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H Kirchner

Publications and source records attributed to H Kirchner.

At least 127 records · Page 7Linked to original sources
PubMed1997

[HBV-DNA positive findings in HBsAg negative blood donors and patients].

There have been repeated discussions as to whether the implementation of anti-HBc screening of blood donations in Germany would be useful. We present several cases of HBsAg-negative patients and blood donors in whose plasma HBV-DNA was mainly found only after enrichment of virus particles by ultracentrifugation. In the case of a seroconverting blood donor, 3 of 4 HBsAg tests could not detect HBsAg. 90% of our HBsAg-negative, but HBV-DNA containing samples (n = 10) were positive for anti-HBc. The 'nested' PCR without previous ultracentrifugation was positive in only under 30% of the samples. Ultracentrifugation is an expensive method and will not be practicable for the testing of all blood donations. We conclude that the HBsAg tests which are available should be subjected to improvement. In addition, the implementation of anti-HBc screening could decrease the risk of posttransfusion HBV infection more effectively than PCR testing from nonenriched serum.

Blood Donors↗
PubMed1997

[Effect of whole blood preparation and leukocyte filtration on storage of erythrocyte concentrates over 42 days].

Leukocyte reduction prior to storage of red cell concentrates (RCC) may reduce the incidence of HLA alloimmunization and may improve the quality of stored RCC. We tested an RCC leukoreduction filter system (Baxter) with an integrated Pall RCM-1 filter and investigated the filtration efficiency and the impact on red cells during storage for 42 days after different whole-blood preparation procedures. After whole-blood donation, all units (n = 9, +6 unfiltered controls per group) were either stored at 22 degrees C for up to 6 h (groups 1, 2, 3) or for 24 h (group 4) RCC were either prepared from a triple blood bag system (PL 146, groups 1, 2) or were buffy-coat-depleted (PL 2209, groups 3, 4). Groups 1, 3 und 4 were filtered immediately, whereas group 2 was stored another 18 h at 4 degrees C before filtration. Filtration efficiency and filtration time were determined. Hemolysis, ATP, 2,3-diphosphoglycerate (2,3-DPG), glucose, electrolytes, lactate, hematocrit, Hb and pH were quantified weekly. White blood cells (WBC) were reduced by 3-4 log10 to 0.1-0.3 x 10(6) (mean) by filtration (all groups) regardless of the RCC preparation. Mean filtration times were 1 h 36 min, 33 min, 29 min, and 18 min for the groups 1 to 4, respectively. There were no major differences for the in vitro storage values except for hemolysis and pH, which were elevated in all filtered units, and potassium, which was elevated in the unifiltered units. In conclusion, prestorage leukocyte filtration of RCC reduced the WBC by 3-4 log10, whereas the extended filtration time was a major disadvantage.

2,3-Diphosphoglycerate↗
PubMed1996

Zinc enhances lipopolysaccharide-induced monokine secretion by alteration of fluidity state of lipopolysaccharide.

Elevated zinc serum concentrations have been shown to restore impaired immune response. Therefore, pharmacologic zinc supplementation has been used to improve immune function, particularly in intensive care patients. In these patients, Gramnegative sepsis, the symptoms of which are predominantly caused by LPS-induced release of monokines, represents a serious problem. We have recently shown that zinc enhances induction of TNF-alpha and IL-1 beta in cultures of PBMC by LPS. By fluorescence polarization and infrared spectroscopic measurements we found that zinc addition leads to decreased fluidity of the hydrocarbon chains of LPS. Experiments at different temperatures showed that the less fluid gel (beta) phase of LPS is more effective in cytokine induction than the more fluid liquid-crystalline (alpha) phase. Our studies suggest that the synergistic effect of zinc on monokine induction by LPS is caused by direct interaction of zinc with LPS altering the fluidity of the hydrocarbon chains. Although this effect is zinc specific, other divalent ions, like cobalt and nickel, with a complex structure and size comparable to those of zinc also enhance LPS-induced monokine secretion but to a much lesser extent. Our data indicate that the zinc level represents a relevant clinical parameter in the treatment of Gram-negative infection. This reveals potential risks in the therapeutic application of zinc.

Adjuvants, Immunologic↗
PubMed1996

Interaction of zinc ions with human peripheral blood mononuclear cells.

