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Biomedical subjects

H Heimpel

Publications and source records attributed to H Heimpel.

At least 127 records · Page 7Linked to original sources
PubMed1990

Establishment and characterization of a new Epstein-Barr virus transformed cell line from a human B cell lymphoma.

We have established a new cell line from a patient with centrocytic B cell lymphoma. Highly purified peripheral blood B cells from patient DUL (WBC counts 158,000/microliters) were infected in vitro with Epstein-Barr virus (EBV), and CD20+ B cells were cloned into 96 well culture plates with the aid of a cell sorter autoclone device. As shown by GTG-banding and Southern blot analysis, out-growing EBV-positive clones had the same chromosomal abnormalities and identical monoclonal IgH gene rearrangement as the original EBV-genome-negative leukemic B cell clone. Surface marker analysis with a panel of monoclonal antibodies revealed identical patterns on EBV-negative and -positive clones, with the exception of PCA1 (reactive with plasma cells) which was negative on freshly explanted leukemic B cells but positive on EBV-converted clones.

Antigens, Surface↗
PubMed1990

Transient pancytopenia. A report from the International Agranulocytosis and Aplastic Study.

From a population-based study on the incidence of potentially drug-associated blood dyscrasias 28 cases were identified with pancytopenia. Who recovered within 90 days after diagnosis. Early recovery occurred more frequently in patients showing normal or increased cellularity of the bone marrow than in patients with bone marrow hypoplasia. Median recovery times of leukocytes were 14 and 10 days and of platelets 21 and 9 days in patients with and without bone marrow hypoplasia, respectively. Age and sex distribution were similar in both groups. Of 28 patients, 11 reported a period of fever before onset of pancytopenia. Sixteen patients in whom information on drug use was available had taken a median of 4 drugs before the onset of symptoms that were related to pancytopenia. From these results we present the hypothesis that transient pancytopenia with or without marrow hypoplasia can be the expression of the same type of bone marrow injury and that drugs or viral infections should be considered as etiological factors.

Agranulocytosis↗
PubMed1990

Aggressive polychemotherapy for acute myelofibrosis.

Acute myelofibrosis is a rare and still ill-defined disease. Based on morphological observation, immunophenotyping and ultrastructural analysis, we support the assumption that acute myelofibrosis is a malignant disorder mainly of the megakaryocytic lineage and is closely related to acute megakaryocytic/blastic leukaemia. Consequently, the 11 patients reported here were treated with aggressive polychemotherapy with combinations including daunorubicin and cytosine arabinoside and 6-thioguanin or VP16-213. 4 complete remissions, 2 partial remissions and 1 minor response were observed. Duration of aplasia was not significantly prolonged. These findings indicate that the use of aggressive polychemotherapy is feasible in acute myelofibrosis and results in a significant number of remissions.

Acute Disease↗
PubMed1990

Antilymphocyte immunoglobulins stimulate peripheral blood lymphocytes to proliferate and release lymphokines.

Five different preparations of antilymphocyte immunoglobulins (ATG) and antithymocyte immunoglobulins (ALG) with good or little clinical response were compared for their hematopoietic and immunological activities. All ATG/ALG lots demonstrated complement-mediated cytotoxicity on peripheral blood mononuclear cells. They had different titers of antibody specificities against lymphocyte cell membrane antigens. Neither clinically effective nor ineffective lots demonstrated any apparent colony stimulating activity on bone marrow mononuclear cells. Purified Natural Killer cells failed to be stimulated by ATG/ALG in liquid culture. ATG/ALG demonstrated potent T-cell stimulating activity comparable to phytohemagglutinin. This stimulation was blocked by anti-IL-2 receptor monoclonal antibodies, and was inhibited dose-dependently by cyclosporin-A. Some clinically ineffective ATG/ALG lots also stimulated T cells to release lymphokines. The differences in these characteristics among ATG/ALG lots provide some clues to guide further efforts to elucidate a key mechanism of therapeutic effectiveness.

Anemia, Aplastic↗
PubMed1990

[Evaluation of 196 patients with chronic myeloid leukemia based on a standard prognosis model].

The clinical course of 196 patients with chronic myelocytic leukemia (CML) was studied. Prognostic factors were analyzed using a standard prognostic model. From a univariate analysis of patients with nonblastic Philadelphia chromosome-positive CML, splenomegaly, bone marrow fibrosis, percentage of blasts and promyelocytes in the peripheral blood and LDH activity were shown to be factors with a significant negative influence on survival. However, age and the platelet count did not influence survival. The standard prognostic model, generated with the 4 variables (1) percentage of blasts and promyelocytes, (2) spleen size, (3) platelet count and (4) age did not provide a useful representation of risk status in this heterogenous patient population. However, the addition of further variables (LDH, additional chromosomal aberrations, percentage of basophiles/eosinophiles and percentage of bone marrow blasts) to the standard model allowed a separation into 2 patient groups: one with low and the other with intermediate to high risk. Our data support the general validity of the prognostic model; however, the applicability of the model may be compromised in hematologic centers with a heterogenous CML population due to the selection of high-risk patients. In this situation additional risk factors may have to be added to the prognostic formula.

