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Biomedical subjects

S Andresen

Publications and source records attributed to S Andresen.

At least 37 records · Page 2Linked to original sources
PubMed2001

[Efficacy of elective lymph node dissection in malignant melanoma of the extremities and trunk. An analysis in view of the sentinel lymph node biopsy].

Elective lymph node dissection (ELND) is increasingly displaced by the Sentinel-lymph node biopsy. In this view we analyzed the efficacy of ELND in the treatment of malignant melanoma of the extremities and the trunc. Between 1979 and 1998 we performed a lymph node dissection in 834 patients (336 male, 498 female; average age 52 years). The analysis of the prospectively collected data was based on those 650 patients in whom an ELND was performed for UICC-stage I (T2) to stage III melanoma. The 5-year survival rate was 75% for all 650 patients. It was 87% for patients suffering from stage I-disease (T2-n = 65), 86% for those with stage II-disease (n = 354) and 47% in case of stage III-disease (n = 231) respectively. In 7 of the 73 patients undergoing ELND for a T2-tumor, in 56 of the 424 patients suffering from T3-tumor and in 38 of the 153 patients with a T4-tumor clinically obvious lymph node metastases had been detected by ELND. Discerning our results, we could demonstrate that a few of our patients profited from ELND, namely the patients in those clinically obvious metastases could be detected and survival could be achieved, i.e. 29 of all 650 electively dissected patients (2 of 7 T2N1-patients, 18 of 56 T3N1-patients and 9 of 38 T4N1-patients). We regard this benefit as an argument not to abandon the histological evaluation of the regional lymph nodes. However, because of the limited efficacy of elective lymphadenectomy, ELND should be displaced by the less invasive Sentinel-lymph node biopsy.

Adolescent↗
PubMed2001

Chemotherapy for acute myelogenous leukemia in the elderly with cytarabine, mitoxantrone, and granulocyte-macrophage colony-stimulating factor.

Remission induction chemotherapy for acute myelogenous leukemia typically combines cytarabine with an anthracycline or anthracycline derivative. To date, no specific combination has emerged as more efficacious than any other. To reduce toxicity and shorten the duration of neutropenia, hematopoietic growth factors are often added to the chemotherapy regimen, especially in elderly patients. In all prospective, randomized, growth factor trials to date, daunorubicin has been the drug selected for combination with cytarabine. We hypothesized that mitoxantrone might be as efficacious in this patient population with perhaps less toxicity when combined with granulocyte-macrophage colony-stimulating factor (GM-CSF). Patients older than age 55 years with a diagnosis of either de novo or secondary, untreated acute myelogenous leukemia were eligible for this clinical trial. Eligible patients were treated with cytarabine 100 mg/m2 infused as a continuous infusion daily for 7 days and mitoxantrone 12 mg/m2 bolus intravenously for the first 3 days of cytarabine. A second cycle of chemotherapy was administered on the fourteenth day of treatment if marrow aplasia was not achieved with the first cycle. Once aplasia was achieved, GM-CSF 250 microg/m2 was given subcutaneously daily until neutrophil recovery. Those patients who achieved complete remission were treated with two cycles of intermediate-dose cytarabine (400 mg/m2 daily for 5 days) and with GM-CSF as consolidation therapy. Of the 30 patients treated, the median age was 69 years (range: 55-76 years) and 18 patients were older than 65 years of age. Seven (23%) patients had secondary acute leukemia and 12 (40%) had poor-risk cytogenetics. Nineteen (63%) achieved a complete remission. Eleven patients were either refractory to treatment or died during their treatment. The toxicity encountered was no more than that reported in similar studies using daunorubicin in combination with cytarabine. Long-term survival was poor, with a median disease-free survival of only 8.1 months in patients who achieved complete remission. In this elderly population of patients with high-risk acute myelogenous leukemia, this combination of cytarabine, mitoxantrone, and GM-CSF resulted in an adequate remission rate with acceptable toxicity. Long-term survival, however, was poor and innovative treatment approaches to maintain remission are needed.

Aged↗
PubMed2001

Communicable disease epidemiology training in Northern Europe.

