[Chemotherapy of non-Hodgkin's lymphoma (NHL)].
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Adult↗
Biomedical subjects
M Pfreundschuh
Publications and source records attributed to M Pfreundschuh.
Phenotypic and genotypic analysis of Hodgkin's disease derived cell lines: histopathological and clinical implications.
Five Hodgkin's disease (HD) derived cell lines were established in vitro in our laboratory in the last seven years. Morphological, cytochemical, immunological and cytogenetic marker analysis demonstrated that the in vitro cells represent genotypically and phenotypically the in vivo Hodgkin (H) and Sternberg-Reed (SR) cells in biopsy specimens. The cultured cells resemble haematolymphoid cells at different stages of maturation. Four of the five continue to grow in vitro as suspension cells after more than 50 months. Four more in vitro HD-derived lines were described recently by several authors. A summary of the various marker characteristics of these in vitro lines is given as a synopsis of the phenotypic marker spectrum and is discussed in comparison with our own cell lines. There is a striking similarity between two of the newly established lines (CO, HDLM-2) and our lines whereas the two other in vitro established cultures seem to resemble cell species further along the line of maturation to B lymphocytes (DEV) and monocytes (SU-HD-1). Gene rearrangement experiments undertaken with the L428, L540, L591 and the CO cell line show that the L428 and 591 cells have undergone gene rearrangement, the L428 being compatible with the genotypic state of a pre-B cell; the L591 cells, similarly rearranged furthermore demonstrated functional light chain rearrangement, compatible with B-cell development. By cytogenetic analysis chromosome 7 was found to be affected in all our described lines. This chromosome appears to be particularly unstable and vulnerable in patients with HD, since all tested cell lines revealed multiple abnormalities of this chromosome, a finding which is in accordance with observations made by other investigators in HD-biopsy cells. Since similar structural changes or loss of chromosome 7 is a characteristic event in cases of secondary acute non-lymphocytic leukaemia, it is speculated that this form of secondary neoplasia could resemble the blast crisis, as observed in chronic myeloid leukaemia.
Cell Line↗
The cell of origin in Hodgkin's disease: conclusions from in vivo and in vitro studies.
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Antibodies, Monoclonal↗
Long-term remission in acute myelogenous leukaemia.
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Adolescent↗
The influence of radiation therapy on T-lymphocyte subpopulations defined by monoclonal antibodies.
We studied the influence of radiation therapy on lymphocyte subpopulations in 17 patients undergoing adjuvant radiation therapy for primary breast cancer, and eight patients receiving brachytherapy and external beam irradiation for primary cancer of the uterus. Radiation therapy reduced B- and T-lymphocytes in proportion to the total lymphocyte population so that their percentages remained unchanged. Determination of helper and suppressor T-lymphocytes before, during and 6 months after completion of radiotherapy revealed that in both groups of patients suppressor T-lymphocytes were more resistant to and recovered faster after radiotherapy. This resulted in a decline of the "immunoregulatory balance" (helper/suppressor ratio). Although this ratio had been higher in both groups of patients than in healthy age- and sex-matched controls before therapy, it became normal and subnormal during and after radiotherapy. The clinical significance of the differential influence of radiotherapy on T-lymphocyte subpopulations remains to be determined.
Adult↗
Effect of neuraminidase treatment on serum reactivity to autologous leukemic blast cells.
The sera of 35 patients with acute lymphoblastic leukemia (ALL) and acute non-lymphoblastic leukemia (ANLL) were tested for reactivity against cell surface antigens of autologous leukemic blast cells by protein A assay (PA), immune adherence assay (IA), and anti-C3 mixed hemadsorption assay (C3-MHA). Autologous serum reactivity was detectable by PA in four cases and by IA and C3-MHA in about half the patients. Autologous serum reactivity occurred more often in ALL than in ANLL. Absorption studies revealed that in one patient only the autologous reactivity was directed against a restricted antigen, which could be detected only on the individual T-ALL blast cells. All other autologous antibodies detected unspecific antigens. Neuraminidase treatment had two effects: first, it increased antibody attachment to antigens which are also present on untreated cells; secondly, after neuraminidase treatment an antigen was detectable on the cell surface which could also be demonstrated on neuraminidase-treated non-leukemic cells (e.g., erythrocytes). Neither of these two effects of neuraminidase treatment seems to be tumor-specific. Possible therapeutic effects of neuraminidase are probably caused by unspecific adjuvant effects of the enzyme.
