bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autologous stem-cell transplantation restores the functional properties of CD14+CD16+ monocytes in patients with myeloma and lymphoma
Authors: Dayyani Farshid , Joeinig Anke , Ziegler-Heitbrock Löms , Schmidmaier Ralf , Straka Christian , Emmerich Bertold , Meinhardt Gerold 
Published: October 2003

AbstractThe CD14+CD16+ monocytes appear to be important to immune defense against infection, as these cells are very potent with respect to tumor necrosis factor (TNF) production, phagocytosis, and antigen presentation. Myeloablative high-dose chemotherapy (HDT) and subsequent autologous stem-cell transplantation (ASCT) are being used increasingly for therapy of hematological malignancies, but the pronounced immunosuppression renders the patients prone to infection. To determine the functional properties of CD14+CD16+ monocytes under these conditions, 15 patients with lymphoma or myeloma were examined. Before HDT, the ratio of CD14+CD16+ cells to the population of the classical CD14++ monocytes was 0.28 ± 0.12; this ratio changed during the course of HDT and ASCT in favor of the CD14+CD16+ monocytes to a maximum of 12.4 ± 7.8 (P&lt;0.001) on day 3.5 ± 1.6 after transplanation (Tx) and returned to 0.11 ± 0.07 (P&lt;0.001) after engraftment on day 11.3 ± 2.2. Although the absolute number of classical CD14++ monocytes declined to less than 1/μl at the nadir, the number of CD14+CD16+monocytes fell from 29.7 ± 9.8/μl to 4.5 ± 3.0/μl at the nadir and increased to 13.8 ± 9.8/μl at the day of discharge from the hospital. Flow cytometric analysis of phagocytosis of fluorescein isothiocyanate (FITC)-labeled Escherichia coli showed that 30 ± 10% CD14+CD16+ monocytes of patients were FITC-positive before Tx, and at engrafment, the percentage of FITC-positive cells had doubled to 60 ± 6% (healthy controls, 41±7%). When determining generation of reactive oxygen species after E. coli ingestion, the CD14+CD16+ monocytes showed a decreased response before Tx (32±12% positve cells), which increased to 53 ± 24% after ASCT. The median fluorescence intensity of human leukocyte antigen (HLA)-DR expression on the CD14+CD16+ monocytes increased from 11 ± 6 before Tx to 17 ± 11 after Tx, and the production of TNF after lipopolysaccharide showed no remarkable difference (46±13 vs. 49±14 channels). At the same time, expression of TNF and of HLA-DR showed a dramatic decrease in the CD14++ monocytes. Taken together after stem-cell Tx, the function of the CD14++ monocytes is impaired, and the functional properties of CD14+CD16+ monocytes recover, indicating that these cells may be important for defense against infections post-ASCT.
Multicentric Study Comparing Intravesical Chemotherapy Alone and With Local Microwave Hyperthermia for Prophylaxis of Recurrence of Superficial Transitional Cell Carcinoma
Authors: Colombo Renzo , Da Pozzo Luigi Filippo , Salonia Andrea , Rigatti Patrizio , Leib Zvi , Baniel Jack , Caldarera Emanuele , Pavone-Macaluso Michele 
Published: October 2003

Purpose: To compare the efficacy and local toxicity of the intravesical instillation of a cytostatic drug versus the same cytostatic agent in combination with local hyperthermia as an adjuvant treatment, after complete transurethral resection (TURB) of superficial transitional cell carcinoma (TCC) of the bladder. Patients and Methods: The study was designed as a prospective, multicentric, randomized trial. Eighty-three patients suffering from primary or recurrent superficial (Ta-T1) TCC of the bladder, after a complete TURB, were randomly assigned to receive intravesical instillations of mitomycin C (MMC) alone, for 41 patients, and MMC in combination with local microwave-induced hyperthermia, for 42 patients. For the combined approach, a new system, Synergo101–1 (Medical Enterprises, Amsterdam, the Netherlands) was used. The effectiveness evaluation end points of the study were evaluation of recurrence-free survival and the estimated probability of recurrence. The safety evaluation end points included subjective and objective side effects and clinical complications. For the efficacy end point, Kaplan-Meier analysis was employed, with the log-rank test for significance. Minimum follow-up time was 24 months. Results: Of the 83 randomly assigned patients, 75 completed the study according to the protocol and had valid cystoscopy results. Survival analysis of the 75 assessable patients demonstrated a highly significant difference in the survival curves in favor of thermochemotherapy. Subjective intolerance and clinical complications were significantly higher but transient and moderate in the combined treatment group. Conclusion: In our series, endovesical thermochemotherapy appears to be more effective than standard endovesical chemotherapy as an adjuvant treatment for superficial bladder tumors at 24-month follow-up, despite an increased but acceptable local toxicity.
Time Course and Predictors of Symptoms After Primary Prostate Cancer Therapy
Authors: Talcott James A. , Manola Judith , Clark Jack A. , Kaplan Irving , Beard Clair J. , Mitchell Sonya P. , Chen Ronald C. , O’Leary Michael P. , Kantoff Philip W. , D’Amico Anthony V. 
Published: October 2003