The five Nordic countries (Denmark, Finland, Iceland, Norway and Sweden) have a long tradition of collaboration in communicable disease epidemiology and control. The state epidemiologists and the immunisation programme managers have met regularly to discuss common challenges and exchange experiences in surveillance and control of communicable diseases. After the three Baltic countries (Estonia, Latvia and Lithuania) regained independence in 1991 and the Soviet Union dissolved, contacts were made across the old iron curtain in several areas, such as culture, education, business, military and medicine. Each of the Nordic communicable disease surveillance institutes started projects with partners in Estonia, Latvia, Lithuania or the Russian Federation. The projects were in such diverse areas as HIV surveillance and prevention, vaccination programmes and antibiotic resistance.

Curriculum↗
PubMed2000

High prevalence of diarrhea but infrequency of documented Clostridium difficile in autologous peripheral blood progenitor cell transplant recipients.

Autologous peripheral blood progenitor cell (PBPC) transplant recipients frequently receive multiple antibiotics for neutropenic fever in addition to high-dose chemotherapy. Although there are many possible causes for diarrhea in this population, empiric therapy for possible C. difficile colitis is common in some centers. This study sought to define the frequency of diarrhea and of a positive C. difficile toxin assay in PBPC transplant recipients. Data were collected on 80 patients enrolled in a randomized trial of two different antibiotic regimens during PBPC transplant. Data included the presence or absence of diarrhea, all microbiologic studies performed during the transplant admission, and all antimicrobials administered during the transplant admission. Of 80 patients enrolled, 61 (76.3%) developed diarrhea. Only 3/61 (4.9%) had a positive C. difficile toxin assay. A total of 122 C. difficile toxin assays were performed; for each positive C. difficile assay, 41 stool samples were analyzed. Twenty courses of oral metronidazole (18/20 empiric) and 10 courses of oral vancomycin (8/10 empiric) were given. A total of 25 of 61 patients with diarrhea (41%) received therapy for possible C. difficile. Diarrhea is common during autologous PBPC transplant but a positive C. difficile assay is uncommon. The practice of empiric therapy for C. difficile in this population in a non-outbreak setting should be re-evaluated. Bone Marrow Transplantation (2000) 25, 67-69.

Administration, Oral↗
PubMed2000

Autologous peripheral blood progenitor cell transplantation for transformed diffuse large-cell lymphoma.

The outcome of patients with transformed diffuse large-cell lymphoma is poor. High-dose chemotherapy and autologous peripheral blood progenitor cell (PBPC) transplantation is the treatment of choice for patients with relapsed nontransformed diffuse large-cell lymphoma. The role of transplantation for transformed lymphoma is poorly studied. We retrospectively reviewed 118 consecutive diffuse large-cell lymphoma patients undergoing autologous PBPC transplantation from 1994 through 1999 and compared 18 transformed diffuse large-cell lymphoma patients with 100 nontransformed patients. The transformed patients were more likely to be older (median age, 52 years vs. 45 years, P = 0.03), had a longer time from diagnosis to transplant (median, 35 months vs. 10 months; P < 0.0001), were more likely to have bone marrow involvement at diagnosis (61% vs. 15%, P = 0.0001), and were more likely to have had 2 or more courses of prior chemotherapy (94% vs. 71%, P = 0.04) than were nontransformed patients. Ninety-nine percent of patients received high-dose busulfan/cyclophosphamide/etoposide as the transplant preparative regimen. Event-free survival and overall survival were similar in the two treatment groups. Four-year overall survival was 53% in the nontransformed group versus 61% in the transformed group; 4-year event-free survival was 37% in the nontransformed group versus 38% in the transformed group. We concluded that autologous PBPC transplantation is a viable and potentially effective treatment option for patients who have transformed diffuse large-cell lymphoma.

Adolescent↗
PubMed1999

LDH elevation after autologous stem cell transplantation.

