Biomedical subjects

A Benner

Publications and source records attributed to A Benner.

At least 55 records · Page 3Linked to original sources

PubMed2001

High plasma basic fibroblast growth factor concentration is associated with response to thalidomide in progressive multiple myeloma.

The aim of this study was to define prognostic factors that might be predictive for response to thalidomide (Thal) in progressive multiple myeloma (n = 54). We examined the concentration of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), two potent heparin-binding mediators of angiogenesis in peripheral blood (PB; PB-VEGF and PB-bFGF) and bone marrow (BM; BM-VEGF and BM-bFGF), in combination with well-characterized predictors for response and survival to chemotherapy. After a median follow-up time of 15 months (range, 0.3-20), 29 patients (pts.) showed at least a minimal response to Thal therapy, whereas 25 pts. were nonresponsive. As shown by univariate analysis, responsive pts. had statistically significant higher concentrations of PB-bFGF (P = 0.009) and beta2-microglobulin (P = 0.03) before therapy, as well as lower hemoglobin (P = 0.008) and albumin (P = 0.02) levels, whereas no statistically significant difference was found for PB-VEGF (P = 0.93). When a multiple logistic regression analysis was performed, PB-bFGF was the only statistically significant predictor for response to therapy (P = 0.01). None of these variables was associated with a prolonged progression-free survival. In conclusion, our findings indicate that high pretreatment plasma bFGF levels in pts. with progressive multiple myeloma are associated with unfavorable parameters of response and survival but nevertheless predict for response to Thal therapy.

Adult↗

PubMed2000

Genomic aberrations and survival in chronic lymphocytic leukemia.

BACKGROUND: Fluorescence in situ hybridization has improved the detection of genomic aberrations in chronic lymphocytic leukemia. We used this method to identify chromosomal abnormalities in patients with chronic lymphocytic leukemia and assessed their prognostic implications. METHODS: Mononuclear cells from the blood of 325 patients with chronic lymphocytic leukemia were analyzed by fluorescence in situ hybridization for deletions in chromosome bands 6q21, 11q22-23, 13q14, and 17p13; trisomy of bands 3q26, 8q24, and 12q13; and translocations involving band 14q32. Molecular cytogenetic data were correlated with clinical findings. RESULTS: Chromosomal aberrations were detected in 268 of 325 cases (82 percent). The most frequent changes were a deletion in 13q (55 percent), a deletion in 11q (18 percent), trisomy of 12q (16 percent), a deletion in 17p (7 percent), and a deletion in 6q (7 percent). Five categories were defined with a statistical model: 17p deletion, 11q deletion, 12q trisomy, normal karyotype, and 13q deletion as the sole abnormality; the median survival times for patients in these groups were 32, 79, 114, 111, and 133 months, respectively. Patients in the 17p- and 11q-deletion groups had more advanced disease than those in the other three groups. Patients with 17p deletions had the shortest median treatment-free interval (9 months), and those with 13q deletions had the longest (92 months). In multivariate analysis, the presence or absence of a 17p deletion, the presence or absence of an 11q deletion, age, Binet stage, the serum lactate dehydrogenase level, and the white-cell count gave significant prognostic information. CONCLUSIONS: Genomic aberrations in chronic lymphocytic leukemia are important independent predictors of disease progression and survival. These findings have implications for the design of risk-adapted treatment strategies.

Adult↗

PubMed2000

Down-regulation of insulin-like growth factor-I receptor and insulin receptor substrate-1 expression in advanced human breast cancer.

