Search PubMed⌕ Search

Biomedical subjects

R Mertelsmann

Publications and source records attributed to R Mertelsmann.

At least 55 records · Page 3Linked to original sources
PubMed1997

Aerobic exercise in the rehabilitation of cancer patients after high dose chemotherapy and autologous peripheral stem cell transplantation.

BACKGROUND: Fatigue and loss of physical performance are frequent problems of cancer patients. In a pilot study, the authors evaluated the feasibility and effects of aerobic training in the rehabilitation of cancer patients after completing high dose chemotherapy. METHODS: Sixteen patients participated in a specially designed rehabilitation program for 6 weeks. The patients entered the program, which consisted of walking on a treadmill, shortly after completing treatment. Sixteen patients who did not train served as controls. Physical performance (maximum speed on the treadmill test), cardiac function, and hemoglobin concentration were compared at the time of discharge from the hospital and 7 weeks later. At the second examination, fatigue and limitations in daily activities due to impaired endurance were assessed during personal interviews. RESULTS: At the time of discharge from the hospital, maximum physical performance (training group: 6.2 +/- 1.1 km/hour; controls: 6.2 +/- 1.3 km/hour) and hemoglobin concentration (training group: 10.1 +/- 1.4 g/dL; controls: 10.1 +/- 1.2 g/dL) were similar for both groups. After 7 weeks, improvement in maximum physical performance (training group: 8.3 +/- 1.6 km/hour; controls 7.5 +/- 1.3 km/hour) and hemoglobin concentration (training group: 13 +/- 1 g/dL controls: 12 +/- 1.4 g/dL) were significantly higher for the training group (P < 0.05). By the second examination, no patient in the training group but 4 controls (25%) reported fatigue and limitations in daily activities due to low physical performance. CONCLUSIONS: Aerobic exercise improves the physical performance of cancer patients recovering from high dose chemotherapy. To reduce fatigue, this group of patients should be counseled to increase physical activity rather than rest after treatment.

Adult↗
PubMed1997

A phase-I clinical study of autologous tumor cells plus interleukin-2-gene-transfected allogeneic fibroblasts as a vaccine in patients with cancer.

Tumor cells transfected to express immunostimulatory cytokines, or admixed with similarly modified bystander cells, are able to induce immune responses against unmodified tumor cells in animal models. For treatment of human patients, a vaccine composed of autologous tumor cells and IL-2-secreting allogeneic fibroblasts was developed. Autologous tumor cells were isolated from biopsy specimens. A clone (KMST 6.14) of an immortalized human fibroblast line that stably secreted 5290 IU IL-2 per 10(6) cells and per 24 hr was obtained by cationic lipofection with an expression construct for human IL-2 and Neo(r). Fifteen patients with refractory malignant tumors received 3-4 injections of irradiated KMST6.14 and autologous tumor cells in a phase-I clinical trial. Increasing transient inflammatory responses without systemic toxicity developed at vaccination sites and after injections with irradiated tumor cells only (p < 0.05). These sites contained a dense infiltrate of CD3+ T cells with numbers of CD4+ helper cells exceeding those of CD8+ cytotoxic T cells (CTL). CD8+ T-cell lines isolated from vaccination sites of 2 malignant melanoma patients but not of renal-cell carcinoma patients exhibited a dominant lytic activity against autologous tumor cells in vitro. CD8+ T-cell clones established from the vaccination site of 1 of 2 renal-cell carcinoma patients preferentially lysed autologous and partially matched allogeneic renal-cell carcinoma cells. In conclusion, a vaccine composed of IL-2 gene-transfected allogeneic fibroblasts and autologous tumor cells is able to enhance specific anti-tumor T-cell responses in vivo without major side-effects. Malignant melanoma and renal-cell carcinoma appear to be promising entities for testing of similar approaches in future therapeutic trials.

Adult↗
PubMed1997

NTS influence on transgene expression from mono- and bicistronic plasmid vectors after lipofection in a human fibroblast cell line.

