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W Hunstein

Publications and source records attributed to W Hunstein.

At least 37 records · Page 2Linked to original sources
PubMed1995

Prevention of catheter-related infections by silver coated central venous catheters in oncological patients.

Catheter-related infection (CRI) is a serious complication of central venous catheterization. We have investigated the efficacy of a silver-coated polyurethane catheter (Pellethane, Fresenius AG, Germany) in preventing CRI in oncological patients receiving chemotherapy in a phase II study. From November 1992 through April 1994, 266 patients were assigned to receive single lumen catheters, either standard uncoated catheters (UC, n = 113) or silver-coated ones (SC, n = 120). Catheters were inserted into the internal jugular vein after institutional approval and informed consent. Duration of catheterization (UC vs. SC = 13.3 vs. 12.7 days) and leukopenia (< 1.0 x 10(9) WBC/l; 4.3 vs. 3.6 days) were similar in both groups demonstrating a comparable risk for infections. Skin reactions at the catheter entry site were recorded daily. CRI and colonization rates were studied by semiquantitatively culturing intradermal and intravascular segments. CRI were confirmed by blood cultures obtained via catheter and from peripheral veins in cases of suspected sepsis or at the end of catheterization. No adverse effects from the silver-coated catheter could be observed. The bacteriological results showed that SC were colonized (> 15 CFU) in 45.1% and UC in 44.2%. CRI developed in 21.2% of the UC patients but only in 10.2% of the SC patients (p = 0.011). We conclude that this new silver-coated central venous catheter is biocompatible and effective in reducing the incidence of catheter-related infections in oncological patients.

Adolescent↗
PubMed1995

Restriction of T cell receptor V beta repertoire in melanoma metastasis responding to immunotherapy.

Restriction of the T cell receptor repertoire suggesting ongoing specific immune mechanisms has recently been described in melanoma tissue by several groups of investigators. The functional relevance for immunotherapy of melanoma, however, has not been established. We studied the T cell receptor repertoire in two melanoma metastases of a patient with a mixed response to immunotherapy. Expression of T cell receptor V beta regions was determined by subgroup-specific semiquantitative RNA polymerase chain reaction (PCR). In the regressing skin lesion a restricted expression of the T cell receptor repertoire and overexpression of three V beta subgroup genes was found; no restriction was present in the simultaneously progressing skin lesion of the same patient, compared with peripheral blood lymphocytes. Comparison of T cell receptor V beta gene expression in two metastatic lesions of a patient with simultaneously growing skin metastases, who did not receive immunotherapy, revealed only minor differences. These observations show for the first time an association between restricted T cell receptor repertoire and responsiveness of melanoma to immunotherapy and suggest a role of T cells using the overexpressed V beta genes for the cytokine-induced tumour regression.

DNA, Neoplasm↗
PubMed1995

Serum interleukin-8 (IL-8) is elevated in patients with metastatic melanoma and correlates with tumour load.

It was recently demonstrated that IL-8 is produced by melanoma cell lines and acts as an essential autocrine growth factor. We studied the constitutive production of IL-8 by melanoma cell lines and the serum concentrations in patients with metastatic melanoma. All of 10 melanoma cell lines investigated constitutively produced IL-8 (mean 315 +/- 58 pg/10(5) cells per 24 h. IL-8 was detectable (mean 159 +/- 13.1 pg/ml) in the serum of 21 out of 56 patients by an enzyme-linked immunosorbent assay (ELISA; detection limit < 100 pg/ml). There was a significant correlation with tumour load, whereas no correlation with metastatic sites was found. No increased IL-8 levels were seen in healthy controls or patients with metastatic renal cell carcinoma. These results suggest that IL-8 is constitutively produced by melanoma cells in vivo.

Cytokines↗
PubMed1995

Addition of dacarbazine or cisplatin to interferon-alpha/interleukin-2 in metastatic melanoma: toxicity and immunological effects.

The combination of chemotherapy and immunotherapy seems to improve response rate in metastatic melanoma. We investigated the effects on toxicity and immunological effects of a single dose of dacarbacin (DTIC; 850 mg/m2) or cisplatin (CDDP; 100 mg/m2) added to subsequent immunotherapy with interferon-alpha (IFN-alpha) and interleukin-2 (IL-2). Twelve patients, who did not respond to IFN-alpha/IL-2 alone were studied. Six received DTIC and IFN-alpha/IL-2, and six received CDDP and IFN-alpha/IL-2. DTIC did not add significant toxicity except for nausea. Significant thrombocytopenia was observed in two patients after CDDP. Although CDDP led to grade 3 nephrotoxicity in two patients, the IL-2-induced fluid retention was less severe than with IFN-alpha/IL-2 alone. Pharmacokinetics of IL-2 were not altered by DTIC, but higher IL-2 serum levels were found in patients with grade 3 nephrotoxicity after CDDP. The IL-2-related induction of secondary mediators (interferon-gamma, tumour necrosis factor-alpha, soluble CD25) was not impaired by chemotherapy and the induction of neopterin was significantly higher after addition of CDDP. One partial response was observed after addition of DTIC to IFN-alpha/IL-2, and one after addition of CDDP. The addition of a single dose of DTIC or CDDP to IFN-alpha/IL-2 is fairly well tolerated and does not abolish induction of secondary mediators. Randomized trials are necessary to test the clinical efficacy.