Purpose: Understanding the distinctive patterns of treatment-related dysfunction after alternative initial treatments for early prostate cancer (PC) may improve patients’ choice of treatment and later help them adjust to its consequences. We characterized the time course of treatment complications while adjusting for potentially confounding pretreatment factors hindering other observational studies. Patients and Methods: In a prospective cohort study of 417 men we assessed urinary, bowel, and sexual function from before primary treatment to 24 months after. To control for potential confounding, we measured sociodemographic and PC prognostic factors, medical comorbidity, and pretreatment function commonly affected by PC and its treatment. Results: Patients who underwent external beam radiotherapy (EBRT), radical prostatectomy (RP), and brachytherapy (BT) differed significantly in sociodemographic factors, cancer prognostic factors, and pretreatment symptom status, especially sexual function. Urinary incontinence increased sharply after RP, while bowel problems and urinary irritation/obstruction rose after EBRT and BT. Sexual dysfunction increased in all patients, particularly after radical prostatectomy, and nerve-sparing surgical technique had little apparent benefit. There was no change in urinary function and little change in overall bowel function after 12 months, but the time course of sexual dysfunction varied by treatment and, for bowel function, by symptom. Multiple regression modeling confirmed that treatment influences all 24-month outcomes, but residual confounding persisted. Conclusion: Pretreatment function and the primary treatment modality for early stage PC strongly predict the affected organ systems and time course of dysfunction. With this information, patients and their physicians may refine their choice of treatment and better anticipate its consequences.
Preoperative Mitomycin, Ifosfamide, and Cisplatin Followed by Esophagectomy in Squamous Cell Carcinoma of the Esophagus: Pathologic Complete Response Induced by Chemotherapy Leads to Long-Term Survival
Authors: Darnton S.J. , Archer V.R. , Stocken D.D. , Mulholland P.J. , Casson A.G. , Ferry D.R. 
Published: October 2003

Purpose: Squamous cell carcinoma of the esophagus remains an aggressive disease with a poor prognosis, even after curative-intent surgery. This article analyzes the impact of preoperative chemotherapy with mitomycin, ifosfamide, and cisplatin (MIC) on a cohort of 68 patients. Patients and Methods: From 1988 to 1994, 68 patients with potentially operable squamous cell carcinoma of the esophagus were entered onto two phase II trials of neoadjuvant chemotherapy with mitomycin 6 mg/m2, ifosfamide 3 g/m2, and cisplatin 50 mg/m2 and received between two and four cycles of treatment at 3-weekly intervals. Two patients were removed from the analysis when they were found to have malignancy other than squamous cell carcinoma of the esophagus. Results: Forty (61%) of 66 patients had a radiologic response to chemotherapy (18 complete responses and 22 partial responses), and 52 (79%) of 66 patients went on to have the primary tumor resected. There were nine pathologic complete responders, seven of whom remain fit and well after at least 60 months of follow-up. The overall median survival was 12.4 months (95% confidence interval, 9.6 to 18.8 months). The complete response and node-negative patients survived significantly longer than those in other categories (log-rank χ2 = 18.8; P < .001): on average 13 months longer than the node-positive or nonresected category (22.0 v 9.4 months). The toxicity of the regimen was low. Conclusion: MIC is an easily administered, well-tolerated, and efficacious regimen as neoadjuvant therapy for patients with squamous cell carcinoma of the esophagus. These results warrant further investigation.
Subcutaneous Interleukin-2 and Interferon Alfa Administration in Patients With Metastatic Renal Cell Carcinoma: Final Results of SCAPP III, a Large, Multicenter, Phase II, Nonrandomized Study With Sequential Analysis Design—The Subcutaneous Administration Propeukin Program Cooperative Group
Authors: Tourani Jean-Marc , Pfister Christian , Tubiana Nicole , Ouldkaci Mahmoud , Prevot Gilles , Lucas Virginie , Oudard Stéphane , Malet Maxime , Cottu Paul , Ferrero Jean-Marc , Mayeur Didier , Rixe Olivier , Sun Xu-Shan , Bernard Olivier , Andre Thierry , Tournigand Christophe , Muracciole Xavier , Guilhot Joelle 
Published: October 2003