We evaluated the survival, transgene production, and copy numbers of integrated plasmid units per host genome after lipofection with mono- and bicistronic plasmid vectors in different cell lines and under various conditions. The addition of an integration enhancing murine sequence nontranscribed spacer (NTS) to the plasmids increased transfection efficiency, survival, and transgene expression. However, in human fibroblast cells this sequence had only marginal effects on overall plasmid copy number in bulk cultures. Clones producing the highest amounts of the transgene contained only one or two copies of plasmid per genome, independent of cell type and plasmid design.

Animals↗
PubMed1997

Induction of tumor-specific cytotoxic T lymphocytes by immunization with autologous tumor cells and interleukin-2 gene transfected fibroblasts.

In a phase I trial designed to study a vaccine composed of autologous tumor cells and interleukin-2 gene transfected fibroblasts we analyzed lymphocytes infiltrating the vaccination site (VIL) in two melanoma patients. Functional studies demonstrated that numbers of MHC class I restricted cytotoxic T cells directed against the autologous tumor had increased at the immunization site in both cases. Analysis of the variability of T cell receptors (TCR) in the VIL of one patient revealed that the cytotoxic T lymphocytes consisted of a predominant population of TCRBV21S3+ T cells. Enrichment of this subpopulation to more than 99% by specific anti-TCRBV21S3 monoclonal antibody linked immunomagnetic beads and sequencing of the TCR-beta chain disclosed exactly the same V-D-J junctional sequence in all eight TCRBV21 transcripts from these VIL. The identical sequence was also detected in all eight TCRBV21 transcripts from the patient's tumor-infiltrating lymphocytes, indicating that the same CTL clone had infiltrated the tumor, circulated in the peripheral blood, and was amplified at the vaccination site. The TCRBV21S3+ T cells were also found to display an MHC class I restricted cytotoxic activity specifically directed against the autologous tumor cells. At the beginning of treatment these cells were undetectable at the vaccination site and delayed-type hypersensitivity testing was negative, contrasting with the positive results after therapy. Thus it is likely that vaccination with autologous tumor cells plus interleukin-2 gene transfected allogeneic fibroblasts had induced not only local accumulation but also an increase in the frequency of circulating tumor specific CTL.

Amino Acid Sequence↗
PubMed1997

Early-onset secondary malignancies after high-dose chemotherapy and autologous hematopoietic stem cell transplantation.

We treated 500 patients with high-dose chemotherapy (HDC) and autologous bone marrow (ABMT) or autologous peripheral blood stem cell transplantation (PBSCT). Treated conditions included leukemia, lymphomas, breast cancer, lung cancer, germ-cell carcinomas, and other solid tumors. In order to assess relapse of primary malignancy or occurrence of new neoplasms, routine screening after ABMT or PBPCT was performed at regular and close intervals. With a total follow-up of 1358 person-years and a median follow-up of 34 months (range 9-91), 10/500 (2%) patients developed second malignancies after PBSCT or ABMT; i.e., one new cancer occurred every 136 person-years. All malignancies were detected at routine follow-up examinations; and 7/10 diagnoses were made in an asymptomatic phase; 6/10 neoplasms were amenable to complete surgical resection, five of which remain in CR at a median of 23+ months after autotransplantation. We conclude that regular and close follow-up examination of patients after autologous hematopoietic stem cell transplantation may be beneficial, since successful treatment of second malignancies is possible in selected cases after early detection.

Adult↗
PubMed1997

High-dose chemotherapy and autologous hematopoietic stem cell transplantation in patients with second primary malignancies.

We treated 500 patients with high-dose chemotherapy and autologous bone marrow or autologous peripheral blood stem cell transplantation. Treated conditions included leukemia, lymphoma, breast cancer, lung cancer, germ-cell carcinoma, and other solid tumors. 10/500 (2%) of patients were treated for a second malignancy diagnosed 12 months to 25 years after their initial neoplasm. Four of these ten patients are in complete remission (CR) of both malignancies at a median follow-up of 29+ months after high-dose chemotherapy and autotransplantation. None of these patients would have been eligible for high-dose chemotherapy and autotransplantation by conventional selection criteria which usually excluded patients with a history of prior malignancies. Conclusion. Conventional exclusion criteria for high-dose chemotherapy and autotransplantation may not adequately reflect the prognosis of patients with second or secondary malignancies treated with this therapeutic modality. High-dose chemotherapy and autologous hematopoietic stem cell transplantation may be of true benefit in selected cases of secondary malignancies.