The ligands, receptors and related signaling proteins of the insulin-like growth factor family are involved in the regulation of breast-cancer cell growth. We investigated the expression pattern of insulin-like growth factor-I receptor (IGF-IR), insulin receptor (IR) and insulin receptor substrate-1 (IRS-1), a core downstream signaling protein, in 69 primary breast-cancer specimens of different grades and in 21 control tissues by immunohistochemistry. In addition, cell proliferation (percentage of Ki67(+) nuclei) and estrogen receptor (ER) expression were determined. IGF-IR, IRS-1 and IR were expressed mainly in epithelial cells. IRS-1 and IGF-IR were expressed at high levels in control tissues and in well and moderately differentiated carcinomas but at low levels in poorly differentiated breast cancers. IR expression did not show a significant correlation with the differentiation grade of the tissues investigated. Statistical analysis (ROC analysis for tumor grade) demonstrated that down-regulation of IGF-IR and IRS-1 correlated better with tumor progression than reduction of ER expression or increase in cell proliferation, IGF-IR showing the best correlation, followed by IRS-1 and, less significant, ER and Ki67. Our findings clearly show that progression of breast cancer is accompanied by a reduction of IGF-IR/IRS-1 expression and that IGF-IR/IRS-1 expression inversely correlates with high proliferation rate in dedifferentiated breast cancers. The strong correlation of IGF-IR and IRS-1 down-regulation with tumor progression suggests the use of IGF-IR and IRS-1 as a novel set of marker proteins for tumor grading.

Adult↗

PubMed2000

Cure of Burkitt's lymphoma in severe combined immunodeficiency mice by T cells, tetravalent CD3 x CD19 tandem diabody, and CD28 costimulation.

To increase the valency, stability, and therapeutic potential of bispecific antibodies, we have constructed a tetravalent tandem diabody (Tandab) that is specific to both human CD3 (T-cell antigen) and CD19 (B-cell marker; S. M. Kipriyanov et al., J. Mol. Biol., 293: 41-56, 1999). It was generated by the functional dimerization of a single chain molecule that contained four antibody variable domains (V(H) and V(L)) in an orientation that prevented intramolecular pairing. Compared with a previously constructed heterodimeric CD3 x CD19 diabody, the Tandab exhibited a higher apparent affinity to both CD3+ and CD19+ cells and longer blood retention when injected into mice. Biodistribution studies in mice bearing Burkitt's lymphoma xenografts demonstrated specific accumulation of the radioiodinated Tandab in a tumor site with tumor-to-blood ratios of 1.5, 8.1, and 13.3 at 3, 18, and 24 h, respectively. Treatment of severe combined immunodeficiency mice bearing established Burkitt's lymphoma (5 mm in diameter) with human peripheral blood lymphocytes, Tandab, and anti-CD28 MAbs resulted in the complete elimination of tumors in all of the animals within 10 days. In contrast, mice receiving human peripheral blood lymphocytes in combination with either the diabody alone or the diabody plus anti-CD28 MAbs showed only partial tumor regression. These data demonstrate that the CD3 x CD19 Tandab may be a promising tool for the immunotherapy of human B-cell leukemias and lymphomas.

Animals↗

PubMed2000

Detection of isolated disseminated tumor cells in bone marrow and blood samples of patients with hepatocellular carcinoma.

BACKGROUND: Patients with hepatocellular carcinoma (HCC) often develop recurrences after curative resection or liver transplantation. Therefore, tumor cell dissemination must have occurred preoperatively or intraoperatively. Current staging methods cannot reliably detect micrometastasis. Reverse transcription-polymerase chain reaction (RT-PCR) for alpha-fetoprotein (AFP) has been used to detect circulating liver cancer cells, but results in blood samples have been contradictory. HYPOTHESIS: AFP-RT-PCR is a specific and sensitive assay for the detection of disseminated tumor cells in central venous blood and bone marrow samples of patients with HCC and has prognostic relevance. DESIGN: Prospective consecutive series. SETTING: University hospital. PATIENTS AND METHODS: We performed preoperative, intraoperative, and postoperative analyses of central venous blood samples and preoperative analysis of bone marrow samples of patients with HCC and patients without malignant disease, using a modified AFP-RT-PCR method. Preoperative serum AFP levels were measured. Clinical follow-up ranged from 4 to 20 months. MAIN OUTCOME MEASURES: Sensitivity and specificity of AFP-RT-PCR, correlation of AFP-RT-PCR results to tumor stage and tumor recurrence. RESULTS: In serial dilution experiments, 50 AFP-expressing HepG2 cells were detected in 10 mL of blood. Peripheral blood samples of 20 healthy volunteers and bone marrow samples of 21 patients with benign diseases consistently tested negative for AFP, whereas 4 of 24 patients with HCC showed AFP expression in bone marrow samples. All these patients had advanced disease; however, correlation of positive RT-PCR results to tumor stage was not significant (P = .07). One of the 4 AFP-positive patients developed an intrahepatic recurrence soon after liver transplantation. Central venous blood of patients with HCC (n = 24) and patients with benign liver diseases (n = 13) equally demonstrated AFP-expressing cells. There was no correlation of RT-PCR results to serum AFP levels. CONCLUSIONS: Perioperative screening for micrometastasis in bone marrow of patients with HCC is sensitive and specific with AFP-RT-PCR and may have prognostic relevance. Alpha-fetoprotein is not a suitable marker for the detection of tumor cells in central venous blood samples.

