A phase II trial of gemcitabine in combination with 5-fluorouracil (24-hour) and folinic acid in patients with chemonaive advanced pancreatic cancer.

BACKGROUND: Gemcitabine (Gemzar) and 5-fluorouracil (5-FU) plus folinic acid (FA) both have proven activity in the treatment of patients with advanced pancreatic cancer. The present study was initiated to investigate the efficacy of gemcitabine in combination with 5-FU-FA. PATIENTS AND METHODS: Thirty-eight patients, median age 60 years (range 34-70) with inoperable, stage IV, pancreatic cancer were enrolled into the study and treated on an outpatient basis. All except one patient received at least one cycle of treatment with gemcitabine (1000 mg/m2), followed by FA (200 mg/m2) and 5-FU (750 mg/m2) administered as a 24-hour continuous infusion on days 1, 8, 15 and 22 of a 42-day schedule. No patient had received prior chemotherapy or radiotherapy. All 38 patients were assessed for efficacy, toxicity and time to progressive disease. RESULTS: Two patients (5%), achieved a partial response and thirty-four patients (89%) achieved stable disease. There were two early deaths (< or = 4 weeks). The median time to progression was 7.1 months (range 0.4-18.1+; 95% confidence interval (95% CI): 5.3-7.9 months). Three patients had a progression-free interval of greater than 12 months and 12 of 38 patients (32%) survived longer than 12 months. The median overall survival was 9.3 months (range 0.5-26.5; 95% CI: 7.3-13.0 months). The incidence of grade 3 and 4 toxicities was low. CONCLUSIONS: The combination of gemcitabine and 5-FU-FA is active and well tolerated and seems to offer an improvement in progression-free interval over both gemcitabine monotherapy and 5-FU-FA therapy.

Sensitivity and specificity of indirect immunofluorescence and Grocott-technique in comparison with immunocytology (alkaline phosphatase anti alkaline phosphatase = APAAP) for the diagnosis of Pneumocystis carinii in broncho-alveolar lavage (BAL).

The purpose of the study was to compare the sensitivity and specificity of the indirect method of immunofluorescence with the immunocytological technique of alkaline phosphatase anti alkaline phosphatase complex (APAAP) for the detection of Pneumocystis carinii by bronchoalveolar lavage (BAL) in HIV-1 positive patients. - 83 HIV-1 positive patients with clinical presentations suggestive of Pneumocystis carinii pneumonia (PcP) were included in the study. 28 samples were found Pc-positive by immunofluorescence (IFT), 26 by Grocott and 29 by APAAP. In comparison to the lab results 33 patients were diagnosed as PcP according to the clinical course (i.e. therapeutic outcome, drugs used, and therapy changes). Compared to the clinical diagnoses, the following lab tests proved to be false positive and false negative: false positive: IF = 1, Grocott = 0, APAAP = 4 (3F6). false negative: IF = 5, Grocott = 7, APAAP = 4 (3F6). - Grocott stain shows insufficient correlation to the clinical diagnoses (p = 0.0156, McNemar-Test, two-tailed). - The two different detection methods (IFT and APAAP) showed no significant statistical difference with regard to their sensitivity (p = 0.3438, McNemar-Test, two tailed) and specificity. Considering cost and time the immunofluorescence technique seems to be the most suitable for the diagnosis of PcP in HIV-1 positive patients.

Randomized, double-blind, placebo-controlled, phase III study of recombinant human granulocyte-macrophage colony-stimulating factor as adjunct to induction treatment of high-grade malignant non-Hodgkin's lymphomas.