Biomarkers, Tumor↗
PubMed1990

Clonal analysis of chronic myeloproliferative disorders using X-linked DNA polymorphisms.

Restriction fragment length polymorphisms of the X-chromosome genes phosphoglycerate kinase and hypoxanthine phosphoribosyl transferase were used to study clonality in peripheral blood leukocytes from 48 women with chronic myeloproliferative disorders (c-MPD). A total of 50% of patients were heterozygous for one or both of the polymorphic loci. These included 17 cases with polycythemia vera, four patients with essential thrombocythemia (ET), and three cases with idiopathic myelofibrosis (IMF). A clear-cut monoclonal X-inactivation pattern was observed in 17 of 24 cases including all IMF patients. Only one patient with PV exhibited a nonclonal composition of her leukocytes, while six cases demonstrated a predominantly clonal pattern in peripheral blood cells. Among the latter category reckoned three of four ET patients. Cell separation analyses were performed in one ET and three PV patients. In all four cases a monoclonal pattern of the granulocyte fraction could be established, while T lymphocytes of these patients were of nonclonal origin. These data suggest that the vast majority of c-MPDs arise from multipotent hematopoietic stem cells. Moreover, this type of clonal analysis might be of help in discriminating between primary MPD and reactive processes.

Adult↗
PubMed1990

[Advantages and problems of interdisciplinary tumor conferences].

Interdisciplinary cancer conferences (ICC), which deal with the problems of individual patients, are an appropriate instrument for coordinating interdisciplinary decisions at an early stage and for ensuring adherence to standard diagnostic and therapeutic procedures. As shown by seven-years experience and data from 1225 cases, about 80% of the decisions made by the conference are followed by the responsible physician. Regular meetings at suitable times and locations, effective preparation with information about the problems to be discussed and rapid distribution of written reports to all participants will guarantee a continuing interest in presenting patients at the ICC.

Combined Modality Therapy↗
PubMed1990

Tumor necrosis factor-alpha, but not lymphotoxin, stimulates growth of tumor cells in hairy cell leukemia.

We investigated the effect of recombinant tumor necrosis factor-alpha (rTNF-alpha) and recombinant lymphotoxin (rLT) in the growth modulation of purified hairy cell leukemia (HCL) cells. In response to rTNF-alpha, HCL cells from five of eight patients showed a 3 to 23-fold thymidine incorporation above their unstimulated controls. The effect was time and dose dependent with a maximum between 10 and 25 ng/ml rTNF-alpha after 120-hr incubation. rLT (1-50 ng/ml), however, could not enhance DNA synthesis in six of six cases. Cell number of rTNF-alpha stimulated cells ranged from 2-3 x 10(6)/ml from days 0-50 whereas cell number of unstimulated controls decreased from 3 x 10(6)/ml at day 0 to 0.01-0.02 x 10(6)/ml after 50 days in culture. rTNF-alpha induced proliferation could be suppressed in all HCL cell populations by 0.3 ng/ml recombinant interferon alpha (100 U/ml rIFN-alpha). TNF binding studies in two patients revealed that both TNF-sensitive HCL cells (1,990 +/- 148 receptors/cell) as well as TNF-insensitive HCL cells (1,261 +/- 101 receptors/cell) express specific receptors for TNF-alpha. These data show that rTNF-alpha and rLT have different effects on the growth of HCL cells. In addition there is a subgroup of patients who show no response to rLT or rTNF-alpha.

Adult↗
PubMed1990

In vivo recruitment of GM-CSF-response myelopoietic progenitor cells by interleukin-3 in aplastic anemia.

Previous studies have indicated that colony-stimulating factors may stimulate myelopoiesis and thus increase the number of circulating white blood cells in patients with hematopoietic failure including aplastic anemia. However, long-term administration of the factor was required to maintain its response. In the present article we report on a patient with severe aplastic anemia undergoing treatment with recombinant human (rh) granulocyte-macrophage colony-stimulating factor (GM-CSF). After an initial response, the patient became refractory to GM-CSF. However, treatment with interleukin (IL)-3 restored responsiveness to GM-CSF, suggesting that IL-3 may have replenished the bone marrow with myelopoietic progenitor cells sensitive to the action of GM-CSF. This observation suggests the value of application of sequentially acting hematopoietic growth factors in aplastic anemia patients.

Anemia, Aplastic↗
PubMed1989

Budd-Chiari syndrome and thrombosis of other abdominal vessels in the chronic myeloproliferative diseases.