Adolescent↗
Monoclonal anti-idiotype antibodies against lymphoma-associated cold agglutinins.
Hybridomas secreting monoclonal antibodies against purified cold agglutinins (CA) from lymphoma patients were screened by a cold hemagglutination inhibition test. Supernatants from positive clones were further tested against several purified CA and paraproteins of different immunoglobulin (Ig) classes. It was shown that most monoclonal antibodies raised by immunization with CA had reactivity against the constant region of IgM. However, clone H-1 produced an anti-idiotypic antibody that reacted exclusively with the CA used for immunization. Using this anti-idiotype antibody, the idiotype could be demonstrated on 25% of the patient's peripheral mononuclear cells. So far, the idiotype could not be demonstrated on the patient's T-cells. Monoclonal antibodies against lymphoma idiotypes are powerful tools for studying the immunobiology of these malignancies and may be useful as specific therapeutic reagents.
Aged↗
Effect of cytotoxic drugs on the function of the hypothalamo-pituitary-adrenal axis.
We measured the serum concentration of thyroid-stimulating hormone (TSH), its response to exogenic TSH-releasing hormone (TRH), as well as cortisol plasma levels before and after stimulation with adrenocorticotrophic hormone in 15 patients before, during and after a chemotherapeutic cycle. 3/6 patients receiving only cytotoxic drugs developed a marked suppression of the TSH response to TRH and 1 of these patients showed an impairment of the adrenal function under chemotherapy. This was also observed in 7/9 patients receiving both cytotoxic drugs and corticosteroids; however, the individual pattern of the impairment was quite variable. 5/9 patients in this group developed a suppression of the TSH response to TRH. Impairment of the hypothalamo-pituitary-adrenal axis function under cytotoxic drugs and/or corticosteroids occurs with great variability and the mechanisms involved in its etiology are not yet fully understood.
Adrenocorticotropic Hormone↗
T-lymphocyte subpopulations in Crohn's disease: definition by monoclonal antibodies.
Thirty-two patients with Crohn's disease (CD) and 32 age- and sex-matched controls were studied for T lymphocytes and T-lymphocyte subpopulations in the peripheral blood, using monoclonal antibodies defining the helper/inducer and the suppressor/cytotoxic compartment. T cells were reduced in patients with CD (P less than 0.05), and this reduction was more pronounced in patients with active disease (P less than 0.01). This T-cell deficiency involves helper and suppressor cells proportionally. The proportion of helper and suppressor cells in CD was independent of disease activity and therapy. We conclude that the T-cell deficiency in CD is a secondary event, and that there is no derangement in the "immunoregulatory ratio" (helper to suppressor cells) in CD which might have served as an explanation for a possible autoimmune mechanism in the pathogenesis of this disease.
Adolescent↗
Natural antibodies to cell-surface antigens of human astrocytoma.
Sera of 200 non-transfused healthy male blood donors were tested for antibody reactivity to cell-surface antigens of cultured astrocytoma cells. Positive reactions were observed only rarely by protein-A assay (PA), in about half the cases by immune adherence assay (IA) and in nearly all cases by anti-C3 mixed hemadsorption assay (C3-MHA). In general, titers were low and only seven sera showed reactivity at 1:1,000. Serum 537 showed the strongest reaction. The anti-astrocytoma reactivity in this serum was due to an IgG antibody. Extensive absorption analysis with a panel of cell lines and fresh cells of both benign and malignant origin, as well al fetal cells, revealed that this serum detected an antigen that was present on most neural-crest-derived tumors (astrocytomas, melanomas and neuroblastomas), on very few other malignant tumors and on fetal brain. The antigen detected by serum 537 shows close relationship to the astrocytoma antigen AJ which had been defined by the serum of a patient with astrocytoma. Both antigens appear to be differentiation antigens present predominantly on non-epithelial neoplasms. The antigen detected by serum 537 is heat-stable and pronase-resistant. The sera of two other healthy donors apparently had a similar specificity, whereas the four other high-titered sera and all other sera detected class-III antigens which were non-specific and not tumor-restricted.