We have anecdotally noted that serum LDH values rise after the infusion of autologous peripheral blood progenitor cells (PBPCs), presumably the result of cellular lysis. To further study this issue, we retrospectively reviewed 203 consecutive patients undergoing autologous PBPC transplant from August 1996 to December 1997. 194 patients were evaluable, having documented LDH values on day -1 to day +5 post-transplant. All patients received cytokine mobilization for PBPC collection, and 99% received a chemotherapy-only preparative regimen. 99% of patients had a rise in serum LDH after PBPC infusion. 76% had a normal LDH prior to PBPC infusion that became abnormally high after infusion; 22% began with an abnormally high value that became higher with the infusion of PBPCs. The LDH rose at least 50% in 91% of patients. 92% of the patients had their peak LDH value occur on day +1 post-transplant. The total dose of CD34+ cells infused negatively correlated with peak percentage change of LDH (P = 0.0007). This result was initially perplexing, as we believed that a higher number of infused cells would correlate with a higher LDH value as a result of in vivo cellular lysis. However, the total number of CD34+ cells also negatively correlated with the number of phereses required to collect our threshold of 2.0 x 10(6) CD34+ cells/kg (P = 0.0001). After adjusting for CD34+ cell dose, we found that the number of phereses correlated highly with a peak percentage of change of LDH (P = 0.001). We conclude that the serum LDH increases universally after autologous PBPC infusion, peaking on day +1. We believe that this rise in serum LDH is a result of cell lysis that occurs ex vivo, and correlates with the number of pheresis procedures required to collect an adequate number of CD34+ cells. This may be a result of increasing red blood cell contamination with more phereses, and resultant RBC hemolysis.

Acyclovir↗
PubMed1998

A randomized study of multi-day infusion of autologous peripheral blood progenitor cells.

Peripheral blood progenitor cells (PBPC) are increasingly used as the source of stem cells in both the autologous and allogeneic settings. Based on previous early non-randomized studies reporting enhanced engraftment following fractionated autologous PBPC infusion, some centers and study groups infuse PBPC over 3 days. To study the possible benefit of multiple day PBPC infusion, 60 patients receiving high-dose chemotherapy and autologous progenitor cell transplantation (ABMT) were randomized to receive their PBPC divided over 1, 2 or 3 days. Stem cells were mobilized with G-CSF 5 microg/kg for 7 days and PBPC were collected on days 5-7. Patients received daily G-CSF 5 microg/kg i.v. over 30 min beginning 4 h after the infusion of the first aliquot of PBPCs. Toxicity was similar for the 1, 2 and 3 day infusion groups. The median time to achieve 500 neutrophils/mm3 was 10, 11 and 11 days in the groups receiving PBPCs over 1, 2 or 3 days, respectively. The median time to achieve a platelet count of 20 x 10(9)/l was 11 days for the group receiving their cells as a single infusion and 12 days in the other two groups. We conclude that expanding PBPC infusion over 2 or 3 days does not enhance engraftment or reduce toxicity.

Adolescent↗
PubMed1998

Delayed G-CSF after autologous progenitor cell transplantation: a prospective randomized trial.

G-CSF is given after autologous progenitor cell transplantation to accelerate neutrophil engraftment. Historically, G-CSF has been started on the day of progenitor cell infusion. To study the timing of the initiation of G-CSF after autologous peripheral blood progenitor cell (PBPC) transplantation, we conducted a prospective, randomized trial comparing the initiation of G-CSF therapy on day 0, day +3 or day +5 after autologous PBPC transplantation. Seventy patients with diagnoses of breast cancer, non-Hodgkin's lymphoma, Hodgkin's disease, or multiple myeloma were prospectively randomized to one of the three treatment arms. All patients were treated with a chemotherapy (only) preparative regimen. The source of hematopoietic reconstitution was PBPC alone (without autologous marrow), and all patients yielded a minimum of 2 x 10(6) CD34+ cells per kilogram. Times to neutrophil engraftment and platelet engraftment were identical in the three treatment groups, with neutrophil engraftment occurring at a median of 10, 11 and 11 days when starting G-CSF on day 0, day 3 or day 5, respectively. Time to platelet transfusion independence was 14, 11 and 14 days by treatment group. We conclude that delaying the initiation of G-CSF from day 0 to day +5 does not affect engraftment and results in cost savings.

Breast Neoplasms↗
PubMed1998

Variables associated with the platelet count 6 weeks after autologous peripheral blood progenitor cell transplantation.