Zinc is an important trace element for immune function. The mechanisms by which zinc ions interact with immune cells are, however, still poorly understood. In the present study, we succeeded in defining transferrin and insulin as proteins which selectively enhance zinc-induced monokine induction in peripheral blood mononuclear cells (PBMC). An involvement of the transferrin receptor and the insulin receptor was ruled out. Zinc stimulation of PBMC resulted in an increase of intracellular free zinc, measured by a zinc-specific fluorescence probe, zinquin, the amount of which could be raised by substitution of neither transferrin nor insulin. Inhibition of second messengers by herbimycin A and HA 1004 revealed a participation of protein tyrosine kinases and of cAMP- and cGMP-dependent protein kinases in zinc-induced monokine secretion. We therefore suggest that zinc acts synergistically with stimulants of the above-mentioned signal transduction pathways by direct influence on the second messenger niveau.

Cells, Cultured↗
PubMed1996

Dysregulation between TH1 and TH2 T cell subpopulations in the elderly.

We investigated the influence of zinc and its binding proteins on the immune system in 21 elderly and 20 young subjects. We detected a deficiency of zinc in the serum of the elderly. Albumin levels were within physiological range, but alpha 2-macroglobulin was significantly increased in the serum of elderly subjects. Using a whole blood assay, we found decreased production of interferon-gamma (IFN-gamma) and soluble interleukin-2 receptors (SIL-2R) in the elderly, whereas interleukin-10 (IL-10) production was greater than in the young controls. To exclude cellular defects, we measured lymphocyte subpopulations. In elderly subjects, we detected lower quantities of CD8+, CD8+/CD45RA+ and CD4+/CD45RO+ cells, but not CD4+ cells, than in young subjects. Other lymphocyte subpopulations were comparable for both groups. These findings suggest a dysregulation between TH1 cells and TH2 cells in the elderly, which may be a result of long-term zinc deficiency. Zinc reconstitution showed no beneficial effects as measured by T cell activity.

Adult↗
PubMed1996

Peripheral blood tyrosinase messenger RNA detection and survival in malignant melanoma.

BACKGROUND: The most widely accepted criteria for the evaluation of prognosis of malignant melanoma are histopathologic and clinical presentation. No currently available laboratory tests provide additional prognostic information. It has recently been suggested that reverse transcription and polymerase chain reaction (RT-PCR)-based detection of tyrosinase messenger RNA (mRNA) in peripheral blood might be useful in the early detection of circulating tumor cells, since tyrosinase is thought to be a melanocyte-specific marker. PURPOSE: To further evaluate the clinical relevance of this potential marker, we examined peripheral blood samples from patients with malignant melanoma in different stages of disease for the presence of tyrosinase mRNA. METHODS: Total cellular RNA was extracted from heparinized peripheral blood cells from 64 patients with malignant melanoma, from five healthy control subjects, and from four patients with other cancers using the RNAzol A method. For analysis of tyrosinase mRNA, RT-PCR was performed as previously described by Smith et al.; the sensitivity of this assay was tested using RNA extracted from human melanoma cells (SK-mel 1 and SK-mel 3 cell lines) serially diluted with peripheral blood obtained from healthy control subjects. Two additional human melanoma cell lines (SK-mel 30 and RPMI-7951) served as positive controls for RT-PCR detection of tyrosinase mRNA. Overall patient survival curves were constructed using Kaplan-Meier estimates. RESULTS: Tyrosinase mRNA was detected by RT-PCR assay of all four of the established melanoma cell lines tested. Nine of the 64 patients with malignant melanoma were found to have detectable tyrosinase mRNA in their peripheral blood cells (tyrosinase-positive patients). The 16 patients with localized primary melanoma did not have detectable tyrosinase mRNA in their peripheral blood cells. Among the 48 patients with metastatic disease, all 27 patients who exhibited no evidence of disease progression were tyrosinase negative. Notably, all nine tyrosinase-positive patients had visceral metastases and were found to exhibit disease progression at the time of the sampling. Four of the nine tyrosinase-positive patients were also found to test negative at times without evidence of progressive disease; one patient became negative after achieving stable disease and three became positive for tyrosinase transcripts on disease progression. The probability of survival from time of sampling was significantly lower in the nine tyrosinase-positive patients when tested versus the 23 patients with comparable disease but without detectable tyrosinase mRNA (two-sided; P < or = .05). CONCLUSIONS: The results of this study demonstrate that the detection of tyrosinase mRNA in cells in the peripheral blood by RT-PCR may be a useful prognostic marker for predicting tumor progression and poor clinical outcome in patients with malignant melanoma.