Of 501 patients with chronic myeloproliferative diseases (c-MPD) 18 developed thrombosis of major abdominal vessels including 6 with hepatic vein thrombosis (Budd-Chiari syndrome). The complication was seen in 14 of 140 (10%) patients with polycythemia vera (PV), 3 of 23 (13%) patients with essential thrombocythemia (ET), 1 of 106 (1%) patients with idiopathic myelofibrosis (IMF), and none of 232 patients with chronic myelogenous leukemia (CML). Leading symptoms and signs were abdominal pain, progressive splenomegaly, widening abdominal girth, ascites, venous collaterals, and nausea and vomiting. The diagnostic modalities with highest specificity were angiography and explorative laparotomy. A causal relationship between the thrombotic event and hematocrit, thrombocyte count, or hemostatic abnormalities at the time of diagnosis could not be established. Detailed laboratory tests of platelet function and coagulation and fibrinolytic parameters of 5 surviving patients did not show any specific defect. Despite medical and surgical intervention, 39% of the patients died within 2 months after diagnosis of the thrombosis. The majority of the survivors developed further complications like liver cirrhosis with portal hypertension and esophageal varices or the short bowel syndrome after extensive bowel resection for mesenterial infarction.

Blood Coagulation Tests↗
PubMed1989

[Reversible germ cell toxicity following aggressive chemotherapy in patients with testicular tumors: results of a prospective study].

The impact of aggressive chemotherapy on reproductive and endocrine gonadal function was prospectively studied in 44 patients with germ cell tumors. Diagnostic procedures to determine gonadal toxicity consisted of hormone determinations, semen analyses, interviews with a standardized questionnaire, and gonadal histology. After chemotherapy all patients showed elevated serum levels of follicle-stimulating hormone (FSH) and azoospermia due to germ cell and stem cell loss. Recovery of spermatogenesis, as indicated by normalization of serum FSH levels and sperm density, occurred in 77% of the patients 25-60 months after cessation of chemotherapy. In all patients serum testosterone and luteinizing hormone (LH) values remained within normal limits after therapy indicating resistance of Leydig cells to cytotoxic drugs. Three patients fathered four healthy children after completion of chemotherapy. These data suggest significant reproductive dysfunction in all men treated for germ cell tumors. However, most patients showed late and complete recovery of spermatogenesis. In contrast, endocrine gonadal function was unaffected after chemotherapy in all patients. FSH and LH are feasible markers to assess drug-induced gonadal toxicity.

Adolescent↗
PubMed1989

A phase I/II study of recombinant interferon alpha 2a and hydroxyurea for chronic myelocytic leukemia.

Nine previously untreated patients with Philadelphia chromosome-positive chronic myelocytic leukemia (CML) were treated with recombinant interferon alpha 2a (rIFN-alpha 2a) and hydroxyurea. Patients received 6 X 10(6) U rIFN-alpha 2a daily for the first week and 3 X 10(6) U rIFN-alpha 2a daily for the second week. As maintenance treatment starting on day 15, patients received 3 X 10(6) U rIFN-alpha 2a 3 times a week. Simultaneously, hydroxyurea was given, starting at a dose of 40 mg/kg on day one. The maintenance dosage was adjusted to the white blood cell count. Two patients responded with complete hematological remissions but without cytogenetic and molecular-genetic improvements. Seven patients responded with partial hematological remissions. Response to therapy was rapid; normal white blood cell counts were reached after a median of 12 days. The doses of rIFN-alpha 2a and hydroxyurea needed to keep the leucocyte count in the normal range were low (3 X 10(6) U rIFN-alpha 2a 3 times per week, 0.5-1.5 g hydroxyurea/day). Acute toxicity of the combination therapy consisted of fever (9 of 9 patients), flulike symptoms (7 of 9 patients), pruritus and/or rash (3 of 9 patients) and evidence of a tumor cell lysis syndrome (1 of 9 patients). The side effects were not dose-limiting. Combination therapy with rIFN-alpha 2a and hydroxyurea for CML is well tolerated and allows quick and effective hematological control of the disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Daunomycin, cytosin-arabinoside and VP-16 (DAV) for myeloid blast crisis of CML.

Nine patients with myeloid blast crisis of Philadelphia chromosome-positive chronic myelocytic leukemia received 1-3 courses of intensive induction chemotherapy with DAT (daunomycin, cytosin-arabinoside and 6-thioguanin) or DAV (daunomycin, cytosin-arabinoside and VP-16). Eight patients responded with clearing of blasts from peripheral blood giving a response rate of 89%. However, bone marrow aplasia with less than 5% blasts was seen in only 2 patients. These 2 patients subsequently received an allogeneic bone marrow transplant and achieved complete remissions of 3 and 6 month duration. All patients died due to progression of blast crisis. Median survival of the group was 164 days. These results were compared to a historical control group of 31 patients with myeloid blast crisis treated with vincristine and prednisone. Despite a significantly better response rate with DAV or DAT (8 of 9 versus 9 of 31, p = 0.01) survival was not significantly different than that of the control group.