Purpose: This outpatient multicenter trial tested the hypothesis that subcutaneous administration of an interleukin-2 (IL-2)/interferon alfa (IFNα) combination produces a response rate greater than 20% in patients with renal cell carcinoma (RCC). Patients and Methods: Patients with metastatic RCC received a 12-week induction treatment with subcutaneous IL-2 (5 days/wk, 9 and 18 million U/d)/IFNα (3 days/wk, 6 million U/d). After evaluation, patients with objective response or stable disease were randomly assigned to maintenance treatment or short consolidation treatment. Results: Lack of benefit was shown at the 12th sequential analysis, and the trial was closed. At the end of the induction period, 26 (21%) of 122 patients had objective responses (including six complete responses). Thirty-three patients (27%) developed severe toxicity requiring dose reductions, delayed treatment, or treatment termination. Survival rates at one, two, and four years were 63%, 38%, and 17%, respectively. Three-year survival was 20% in patients with two poor prognosis factors and 37% in patients with one or no poor prognosis factors (P = .016). Three-year survival was significantly better (P < 10−3) in patients with erythrocyte sedimentation rate less than 35 mm (43%) compared with those with 1-hour sedimentation rate greater than 35 mm (19%). Conclusion: This study confirms the importance of prognostic factors when initiating cytokine immunotherapy in patients with metastatic RCC and underlines the prognostic value of erythrocyte sedimentation rate before treatment initiation. Nonetheless, this subcutaneous IL-2/IFNα combination does not improve response rate or survival compared with subcutaneous IL-2 alone, although a definitive conclusion cannot be drawn in the absence of a randomized study comparing the two treatments.
Binet’s Staging System and VH Genes Are Independent but Complementary Prognostic Indicators in Chronic Lymphocytic Leukemia
Authors: Vasconcelos Yuri , Davi Frédéric , Levy Vincent , Oppezzo Pablo , Magnac Christian , Michel Ariane , Yamamoto Mihoko , Pritsch Otto , Merle-Béral Hélène , Maloum Karim , Ajchenbaum-Cymbalista Florence , Dighiero Guillaume 
Published: October 2003

Purpose: Rai’s and Binet’s staging systems have contributed significantly to the identification of major prognostic groups in chronic lymphocytic leukemia (CLL), though they fail to accurately predict disease progression at the individual level. Biologic factors, such as the mutational status of the immunoglobulin heavy-chain variable genes (VH, cytogenetics, CD38 expression, and some serum markers, have recently improved prognostic assessment in CLL. In this study, we analyzed the prognostic value of VH mutational status within the different stages of Binet’s classification in 145 patients. Patients and Methods: Our series consisted of 83 VH mutated (MT) and 62 VH unmutated (UM) patients. MT cases predominated within Binet’s stage A (70%), whereas UM cases predominated among stages B and C (62%). Results: Median overall survival (OS) was 84 months for UM patients and was not achieved for the MT group (70% 12-year survival, P < .0001). Concerning Binet’s stage A, both median OS and progression-free survival were significantly shorter for UM patients when compared with those of MT patients (97 months v not achieved, P = .0017; and 42 v 156 months, P < .0001), which compared favorably with the classical A′ and A″ substaging. The VH mutational profile could also segregate stage B and C patients into two groups with different survival patterns (median OS, 78 v 120 months for UM and MT patients, respectively; P = .002). Conclusion: The significant survival differences observed between the VH mutational groups, among stage A and stage B and C patients, indicate that Binet’s classification and VH genes are independent prognostic variables and are most likely complementary.
Assessment of Differences in Patient Populations Selected for or Excluded From Participation in Clinical Phase III Acute Myelogenous Leukemia Trials
Authors: Mengis Catherine , Aebi Stefan , Tobler Andreas , Dähler Werner , Fey Martin F. 
Published: October 2003

Purpose: To compare patients treated in or outside clinical protocols, using de novo acute myeloid leukemia (AML) as a model disorder. Patients and Methods: We retrospectively compared the characteristics of all patients with de novo AML diagnosed in the referral area of our university hospital between 1985 and 1994. Results: Of a total of 170 AML patients, 45% were included in a phase III trial for the treatment of AML and 55% were treated outside a protocol. Another 45 patients were registered only at diagnosis but were treated elsewhere. Nonstudy patients differed significantly from patients included in clinical trials with respect to age and performance status at clinical presentation, comorbidity, and type of AML. The great majority of patients excluded from trial participation showed distinct exclusion criteria, such as advanced age and severe comorbidity. Study patients were treated significantly more often with curative intent and achieved better response and survival. Patients treated in an equivalent manner but outside a protocol showed no significant difference in survival compared with patients enrolled onto a trial. Conclusion: Study patients were not representative for the entire population of patients with AML; many patients were excluded from phase III trial participation for failure to meet stringent entry criteria. Therefore, results of phase III studies may not be extrapolated to all AML patients but should only be applied to patients who do not differ in substantial characteristics from the study population.
Three-Arm Randomized Study of Two Cisplatin-Based Regimens and Paclitaxel Plus Gemcitabine in Advanced Non–Small-Cell Lung Cancer: A Phase III Trial of the European Organization for Research and Treatment of Cancer Lung Cancer Group—EORTC 08975
Authors: Smit Egbert F. , van Meerbeeck Jan P.A.M. , Lianes Pilar , Debruyne Channa , Legrand Catherine , Schramel Franz , Smit Hans , Gaafar Rabab , Biesma Bonne , Manegold Chris , Neymark Niels , Giaccone Giuseppe 
Published: October 2003