Bone Marrow↗

PubMed2000

Risk of false positive results in comparative genomic hybridization.

Comparative genomic hybridization, a widely used method for screening for genomic imbalances, suffers from a lack of standardized evaluation. In order to compare a recently proposed data-driven procedure with the commonly used fixed cutoff values, we tested 257 events by both procedures as well as by fluorescence in situ hybridization using selected probes. With the data-driven procedure, a much higher fraction (42/218 vs. 8/218) of false positive results was obtained, whereas a higher sensitivity with respect to the detection of imbalances (30/39 vs. 19/39) was reached. Based on the significantly higher positive likelihood ratios and the positive predictive value, we strongly recommend the use of fixed diagnostic thresholds, because the alternative procedure generates an unacceptably high portion of incorrectly scored chromosomal imbalances. Genes Chromosomes Cancer 28:353-357, 2000.

Chromosome Aberrations↗

PubMed2000

[Functional magnetic resonance tomography in the diagnosis and therapy monitoring in multiple myeloma].

AIM OF THE STUDY: Investigation of the quantitative microcirculation parameters amplitude A and exchange rate constant k21 determined by contrast-enhanced dynamic magnetic resonance imaging (d-MRI) in multiple myeloma (MM). METHODS: d-MRT of lumbar spine and right spina iliaca superior posterior of 16 controls (ctr) and 35 patients with active MM. Generation of colour-coded images of microcirculation parameters superimposed onto static MRI images. RESULTS: Amplitude A and k21 parameters were significantly increased in patients with MM and down modulated by therapy in 7 of 8 MM cases in a follow-up investigation [p < 0.01; median Actr = 0.2 (0.09-0.4); median AMM = 0.93 (0.2-1.52); median k21ctr = 0.09 min-1 (0.03-0.9); median k21MM = 4.57 min-1 (0.21-23.8)]. Thirteen patients revealed a "diffuse" and 22 a "focal" pattern of distribution of microcirculation parameters. Bone marrow biopsies in 8 cases revealed an correlation between bone marrow plasma cell infiltration and increased microcirculation parameters. CONCLUSION: Identification of microcirculation changes by d-MRI is a novel imaging technique for the detection and monitoring of MM bone lesions.

Antineoplastic Agents, Alkylating↗

PubMed2000

A new way for surgical education--development and evaluation of a computer-based training module.

Computer-based training (CBT) programs teach the material of a specific field and at the same time offer various ways of objectively assessing the knowledge gained. The interactive use of multi-media components such as text, graphics, animation, sound, digital slide shows, and videos as well as quizzes can theoretically facilitate the learning process. The aim of this study was the development and evaluation of a CBT-program by surgeons for student training. Using SuperCard, a teaching module for Distal Radius Fracture (DRF) was developed, which contains detailed clinical information. Video clips and vivid animations combine theoretical knowledge with practical experience. Fourth-year medical students (n = 103) were tested after using the module for 90 min. Other students (n = 47) served as the control group. In a 90 min lecture, DRF was discussed. CBT gained in all evaluated criteria (distinctiveness, detailed description, presentation of materials, structure, motivation for learning, time saved learning and memory retention) 15-20% better scores than the lecture. Although 82% of the students stated that their experience with computers was limited or insufficient, 100% found the use of CBT systems useful in student teaching. Most of them suggested the use of such programs as a method of exam preparation/self study (90%) or as a supplement to a lecture (40%). Based on these evaluations, CBT modules are an appropriate future teaching and learning system that is well accepted. In conclusion, the results of this study show that CBT-programs could be a valuable supplement to medical education. In addition, further development of CBT-programs and their use as information systems for surgical residency programs at universities can be suggested.

