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Biomedical subjects

J Thaler

Publications and source records attributed to J Thaler.

At least 109 records · Page 6Linked to original sources
PubMed1989

Combination effects of human recombinant interferon (alpha-2-arg, gamma) and cytotoxic agents on colony formation of human melanoma and hypernephroma cell lines.

Malignant melanoma and hypernephroma show marginal response to chemotherapeutics and interferons when used as single agents. Using a modified soft agar clonogenic assay we investigated the antiproliferative effects of combinations of vinblastine, bleomycin, adriamycin, interferon alpha and gamma. On the hypernephroma cell line combinations of bleomycin and adriamycin with interferon gamma as well as combinations of both interferon types resulted in a synergistic antiproliferative effect. On the melanoma cell line combinations of bleomycin and adriamycin with interferon alpha and combinations of vinblastine with interferon gamma acted in a synergistic manner. All other combinations tested were only additive. Thus far, we could not find any antagonistic effect of interferons and chemotherapeutics.

Antineoplastic Agents↗
PubMed1989

GM-CSF treatment in aplasia after cytotoxic therapy.

GM-CSF was used to overcome fatal myelosuppression after cytotoxic chemotherapy. Two different application modalities were compared: a continuous 24 h infusion was more effective compared to a 30 min short term infusion. Using the former modality at a dose of 10 micrograms/kg/d for five days very impressive responses were observed. No major side effects did occur. The first 13 patients treated in this way included 8 AML cases. Only one of these latter patients had a leukemia relapse. However, in this patient the immediate GM-CSF response was clearly separated from the relapse occurring later in the observation period. Thus, the preliminary results of the present paper suggest that GM-CSF besides of being very efficient in accelerating granulocyte recovery does not stimulate the growth of AML blasts in vivo in patients with only minimal residual disease.

Adolescent↗
PubMed1989

Response to pentostatin in hairy-cell leukemia refractory to interferon-alpha. The European Organization for Research and Treatment of Cancer Leukemia Cooperative Group.

Interferon-alpha (IFN-a) or 2'-deoxycoformycin (pentostatin; DCF) have each been shown to be highly active in hairy-cell leukemia (HCL). In this phase II study of the Leukemia Cooperative Group of the European Organization for Research and Treatment of Cancer (EORTC), the efficacy and toxicity of DCF were investigated in patients who were resistant to IFN-a treatment. Resistance was defined as: (1) progressive disease (PD) under IFN-a therapy for more than 2 months; (2) stable disease (SD) after more than 6 months of IFN-a treatment; (3) relapse within 3 months of discontinuing IFN-a; and (4) intolerance to IFN-a because of World Health Organization (WHO) grade 3 or 4 toxicity. DCF was applied at a dosage of 4 mg/m2 weekly x 3, then 4 mg/m2 every other week x 3. Responders were given a maintenance therapy once per month for a maximum of 6 months. At the time of report, 33 patients with resistant disease were evaluable for response and toxicity. Median duration of IFN-a therapy before DCF administration was 14.7 months (range, 1 to 41 months). Complete remissions (CRs) were achieved in 11 patients and partial remissions (PRs) in 15, resulting in a total response rate of 78.8%. Median interval between beginning of DCF therapy to best response was 3.9 months with a range from 2.0 to 7.0 months. Two patients who achieved PR have relapsed 7 and 14 months after cessation of DCF therapy. The median duration of response was over 11.5 months (range, over 3.0 to over 24.0 months). Three patients died within the first 6 weeks of DCF treatment: one of drug-unrelated cardiomyopathy and two of fungal pneumonia. The patients with early death (n = 3) and nonresponsive disease (n = 4) received IFN-a treatment for a longer period (median, 18.0 months) than did the 26 responsive patients (median, 10.0 months). Major side effects included nausea, skin rash, and infections and were otherwise mild. Thus, DCF is highly active in patients with HCL resistant to IFN-a.

Adult↗
PubMed1989

Pentostatin (2'deoxycoformycin) for the treatment of lymphoid neoplasms.

Knowledge of the vital role of adenosine deaminase in lymphatic tissues has led to the development of enzyme inhibitors for treatment of lymphoid neoplasms. Deoxycoformycin is a potent ADA inhibitor and has been shown to be active in acute lymphoblastic leukemia at high doses but associated with unpredictable toxicity. In indolent lymphocytic leukemia or lymphoma with low ADA concentrations, this drug is effective at low doses with mild toxicity. The on-going EORTC trial shows that pentostatin is highly effective in hairy cell leukemia and can achieve durable complete remissions even if interferon alpha has failed. It will probably play an important role in the treatment of prolymphocytic leukemia, T- and B-cell chronic lymphocytic leukemia and Sézary syndrome.