While abundant data exist documenting variables associated with early platelet engraftment after autologous PBPC transplantation, data concerning later sustained platelet engraftment is sparse. We retrospectively examined a series of 80 patients undergoing autologous PBPC transplantation with respect to their platelet count 6 weeks after transplant. Underlying diagnoses included breast cancer (n = 33), non-Hodgkin's lymphoma (n = 32), Hodgkin's disease (n = 9), and other hematologic malignancies (n = 6). Patients received G-CSF for PBPC mobilization and collected a target threshold number of 2.0 x 10(6) CD34+ cells per kilogram. A univariate analysis revealed that a diagnosis of breast cancer, fewer courses of prior chemotherapy, younger age and complete remission were associated with a higher 6-week platelet count. Additionally, the ability to collect the threshold number of CD34+ with fewer sessions of leukapheresis was also associated with a higher 6-week platelet count. The platelet count and the white blood cell count at the initiation of PBPC collection was also associated with a higher 6-week platelet count. A multivariate analysis revealed a higher platelet count on the first day of pheresis, fewer phereses required to collect 2 x 10(6) CD34+ cells per kilogram, and a diagnosis of breast cancer were all associated with a higher 6-week post-transplant platelet count. Seven patients failed to reach a 6-week platelet count of 30 x 10(9)/l and an additional five patients had a platelet count of 30-50 x 10(9)/l. We conclude that underlying clinical characteristics, as well as hematologic variables at the time of PBPC collection, influence later, sustained platelet engraftment. A percentage of patients have poor sustained platelet engraftment and may be candidates for new cytokines that specifically target megakaryocyte growth and development.

Adult↗
PubMed1997

G-CSF post-autologous progenitor cell transplantation: a randomized study of 5, 10, and 16 micrograms/kg/day.

G-CSF is routinely administered after autologous bone marrow or peripheral blood progenitor cell transplantation to enhance neutrophil engraftment. However, many different doses of G-CSF have been described with no clear consensus on the most cost-effective dose. We performed a prospective randomized trial examining the efficacy of three different doses of G-CSF post-autologous transplant (5, 10, or 16 micrograms/kg/day). Fifty-seven consecutive patients with breast cancer (n = 30), non-Hodgkin's lymphoma (n = 16), Hodgkin's disease (n = 6), multiple myeloma (n = 2), acute leukemia (n = 2), and testicular cancer (n = 1) were randomized, with 19 patients enrolled in each of the three treatment groups. All patients underwent a high-dose chemotherapy preparative regimen and received an autologous peripheral blood progenitor cell (PBPC) transplant (without bone marrow), with G-CSF beginning on day 0. There was no difference in time to neutrophil engraftment among the three treatment groups (mean 10.2 to 10.8 days). There is a trend towards earlier platelet engraftment in the patient group receiving 5 microgram/kg/day of G-CSF. The total cost of G-CSF by dose group was $2900, $4400, and $6500 per patient. We conclude that there was no advantage to the use of higher doses of G-CSF after autologous transplantation, and that lower doses are associated with lower costs.

Adult↗
PubMed1997

Durability of remission after ABMT for NHL: the importance of the 2-year evaluation point.

Few series describing the results of autologous bone marrow transplantation (ABMT) for the treatment of non-Hodgkin's lymphoma report mature follow-up. We retrospectively reviewed 110 adults with NHL treated with ABMT from 1988 to 1993. Overall survival and relapse-free survival were 50% and 35%, respectively. Estimated median relapse-free survival was 16 months. There was no statistically significant difference in relapse-free or overall survival by low, intermediate, and high-grade histologies, as defined by the International Working Formulation. The most powerful negative prognostic variable was an elevated LDH at the time of transplant (relapse-free survival 17% vs 42% for those with a normal LDH). Forty-seven patients were in complete remission 2 years after transplant. Extended follow-up revealed that 100% of patients with high-grade histologies remained in complete remission, whereas patients with intermediate-grade and low-grade histologies remained at risk of relapse with longer follow-up. Of 22 patients with diffuse large cell lymphoma (LCL) or immunoblastic (IBL) histologies, eight of eight with IBL remain in continued remission, while four of 14 with LCL relapsed 24-48 months after ABMT. We conclude that patients with high-grade histologic subtypes of NHL who are in complete remission 2 years after ABMT are likely to be cured. However, patients with intermediate and low-grade histologic subtypes are at continued risk of relapse and require appropriate clinical surveillance for at least 48 months after ABMT.

