Gemcitabine and carboplatin in intensively pretreated patients with metastatic breast cancer.

BACKGROUND: Patients with metastatic breast cancer (MBC) are increasingly exposed to anthracyclines and taxanes either during treatment of primary breast cancer or during initial therapy of metastatic disease. The combination of gemcitabine and carboplatin was therefore investigated as an anthracycline- and taxane-free treatment option. PATIENTS AND METHODS: MBC patients previously treated with chemotherapy were enrolled in a multicenter phase II study. Treatment consisted of gemcitabine (1,000 mg/m(2) i.v. on days 1 and 8) and carboplatin (AUC 4 i.v. on day 1) applied every 3 weeks. RESULTS: Thirty-nine patients were recruited, and a total of 207 treatment cycles were applied with a median of 5 cycles per patient. One complete response and 11 partial responses were observed for an overall response rate of 31% (95% CI: 17-48%). Twelve patients (31%) had stable disease. Median time to progression was 5.3 months (95% CI: 2.6-6.7 months) and median overall survival from start of treatment was 13.2 months (95% CI: 8.7-16.7 months). Grade 3/4 hematological toxicity included leukopenia (59%/5%), thrombocytopenia (26%/23%) and anemia (10%/0%). Nonhematological toxicity was rarely severe. CONCLUSION: Combination chemotherapy with gemcitabine and carboplatin is an effective and generally well-tolerated treatment option for intensively pretreated patients with MBC. Due to a considerable incidence of severe thrombocytopenia it would be reasonable to consider starting gemcitabine at the lower dose level of 800 mg/m(2).

[Ultra-high dose thrombolytic therapy with streptokinase in peripheral venous thrombosis]. / Ultrahochdosierte Thrombolysetherapie mit Streptokinase bei peripherer Phlebothrombose.

56 patients with deep vein thrombosis (lower limb) and two patients with vena subclavia thrombosis were treated for six hours/day according to an ultrahigh dosage scheme (1,500,000 U/h streptokinase). An average number of three cycles was applied. Complete recanalization could be demonstrated in 23 patients (43%) with lower limb thrombosis, whereas a partial recanalization was demonstrable in 40% (22 patients). A complete thrombolysis could be achieved in one patient with vena subclavia thrombosis. Severe side effects were one intracerebral hemorrhage and one major lung embolism, causing death in both patients. Ultrahigh dosage thrombolysis with streptokinase is an effective therapeutic regimen and is considered to be an alternative to standard fibrinolytic procedures.

Dose-response relationship in the treatment of idiopathic thrombocytopenic purpura with intravenous immunoglobulin.

The dose-response relationship in the intravenous immunoglobulin treatment of idiopathic thrombocytopenic purpura was studied in 20 adult patients in a multicenter prospective crossover trial. The rate of response increases from 3 out of 11 (27%) to 6 out of 10 treatment periods (60%) by raising the 7S-IgG dose given on 5 consecutive days from 164.50 +/- 24.55 to 359.65 +/- 58.62 mg/kg body weight. The onset and duration of response as well as the peak platelet count were found to be independent of the doses. A long-term benefit induced by intravenous immunoglobulin treatment could be achieved in 2 out of 14 patients with chronic idiopathic thrombocytopenic purpura.

Age-related morphology of the normal pancreas on computed tomography.

Abdominal computed tomographic scans were performed on a group of 360 patients between the ages of 20 and 80 years. The anteroposterior diameter of the pancreatic head, body, and tail, the age-related ratio of vertebral body-pancreas diameter, and the external and internal contours of the organ were analyzed. The age-related changes in the pancreas were compared with known anatomical findings.

Trisomy 7 and 8 in Ph-negative chronic eosinophilic leukemia.