Adult↗

PubMed2000

Enhanced urinary excretion of cysteinyl leukotrienes in patients with acute alcohol intoxication.

BACKGROUND & AIMS: Leukotrienes are proinflammatory mediators. Ethanol inhibits the catabolism of both cysteinyl leukotrienes (leukotriene E(4) [LTE(4)] and N-acetyl-LTE(4)) and leukotriene B(4) (LTB(4)) in hepatocytes. We examined the metabolic derangement of leukotriene inactivation by ethanol in humans in vivo. METHODS: LTE(4), N-acetyl-LTE(4), LTB(4), and 20-hydroxy-LTB(4) were quantified in urine samples from 16 patients with acute alcohol intoxication (mean blood ethanol, 75 mmol/L). In 9 healthy volunteers, urinary LTE(4) was determined before and after ethanol consumption (mean blood ethanol, 14 mmol/L). RESULTS: The excretion of LTE(4) during alcohol intoxication was 286 compared with 36 nmol/mol creatinine in healthy subjects (P < 0.01); the corresponding values for N-acetyl-LTE(4) were 101 and 11 nmol/mol creatinine, respectively (P < 0.001). This excretion of cysteinyl leukotrienes decreased when the blood ethanol concentration returned to normal. LTB(4) and 20-hydroxy-LTB(4) were detectable only in patients with excessive blood ethanol concentrations (mean, 95 mmol/L). In healthy volunteers, LTE(4) excretion increased 3-5 hours after ethanol consumption (mean peak concentration of 1.5 nmol/L compared with 0.5 nmol/L for basal values; P < 0.005). CONCLUSIONS: Ethanol at high concentration induces increased leukotriene excretion into urine. These changes are consistent with inhibition of leukotriene catabolism and inactivation induced by ethanol, as well as with a higher leukotriene formation caused by ethanol-induced endotoxemia.

Acute Disease↗

PubMed2000

Evaluation of the kinetics of the bone marrow tumor load in the course of sequential high-dose therapy assessed by quantitative PCR as a predictive parameter in patients with multiple myeloma.

The aim of this investigation was to examine the possible clinical significance of the kinetics of bone marrow (BM) tumor load during the course of sequential high-dose therapy (HDT) as assessed by quantitative PCR in patients with multiple myeloma. In 20 patients with multiple myeloma (MM) treated with two consecutive cycles of HDT followed by autologous peripheral blood stem cell transplantation (PBSCT), clonotypic cells in the peripheral blood (PB) and BM were quantitated by PCR using allele-specific oligonucleotides (ASO) prior to the first, immediately prior to the second, and after the second HDT. The median proportion of clonotypic cells in the BM was 1.27% before the first HDT (range, 0.03-70%), 0.17% after the first (range, 0.001-22%), and 0.05% after the second HDT (range, 0.00009-1.44%). The median number of circulating clonotypic cells was 65/ml (range, 0.9-10842) prior to HDT, 2.7/ml (range, 0-315) after the first, and 3.5/ml PB (range, 0.7-97) after the second HDT. While the median BM tumor load decreased during the first (P = 0.03) and second (P = 0.044) HDT cycles, only the first cycle resulted in a reduction of clonotypic cells in the PB (P = 0.00078 and P= 1.0, respectively). In seven patients, the BM tumor load did not decrease below the initial level after one or two cycles of HDT. All of these patients developed progressive disease (median, 19 months post first cycle; range, 10-21). Of the remaining 13 patients, only four relapsed (18, 19, 21 and 22 months after the first cycle of HDT), while nine remain in response (median followup, 29 months; range, 18-41) (log-rank test P = 0.0009). Our results indicate that the kinetics of the BM tumor load is a predictive parameter in patients with MM and identifies those patients who could benefit from further therapy including new treatment modalities.

Adult↗

PubMed2000

Detection of hematogenic tumor cell dissemination in patients undergoing resection of liver metastases of colorectal cancer.