Adult↗
PubMed1996

[Interleukin 2 based ambulatory therapy of metastatic renal cell carcinoma].

BACKGROUND: In metastatic renal cell carcinoma, strictly immunomodulatory maneuvers using systemic interleukin-2 have produced objective tumor remissions and led to an effective palliation. The goals of an improved cost effectiveness and therapeutic index of interleukin-2 require the design of risk factor adapted individual therapeutic strategies for the outpatient setting. PATIENTS AND METHODS: In 215 consecutive single institution patients with advanced metastatic renal cell carcinoma, the efficacy and tolerance of different subcutaneous recombinant interleukin-2 (rIL-2) based home therapies was assessed. Independent risk factors at pre-treatment level were identified and patient survival was compared between risk groups and therapies. Treatment consisted of s.c. rIL-2 alone and s.c. rIL-2 in combination with recombinant interferon-alpha 2 (rIFN-alpha 2), with or without intravenous 5-fluorouracil (5-FU). RESULTS: Overall objective response rate in 215 patients was 33% (95% confidence interval, 26 to 39%). Among patients receiving rIL-2 alone (n = 16), there was 1 partial remission (overall response, 6%). In patients on rIL-2 and rIFN-alpha 2 in combination (n = 79), 6 complete and 16 partial remissions occurred (overall response, 28%). Of 120 patients receiving a combination of rIL-2, rIFN-alpha 2 and 5-FU, 13 patients achieved a complete and 34 a partial remission (lung, liver, local relapse, bone, adrenal, pleural, and thyroid metastases; overall response 39%). Duration of complete and partial remissions ranged from 10 to 55+ months, and 3 to 32 months, respectively, in rIL-2/rIFN-alpha 2 treated patients, and from 8+ to 47+ months and from 3 to 31+ months, respectively, in rIL-2/rIFN-alpha/5-FU treated patients. Of all patients 5% achieved long-lasting remissions and remain disease-free. In the majority of patients, systemic toxicity of s.c. rIL-2 based protocols was limited to grade 1 or 2 constitutional symptoms i.e., fever, chills, malaise, and anorexia; this allowed for an outpatient therapy. No life-threatening toxicity and no toxic deaths occurred. CONCLUSIONS: The present outpatient rIL-2 triple drug combination protocol was as effective as the most aggressive i.v. rIL-2 regimen available; it substantially improved the therapeutic index and cost effectiveness of rIL-2 therapy in metastatic renal cell carcinoma stratified for risk.

Adult↗
PubMed1996

Increased CD56+ natural killer cells and related cytokines in major depression.

Twenty-seven inpatients with major depression were examined four times within 6 weeks to assess CD56+ natural killer (NK) cell counts by flow cytometry and to assess the related lymphokines interleukin-2 and interferon-gamma in a whole blood assay after mitogen stimulation with phytohemagglutinin (PHA). The patient showed significantly higher counts of the fraction of 56+ NK cells and a greater lymphokine response to PHA than the controls. A significant correlation between lymphokine secretion and CD56+ cell counts was detected in the patients' acute clinical stage, but not in healthy controls or in patients after clinical improvement.

Adult↗
PubMed1996

The intracellular localization of human cytomegalovirus DNA in peripheral blood leukocytes during active infections by high-resolution fluorescence in situ hybridization.

Although viremia is an integral part of the pathogenesis of human cytomegalovirus (HCMV) disease, the interaction between HCMV and circulating leukocytes of actively infected patients remains an area of uncertainty. It is still a matter of dispute, whether leukocytes support viral replication with subsequent production of infectious virus. In a new approach we developed and applied a sensitive fluorescence in situ hybridization assay for the precise intracellular localization of HCMV genomes in leukocytes. It was shown that in vivo HCMV genomes were exclusively localized in the cytoplasm of leukocytes, indicating that the majority of these cells are virus carriers or abortively infected. Though this method easily detects single copy genes in metaphase chromosomes, the number of HCMV DNA positive leukocytes was significantly lower than the number of HCMV pp65 antigen positive cells. In relation to the pp65 antigen positive cells, only 1-4% of these cells were DNA positive. In addition, the much lower frequency of HCMV immediate early antigen positive leukocytes in comparison to the pp65 antigen positive cells and the impossibility of detecting other viral antigens support the hypothesis that the origin of pp65 found in leukocytes results mainly from protein uptake.

