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Biomedical subjects

H W Pees

Publications and source records attributed to H W Pees.

17 recordsLinked to original sources

The BFM-protocol for HIV-negative Burkitt's lymphomas and L3 ALL in adult patients: a high chance for cure.

During a period of 9 years we used the pediatric BFM-NHL protocol for treatment of 14 adult patients with Burkitt's lymphoma or L3 acute lymphoblastic leukemia. Ten of 14 patients obtained a complete remission including 5/8 with stage-IV disease or B-ALL. After a median follow-up of 55 months none of these ten patients relapsed. The projected survival after 8 years is 71%. Toxicity was moderate, with one early death; a tumor lysis syndrome occurred in four patients. From our experience we conclude that the BFM-NHL protocol is very effective in adult patients, with a high cure rate and acceptable toxicity, even in advanced stages of disease.

Adolescent

[HIV infection in stage IV C-2 (CDC). Increase in the p24 antigen value before critical decrease in CD4+ lymphocytes].

The Center for Disease Control proposed a classification system of HIV-infection including a symptomatic stage IV C-2 with secondary infections like thrush, oral hairy leukoplakia and herpes zoster. Because the prognostic value of these symptoms for the development of AIDS has been proven and the CDC-classification does not include any immunological parameters we analyzed the numbers of CD4+-lymphocytes and the frequency of HIV-antigen in 65 HIV-infected individuals. When entering stage IV C-2, the incidence of HIV-antigenemia was as high as in full blown AIDS (53% and 60%, respectively). However, we observed no decrease of CD4+-lymphocytes as compared to earlier CDC-stages.--We conclude that in stage IV C-2 the increase of viral protein production proceeds independently from CD4+-status.

CD4 Antigens

Effects of human alpha-interferon on granulocyte-macrophage progenitor cells (CFU-GM) in vitro.

Two preparations of human interferon (IFN)-alpha were assessed for their influence on granulocyte-macrophage progenitor cells (CFU-GM) in vitro. Both highly purified human IFN-alpha Ly and recombinant IFN-alpha 2a suppressed CFU-GM colony formation in a dose-dependent manner using low-density bone-marrow target cells. Suppression of CFU-GM colony formation was accompanied by an increase in clusters. However, depletion of monocytes, T lymphocytes and B lymphocytes from low-density bone-marrow cells resulted in insensitivity of progenitor cells to IFN-alpha. These results demonstrate that the effects of human IFN-alpha on myeloid progenitor cells (CFU-GM) are mediated by accessory cells within the bone marrow.

Cell Division

[Sequential high-dose cytarabine therapy in combination with asparaginase in acute myeloid leukemia].

Between 1984 and 1987 14 patients with acute non-lymphocytic leukemia were treated with sequential high-dose cytosine arabinoside in combination with asparaginase. Twelve patients were suffering from refractory leukemia; in these patients complete remissions were achieved in 58%. The efficacy of this schedule was much better in patients with substantial leukemia cell reduction due to antecedent conventional therapy and no more than 25% blast cells in the bone marrow. In this subgroup complete remissions were achieved in 75% and 86% respectively, taking into account only the completed treatment courses. Beside the well-known side-effects such as alopecia, nausea, vomiting and hepatotoxicity, we observed an increase in severe infections. Three patients died of pulmonary mycosis.

Adult

[Beta interferon therapy in hairy cell leukemia].

Eleven patients with histologically proven hairy-cell leukemia were treated for 2 to 6 months with a natural beta-interferon (beta-IFN) preparation (3 X 4 million units week i.v.). Three of the eight evaluable patients experienced a partial response, two a minor response, and three no improvement. A reduction of the hairy-cell infiltration of the bone marrow was observed in one patient. Typical IFN side-effects with flu-like symptoms were noted. These results demonstrate that IFN-beta has some clinical efficacy in hairy-cell leukemia.

Adult

Effective treatment of lymphomas of Burkitt's type and B-ALL in adults.

Malignant lymphomas, Burkitt's type, and B-ALL are rarely encountered in adult patients. Rapid initial responses are usually followed by early relapse and death. In a pilot study four adult patients, two presenting with B-ALL, were successfully treated with an aggressive protocol developed by the BFM study group for childhood lymphomas of B-type. Rapid clearance of tumor masses was achieved in all patients; no relapse occurred during an observation period ranging from 19-33 months of complete remission.

Adolescent

[Diagnosis and radio-chemotherapy of the neuroblastoma in adults].

The neuroblastoma in the adult is a rare disease which has a bad prognosis. Until now, there are no generally accepted therapy conceptions. The clinical symptoms of the patient whose case is presented here were above all pains in the pelvic region. The histologic diagnosis was difficult and could be proved only by additional examinations of other metastases. Although the primary tumor was searched for intensively, is was only found 20 months later. Especially radiotherapy, but also chemotherapy (CYVADIC regimen) have proved to be effective. Above all, the quality of life could be largely maintained over a period of 26 months.

Adult

[The influence on PHA-stimulation by inhibition of prostaglandin synthesis in vitro in patients with Hodgkin's disease (author's transl)].