Adult↗
PubMed1997

Platelet transfusion requirements during autologous peripheral blood progenitor cell transplantation correlate with the pretransplant platelet count.

The use of primed peripheral blood progenitor cells (PBPC) has improved platelet engraftment following autologous bone marrow/PBPC transplantation (ABMT). The thrombocytopenia associated with ABMT generally lasts 14-18 days, and is associated with variable platelet transfusion requirements. Little, if any, data exist examining prognostic parameters for platelet transfusion requirements during autologous transplantation. We retrospectively examined 286 consecutive patients undergoing autologous transplantation from 1 January 1994 to 1 June 1996 with respect to platelet engraftment and platelet transfusion requirements. One hundred and fifty four patients were transplanted for breast cancer (54%), 72 for non-Hodgkin's lymphoma (25%), 35 for Hodgkin's disease (12%), 13 for acute leukemia (5%), eight for myeloma (3%), and four for other malignancy (1%). The median age was 44. All patients received cytokine priming, usually with G-CSF, for the procurement of PBPC. The median number of CD34+ cells collected was 4.3 x 10(6)/kg. All patients received a chemotherapeutic preparative regimen and all received an autologous transplant using PBPC alone. The median time to a platelet count of 20 x 10(9)/l was 13 days. Patients beginning the transplant with a less than normal platelet count (less than 150 x 10(9)/l) engrafted in 17 days, and received a median number of seven platelet transfusions, as compared with platelet engraftment of 12 days, and four platelet transfusions, for patients beginning the transplant with a normal platelet count (P = 0.001). Both groups of patients received an equivalent dose of CD34+ cells. We conclude that thrombocytopenia at the initiation of autologous transplantation is associated with increased platelet transfusion requirements, independent of the dose of CD34+ cells infused.

Adult↗
PubMed1995

Recognition performance of subjects with color-vision deficiencies on a polychromatic sonar screen for ship navigation.

To facilitate differentiation between objects that are approaching, stationary, and moving away, these objects are represented in different colors on the screens of sonar locating devices used in ship navigation. Yellow represents stationary objects, and represents approaching objects, and green represents those objects moving away. A total of 46 subjects with normal color vision and 184 individuals with color-vision deficiencies, among them 29 deuteranopic, 100 deuteranomalous, 21 protanopic and 34 protanomalous individuals, were investigated for their ability to identify different signals. Ten different objects were presented for a period of 64 s each. As a minimal requirement it was established that 50% of the respective experimental group be capable of recognizing the objects within half of this time. Whereas 73.3% of the subjects with normal color vision could meet this requirement, none of the subjects in the different groups with color-vision deficiencies could do so. Only 16.1% of the deuteranopic subjects, 33.1% of the deuteranomalous individuals, 16.2% of the protanopic subjects, and 37.6% of the protanomalous individuals detected all objects within 32 s. No appreciable difference in the ability to recognize signals occurred among the different groups of subjects with color-vision deficiencies.

Color Perception↗
PubMed1995

Outpatient bone marrow harvest: the Cleveland Clinic experience.

Patients undergoing a bone marrow harvest have traditionally been hospitalized for several days. Recently, the feasibility of outpatient bone marrow harvesting has been reported. We retrospectively examined the results of 485 patients undergoing an outpatient bone marrow harvest from 1989 to 1993. One hundred and eleven patients were normal donors and the remaining patients were undergoing a bone marrow harvest for autologous transplants. Four hundred and eighty one patients (99%) were discharged within 12 h of the harvest and none have developed long-term complications from the procedure. We additionally analyzed harvest yield with respect to time under anesthesia and underlying diagnosis. Surprisingly, time under anesthesia correlated negatively with harvest yield (P = 0.0001). After adjusting for volume harvested and time under anesthesia, harvest yield was higher in normal donors and patients with breast cancer than for patients with non-Hodgkin's lymphoma and Hodgkin's disease. We conclude that outpatient harvesting is safe. The negative correlation of time under anesthesia with harvest yield may be a result of variables which are difficult to quantify, such as bone marrow microenvironment.