Antigens, Viral↗
PubMed1996

Investigations of cytokine production in whole blood cultures of paranoid and residual schizophrenic patients.

In an attempt to define potential immunological dysfunctions in schizophrenia, we determined the production of interleukin-2 (IL-2), interleukin-4 (IL-4), interferon-gamma (IFN-gamma), and soluble IL-2 receptor (sIL-2R) in a whole-blood assay after stimulation with phytohemagglutinin (PHA) as well as the serum concentrations of sIL-2R. Because CD4+CD45RO+T cells are the main producers of IFN-gamma, we determined the percentage of these cells, as well as of panT, CD4+T, and CD8+T cells, by flow cytometry. A whole-blood count was performed in addition. Two groups of patients were examined, paranoid-type and residual-type schizophrenics. The numbers of both monocytes and neutrophils, but not of lymphocytes, were increased significantly in the schizophrenic sample. The IFN-gamma production of the schizophrenics as a whole group, and of the paranoid patients, was reduced significantly in comparison with the control group (p < or = 0.05). The residual patients produced less IFN-gamma than the controls, but more than the paranoid patients. The latter differences did not reach statistical significance. The production of IL-4, which physiologically antagonizes the production of IFN-gamma, was not significantly higher in the patient group. No changes in the lymphocyte subpopulations were observed. The production of IL-2 showed a trend toward reduction in paranoid patients, but not in residual schizophrenics. The serum sIL-2R levels were elevated slightly in schizophrenics when compared with controls. In order to rule out a possible effect of cortisol on cytokine production, 20 schizophrenics were compared with 20 age- and gender-matched controls. However, neither elevated cortisol levels were detected in the schizophrenic sample, nor significant intercorrelations between cortisol levels and cytokine production, or levels of sIL-2R, respectively. In summary, our data reinforce the possibility of immune dysfunction in schizophrenia and point to the possible relevance of disease subgroups in this respect.

Adult↗
PubMed1996

Fluorescence in situ hybridization with cosmid clones for the detection of human cytomegalovirus DNA in peripheral blood leukocytes.

Radioactive in situ hybridization techniques or enzymatic detection procedures of hapten-modified human cytomegalovirus (HCMV) probes have been widely used for studying the infection of peripheral blood leukocytes with HCMV. This report describes significant improvements in terms of signal resolution which can be obtained by applying a highly sensitive fluorescence in situ hybridization (FISH) technique in conjunction with a large subgenomic HCMV DNA probe. Three cosmid clones spanning 119.1 kb of the HCMV genome (230 kb) were used to construct the digoxigenin-11-dUTP-labeled probe which was found to be superior to a total HCMV probe representing the entire genome. Crucial hybridization parameters were analyzed systematically in order to ensure optimal resolution power and sensitivity. The protocol was successfully applied to HCMV-infected fibroblasts and peripheral blood leukocytes of 12 transplant patients and unambiguously facilitated the precise intracellular localization of HCMV genomes in infected cells. Because of its excellent resolution properties, accompanied by the virtual absence by any background staining, we recommend the use of this protocol as a sensitive approach for further virological analyses of the interactions between HCMV and peripheral blood leukocytes at the single-cell level.

Cloning, Molecular↗
PubMed1996

In-vivo evaluation of random donor platelet concentrates from pooled buffy coats.

Random-donor platelet concentrates (PC) prepared from pooled buffy coats have recently been described as an alternative method for platelet preparation. We evaluated such PCs in the clinical setting compared with a standard PC from platelet apheresis. PCs were prepared either from pools of buffy coats (BC-PC) or from single donors (SD-PC) with the cell separator CS-3000 plus. PCs were stored for up to 5 days before transfusion. We compared fresh PC (day 1) with stored (day 2-3) and long-stored PC (day 4-5). For analysis, platelet increment in the recipient was determined immediately and 16-22 h (mean 20 h) after transfusion, corrected for total body area and transfused platelets (CCI). A total of 316 PCs were administered to 36 thrombocytopenic patients suffering from various hematological disorders. Patients with detectable HLA or platelet-specific antibodies or splenomegaly were excluded from the study. Mean platelet content of the PC was 262 x 10(9) for BC-PC and 251 x 10(9) for SD-PC. The 20-h CCI after transfusion of fresh PC was slightly higher with BC-PC than with SD-PC (14.5 versus 11.9; p = 0.19), but values did not differ significantly between the two types of PC on any day of storage. For BC-PC, 20-h CCI decreased with further storage by 30% (10.2; p = 0.02). For SD-PC a decrease by 9% was not significant. In conclusion, platelet concentrates prepared from pools of buffy coats showed excellent transfusion results when administered fresh, but storage decreased the CCI by 30%. No significant difference from PCs from plateletpheresis was observed on any day of storage. Both types of platelet concentrates were capable of sufficient platelet increment even when stored for up to 5 days.