The results of cytogenetic analyses of bone marrow and peripheral blood cells in a 67-year-old male with chronic eosinophilic leukemia (EL) are described. Although the patient showed leukocytosis with marked eosinophilia, initial chromosome findings in bone marrow revealed a normal male karyotype. Seven months later, more than 80% of bone marrow cells had a hyperdiploid karyotype (48,XY, +7, +8), the remaining cells being normal. Seven weeks later, the identical abnormal karyotype was observed in about 30% of banded metaphases of stimulated peripheral blood cells. No mitoses were found in unstimulated cultures. No Ph chromosome was observed. So far, trisomy 8 has been described for only two cases of EL, whereas trisomy 7 has never been observed.

Acute eosinophilic leukemia: characterization by cytochemistry, chromosomal analysis, and in vitro colony formation.

A pericentric inversion of chromosome 16 and acute myelomonocytic leukemia [AMMoL, M4 French-American-British (FAB)] with abnormal bone marrow eosinophils has recently been shown to form a new cytogenetic-clinicopathological entity. A patient otherwise undistinguishable from the more typical cases but lacking the FAB criteria for AMMoL is described. In such a situation, in vitro colony formation closely resembling that of acute myoblastic leukemia together with the clinical, morphological, cytochemical, and cytogenetic characteristics reported might serve as an indicator that these patients run an acute course justifying a diagnosis of acute eosinophilic leukemia and immediate institution of aggressive chemotherapy. The importance of the in vitro growth pattern regarding the differential diagnosis of disorders associated with predominant proliferation of eosinophils is discussed.

[Possibilities and limitations of computerized tomography in the staging of the subdiaphragmatic spread of Hodgkin's disease]. / Möglichkeiten und Grenzen der Computertomographie im Staging der subdiaphragmalen Ausbreitung des M. Hodgkin.

The value of computed tomography in the assessment of subdiaphragmatic spread was studied prospectively in 72 patients with so far untreated, histologically confirmed Hodgkin's disease. In 17 patients (23.6%) computed tomography (CT) diagnosed subdiaphragmatic involvement, with no false-positive results. In 55 (76.4%) CT was within normal limits. In 30 patients exploratory laparotomy gave false-negative results in 7 (23.4%). The causes of false-negative results in CT are that lymph-nodes which were not enlarged but involved were not demonstrated and spleen involvement was not identified. Including those correctly positively diagnosed cases (17), CT had a sensitivity of 70.8% and a false-negative rate of 29.2%. It is concluded that when CT is within normal limits only exploratory laparotomy can with certainty exclude subdiaphragmatic involvement.

Urinary glycoproteins in acute leukemias: a 41 000 dalton glycoprotein follows the kinetic of cytoreduction.

Glycoproteins of leukemic cells and 24-hour urinary proteins were subjected to SDS polyacrylamide gel electrophoresis followed by affinity labelling I125 with Concanavalin A, indicating glycoproteins with mannose and/or glucose carbohydrate residues. Among the cellular glycoproteins a 41 000 dalton glycoprotein appeared under induction therapy in close correlation to the reduction of leukemic cells in ALL as well as in AML.

Hemolytic anemia with pyruvate kinase deficiency presenting as paravertebral myelolipoma.

The case of a patient with erythrocyte pyruvate kinase (PK) deficiency hemolytic anemia leading to extramedullary hematopoiesis in a paravertebral myelolipoma is presented.

Impaired protein synthesis in leukemic hairy cells induced by splenectomy.

A case of hairy-cell leukemia in which protein synthesis by the leukemic hairy cells could be followed-up before and after splenectomy is presented. After splenectomy a remarkable reduction of initially enhanced protein synthesis was found. This observation supports the view that the splenic microenvironment has an important influence on the proliferative activity of hairy cells.

[Reactive leukemoid plasmacytosis with polyclonal hypergammaglobulinemia during streptokinase therapy]. / Reaktive leukämoide Plasmozytose mit polyklonaler Gammaglobulinvermehrung unter Streptokinasetherapie.