Adjuvants, Immunologic↗
PubMed1995

Treatment of systemic mastocytosis with interferon-gamma: failure after appearance of anti-IFN-gamma antibodies.

We report a case of a patient with systemic mastocytosis who was treated with interferon-gamma. Because of severe diarrhoea, nausea and weight loss due to mast cell infiltration of the gastric mucosa the patient received 150 micrograms d-1 interferon-gamma subcutaneously for 10 months. During therapy, the plasma concentrations of IL-3, IL-4 and GM-CSF, which seem to play a role in mast cell growth and differentiation were monitored. The patient had good symptomatic relief and the initially very high eosinophil counts in the peripheral blood showed a partial reduction. However, after 4 months of therapy the patient relapsed. In serum obtained after the relapse, but not in stored serum from the beginning of the therapy, neutralizing antibodies against interferon-gamma were found. Therefore an initial response to the therapy and a secondary failure mediated by treatment-induced antibodies against recombinant interferon-gamma might be suggested. Interferon-gamma may be a well tolerated therapeutic option in systemic mastocytosis. However, treatment-induced neutralizing antibodies against recombinant interferon-gamma should be considered if secondary treatment failure occurs.

Aged↗
PubMed1994

Patient characteristics associated with successful mobilizing and autografting of peripheral blood progenitor cells in malignant lymphoma.

For patients with advanced-stage or poor-prognosis malignant lymphoma, high-dose therapy with peripheral blood progenitor cell (PBPC) support may become a first-line treatment. The duration of severe cytopenia in this setting is inversely related to the number of PBPCs autografted. In a retrospective analysis, we therefore looked for factors influencing the yield of PBPCs in 61 patients (16 with high-grade and 29 with low-/intermediate-grade non-Hodgkin's lymphoma [NHL], and 16 with Hodgkin's disease) who received cytotoxic chemotherapy and filgrastim (R-metHuG-CSF, 300 micrograms/d; median, 4.2 micrograms/kg/d; range, 2.7 to 6.6 micrograms/kg/d; subcutaneously). Sixteen patients had active disease, while 45 were in partial remission (PR) or complete remission (CR) after conventional therapy. A median of three leukaphereses (range, one to 10) resulted in a median of 5.7 x 10(6) CD34+ cells/kg (range, 0.03 to 31.1 x 10(6)). Previous cytotoxic chemotherapy and irradiation adversely affected the yield of CD34+ cells. Each cycle of chemotherapy is associated with an average decrease of 0.2 x 10(6) CD34+ cells/kg per leukapheresis in nonirradiated patients, while large-field radiotherapy reduces the collection efficiency by an average of 1.8 x 10(6)/kg CD34+ cells. The collection efficiency was also significantly lower in patients with Hodgkin's disease. However, except for one, all had been previously irradiated. In contrast, age, sex, disease status, bone marrow involvement during mobilization, and the time since the last chemotherapy or radiotherapy were not significantly related to the collection efficiency. Following high-dose conditioning therapy, 42 patients were autografted with filgrastim-mobilized PBPCs. Hematological recovery (neutrophils > or = 0.5 x 10(9)/L and an unsupported platelet count > or = 20 x 10(9)/L) within 2 weeks was observed in patients autografted with > or = 2.5 x 10(6) CD34+ cells/kg. In seven patients, the quantity of CD34+ cells reinfused was below this threshold. They required a median of 17 days (range, 11 to 34) and 31 days (range, 13 to 141) for neutrophil and platelet recovery, respectively. If autografting with PBPCs in malignant lymphoma with poor prognosis is being considered, mobilization and harvesting should be planned early after initial diagnosis to avoid exhaustion of hematopoiesis by cumulative toxicity.

Adolescent↗
PubMed1994

CD34 selection for purging in multiple myeloma and analysis of CD34+ B cell precursors.