OBJECTIVE: To determine the extent of pre- and intraoperative hematogenic tumor cell dissemination in patients undergoing liver resection for metastatic colorectal cancer. SUMMARY BACKGROUND DATA: For patients with hepatic metastases of colorectal cancer, liver resection is the only potentially curative therapy. However, 38% to 53% of patients develop extrahepatic tumor recurrence, probably caused by tumor cells disseminated before or during surgery not detected by current staging systems. METHODS: Blood samples harvested before, during, and after surgery from 41 patients and bone marrow samples from 30 patients undergoing resection of liver metastases of colorectal cancer were analyzed for disseminated tumor cells using cytokeratin 20 reverse transcriptase-polymerase chain reaction. RESULTS: Tumor cells were detected in the blood samples of 26 of the 41 patients (63.4%) and in the bone marrow samples of 8 of the 30 patients (26.7%). Tumor cells were detected significantly more often during surgery than before or after surgery. Intraoperative tumor cell dissemination was detected in 41.7% of patients undergoing resection of two or more liver segments but only 14.3% of patients undergoing resection of one liver segment. Compared with resection of primary colorectal cancer, major liver resection carries an increased risk for intraoperative tumor cell dissemination. CONCLUSIONS: Detection of disseminated tumor cells in patients undergoing liver resection for metastases of colorectal cancer using cytokeratin 20 reverse transcriptase-polymerase chain reaction might help to identify patients at high risk for tumor recurrence who may benefit from adjuvant therapy. Major liver resection of metastases leads to frequent intraoperative tumor cell shedding, possibly preventable by alternative surgical strategies.

Adult↗

PubMed2000

Detection of hematogenous micrometastasis in patients with transitional cell carcinoma.

PURPOSE: Cytokeratin 20 (CK 20) is selectively expressed in urothelium, gastric intestinal epithelium, in Merkel cells and in a variety of malignant neoplasms. CK 20 RT-PCR assay has been extensively used to detect isolated cancer cells in peripheral blood, lymph nodes and bone marrow samples of patients with colorectal carcinoma. Since CK-20 is also actively expressed in transitional cell carcinoma (TCC), we analyzed, whether CK 20 Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) is suitable to detect residual tumor cells in patients with transitional cell carcinoma of the bladder and the upper urinary tract. MATERIALS AND METHODS: Nested Reverse Transcriptase Polymerase Chain Reaction assay was used to analyze CK 20 transcripts in peripheral venous blood samples and tumor biopsies of 49 patients with transitional cell carcinoma. Blood samples of 22 healthy volunteers served as negative controls. RESULTS: CK 20 mRNA was detectable in blood samples of 12 of 49 patients with TCC. All blood samples of the control group tested negative. The detection rate for CK 20 mRNA significantly correlated (p = 0.0019, Cochran-Armitage Trend Test) to the stage of disease and increased from 0% in stage pTa to 63% in stage pT4. CONCLUSIONS: These results suggest that CK 20 is a suitable marker for the detection of disseminated TCC cells in peripheral venous blood samples and may be helpful in the molecular staging of TCC patients. The prognostic relevance has to be evaluated in further followup.

Aged↗

PubMed2000

Interleukin-6 and its surrogate C-reactive protein are useful serum markers for monitoring metastasized malignant melanoma.

Malignant melanoma cells are known to secrete interleukin-6, and elevated interleukin-6 serum levels were reported to correlate with shorter median survival rates. We, therefore, investigated serum values of interleukin-6 and its surrogate C-reactive protein for the ability to discriminate progressive from non-progressive metastatic melanoma disease. Just prior to re-staging examinations, interleukin-6, C-reactive protein and the conventional parameter lactate dehydrogenase were determined in 74 patients with stage IV malignant melanoma according to the criteria of the American Joint Committee on Cancer. We found all tested serum parameters to be significantly elevated in progressive disease. Calculating sensitivities and specificities by logistic regression analysis, the highest sensitivities, according to the established thresholds, were found for interleukin-6 and C-reactive protein with 86% and 76%, respectively. Lactate dehydrogenase had the highest specificity with 94%. Calculating Somers' D rank correlation and the area under the "Receiver Operating Characteristic" curve, all three parameters showed high ability to driscriminate progressive from non-progressive disease. By multiple logistic regression, lactate dehydrogenase was identified to be the most statistically significant marker for progressive disease. We conclude that, comparable to lactate dehydrogenase, interleukin-6 and its surrogate C-reactive protein are useful serum markers for monitoring metastatic malignant melanoma.