Adult↗
PubMed1997

Acute myelomonocytic leukemia secondary to synchronous carcinomas of the breast and lung, and to metachronous renal cell carcinoma.

We describe a patient in whom synchronous breast cancer and small-cell lung cancer, and metachronous renal cell carcinoma were diagnosed within an 11 months period. All three tumors were treated surgically, followed by administration of tamoxifen, adjuvant chemotherapy with etoposide (2.8 g/m2 total) and vindesine, and administration of interferon alpha and flutamide. The patient developed acute myelomonocytic leukemia 26 months after discontinuation of etoposide-containing chemotherapy. This pattern of multiple neoplasms fits the wider disease spectrum associated with germline mutations of the p53 gene; however, analysis of p53 exons 5-8 did not disclose any sequence abnormalities in this patient. In conclusion, clustering of four (synchronous and metachronous) malignancies may on rare occasions occur in an individual patient and in the absence of a family history of cancer; the sequence during which treatment of primary malignancies may result in treatment-related acute myelocytic leukemia is discussed.

Breast Neoplasms↗
PubMed1997

Clinical and immunomodulatory effects of repetitive 2-day cycles of high-dose continuous infusion IL-2.

High-dose interleukin-2 (IL-2) treatment has demonstrated promising antitumour activity in renal cell carcinoma (RCC) and malignant melanoma (MM) and has been shown to induce broad immunological effects. The optimal IL-2 dose and schedule, however, still remain to be defined. We studied a treatment protocol consisting of five repetitive cycles of high-dose recombinant (rh) IL-2 (24 x 10(6) U/m2/day) administered weekly on two consecutive days by continuous intravenous infusion. 17/19 were RCC patients, 2 of whom responded with a complete remission (CR) and 3 with a partial response (PR) (CR + PR: 29%; median response duration of 11.5+ months (range: 3-14 months)). IL-2 induced a pronounced increase of lymphocytes and pro-inflammatory cytokines IL-8, IL-5, gamma-IFN, TNF- alpha and TNF-beta (p < 0.05) that peaked in cycle 3. With subsequent therapy, serum levels of these cytokines, NK, T cells and eosinophils decreased, whereas serum IL-10 levels progressively increased with maximum levels achieved after the fifth week of treatment, suggesting that it may be involved in dampening the inflammatory response induced by IL-2. Absolute numbers of activated T cells and NK cells remained elevated as compared to baseline for at least 4 weeks after treatment cessation. Based on these observations, future scheduling of IL-2 will be done at 3 weekly 2-day cycles separated by a week 4 treatment-free interval in order to increase further the 29% objective response rate achieved in this study.

Adult↗
PubMed1997

Immunostimulatory cytokines in somatic cells and gene therapy of cancer.

The use of immunostimulatory cytokines has become an increasingly promising approach in cancer immunotherapy. The major goal is the activation of tumour-specific T lymphocytes capable of rejecting tumour cells from patients with low tumour burden or to protect patients from a recurrence of the disease. Strategies that provide high levels of immunostimulatory cytokines locally at the site of antigen have demonstrated pre-clinical and occasional clinical efficacy. Animal models using poorly immunogenic tumours revealed that tumour cells genetically engineered to produce cytokines like IL-2, IL-4, IL-7, IL-12, IFNs, GM-CSF or TNF-alpha were found to be effective in eradicating disseminated tumours. Experimental data obtained from these different animal models are reviewed here to provide an overview of this rapidly evolving field. The data obtained so far from clinical trials involving cytokine gene-modified cells have provided important information regarding the feasibility, safety, immunological effects and occasional clinical responses.

Animals↗
PubMed1997

Dose-intense therapy with etoposide, ifosfamide, cisplatin, and epirubicin (VIP-E) in 107 consecutive patients with limited- and extensive-stage non-small-cell lung cancer.