Selection of CD34+ hematopoietic progenitor cells from autografts may be performed in multiple myeloma (MM) to minimize contamination with tumor cells. This approach is based on the assumption that the malignant cells do not express the CD34 antigen. Therefore, we first compared the CD34+/CD10+ and CD34+/CD19+ subpopulations from bone marrow (BM) and peripheral blood (PB) of fourteen MM patients and five normal controls. No difference between the respective early B cell subsets of both groups could be observed. Using tricolor flow cytometry, the CD19 expression on CD34+/CD10+ cells in BM was found to increase continuously from CD19- to CD19dim. In contrast, circulating CD34+/CD10+ cells did not coexpress the CD19 antigen. This population may contain myeloid progenitor cells or bipotential progenitor cells of the myeloid and lymphoid lineage as suggested by data obtained with fetal liver cells. Further functional studies are required. Enrichment of CD34+ cells with immunomagnetic beads was performed from BM of three MM patients and four normal donors. The CD34+ cells were selected with the HPCA-1 antibody and detached from the beads with chymopapain. Compared with the starting cell preparation, a 3.97 +/- 0.48 log (mean +/- SE) reduction of plasma cells could be achieved after CD34 selection. On morphological examination, 84% +/- 4% of the cells in the CD34+ fraction (MM) were immature blasts. The plating efficiency for hematopoietic colony forming cells was 9.7% +/- 2.8% in the CD34 selected fraction of the MM group, reflecting a 51-fold increase as compared with the starting population.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, CD↗
PubMed1994

Multidrug resistance phenotype in patients with chronic lymphocytic leukemia as detected by immunofluorescence (FACS) and northern blot analysis.

The multidrug resistance (MDR) phenotype has been demonstrated to be related to the overexpression of P-glycoprotein, a 170 kDa transmembrane efflux pump. We studied P-glycoprotein expression in 40 patients with chronic B-cell leukemias by FACS analysis using MoAb c219, which recognizes both the MDR1 and the MDR3 gene product. We found significantly elevated P-glycoprotein expression in these patients as compared with normal controls. Patients who had received previous chemotherapy regimens containing MDR-related drugs showed significantly higher P-glycoprotein expression with MoAb c219 than those patients who had been untreated. Northern blot analysis of MDR1 and MDR3 gene expression in 32 of the patients gave a similar result: in the analysis of total RNA four of six patients (66%) pretreated with either vinca alkaloids or anthracyclines were MDR1 positive as opposed to 6 of 26 (23%) who had no treatment or treatment without these agents. In contrast, MDR3 expression was found more frequently (63%), but was randomly distributed in the differently treated groups. Increasing the sensitivity level by analysis of enriched mRNA (polyA+RNA) led to the detection of MDR1 and MDR3 expression all B-CLL patients. We conclude that a basic elevated P-glycoprotein expression is intrinsic in CLL cells, which is possibly upregulated under chemotherapy. This might be responsible for initial and acquired chemotherapy resistance in CLL patients. Follow-up of the B-CLL patients over 46 months showed that the median survival time for MDR1+ patients was 19 months as opposed to 46 months for MDR1- patients (p < 0.01). There was no statistical difference in survival between MDR3+ and MDR3- patients. In the MDR1+ group, eight of nine patients had developed resistance to the therapy with MDR-related drugs. The expression of MDR1 might, therefore, predict treatment failure with MDR-related drugs and be a negative prognostic factor.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Immunotherapy of metastatic melanoma with interferon-alpha and interleukin-2: pattern of progression in responders and patients with stable disease with or without resection of residual lesions.

This evaluation was performed in melanoma patients after successful immunotherapy to describe the pattern of relapse. 63 patients received interferon (IFN)-alpha and high-dose interleukin (IL)-2, resulting in three complete responses (CR), 13 partial responses (PR), three mixed responses (MR) and 17 stable diseases (SD). Median duration of response was 7 months (range 3-28) without surgery. Most relapses occurred at pre-existing sites. Duration of CR was 14-37+ months. In 11 patients, residual tumour lesions were resected. Interestingly, histology revealed almost complete tumour regression in 6 patients, including 2 of 4 with SD. 5 of these 11 patients have relapsed so far, 6 patients are still free of disease with a median of 17 months (range 8-34). Following relapse, 4 of 6 patients responded to retreatment with the identical IFN alpha/IL-2 protocol. The authors conclude that initial disease progression is mostly at previous sites of disease. Resection of residual lesions may offer a chance for extended disease-free survival similar to patients with CR to immunotherapy. Retreatment of relapsing patients is favourable.

Cohort Studies↗
PubMed1994

Regional adoptive immunotherapy with interleukin-2 and lymphokine-activated killer (LAK) cells for liver metastases.