Adult↗
PubMed1996

Cytokine production of neutrophils is limited to interleukin-8.

Since granulocytes are one of the first cell types at sites of inflammation, investigation of their capacity to produce cytokines has concentrated on interleukin-1 beta (IL-1 beta), IL-6, IL-8 and tumour necrosis factor-alpha (TNF-alpha). However, the results are subject to controversy. Incapability to produce cytokines as well as a broad panel of cytokines induced by isolation procedures are reported. The purpose of this study was to investigate the capacity of non-prestimulated neutrophils to produce the above-mentioned cytokines in response to stimulation with lipopolysaccharide or zymosan. In reverse transcription-polymerase chain reactions, we found IL-8 mRNA directly after isolation in unstimulated cells, whereas mRNA for IL-1 beta, IL-6 and TNF-alpha only appeared after stimulation. By means of flow cytometry we ruled out the possibility of prestimulation of the neutrophils during isolation, proving that IL-8 mRNA is produced constitutively by neutrophils. In enzyme-linked immunosorbent assays we found that, compared with controls, only IL-8 was released at significantly higher levels after 24 hr of stimulation, giving a further indication that neutrophils have an immunoregulatory influence driven by IL-8. We can confirm neither a constitutive nor a post-stimulatory release of IL-1 beta, IL-6, or TNF-alpha by neutrophils, as had been reported by others. These observations may be due to prestimulation, handling and culturing of the granulocytes, or to monocyte contamination. Collectively, our results show that granulocytes have a preformed capacity to produce the cytokine IL-8 and that the production of proinflammatory cytokines by neutrophils is limited to IL-8.

Cell Separation↗
PubMed1996

Rapid typing for human platelet antigen systems-1, -2, -3 and -5 by PCR amplification with sequence-specific primers.

Typing for human platelet antigens (HPA) is useful in a variety of clinical situations. We developed a method for genotyping for HPA-1, -2, -3 and -5 by means of the PCR amplification with sequence-specific primers (PCR-SSP) technique. Primer sets were designed to allow PCR amplification for all systems using the same assay conditions. Specificity and sensitivity of the method were assessed in a blind quality control study (n = 112). In 111 cases, results obtained by PCR-SSP were identical as compared with PCR-restriction fragment length polymorphism technique. One discrepancy was found to be due to a typing error in the data sheet. The results of the PCR-SSP technique were available within 3 h. We conclude that genotyping based on PCR-SSP enables rapid typing for HPA systems, which makes this technique feasible in most clinical settings where urgent HPA typing is required.

Antigens, Human Platelet↗
PubMed1996

Chemokines in stored platelet concentrates.

BACKGROUND: Platelets contain several mediators, belonging to a family of proinflammatory cytokines named chemokines, that are stored in the organelles. Release and accumulation of these chemokines during storage of platelet concentrates (PCs) might be responsible for nonhemolytic transfusion reactions. STUDY DESIGN AND METHODS: Analysis was done of pH and the levels of platelet factor 4, beta-thromboglobulin, interleukin 8, RANTES, macrophage-inflammatory protein-1 alpha, lactate dehydrogenase, and serotonin in the supernatant of stored PCs on Days 1, 3, 5, and 8. PCs were prepared by apheresis or from pools of four buffy coats. Buffy coat PCs were filtered before storage. RESULTS: Nonfiltered apheresis PCs, which had a higher white cell contamination (p < 0.01), contained significantly more platelets than did buffy coat PCs (p = 0.02). The pH decreased significantly in apheresis PCs (p = 0.01), whereas there was a significant increase in lactate dehydrogenase (p < 0.001). In buffy coat PCs, pH remained stable and lactate dehydrogenase increased moderately. Concentrations of platelet factor 4 and beta-thromboglobulin increased steadily in both preparations over the storage period (p < 0.001). Macrophage-inflammatory protein-1 alpha was hardly detectable in the supernatant of both PCs, while RANTES levels increased significantly with storage time (p < 0.001). Interleukin 8 was not found in the supernatant of any PCs, with the exception of one apheresis PC with high white cell contamination (> 10(9)/ L). Serotonin levels were higher in apheresis PCs (p = 0.01), but the levels did not correlate with storage time. CONCLUSION: Platelet factor 4, beta-thromboglobulin, and RANTES were released from platelets during storage and accumulated over time in the PCs. These chemokines might play a causative role in nonhemolytic transfusion reactions because of their inflammatory potential, but the clinical effects of the transfusion of PCs with high chemokine contents remain to be investigated.