Adenosine↗
PubMed1989

Expression of leucocyte function-associated antigen-1 and 7F7-antigen, an adhesion molecule related to intercellular adhesion molecule-1 (ICAM-1) in non-Hodgkin lymphomas and leukaemias: possible influence on growth pattern and leukaemic behaviour.

In 160 non-Hodgkin lymphomas (NHL) of B and T cell origin the expression of leucocyte function-associated antigen-1 (LFA-1) and one of its counter-structures named 7F7-antigen was studied. Functional and structural similarities and the 7F7-reactivity of pICAM-1 transfected COS-cells prove that 7F7-antigen is identical with ICAM-1. The expression of both adhesion structures occurred variably and clearly depended on the maturation stage and on the B and T cell origin of lymphomas but was not associated with the proliferative status of tumour cells. The concomitant expression of both adhesion molecules was a characteristic feature of germinal centre derived NHL, particularly of those with neoplastic follicular structures (corr. contingency coeff. = 0.506; P less than 0.02), whereas both adhesion structures were less often expressed on lymphomas with a more diffuse pattern of tumour infiltration. Most B-NHL of low-grade malignancy expressed LFA-1 while their counterparts of high-grade malignancy often tended to be LFA-1 negative. In B cell neoplasias of low-grade malignancy the lack of ICAM-1 and a leukaemic course of the disease were significantly correlated (P less than 0.0005). The results indicate that the differential expression of both adhesion molecules may account for distinct patterns of growth and spread in subtypes of lymphoid malignancies.

Antigens, Differentiation↗
PubMed1989

Comparison of clinical efficacy and toxicity of conventional and optimum biological response modifying doses of interferon alpha-2C in the treatment of hairy cell leukemia: a retrospective analysis of 39 patients.

Hairy cell leukemia (HCL) has been shown to be extraordinarily sensitive to treatment with alpha-interferon (IFN). In order to define clinically effective IFN doses associated with minimal toxicity, the therapeutic efficacy and side effects of recombinant IFN-alpha-2C treatment of HCL were compared for two different dose regimens: 18 patients (group A) received conventional doses of recombinant IFN-alpha-2C (2 x 10(6)U/m2) for a median time of 35 weeks (range 26-52 weeks), and 21 patients (group B) received optimum biological response-modifying doses of IFN-alpha-2C (0.2-0.6 x 10(6)U/m2) for a median time of 31 weeks (range 12-52 weeks). Interferon was administered daily subcutaneously for 3 months and then every second or third day. Induction of neopterin excretion was chosen as the marker for definition of biological response. The smallest IFN dose causing maximum in vivo induction of biosynthesis of the GTP-degradation product neopterin was deemed "biologically optimal." Both dose regimens were effective, but the low-dose regimen was almost free of toxicity. Thus, in HCL patients alpha-IFN related toxicity can be separated from its antineoplastic activity. Low doses of alpha-IFN should be considered for treatment of HCL patients who develop toxic side effects and for primary treatment of HCL patients with severe cytopenia.

Adult↗
PubMed1988

abl oncogene expression in non-Hodgkin lymphomas: correlation to histological differentiation and clinical status.

Eight reactive lymphatic tissues, 166 cases of non-Hodgkin lymphomas (NHL) and 11 cases of multiple myeloma were investigated for expression of the c-abl protein using the poly-clonal anti-abl antibody 4411 and an indirect peroxidase technique. In selected cases the results were compared to those obtained with a second polyclonal and 2 monoclonal anti-abl antibodies. In 7 cases, Northern blot analysis of abl-mRNA was performed in parallel. In reactive lymphatic tissues, cells positive for the 4411 antibody were confined to the B-cell areas, i.e., to the mantle zone and parts of the germinal center. In NHL, a positive staining of the cell membrane was predominantly detectable in lymphomas putatively originating in the germinal center or mantle zone (in particular in centrocytic NHL), independent of their proliferative activity. Clinically, 7 out of 8 abl-positive cases of chronic lymphocytic leukemia (CLL) had a more aggressive course of disease, whereas "progressive disease" occurred in only 7 out of 19 c-abl antigen-negative cases. When the clinical status of 78 patients with NHL and 11 patients with multiple myeloma was related to c-abl expression, c-abl-positivity was mostly confined to patients in advanced tumor stages [p less than 0.001 (NHL)].

Animals↗
PubMed1988

Interferon-alpha-2 in the treatment of idiopathic myelofibrosis.