A phase lb trial of a novel regional approach to adoptive immunotherapy is reported. Patients with liver metastases received continuous high-dose infusion of interleukin-2 (IL-2) into the splenic artery or intravenous infusion with subsequent transfer of lymphokine-activated killer (LAK) cells into the portal vein or the hepatic artery. Trafficking studies revealed homogeneous distribution of the LAK cells within the liver. The usual side-effects of IL-2 and LAK cells occurred without limiting liver toxicity. One partial (7+ months) and two complete responses (36 and 26+ months) were observed in 9 patients with metastases from cutaneous melanoma. None of 6 patients with metastases from ocular melanoma responded.

Eye Neoplasms↗
PubMed1994

Characterization of peripheral blood progenitor cells mobilized by cytotoxic chemotherapy and recombinant human granulocyte colony-stimulating factor.

The purpose of this study was to evaluate the antigenic profile of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood progenitor cells (PBPC) in patients with non-Hodgkin's lymphoma (NHL), Hodgkin's disease (HD), and multiple myeloma (MM). The mobilization regimens consisted of high-dose cytarabine/mitoxantrone for patients with NHL, DexaBEAM for patients with HD, and high-dose cyclophosphamide (4 or 7 g per m2) for patients with MM. Cytotoxic therapy was supported by recombinant human G-CSF (Filgrastim, 300 micrograms/day sc) to shorten the period of neutropenia and to increase the number of circulating hematopoietic progenitor cells. The mean numbers of circulating CD34+ cells/microliters during leukocyte recovery were different between patient groups, 80.5 +/- 9.8 (mean +/- SEM) in low-grade NHL and 51.2 +/- 9.7 in high-grade NHL compared with 31.3 +/- 6.9 in HD and 24.4 +/- 4.1 in patients with MM. As a result, the greatest numbers of CD34+ cells/kg collected per leukapheresis were observed in patients with NHL, whereas the collection efficiency was substantially lower in patients with HD or MM. Patients with MM had also the smallest proportion of CD34+ cells in the mononuclear cell fraction (mean 0.79 +/- 0.10% versus 2.15 +/- 0.19% in low-grade NHL) but the greatest proportion of early CD34+ HLA-DR- progenitor cells (mean 2.38 +/- 0.51 versus 0.84 +/- 14% in low-grade NHL). Patients with MM had a mean proportion of CD34/c-kit+ cells that was twofold greater than that observed in patients with high- or low-grade NHL.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Detection of residual tumor cells in patients with malignant melanoma responding to immunotherapy.

Recently, a highly sensitive assay combining reverse transcription and polymerase chain reaction (PCR) to assess for melanoma cells in peripheral blood has been developed. Detection of tyrosinase mRNA, a tissue-specific enzyme in melanocytes and melanoma cells, indicates the presence of melanoma cells in peripheral blood. We examined blood samples and bone marrow aspirates from 28 patients with metastatic malignant melanoma for presence of melanoma cells prior to and after therapy with interferon (IFN)-alpha and interleukin (IL)-2. Ten patients showed antitumor response to immunotherapy, including three complete (CR) and seven partial remissions (PR). Four patients (three PR, one stable disease) underwent subsequent resection of residual tumor lesions and had no clinical evidence of disease after surgery. Tyrosinase mRNA was detected in blood and bone marrow samples from all patients with malignant melanoma prior to and after immunotherapy, including those with no clinical evidence of disease (median disease-free survival 21 months, range 19-28 months). Tyrosinase transcripts were also detected in all patients with amelanotic melanoma. In contrast, no tyrosinase mRNA was detectable in any of 30 healthy persons or in six patients with other malignancies. The presence of residual melanoma cells may be an important indicator of occurrence of delayed relapse.

Base Sequence↗
PubMed1994

HLA class I alleles and responsiveness of melanoma to immunotherapy with interferon-alpha (IFN-alpha) and interleukin-2 (IL-2).

MHC-restricted recognition of melanoma cells by cytotoxic T lymphocytes is an important mechanism in vitro. Several HLA alleles can function as restriction elements for melanoma cell recognition. In this study we investigated whether there is a correlation between responsiveness of patients with metastatic melanoma (MM) to immunotherapy and the HLA type of the patient. Seventy-two patients received immunotherapy with IFN-alpha and IL-2 according to two different schedules with an overall response rate of 24%. In 54 patients, including 16 responders and 16 patients with stable disease, in whom peripheral blood lymphocytes were available, we determined HLA haplotypes. As a control group we prospectively determined HLA types in 67 melanoma patients of all stages who underwent surgery or received chemotherapy and of 126 healthy donors from our blood bank. Two HLA alleles that have been shown to function as restriction elements in vitro were observed more frequently in responding patients, namely Cw7 (p = 0.014) and A1 (p = 0.19). No association was found for A2 and B44. These observations provide evidence that the responsiveness of MM to immunotherapy with IL-2 is associated with certain HLA types, suggesting an important role of HLA-restricted T lymphocytes for IL-2-induced tumour regression.

Alleles↗