Improved results were found for elderly ALL patients between 35 and 65 years of age, whose median remission duration and CCR rate are 19 months and 40% respectively, compared to 15 months and 26% in the former study 01/81. The consolidation therapy has apparently also benefited patients with the immunological subtype c-ALL, for whom the CCR rate at 3 years is 53% in comparison to the previous value of 34%.

Adolescent↗
PubMed1988

[Multicenter prospective risk-adapted study on the therapy of non-Hodgkin's lymphomas of high malignancy. Use of COP-BLAM/IMVP-16 and randomized adjuvant radiotherapy--study concept and preliminary results].

In a multicenter prospective randomized therapeutic trial in advanced (stage II-IV disease, Ann Arbor classification) high-grade malignant non-Hodgkin's lymphomas (NHL, Kiel classification) a sequential combination of the COP-BLAM (5 cycles) and the IMVP-16 (2 cycles) protocols was employed. Response was first determined after 2-3 cycles. In a response-adapted manner the therapy was immediately switched to IMVP-16 if only a partial remission or no response was obtained as evidenced by the first restaging. The aim of the study is the investigation of the efficiency of this concept to induce stable remissions. In an additional randomized trial, involving all patients reaching complete remissions after chemotherapy (second restaging), the prognostic relevance of adjuvant radiotherapy as compared to therapy-free follow-up is evaluated. Eighty percent of the 191 recruited qualified patients have so far become evaluable. Complete clinical remissions were achieved in 76/148 (51%) of the patients up to the first, in 52/85 (61%) of the patients up to the second restaging. Only in a few cases did the expected toxicity of intensive polychemotherapy reach WHO grade 3-4, including nausea and diarrhea, infections, septic complications, myelotoxicity, and stomatitis. Four of the 29 deaths recorded so far occurred in complete remission due to treatment-related complications, whereas 22/29 (76%) died in progression and 3 of unrelated causes.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Prognostic factors in a multicenter study for treatment of acute lymphoblastic leukemia in adults.

In a prospective multicenter study, 368 acute lymphoblastic leukemia (ALL) patients aged 15 to 65 years were treated with an intensified induction and reinduction regimen; 272 (73.9%) achieved complete remission (CR). The median remission duration (MRD) is 24.3 months, and the probability of being in continuous CR (CCR) at greater than 5 years is .37. The median survival for all 368 patients is 27.5 months, and the probability of being alive at 5 years is .39. For the 272 patients in remission the median survival is 58.4 months, and the probability of being alive at 5 years is .49. A lower CR rate was seen for patients with bleeding at diagnosis or with splenomegaly/hepatosplenomegaly. The prognostic factors unfavorable for remission duration were time to CR greater than 4 weeks v less than 4 weeks (P = .0002), age greater than 35 years v less than 35 years (P = .0008), leukocyte count greater than 30,000/microL v less than 30,000/microL (P = .0112), and null ALL v common ALL (c-ALL)/T cell ALL (T-ALL) (P = .05). The remission duration correlated strongly (P = .0001) with the number of these independent prognostic factors. In patients with none of these adverse factors the MRD has not yet been reached, with one adverse factor the MRD is 21.9 months, and with two or three adverse factors the MRD is only 9.6 months. For the immunologic subtype T-ALL, the probability of being in CCR at greater than 5 years is .55; for c-ALL, .34; and for null ALL, .24. According to these results, patients were stratified into a low-risk group with a CCR rate of .62 and a high-risk group with a CCR rate of .28, with the latter now allocated to either further chemotherapy or bone marrow transplantation in first remission.

Adolescent↗