We investigated the effect of human recombinant DNA-derived IFN-alpha-2 given in a dose of 1-2 X 10(6) units daily by subcutaneous injection to five patients with advanced idiopathic myelofibrosis (IM). Transfusion dependent anemia and symptomatic splenomegaly were taken as inclusion criteria for this pilot study. Two patients succumbed, one and three months after starting interferon-treatment because of pneumonia and traumatic cranial injury, respectively. While on IFN-treatment no improvement of cytopenia or reduction of splenomegaly was seen in four of the patients. In one patient, however, the requirement for erythrocyte transfusions decreased from 5 to 1.7 monthly upon IFN-treatment. After two, four and six months respectively IFN-treatment had to be stopped in these cases because of progressive thrombocytopenia and/or neutropenia. These observations suggest, that IFN-alpha might be of only marginal value in the treatment of advanced idiopathic myelofibrosis.

Aged↗
PubMed1988

Deoxycoformycin in therapy of refractory lymphoid neoplasms.

Knowledge of the vital role of the purine degradative enzyme adenosine deaminase (ADA) in the differentiation of T and B lymphocytes has stimulated interest in the pharmacologic inhibition of ADA as specific cytotoxic therapy for lymphoproliferative diseases. 2'-Deoxycoformycin (DCF) is a tight-binding ADA-inhibitor and has shown activity in T and B cell neoplasms. In this phase-II study, the efficacy and toxicity of DCF in chronic T and B cell neoplasms is investigated. We report the preliminary results of treatment in 27 patients (8 with Sézary syndrome, 11 with B-chronic lymphocytic leukemia (CLL), and 8 with hairy cell leukemia (HCL)), who were refractory to conventional therapy. DCF was applied at a dosage of 4 mg/m2 weekly x 3, then 4 mg/m2 every other week x 3. Three of the 8 patients with Sézary syndrome and 3 of the 11 patients with B-CLL attained a partial remission. One complete and 7 partial remissions have been achieved thus far in the 8 patients with HCL refractory to interferon alpha treatment. Other than nausea in 10 patients (mainly grade 1 and 2), transient skin rash in 4 patients and Herpes infections in 4 patients (mainly grade 2), no other major toxicities were observed. Thus DCF is highly active in hairy cell leukemia that did not respond to interferon alpha, and shows moderate activity in refractory Sézary syndrome and B-CLL.

Antineoplastic Agents↗
PubMed1987

Diagnostic and prognostic value of immunohistological bone marrow examination: results in 212 patients with lymphoproliferative disorders.

Cryostat sections of 246 consecutive bone marrow biopsies from 212 patients with lymphoproliferative disease were investigated using a panel of monoclonal antibodies (MOAb's) and an immunoperoxidase technique. Bone marrow involvement was demonstrated by immunohistological examination in 121/160 patients (76%) with non-Hodgkin lymphomas (NHL) and 16/23 patients (70%) with plasma cell malignancies; the definite immunological diagnosis could be performed in 77% and 88%, respectively. Reactivity with the MoAb Ki-67 correlated with clinical parameters: in all cases exhibiting more than 5% positive cells an unfavourable course was seen, independent of the histological subtype. Another MoAb of potential prognostic relevance is KiM 4 b, which reacts with follicular dendritic cells (FDC). Besides the presence of FDC in germinal center tumors (CB/CC and CC-NHL) we found FDC in a minority of cases with B-CLL (5/44) and IC lymphoma (4/18). In the latter group 3/4 patients showed a favourable clinical course (vs 2/14 without FDC). The MoAb Tü 1 could discriminate between the lymphoplasmocytoid (11/12 positive) and the lymphoplasmocytic (0/6 positive) subtype of IC lymphoma and has proven of diagnostic importance. Expression of IL-2 receptors, detected by MoAb anti-Tac (CD 25), was demonstrated on leukemic cells from patients with hairy cell leukemia (100%), B-CLL (82%), IC (61%), CC (50%) and CB/CC lymphoma (50%). A considerable number of reactive T-lymphocytes (5%-60% of tissue cells) were identified among the neoplastic B cells with a predominance of CD4+ cells in most cases with NHL, whereas the CD4+/CD8+ ratio was significantly lower in myelomas and non-infiltrated bone marrows. The potential meaning of these findings is discussed. The immunohistological bone marrow analysis represents an important additional method in the diagnostic procedures of lymphoproliferative diseases involving the bone.

Antibodies, Monoclonal↗
PubMed1987

Progressive preleukemia presenting amegakaryocytic thrombocytopenic purpura: association of the 5q- syndrome with a decreased megakaryocytic colony formation and a defective production of Meg-CSF.