Absorption↗
Multicentre study on intensified remission induction therapy for acute myeloid leukemia.
In a cooperative study at 13 centres in the Federal Republic of Germany, 213 adult patients with AML were treated for remission induction by a 9-day regimen consisting of cytosine arabinoside, daunorubicin and thioguanine (TAD) according to previously described sequencing. Complete remission was achieved in 70% of all patients. Complete remission rate was 57% in the 49 patients 60 years of age and older and 74% in the 164 patients under 60 years. Sixty-eight per cent of all complete remissions and 75% of those in the higher age group were induced by one induction course. Median survival was 10 months for all patients treated and 16 months for responders. Median remission duration was 13 months with 72 patients still in continuous remission for 1-31 months. Remission duration was not significantly different for patients treated either by monthly maintenance therapy or induction type consolidation without further therapy. However, patients completing two consolidation courses had a significantly longer remission duration of 22 months. Compared to similar multicentre studies on AML therapy the intensified induction regimen applied in this study shows an improvement even in older patients.
Adolescent↗
Serologic analysis of nitrosourea-induced rat gliomas.
Inbred CDF rats (cesarean-delivered F344 rats) were immunized with either a nitrosourea-induced glioma EA-285 or its subline EA-285A and both with and without Corynebacterium parvum. A humoral immune response in syngeneic rats to the immunizing tumor was demonstrated with micromodifications of different rosette assays (immune adherence assay, protein-A assay, and anti-C3-mixed hemadsorption assay). Extensive absorption studies of two immune sera with the highest reactivity revealed two glioma-specific antigens (or two components of one antigen) on the cell surface of the cloned tumor subline. One antigen was present only on the cell surface of the subline of the glioma used for both immunization and absorption analyses. The other antigen appeared on the cell surface of both the cloned subline EA-285A and the parental cell line EA-285. These preliminary studies showed that CDF rats immunized against a syngeneic glioma mounted a humoral immune response that appeared to be individually tumor-specific.
Animals↗
T-lymphocyte subpopulations in the peripheral blood of patients with Crohn's disease.
Samples of peripheral blood from 26 patients with Crohn's disease (CD) and 26 healthy age- and sex-matched controls were tested simultaneously for B and T lymphocytes and T-lymphocyte subpopulations with receptors for IgM (TM) and IgG (TG). Patients with CD had reduced proportions of T lymphocytes, and this reduction showed a significant correlation to the CD activity index (r = -0.65, p less than 0.01). There was slight reduction of TM only (p less than 0.05) inpatients with highly active disease but not in the total population of patients studied. Proportions of B and TG cells were similar in patients and controls. Patients with no clinical or radiological but histological signs of active disease had T lymphocytes and subpopulations like patients with inactive disease. This suggests that the reduction of T cells and T-cell subpopulations in CD are secondary effects. With regard to T-lymphocyte subpopulations, our results are in contrast to a recently published report and do not suggest that analysis of T cells according to the expression of Fc receptors helps in the understanding of functional changes in the T-cell system in patients with CD.
Adolescent↗
Autologous antibodies to meningioma cell surface antigens.
Sera of 32 patients with meningioma were tested for reactivity to cell surface antigens of autologous meningioma cells with protein-A assay (PA), immune adherence assay (IA), and anti-C 3-mixed hemadsorption assay (C3-MHA). Antibodies against autologous meningioma could be detected in 6/32 patients by PA, in about half the patients by IA and in almost all patients by C3-MHA with titers ranging from 1:2 to 1:28. Only the serum reactivity detected by C3-MHA was high enough for analysis of the specificity of the reaction by absorption tests. By absorption with a panel of autologous, allogeneic and heterologous cells we were unable to demonstrate a meningioma-specific antigen. Most autologous sera detected oncofetal antigens. Serum reactivity to autologous meningioma showed no correlation to antibodies to SV-40.