Adult↗
PubMed1993

Phase I trial of recombinant granulocyte-macrophage colony-stimulating factor in patients with lung cancer: clinical and immunologic effects.

Recombinant granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) may enhance the functional activity of monocytes and macrophages in vitro and in vivo and thereby have antitumor activity. A phase I trial using rhuGM-CSF was performed; the trial included 17 patients with unresectable and/or metastatic lung cancer. rhuGM-CSF was administered as a continuous infusion for 14 days at four dose levels: 60 micrograms/m2, 125 micrograms/m2, 250 micrograms/m2, and 500 micrograms/m2. Dose-limiting toxicity was pulmonary and occurred at 500 micrograms/m2, with the maximal tolerated dose (MTD) identified as 250 micrograms/m2. The hematologic effects of rhuGM-CSF included leukocytosis with significant correlations between dose level and the numbers of neutrophils, monocytes, eosinophils, and lymphocytes. Bronchoalveolar lavage was performed for 14 patients, and no effect on alveolar macrophage numbers was detected. Tumor biopsies were obtained in two patients, and no changes in macrophage infiltrates were detected with use of immunohistochemical studies. Serum levels of GM-CSF reached a steady state during week one and decreased or were undetectable during week two. No evidence of tumor regression was seen. rhuGM-CSF when administered as a continuous infusion was well tolerated and appears to modulate monocyte numbers and function in vivo.

Adult↗
PubMed1991

Induction of cytokine messenger RNA and secretion in alveolar macrophages and blood monocytes from patients with lung cancer receiving granulocyte-macrophage colony-stimulating factor therapy.

Human granulocyte-macrophage colony-stimulating factor (GM-CSF) promotes the proliferation and differentiation of hematopoietic progenitor cells. Although preliminary data are available from clinical trials, the effect of GM-CSF on gene expression of immunocompetent cells in treated patients has not been studied. We previously demonstrated that in vitro treatment with GM-CSF also enhances maturation-related anti-tumor activities in mononuclear phagocytes. The purpose of the present study was to examine the effects of in vivo recombinant GM-CSF therapy on alveolar macrophages and blood monocytes, to determine if these cells demonstrated differential expression of cytokine genes, cytokine production, and tumoricidal activity. Alveolar macrophages and blood monocytes were isolated from 13 patients receiving a range of GM-CSF doses (60-250 micrograms/m2/day) by continuous infusion over a 2-week period. Both monocytes and macrophages were isolated prior to therapy and at day 10 of the infusion. Monocytes, in addition, were isolated on day 3 of infusion. Results indicated that GM-CSF therapy enhanced expression of tumor necrosis factor, interleukin 1, and interleukin 6 mRNA in both monocytes and alveolar macrophages. Differential responses, however, were observed in cytokine secretion; monocytes demonstrated enhanced secretion of all three cytokines by day 3 of treatment, but alveolar macrophages showed only enhanced interleukin 6 secretion at day 10. Monocyte tumoricidal activity after in vitro lipopolysaccharide stimulation was also significantly elevated by day 3 of treatment, but at day 10 activity was not statistically different from pretreatment values in either monocytes or alveolar macrophages. These data indicate that GM-CSF exerts striking time-dependent modulatory effects on gene expression and functional activities of monocytes and alveolar macrophages in vivo, although the responses of the two cell types differ with respect to cytokine secretion.

Gene Expression Regulation, Neoplastic↗
PubMed1988

Phase II evaluation of sequential hepatic artery infusion of 5-fluorouracil and hepatic irradiation in metastatic colorectal carcinoma.

Twenty-seven patients with measurable liver metastases from colorectal carcinoma were entered on a protocol of intermittent hepatic artery infusion (HAI) of 5-fluorouracil (5-FU) followed by consolidation with hepatic irradiation. Five partial responses were observed in 23 evaluable patients. Median duration of response was 3.5 months. A response was evident after chemotherapy alone in four of five responders. Hepatic irradiation converted one patient with stable disease after chemotherapy to a partial responder. Median survival for all patients was 9.0 months (range 1.5-34.0). Combined modality treatment with HAI of 5-FU followed hepatic irradiation was well tolerated but did not appear to be synergistic.

Colonic Neoplasms↗