The authors present a patient with the typical clinical picture of an acquired amegakaryocytic thrombocytopenic purpura. After 16 months of observation, the patient developed acute myelomonocytic leukemia. During the preleukemic phase and after progression to overt leukemia, serial in-vitro analyses of megakaryocytic, granulocytic, erythrocytic and T-lymphocytic colony growth were carried out in a microagar culture system. At presentation, a marked diminution of CFU-M was observed, whereas CFU-E, BFU-E, CFU-C and CFU-TL were in the normal range. The CFU-M number remained at its low level during the whole observation period. The CFU-C number declined steadily during the preleukemic period, while BFU-E, CFU-E and CFU-TL remained constant until January 1985 when the patient developed AML. After progression to overt leukemia, a distinct reduction became evident in all colony-forming cells. Cytogenetic studies performed during the preleukemic phase indicated the presence of a 5q- chromosome. The authors submit evidence here that the patient was not only characterized by defective megakaryocytic colony formation but also by a deficiency of functional megakaryocyte colony-stimulating activity. No humoral or cellular inhibitors of CFU-M colony formation were found. It is concluded that in preleukemia with a 5q- chromosome the megakaryocytic cell lineage may be involved in the process that precedes overt leukemia at an earlier time than cells of granulocytic and erythrocytic lineages. In addition, it is shown here that megakaryocytopoiesis during the preleukemic period can be characterized by two different defects: first, an intrinsic megakaryocytic stem cell defect and, second, a deficiency of functional megakaryocytic colony-stimulating activity.

Adult↗
PubMed1986

[Studies of immunologic markers in malignant lymphomas: diagnostic and prognostic relevance].

Immunological markers important for the diagnosis of the following subtypes of Non-Hodgkin lymphomas (NHL) are discussed: lymphocytic lymphomas (i.e.: B-CLL, immunocytic NHL, prolymphocytic- and hairy cell leukemia), NHL derived from follicular center cells (centrocytic, centroblastic/centrocytic and centroblastic NHL), lymphomas with blastoid appearance (various forms of lymphoblastic and "large cell" NHL) and disorders of T lymphocytes (NHL) of peripheral T cells and T gamma lymphocytosis with neutropenia). In these disorders, the patterns of leukocyte surface antigens like T1 (CD5), Tac (CD25), CALLA (CD10), FMC7, Tü1 and Tü33 as well as staining for the terminal transferase (TdT) and of dendritic follicular cells have been examined by investigating specimens of a large group of patients. Apart from the diagnostical value, these evaluations have contributed to a better understanding of normal B cell differentiation whereas the role of marker studies as independent prognostic factors requires additional prognostic studies. Finally, the value of immunoperoxidase or alkaline phosphatase staining of cryostat sections of bone marrow biopsies is emphasized, which allowed the diagnosis and classification of 74% of 92 NHL studied by this technique.

Antibodies, Monoclonal↗
PubMed1985

[Immunocytologic diagnosis of leukemia and lymphoma: monoclonal antibodies in the differential diagnosis of hematologic neoplasms].

Malignant lymphomas and leukemias are related to maturation stages of distinct subpopulations of hematopoietic or lymphoid cells as defined by immunocytological methods. We first describe various monoclonal antibodies, and the methodology employed in our investigations and report on recent developments in the standardization of these reagents (part 1). The maturation sequence of normal lymphoid cells and their precursors in the bone marrow, thymus and the peripheral lymphoid organs are discussed in part 2. Typical immunomorphological findings in Non Hodgkin Lymphomas (NHL) are summarized in respect to lymphocytic NHL (CLL, lymphoplasmocytoid NHL, hairy cell and prolymphocytic leukemia, some lymphomas of peripheral T-lymphocytes), to NHL of follicular center cells (centroblastic-centrocytic, centrocytic NHL), to "large cell" NHL (centroblastic, immunoblastic NHL, large cell NHL derived from T-lymphocytes or "lymphomas" of macrophage origin) and to lymphoblastic NHL (derived from T-lymphocytes, pre-B lymphocytes and Burkitt-type). Findings in multiple myeloma are also summarized in part 3. Immunocytological features of the normal Myelo-, Mono-, Erythro- and Thrombopoieses are discussed in part 4. The reactivity of some monoclonal antibodies with precursor cells of these cells (CFU-GM, BFU-e and CFU-e, CFU-M) are also described. Finally we summarized the immune phenotype of acute leukemias (part 5) in respect to acute lymphoid leukemias (cALL, T-ALL, O-ALL, B-ALL), to acute non lymphoid leukemias (M1-M6 type according to the FAB-Classification) and to blastic stages of chronic leukemias.

Antibodies, Monoclonal↗