Aged↗

PubMed1999

Immune response to human papillomavirus 16 L1E7 chimeric virus-like particles: induction of cytotoxic T cells and specific tumor protection.

Expression of human papillomavirus type 16 (HPV 16) fusion proteins LI deltaCE7(1-55) and LI deltaCE7(1-60) (carboxy-terminal deletion of LI replaced by 55 or 60 amino-terminal amino acids of E7) leads to formation of chimeric papillomavirus-like particles (CVLPs). After "infection" of cells by CVLPs, the chimeric proteins can be detected in the cytosol and the endoplasmic reticulum (ER), suggesting that they are intracellularly processed via the MHC class I pathway and, therefore, able to activate cytotoxic T lymphocytes (CTLs). To investigate the cytotoxic immune response against HPV 16 LI deltaCE7(1-60) and LI deltaCE7(1-55) CVLPs, we immunized C57Bl/6 mice with various CVLP doses without adjuvant. Two weeks after immunization, spleen cells were prepared and stimulated in vitro using HPV 16 E7-expressing transfectants of the tumor cell line RMA. In 51Cr-release cytotoxicity assays, spleen cells of mice vaccinated with LI deltaCE7(1-60) CVLPs specifically lysed the RMA-E7 transfectants as well as RMA cells loaded with the peptide E7(49-57), which represents an H2-Db-restricted CTL epitope. This demonstrates that CVLPs induce an E7-specific CTL response in mice in the absence of an adjuvant. Furthermore, immunization with CVLPs prevented outgrowth of E7-expressing tumor cells even if inoculation of cells was performed 2 weeks before vaccination. We conclude from our data that CVLPs show promise for therapy of HPV-associated lesions.

Animals↗

PubMed1999

No evidence of p53 allele-specific predisposition in human papillomavirus-associated cervical cancer.

The potential association of distinct polymorphisms of the tumor suppressor gene p53 with an increased susceptibility to malignant transformation has been reported for various cancer entities. Most recently, p53 protein containing an arginine residue in codon 72 was shown to be more effectively degraded by the E6 oncoprotein of human papillomavirus (HPV) than the corresponding proline isoform in cervical carcinoma cells. Additionally, a seven times higher risk of cervical cancer for Arg homozygotes was suggested. We set out to confirm this allele-specific predisposition on a larger population, comprising 87 cervical cancer and 151 normal control samples. However, there was no significant difference in the observed frequencies of homozygous Arg genotypes in cervical cancer patients (52.8%) and normal controls (55.7%). Furthermore, the prevalence of the Arg/Arg allelotype did not vary between HPV+ (n = 75) and HPV- (n = 12) carcinoma samples. Thus, our investigation of a larger set of clinical samples does not support the proposed association of any polymorphic status of p53 at codon 72 with an elevated risk for cervical cancer.

Alleles↗

PubMed1999

Incidence and clinical significance of 6q deletions in B cell chronic lymphocytic leukemia.

Deletions affecting the long arm of chromosome 6 (6q) are among the most commonly observed chromosomal aberrations in lymphoid malignancies and have been identified as adverse prognostic factor in subsets of tumors. Whereas at least two regions of minimal deletion have been established, one in 6q21-q23 and another in 6q25-q27, no tumor suppressor gene that might be involved in the pathogenesis of lymphoid malignancies has been so far identified from these segments. For B cell chronic lymphocytic leukemia (B-CLL) conflicting data have been reported regarding the incidence and prognostic significance of 6q deletions. In the current study we have used two YAC clones mapping to deletion regions in bands 6q21 and 6q27 as probes for fluorescence in situ hybridization (FISH) in a large series of B-CLL cases to analyze the incidence, localization and clinical significance of 6q aberrations. Among 285 patients with B-CLL studied we identified 21 cases (7%) with 6q deletions. All deletions were found with the probe mapping to 6q21 while the 6q27 region was deleted only in a third of these cases. Analysis of the clinical characteristics and laboratory parameters showed that the patients with 6q deletions had higher white blood cell counts and more extensive lymphadenopathy. However, the overall survival and the treatment-free intervals were similar in the two groups. We conclude that deletions in 6q21 occur in 7% of B-CLL and identify a subgroup of patients characterized by a larger tumor mass but no inferior outcome.