We evaluated recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; Sandoz Pharma [Basel, Switzerland]/Schering-Plough [Kenilworth, NJ]) as an adjunct to a modified (mainly cyclophosphamide and doxorubicin increased 1.5-fold) COP-BLAM regimen in the primary treatment of high-grade malignant non-Hodgkin's lymphomas (NHL). Patients (n = 182; stage II-IV; age, 15 to 73 years) were randomized to rhGM-CSF (400 micrograms) or placebo for 7 days subcutaneously after chemotherapy. Efficacy was analyzed for patients receiving at least 70% of study medication (n = 125). The frequency of clinically relevant infection was reduced by rhGM-CSF (28 v 69 infections, 16 v 30 patients, P = .02) with a cumulative probability of remaining infection free in 70% versus 48% (P = .05 log rank test at 190 days). Periods of neutropenia (P = .01 in 5 of 6 courses), days with fever (2.1 v 4.0, P = .04) and days of hospitalization for infection (3.5 v 8.0 days, P = .01) were significantly reduced. Complete response (CR) rates, assessed by prognostic risk, were 15 of 19 (79%) in treated versus 20 of 21 (95%) in controls in the low-risk group (P = .12). In the high-risk group, 31 of 45 (69%) treated patients achieved CR versus 25 of 52 (48%) of controls (P = .04). No difference in survival has been seen after 1 year. Only injection site reactions (45% treated v 7% controls) and rash (26% v 2%) occurred more frequently in treated patients (n = 176). These data show that rhGM-CSF is well tolerated in most patients with NHL, significantly reduces infection, and improves response.

Soluble interleukin 2 receptors in patients after bone marrow transplantation.

An enzyme-linked immunosorbent assay was used to quantify soluble interleukin 2 receptor (IL2R) in the serum of 25 patients prior to allogeneic or autologous bone marrow transplantation and in the early post-transplantation period. A significant correlation between IL2R and the occurrence of fever and/or graft-versus-host disease (GVHD) could be shown. Patients with moderate to severe GVHD (grade II-IV) had significantly higher IL2R levels (median 480 U/ml) than patients without or with acute GVHD grade I (median 139 U/ml). In patients without or with acute GVHD grade I, significant differences in the maximum IL2R levels depended on the duration of fever greater than or equal to 38 degrees C. Evaluation of the peak IL2R levels in patients with fever lasting longer than 6 days led to a median of 260 U/ml and in patients with fever lasting less than 6 days to a median of 118 U/ml. In patients without or with acute GVHD grade I, who developed fever lasting longer than 6 days, IL2R levels started to rise with the onset of fever, reached peak values during temperature maximum and declined parallel with temperature normalization. In patients without or with acute GVHD grade I who developed fever lasting for only 6 days or less IL2R levels remained within the normal range. In patients with acute GVHD grade II-IV, IL2R levels began to rise with the onset of fever, and then continued to rise despite temperature normalization. The peak levels were reached in the early period of acute GVHD. Our observations in BMT patients show that severe infections and acute GVHD are associated with a stimulation of the immune system leading to elevated IL2R serum levels.

[CEA as a tumor marker on the cell surface and in the exudate. Comparison in thoracoscopy examined pleural effusions]. / CEA als Tumormarker auf der Zelloberfläche und im Exsudat. Vergleich bei thorakoskopisch untersuchten Pleuraergüssen.

A prospective comparison was conducted in 43 patients to assess comparatively the ranking of cytology and CEA determined in the pleural effusions and by immunocytology on the cell surface (the latter two compared with each other) and then juxtaposed with the information obtained by histology via thoracoscopy. It was found that the yield achieved by cytology was comparable with that obtained by immunocytology. The maximum sensitivity was established with the adenocarcinoma.

[ABO blood groups and platelet transfusion]. / AB0-Blutgruppen und Plättchentransfusion.

Platelet transfusion without regard for AB0 compatibility is controversially discussed. Therefore, we studied the success of 136 AB0 compatible and 52 incompatible platelet applications in 37 patients. Our results suggest, that AB0 matching can improve the response of platelet transfusion.

[Can thrombocyte crossmatching improve the efficiency of platelet transfusion?]. / Kann der Thrombozytencrossmatch die Effizienz der Plättchentransfusion verbessern?

We did crossmatching in 220 transfusions of single donor platelet concentrates using the purchaseable solid phase immunoassay Capture-P (Immucor, Rödermark, FRG), checking posttransfusion response by calculating the corrected count increment (CCI). Our results show that posttransfusion response in transfusions of ABO major incompatible platelet concentrates is virtually reduced only in those transfusions accompanied by a positive crossmatch in Capture-P. As Capture-P can detect IgG antibodies only, positive test results could well be due to a reaction of recipient immune isoagglutinins with ABH antigens expressed on donor platelets, therefore.

[Stem cell concentrates in autologous transplantation]. / Stammzellkonzentrate in der autologen Transplantation.