Adherent mononuclear cells may have suppressor functions mediated by prostaglandins (PG). In the present study we tested a large number of normal donors and patients with Hodgkin's disease (HD) using PHA and the prostaglandin inhibitor indomethacin (IM). Stimulation of mononuclear cells from 24 healthy volunteers with PHA led to a mean response of 27 833 cpm; addition of IM caused a 32% increase of 3H-thymidine incorporation. The corresponding values for 30 patients with HD stages IIA-IVB were 14,064 cpm and 70% increase with IM. The effect of the drug was much more pronounced during relapse or progression than in untreated patients. There was an inverse relationship between PHA-response and per cent increase both in normal donors and Hodgkin patients. Depletion of adherent cells using Sephadex G-10 columns abolished the effect of IM completely, but PHA-stimulation was also slightly depressed. Our failure to observe an increase of the mitogen response after removal of monocytes may be related to the technique employed. However, an additional defect of Hodgkin lymphocytes must be considered.

Adolescent

Cytotoxic immune response of meningioma patients towards allogeneic and autologous tumour cells before and after surgery.

Cell-mediated cytotoxicity (CTX) of meningioma patients towards meningioma cells and fibroblasts was studied in vitro before and after surgery, using the 3H-proline microcytotoxicity test. When incubated with allogeneic target cells before surgery, lymphocytes from three out of seven donors showed a specific destruction of meningioma tissue, and two were cytotoxic on both types of targets. Five patients were tested against their own tumour and against skin fibroblasts; this was feasible by keeping their lymphocytes frozen in liquid nitrogen until their target cells grew as suitable monolayers in vitro. Three patients showed a specific cytotoxic response. After excision of the tumour a gradual loss of this reactivity was observed in both allogeneic and autologous systems. Sera of three patients, whose lymphocytes were not reactive against their own tumour, induced antibody-dependent cellular cytotoxicity (ADCC) towards autologous tumours if normal effector cells were used. This type of response was detectable mainly in postoperative sera, and could not be elicited in autologous lymphocytes. On the contrary, autologous sera inhibited CTX of meningioma effector cells. The data suggest that meningiomas can induce a complex immunological response in the host, which is dependent on the presence or absence of a large tumour burden.

Antibody-Dependent Cell Cytotoxicity

Influence of surgery and dexamethasone on cell-mediated immune responses in patients with meningiomas.

Cell-mediated cytotoxicity (CTX) was studied in meningioma patients before and within 2 weeks of complete excision of the tumour, using the [3H]-prolin- microcytotoxicity test. Three of 7 patients tested before surgery showed specific CTX, 2 revealed a "non-specific" (tumour-unrelated) response, and 2 were non-reactive. After surgery, CTX decreased from 84 to 50% in one patient and became negative in 2 others previously positive. One of 2 patients showing "non-specific" CTX preoperatively became positive, while the other remained unchanged. All patients were receiving dexamethasone (DXM) at the time they were tested. Lymphocyte responses to PHA were not significantly different before or after surgery (i.e. after prolonged treatment with DXM), from healthy controls. Blocking activity could be detected in the sera of all 3 patients before surgery. This activity was not specific for meningiomas. Paradoxically, the same sera did not inhibit the proliferative response to PHA. Serum from only one patient consistently suppressed the blastogenic response of homologous lymphocytes to PHA. Inhibitory activity was associated with the IgG fraction of his serum.

Cytotoxicity Tests, Immunologic

Cell-mediated immune response of patients with meningiomas defined in vitro by a [3H]proline microcytotoxicity test.

Cell-mediated cytotoxicity (CTX) of meningioma patients was assessed postoperatively by a [3H]proline microcytotoxicity test. Autologous and allogeneic tumour cells were used for prelabelling with isotope and peripheral blood lymphocytes added in a ratio of 200:1. After 60 hg the plates were washed and residual CMP counted. Control target cells consisted of normal skin fibroblasts. CTX was calculated in percentage reduction compared to cultures incubated with control lymphocytes. Specific CTX on meningioma cells (i.e. not destroying control cells) greater than 20% was considered 'positive' if significant at P less than 0-05. Fifteen of twenty-three meningiomas showed specific CTX (65%). Among eight CNS tumours of different type and thirteen non-malignant diseases and normals only three (14%) were specifically cytotoxic for meningioma cells. A cross-reaction could be demonstrated between autologous and allogeneic meningioma target cells. However, no activity of lymphocytes from patients with meningiomas on glioblastoma cells and foetal brain tissue could be found at the ratio used for evaluation. Evidence is presented indicating that a cellular immune response as measured in the microcytotoxic test may be dependent on a residual or recurrent tumour in the body.

Antigens, Neoplasm

[The lymphocyte cytotoxicity test in tumor immunology (author's transl)].

The cytotoxic action of lymphocytes on cancer cells in vitro indicates sensitization of the patient against his own tumor. The technical difficulities of this test and possibilities of standardization and simplifying the procedure are discussed. Critical steps are isolation of lymphocytes and culturing target cells without loosing their specific antigenic structure. The need for specificity controls both for lymphocytes and tumor cells is emphasized. Labelling tumor cells with isotopes represents a major improvement in evaluating the result. The role of thymus- and bone marrow-dependent lymphocytes as well as blocking factors in the serum of tumor patients can be analyzed in the cytotoxic assay. A better understanding of these mechanisms may facilitate a therapeutic approach by manipulating the interaction of tumor cells and host.

Animals