Chromosome Deletion↗

PubMed1999

Peripheral blood progenitor cell (PBPC) counts during steady-state haemopoiesis enable the estimation of the yield of mobilized PBPC after granulocyte colony-stimulating factor supported cytotoxic chemotherapy: an update on 100 patients.

Peripheral blood progenitor cells (PBPC) can be mobilized using chemotherapy and granulocyte colony-stimulating factor (G-CSF). We and others previously reported a correlation of steady-state PBPC counts and the PBPC yield during mobilization in a small group of patients. Here we present data on 100 patients (patients: 25 non-Hodgkin's lymphoma (NHL), five Hodgkin's disease, 35 multiple myeloma (MM), 35 solid tumour) which enabled a detailed analysis of determinants of steady-state PBPC levels and of mobilization efficiency in patient subgroups. Previous irradiation (P = 0.0034) or previous chemotherapy in patients with haematological malignancies (P = 0.0062) led to a depletion of steady-state PB CD34+ cells. A correlation analysis showed steady-state PB CD34+ cells (all patients: r = 0.52, P < 0.0001; NHL patients, r = 0.69, P = 0.0003; MM patients: r = 0.66, P = 0.0001) and PB colony-forming cells can reliably assess the CD34+ cell yield in mobilized PB. In patients with solid tumour a similar trend was observed in mobilization after the first chemotherapy cycle (r = 0.51, P = 0.05) but not if mobilization occurred after the second or further cycle of a sequential dose-intensified G-CSF-supported chemotherapy regimen, when premobilization CD34+ counts were 18-fold elevated (P = 0.004). When the patients with MM (r = 0.63, P = 0.0008) or with NHL (r = 0.65, P = 0.006) were analysed separately, a highly significant correlation of the steady-state PB CD34+ cell count to the mean leukapheresis CD34+ cell yield was found, whereas no correlation was observed for patients with a solid tumour. For patients with haematological malignancies estimates could be calculated which, at a specific steady-state PB CD34+ cell count, could predict with a 95% probability a defined minimum progenitor cell yield. These results enable recognition of patients who mobilize PBPC poorly and may assist selection of patients for novel mobilization regimens.

Adult↗

PubMed1999

S100-Beta, melanoma-inhibiting activity, and lactate dehydrogenase discriminate progressive from nonprogressive American Joint Committee on Cancer stage IV melanoma.

PURPOSE: Monitoring advanced malignant melanoma, serum levels of S100-beta (S100beta) and melanoma-inhibiting activity (MIA) were assessed for the ability to discriminate progressive from nonprogressive disease. S100beta and MIA were supposed to be superior to conventional variables, such as lactate dehydrogenase (LDH) level. PATIENTS AND METHODS: Seventy-one patients with stage IV malignant melanoma according to the criteria of the American Joint Committee on Cancer (AJCC) were included in the study. Results of restaging examinations were used as an independent reference standard for diagnosing progressive disease, and S100beta, MIA, LDH level, and erythrocyte sedimentation rate (ESR) were determined in venous blood just before restaging. Sensitivities and specificities of the parameters were calculated by logistic regression analysis. Discrimination ability was assessed by Somers' D(xy) rank correlation and the area under the receiver-operating characteristic curve (ROC-AUC). RESULTS: All tested serum parameters were significantly elevated in patients with progressive disease. The highest sensitivities according to the established thresholds were found for S100beta and MIA (91% and 88%, respectively). LDH had the highest specificity (92%). ESR was dropped from the analysis because of low specificity. In calculating Somers' D(xy) and ROC-AUC values, S100beta, MIA, and LDH showed high discrimination ability. By multiple logistic regression, LDH was identified to be the only statistically significant marker for progressive disease. S100beta and MIA did not provide additional significant information because of their high correlation with LDH with respect to clinical outcome. CONCLUSION: Elevated serum levels of S100beta, MIA, and LDH indicate current disease progression in AJCC stage IV melanoma. LDH was the most relevant overall parameter.

Adult↗