Blood Platelets↗
PubMed1996

Cytokines and tumor vaccination.

Patients with locally advanced stages of renal cell carcinoma are at high risk of relapse or progress even after initial radical surgery. Based on the proven efficacy of adoptive and active immunotherapeutic approaches of metastatic renal cell carcinoma, a phase II trial was started in 1989 using autologous, Newcastle disease virus modified and lethally irradiated tumor cell vaccines in combination with low-dose recombinant interleukin-2 (1.8 million U) and recombinant interferon-alpha 2a (1.0 million U) for a surgical adjuvant treatment. Patients were vaccinated (subcutaneous injection) once a week for 8-10 weeks and the treatment was started about 4-10 weeks after surgery. Up to now more than 208 patients with locally advanced renal cell carcinoma (stages pT2-3a, N1-2, M0; pT3b-4, N0-2, M0) were vaccinated after initial radical surgery (tumor nephrectomy with lymph node dissection and ipsilateral adrenalectomy and if necessary in combination with en bloc removal of venous extensions). We overview a follow-up of 203 evaluable patients with a median disease-free survival of 21 months (range of 2-64 months). During this observation period 18 relapses (8.9%) were diagnosed with 3 local relapses (1.5%), 10 lymph node metastases (5%) and/or distant organ metastases in 9 cases (4.5%). These progressive patients' disease was treated by surgery and/or combined immunochemotherapy. Toxicity encountered on this tumor cell vaccination was mild (WHO grade 1) and was characterized by flu-like symptoms and fever up to 38.8 degree Celsius for some hours beginning at 4 hours after the vaccine/cytokine application. Occasionally a transient local inflammation at the site of injection was observed. The comparison of the risk-factor-adapted group of adjuvant treated renal cell carcinoma patients (locally advanced stages) with historical data gave evidence for an improvement in disease-free survival on vaccination treatment. Although this was not a prospective randomized trial, we can summarize that the surgical adjuvant treatment of autologous tumor vaccines in combination with low-dose cytokines may improve relapse-free and overall survival in patients with locally advanced renal cell cancer.

Adult↗
PubMed1996

Linomide and interleukin-2 in patients with advanced renal cell carcinoma.

Quinoline-3-carboxamide (Linomide) is a novel, synthetic immunomodulator acting via immunologic and non-immunologic mechanisms. It has shown efficacy against various malignancies, experimental autoimmune encephalomyelitis, and septic shock in animal models and has been investigated for clinical use in minimal residual myeloid leukemia with promising results. Interleukin-2 has shown considerable efficacy in palliative anti-tumor-treatment of advanced renal cell cancer, revealing remission rates of up to 40% in combination therapy regimens. Linomide is reported to exhibit synergistic effects with interleukin-2. Here we report on a clinical phase I/II study examining tolerance and efficacy of a combination therapy schedule of SQ interleukin-2 and PO Linomide in advanced renal cell cancer. Seventeen patients received 10 IU/m2 interleukin-2 per week for 8 weeks, resting interleukin-2 for another 8 weeks. In week 5 they started 5 mg Linomide daily, continued with 10 mg from week 7 to 16. No objective remissions were observed. Among 15 patients evaluable for response, 10 (66.7%) were progredient during the study. Three patients died during the observation period, including two not evaluable for response. Median survival was 4.0 months, median progression-free survival 2.5 months with a Kaplan-Meier estimate of 3.63 months. Fever, reduced general condition, nausea/vomiting, dyspnea, anorexia, chills and hypotension were the most common side effects, reaching WHO grade 3 in 6 and grade 4 in 2 cases. In summary, Linomide in combination with interleukin-2 provides no advantages in efficacy or toxicity over other therapy regimens employing interleukin-2.

Adjuvants, Immunologic↗