For some years, there has been an increasing success in transplanting PBSC instead of autologous bone marrow in patients suffering from leukemic diseases. In healthy cytapheresis donors, we achieved peripheral blood mononuclear cell (PBM) recoveries of 74%, using a discontinuous flow separation technique (Haemonetics V50, Lymphosurge). At the moment, we have collected PBSC from 4 patients (3 AML, 1 ALL) in 28 cytapheresis procedures ranging from 12.9% to 80.1% (mean: 40.1%), whereas stem cell recoveries, defined by CFU-GM, were significantly better (mean: 66%). At present, one of these patients has been transplanted with PBSC alone, receiving 2.11 x 10(8) PBM/kg with 2.8 x 10(4) CFU-GM/kg. His posttransplantation cytopenia was shorter compared to other patients undergoing autologous bone marrow transplantation. The period of disease-free survival is now more than eight months while he is completely reintegrated into social and working life.

A flow cytometric assay for the determination of cell proliferation with a monoclonal antibody directed against DNA-methyltransferase.

The enzyme DNA-methyltransferase is responsible for the methylation of a newly synthesized DNA-strand. A monoclonal antibody directed against DNA-methyltransferase was used to determine cell proliferation by means of flow cytometry. The reactivity of DNA-methyltransferase antibody was compared with the known proliferation markers transferrin-receptor and Ki67. All three methods showed comparable reactivity with the erythroblastic cell line K562 (86%, 81%, 76% respectively). In a second set of experiments peripheral blood mononuclear cells were stimulated with phytohaemagglutinin; in three experiments, a mean of 63% of the cells reacted with DNA-methyltransferase antibody after 72 h of culture as compared to a mean of 6% in the case of unstimulated control cells. HL60 cells were incubated with DMSO and harvested on day 5 of culture. The results obtained show that in differentiated cells the fraction positive with DNA-methyltransferase antibody decreased to levels below 10%. It is concluded that the technique described is a fast and easy method for the flow cytometric determination of cellular proliferation.

Evidence of cross-reactivity of 'carcinoma-specific' KC4 monoclonal antibody with activated mesothelial cells and phytohemagglutinin-stimulated lymphocytes.

Carcinoma-specific antibodies would be a useful tool in immunocytology of serous effusions. We tested the carcinoma-'specific' monoclonal antibody KC4 with cells obtained from pleural effusions evaluated by thoracoscopy and pleural biopsies. KC4 reacted most strongly with carcinoma cells. However, activated mesothelial cells also expressed this marker strongly. Lymphocytes stimulated with phytohemagglutinin were also stained by KC4. Thus KC4 appears to detect a proliferation antigen rather than a carcinoma-specific antigen.

[Prospective comparison of the diagnostic value of cytology and immunocytology in pleural effusion studied by thoracoscopy and biopsy]. / Prospektiver Vergleich der diagnostischen Wertigkeit von Zytologie und Immunzytologie bei thorakoskopisch-bioptisch untersuchten Pleuraergüssen.

Two issues have been elaborated: the value of immunocytochemistry in the diagnosis of pleural effusions, and the reactivity of the investigated antibodies with different classes of cells in pleural effusions. Effusions of unknown origin from 38 patients were investigated using thoracoscopy, pleural biopsies, conventional cytology, and immunocytochemistry. The following antibodies were used: those monoclonal against various leukocyte antigens, macrophage antigens, epithelial membrane antigen (EMA), various cytoskeleton antigens, and melanoma antigens; those polyclonal against CEA and ferritin. All of the techniques used showed 18 patients (48%) as having a tumor-cell negative effusion. A pleural tumor with a malignant effusion showed in 13 patients (34%); in 12 of these immunocytochemistry also revealed tumor cells. Seven patients (18%) had a tumor of the pleura with a tumor-cell negative effusion; in 2 of these immunocytochemistry revealed a tumor-cell positive effusion. There was no difference with regard to the number of NK cells in patients with inflammation of the pleura and negative cytology and patients with tumor of the pleura and malignant effusion (3% vs 4.5%). Tumor cells were mainly stained by EMA, cytokeratin, and CEA. CEA was the only antibody to be tumor-cell specific, while EMA and cytokeratin were expressed by mesothelial cells also. The antibody against ferritin was a significant marker for mesothelial cells.