BACKGROUND: We conducted a phase I/II trial to assess the feasibility and activity of combination chemotherapy with etoposide, ifosfamide, cisplatin, and epirubicin in limited-stage (LS, stage I-IIIB) and extensive-stage (ES, stage IV) non-small-cell lung cancer (NSCLC). End-points were treatment-related morbidity and mortality, response rate, duration of response, and survival. PATIENTS AND METHODS: Chemotherapy followed by granulocyte colony-stimulating factor was given at a dose of etoposide (500 mg/m2), ifosfamide (4000 mg/m2), cisplatin (50 mg/m2), and epirubicin (50 mg/m2) (VIP-E) to 107 patients with NSCLC. Twenty-five patients with qualifying responses proceeded to high-dose chemotherapy with autologous peripheral blood stem cell transplantation after etoposide (1500 mg/m2), ifosfamide (12,000 mg/m2), carboplatin (750 mg/m2) and epirubicin (150 mg/m2) (VIC-E) conditioning. RESULTS OF CONVENTIONAL-DOSE VIP-E: 35 of 102 (34%) evaluable patients responded (2 CR's, 33 PR's), 33/102 patients (33%) showed no change (NC); the remainder of patients progressed with therapy (PD). Objective response rate was 68% (4% CR, 64% PR) in LS-NSCLC and 23% (1.4% CR, 21.4% PR) in ES-NSCLC. Median duration of survival was 13 months in LS-NSCLC and 5.5 months in ES-NSCLC. Two-year survival was 26% in LS and 2% in ES-NSCLC. RESULTS OF HIGH-DOSE VIC-E: 23 of 24 evaluable patients improved or maintained prior responses (92%), I patient showed NC. Treatment mortality was 4%. Median duration of survival was 17 months in LS-NSCLC and 10 months in ES-NSCLC. Two-year survival was 30% in LS and 8% in ES-NSCLC. CONCLUSION: Response-rates and survival after conventional-dose VIP-E chemotherapy are comparable to other published trials of combination chemotherapy in NSCLC. Toxicity and mortality is acceptable in limited stage, but unacceptably high in extensive stage NSCLC. Although better response-rates were achieved in the high-dose arm, they did not translate into improved survival. Most stage IV NSCLC-patients will neither benefit from VIP-E conventional dose, nor from VIC-E high dose chemotherapy. Whether selected LS-patients with partial or complete responses to VIP-E induction chemotherapy could benefit from dose intensification in an adjuvant or neo-adjuvant setting remains to be determined.

Adult↗
PubMed1997

The transjugular stent implantation for the treatment of malignant portal and hepatic vein obstruction in cancer patients.

BACKGROUND: The increase in portal vascular resistance is a significant complication of metastatic disease to the liver or locally advanced cancer, e.g., biliary cancer. PATIENTS AND METHODS: This paper describes the successful palliative treatment of two cancer patients with portal hypertension presenting with the symptoms of tense ascites, mesenteric congestion, and severe variceal bleeding. By creating a stenttract between a hepatic vein and a main branch of the portal vein and/or by placing an extendable stent into the portal vein, the transjugular intrahepatic portosystemic stent-shunt (TIPS) technique was used to decompress the portovascular system. RESULTS: The TIPS-technique offers a new, safe and effective palliation for malignant portal hypertension. In both patients, the symptoms of the portal hypertension disappeared after the procedure. This was accompanied by a significant improvement of the patients performance status allowing an early ambulation. CONCLUSION: Our findings demonstrate the feasibility and effectiveness of the TIPS procedure as a minimal invasive treatment for portal vein decompression in selected tumor patients.

Biliary Tract Neoplasms↗
PubMed1997

Dose-intense therapy with etoposide, ifosfamide, cisplatin, and epirubicin (VIP-E) in 100 consecutive patients with limited- and extensive-disease small-cell lung cancer.