Antibodies, Neoplasm↗
Tumor-specific antigens.
Based on autologous serological typing of cultured astrocytoma cells from 30 patients, three classes of surface antigens have been defined. Class I antigens are restricted to autologous astrocytoma cells. Class II antigens are shared by autologous as well as certain allogeneic tumors, but are not detected on normal cells. Class III antigens are not tumor-specific and are found on both normal and malignant cells. This analysis of human astrocytoma, with the recognition of three classes of surface antigens recognized by autologous sera, resembles the results of autologous typing of human malignant melanoma, acute leukemia, and renal carcinoma.
Antigens, Neoplasm↗
Cell surface antigens of human renal cancer defined by autologous typing.
Sera from 28 patients with renal cancer were tested for reactivity with surface antigens of cultured autologous renal cancer cells. Four serological assays were used to survey sera for autologous antibody. Immune adherence, protein A, and C3-mixed hemadsorption assays detected reactivity in a high percentage of patients (80-100%), whereas mixed hemadsorption assays were negative with sera from all but one patient. Reactive sera from six patients were analyzed by absorption tests with autologous, allogeneic, and restricted to autologous renal cancer cells; class 2 antigens, present on certain allogeneic renal and nonrenal cancer cells; and class 3 antigens, found on a wide variety of normal and malignant cell types. The sera of one patient detected class 1, 2, and 3 antigens, the sera of three patients detected class 2 antigens, and the sera of two patients detected class 3 antigens. This analysis of renal cancer, with the recognition of three classes of surface antigens recognized by autologous sera, resembles the results of autologous typing of three other human malignancies: malignant melanoma, acute leukemia, and astrocytoma. Evidence provided by autologous typing of these cancers indicates that class 1 and class 2 antigens are tumor-restricted and that under certain circumstances these antigens are immunogenic for the autologous host.
Adult↗
Leukocyte alkaline phosphatase in malignancies.
The leukocyte alklaine phosphatase (LAP) levels were determined in 183 patients with malignant diseases and 71 normal controls. The median LAP scores were 64 units (range 0 to 290) for the patients and 55 (range 2 to 158) for the controls, respectively, and no significant difference could be established. When analyzed according to primary malignancy, only in patients with Hodgkin's disease (n = 14) was the median value higher than normal (p less than 0.001). In patients with distant metastases (n = 48), higher LAP levels were demonstrated (M = 76, range 21 to 290) as compared to patients with no evidence of metastases (M = 53, range 0 to 229), (p less than 0.01). Thus, LAP activity has very limited value in the diagnosis of malignancies. Its elevation in the presence of malignant disease might, however, indicate metastases.
Adult↗
Serological analysis of cell surface antigens of malignant human brain tumors.
Sera from 30 patients with astrocytoma were tested for antibody reacting with cell surface antigens of cultured autologous astrocytoma cells. Ten percent of the patients had antibody detectable by mixed hemadsorption assays, approximately 50% by immune adherence and protein A assays, and 100% by anti-C3-mixed hemadsorption assays. Absorption analysis of reactive sera with autologous, allogeneic, and xenogeneic cells permitted the definition of three classes of astrocytoma cell surface antigens. Class I antigens showed an absolute restriction to autologous astrocytoma cells. Class II antigens were shared by all astrocytomas tested and could be detected also on neuroblastoma, sarcoma, and some (but not all) melanoma cell lines; these antigens were not found on cell lines derived from carcinomas or normal tissues. Class III antigens were widely distributed on cultured normal and malignant cells of human and animal origin. In this series, sera from 2 patients recognized class I antigens, 4 patients' serum recognized class II antigens, and 13 patients' sera recognized class III antigens. Absorption tests have shown that the AJ (class II) antigen of astrocytoma is serologically related to the previously described AH (class II) antigen of melanoma; in tests of nine melanoma cell lines, there was a correspondence between the AJ and AH phenotypes. This method of autologous typing provides a way to classify the cell surface antigens of astrocytomas and to assess the clinical significance of humoral immunity to these antigens.
Antibody Specificity↗