Adult↗
PubMed1989

Cryocrystalglobulinemia: pH-dependent precipitation of a monoclonal IgG-kappa-immunoglobulin.

Cryoglobulinemia is seen in a minority of patients with plasma cell dyscrasias and can be of clinical relevance if intravascular gelling or precipitate formation occurs at low temperatures. We observed a patient suffering from IgG-kappa multiple myeloma which was complicated by instability of the immunoglobulin forming crystalline precipitates at low pH and low temperature. Short exposure to extreme cooling initiated an unusual course terminating in disseminated vascular occlusion and fatal outcome which was connected with an adverse effect of blood exchange. Crystal formation was noticed in anticoagulated blood samples even at 37 degrees C. In vitro studies showed a critical pH dependency of solubility of the immunoglobulin close to the physiological pH of the blood. These observations suggest that the fatal outcome was due to a vicious circle of ischemia, metabolic acidosis and intravascular precipitations, initiated not only by low acral temperatures but by cold-induced ischemic tissue acidosis as well. Serum of patients with monoclonal gammopathy and cryoglobulinemia should be tested for pH dependent immunoglobulin insolubility.

Aged↗
PubMed1989

Polycythemia vera. A clinical study of 141 patients.

The clinical course of 141 unselected patients (64 m, 77 f, median age 59) with polycythemia vera (PV), treated during the period 1967 to 1986 was analyzed to study prognostic factors and the correlation between treatment strategies and complication rates. Therapy was performed according to a prospectively defined treatment protocol. Primary control of the disease was achieved by phlebotomy. Marrow suppression by radioactive phosphorus or low dose busulphan was used only as a second-line therapy or to lower high platelet counts. The clinical course of the patients was characterized by a low rate of acute leukemia (4%) and a high rate of thromboembolic complications (40%). Myelofibrosis developed in 17 patients (12%). Median survival of the patents was 9.4 years. The prognostic influence of several parameters at the time of diagnosis was tested: age, sex, spleen size, percentage of blood blasts + promyelocytes, leucocyte count, platelet count, hemoglobin, hematocrit, reticulocyte count and the values of the lactate-dehydrogenase (LDH) and the alkaline neutrophil phosphatase (ANP) all had no significant influence on the length of survival. The prognosis of PV patients with atypical disease presentation at diagnosis was not different from patients with typical disease.

Adult↗
PubMed1989

Evaluation of remission state in chronic myeloid leukemia patients after bone marrow transplantation using cytogenetic and molecular genetic approaches.

The remission state of 13 Philadelphia positive chronic myeloid leukemia patients was studied after bone marrow transplantation (BMT) by cytogenetic and Southern blot analysis of the breakpoint cluster region (BCR) gene. Eight of 13 patients showed neither clinical nor genetic evidence of residual disease. In two patients hematological relapse was confirmed by cytogenetic and molecular analysis. Evidence for residual leukemic cells in otherwise complete remission was obtained genetically in three patients. One of the latter cases revealed BCR rearrangement despite negative cytogenetic findings, while in another patient cytogenetic relapse was observed without demonstrable rearrangement within the major BCR. Our results may indicate that cytogenetic and molecular genetic methods complement rather than replace each other for the detection of residual CML cells after BMT.

Adolescent↗
PubMed1989

Tumor necrosis factor induces proliferation of neoplastic B cells from chronic lymphocytic leukemia.

The biologic effects of recombinant tumor necrosis factor-alpha (rTNF-alpha) and the expression of specific TNF membrane receptors on isolated neoplastic B cells from previously untreated patients with chronic lymphocytic leukemia (CLL) were investigated in vitro. Isolated B cells were incubated up to six days with various concentrations of rTNF-alpha (0.1 to 100 ng/mL). B cells from most patients proliferated ranged from two to 104 times that of unstimulated cells from the same patients. An optimal proliferative effect was achieved at 25 ng/mL rTNF-alpha and an incubation time between 96 and 120 hours, whereas a low concentration of rTNF-alpha (1 ng/mL) reduced [3H]TdR incorporation in four cases. Metaphase cells were detected in the rTNF-alpha-stimulated cultures that proliferated in response to rTNF-alpha. B cells from three of ten patients proliferated spontaneously and proliferation was further enhanced in two patients by rTNF-alpha. TNF binding assays gave a value of approximately 390 to 1,400 binding sites/cell for TNF and a dissociation constant (kd) of approximately 60 pmol/L. These data indicate that rTNF-alpha, in contrast to its cytotoxic/cytostatic effects, can also induce proliferation of tumor cells.

Adult↗