Plasma cells are occasionally encountered in peripheral blood during fibrinolytic treatment with streptokinase. Leukaemoid plasmocytosis and increase of immunoglobulins were observed in a 44-year-old patient in connection with streptokinase treatment. Mature stages of plasma cells could be demonstrated in peripheral blood. The observed phenomena are considered as exaggerated immune response to foreign protein. They are of no disease value as they are only concomitant reactions to streptokinase treatment. Spontaneous regression occurred.

The success rate of fibrinolytic therapy in fresh and old thrombosis of the iliac and femoral veins.

Since it is still a wide-held belief that fibrinolytic therapy can clear thrombi from deep veins only while they are fresh, we retrospectively analyzed the phlebographic results obtained in 85 patients with thrombosis of the iliac and/or femoral veins with symptoms present for 1 day to 8 weeks prior to treatment. Streptokinase, urokinase, or both drugs successively were administered in these patients for a mean of 9 days (range: 2 to 26 days). Complete or partial resolution of the thrombotic occlusion was obtained in 94%, 82%, and 69%, respectively, in those patients who presented within 3 days, 1 to 2 weeks, and 3 to 4 weeks after the first appearance of symptoms. With a delay of 5 to 8 weeks the results were uniformly poor with only 1 partial recanalization in 7 patients.

[Skin metastasis of a teratocarcinoma]. / Hautmetastasen eines Teratokarzinoms.

Various tumors develop skin metastasis with a variable incidence. Skin metastasis is rare in teratocarcinoma of the testis [1]. This report deals with a case history in which a teratocarcinoma developed metastasis in the skin of the face and head.

Early tumor and leukemia response to alkyllysophospholipids in a phase I study.

In a phase I study on the toxicity and toleration of alkyllysophospholipids, tumor and leukemia responses have been noted in the first treated patients. Six patients with solid malignomas of different histologic types and one patient with acute myeloid leukemia are evaluable so far. All of them suffered from metastatic or wide-spread disease, were refractory to adequate polychemotherapy or other treatment modalities, or have been found untreatable because of poor general condition. Four cases revealed objective tumor and leukemia response with a minor response in a hypernephroma, two partial remissions in nonsmall cell bronchogenic carcinomas and reduction of leukemic blasts to less than 10% in acute myeloid leukemia. Limiting toxicity started with doses of 20 mg/kg given daily showing transient injury of renal and liver functions.

Protein synthesis in the blood lymphocytes of chronic lymphocytic leukemia and its relationship to prognosis.

Protein synthesis primed by endogenous messenger RNA (mRNA) as well as polyuridylic acid-[poly (U)] directed polyphenylalanine synthesis was measured in extracts of blood lymphocytes from a series of 50 chronic lymphocytic leukemia (CLL) patients and compared with the prognostic stage. Patients were clinically classified according to the new international workshop classification [4]. There were 23 patients at stage A, 14 at stage B and 13 at stage C. Extracts from patients of the high risk group (stage C), defined by anemia and/or thrombocytopenia, exhibited a significantly higher poly (U)-translation activity than extracts from low and intermediate risk patients-stages A and B--(P less than 0.01). This finding has a sensitivity of 62% but a specificity of 100%. During follow-up, an increase of poly (U)-translation and endogenous protein synthesis was observed after changing from stages A or B to stage C. Activity of protein synthesis could neither be correlated with proliferation activity, as measured by lymphocyte doubling time, nor with the expression of immunologic surface markers, nor with serum immunoglobulin (Ig) levels.

Response of acute myelomonocytic leukemia to alkyl-lysophospholipids. A case report.

Acute myelomonocytic leukemia refractory to treatment with daunomycin, cytosin arabinoside and thioguanine morphologically and clinically responded twice to therapy with alkyl-lysophospholipids (ALP). Beginning 48 h after treatment leukemic cells developed large vacuoles in cytoplasm and nucleus which disrupted the continuity of the cell membranes. Normal hematopoietic cells remained morphologically unchanged. Within 14 days of first ALP treatment leukemic cells in peripheral blood were reduced to less than 10%, but normal hematopoiesis recovered under therapy with an increase of granulocytes.