BACKGROUND: We conducted a phase I/II trial to assess the feasibility and activity of VIP-E chemotherapy in small-cell lung cancer. End-points were treatment-related morbidity and mortality, response to treatment. duration of response, and survival. PATIENTS AND METHODS: Two cycles of combination chemotherapy followed by granulocyte colony-stimulating factor (G-CSF) were given at a dose of etoposide (500 mg/m2), ifosfamide (4000 mg/m2), cisplatin (50 mg/m2), and epirubicin (50 mg/m2) to 100 consecutive patients with SCLC. Thirty patients (19 with LD, and 11 with ED SCLC) proceeded to VIC-E high-dose chemotherapy with autologous peripheral blood stem cell transplantation (PBSCT) at a cumulative dose of etoposide 1500 mg/m2, ifosfamide 12,000 mg/m2, carboplatin 750 mg/m2 and epirubicin 150 mg/m2 (VIC-E). Surgical resection of primary tumor was attempted at the earliest feasible point. Thoracic irradiation was given after completion of chemotherapy. RESULTS of conventional-dose VIP-E: 97 patients were evaluable for response. Objective response rate was 81% in LD-SCLC (33% CR, 48% PR; excluding patients in surgical CR) and 77% in ED-SCLC (18% CR, 58% PR). Treatment mortality was 2%. Median survival was 19 months in LD-SCLC and 6 months in ED-SCLC. Two-year survival was 36% in LD and 0% in ED SCLC. RESULTS OF HIGH-DOSE VIC-E: All 30 patients improved on or maintained prior responses. Four patients (13%) died of treatment-related complications. Median survival was 26 months in LD-SCLC and 8 months in ED-SCLC. Two-year survival was 53% in LD and 9% in ED SCLC. CONCLUSION: VIP-E chemotherapy is an effective induction therapy for SCLC. Compared with traditional protocols such as ACO or carboplatin/etoposide, response rates are slightly improved, while survival is not different. In the LD SCLC subgroup, high-dose chemotherapy improved response rates and survival, especially for patients in surgical CR prior to high-dose therapy. In ED SCLC, however, higher response-rates did not translate into improved survival. Selected LD-SCLC patients with good partial or complete remissions after prior therapy may benefit from HDC and PBSCT.

Adult↗
PubMed1997

Correlation between physical performance and fatigue in cancer patients.

BACKGROUND: Fatigue and a reduction in physical ability are common and often severe problems of cancer patients regardless of disease stage and modality of treatment. However, while physical performance can be assessed objectively with laboratory tests, fatigue is a subjective phenomenon whose perception is influenced by past experience and expectations for the future. PATIENTS AND METHODS: To evaluate the correlation between fatigue and physical impairment, we assessed maximal physical performance with a treadmill test, and mental state with two questionnaires, the Profile of Mood States (POMS) and the Symptom Check List (SCL-90-R), in a successive series of 78 cancer patients with solid tumors or hematological malignancies. RESULTS: A weak association between fatigue and maximal physical performance was found (r = -0.30; P < 0.01). However, intensity of fatigue showed a strong correlation with several indicators of psychological distress such as depression (r = 0.68), somatization (r = 0.64) and anxiety (r = 0.63; P for all < 0.001). Furthermore, patients with lower levels of physical performance had significantly higher scores for depression (P = 0.005), somatization (P = 0.03) and anxiety (P = 0.08), and significantly lower scores for vigor (P = 0.05) than their counterparts whose physical performance was higher. CONCLUSIONS: We conclude that fatigue in cancer patients may be related to mood disturbance but appears to be independent of physical performance. Moreover, low physical performance can be viewed as an independent predictor of mental distress in cancer patients.

Adolescent↗
PubMed1997

Treatment of relapsed non-Hodgkin's lymphoma after BEAM chemotherapy and autologous transplantation by BU/CY chemotherapy and salvage transplantation.

We report a patient with centroblastic non-Hodgkin's MALT lymphoma of the stomach treated initially with surgery and post-operative chemotherapy and radiotherapy. First relapse was treated with high-dose BEAM chemotherapy and autologous peripheral blood stem cell transplantation (PBSCT). Second, systemic relapse was treated with high-dose BU/CY and second PBSCT. Today, the patient is in complete remission at 27+ months. The case indicates a curative potential for high-dose BU/CY chemotherapy as salvage therapy for relapsed high-grade lymphoma after BEAM and autologous PBSCT. This may have implications for the prevention as well as for the management of lymphoma relapse after high-dose chemotherapy (HDC) and autologous PBSCT.

Adult↗