Purpose: To compare the therapeutic efficacy of paclitaxel plus cisplatin (arm A) versus gemcitabine plus cisplatin (arm B) and arm A versus paclitaxel plus gemcitabine (arm C) in chemotherapy-naive patients with advanced non–small-cell lung cancer (NSCLC). Materials and Methods: Patients were randomly assigned to receive either paclitaxel 175 mg/m2 (3-hour infusion, day 1) or gemcitabine 1,250 mg/m2 (days 1 and 8) both combined with cisplatin 80 mg/m2 (day 1) or paclitaxel 175 mg/m2 (3-hour infusion, day 1) combined with gemcitabine 1,250 mg/m2 (days 1 and 8). Primary end point was comparison of overall survival for B versus A and C versus A. Secondary end points included response rate and duration, progression-free survival, toxicities, quality of life [QoL], and cost of treatment. Results: Four hundred eighty patients (arm A, 159; arm B, 160; arm C, 161 patients) were enrolled; all baseline characteristics were balanced. Median survival times were as follows: arm A, 8.1 months; arm B, 8.9 months; arm C, 6.7 months. Response rates were 31.8% for arm A, 36.6% for arm B, and 27.7% for arm C. Other than myelosuppression (B v A, P < .005), no statistically or clinically significant differences were observed for secondary end points. The average treatment costs were 25% higher in arm C as compared with arms A and B. Conclusion: Gemcitabine plus cisplatin and paclitaxel plus gemcitabine do not increase overall survival in patients with advanced NSCLC as compared with paclitaxel plus cisplatin. Treatment was well tolerated, and most QoL parameters were similar, but costs associated with the nonplatinum arm were highest.
Efficacy and Safety of Rasburicase (recombinant urate oxidase) for the Prevention and Treatment of Hyperuricemia During Induction Chemotherapy of Aggressive Non-Hodgkin’s Lymphoma: Results of the GRAAL1 (Groupe d’Etude des Lymphomes de l’Adulte Trial on Rasburicase Activity in Adult Lymphoma) Study
Authors: Coiffier Bertrand , Mounier Nicolas , Bologna Serge , Fermé Christophe , Tilly Hervé , Sonet Anne , Christian Bernard , Casasnovas Olivier , Jourdan Eric , Belhadj Karim , Herbrecht Raoul 
Published: October 2003

Purpose: Hyperuricemia and tumor lysis syndrome are well-known complications during induction treatment of aggressive non-Hodgkin’s lymphomas (NHLs). Usual prophylaxis and treatment of hyperuricemia consist of hydration, alkalinization, and administration of allopurinol. This study was designed to evaluate the efficacy and the safety of rasburicase (recombinant urate oxidase) in adult patients with aggressive NHL during their first cycle of chemotherapy. Patients and Methods: A total of 100 patients from Groupe d’Etude des Lymphomes de l’Adulte centers, with diffuse large B-cell lymphoma (n = 79); anaplastic large-cell lymphoma (n = 6); peripheral T-cell lymphoma (n = 8); transformation of indolent lymphoma (n = 5); Burkitt’s lymphoma (n = 1); and lymphoblastic lymphoma (n = 1) were enrolled from May 2001 to June 2002. Before chemotherapy, 66% of patients had elevated lactate dehydrogenase (LDH), including 28% with LDH above 1,000 U/mL. Eleven percent of patients were hyperuricemic (uric acid [UA] > 450 mmol/L or > 7.56 mg/dL). Rasburicase 0.20 mg/kg/d intravenously for 3 to 7 days was started the day before or at day 1 of chemotherapy. UA levels were measured 4 hours after rasburicase injection, then daily during treatment. Results: All patients responded to rasburicase, as defined by normalization of UA levels maintained during chemotherapy. The control of UA was obtained within 4 hours after the first injection of the drug. Creatinine levels and other metabolites were also controlled with the administration of rasburicase. No patient exhibited increased creatinine levels or required dialysis during chemotherapy. Conclusion: Rasburicase is the treatment of choice to control UA and prevent tumor lysis syndrome in adult patients with aggressive NHL.
Combined Analysis of Two Multicenter, Randomized, Placebo-Controlled Studies of Pamidronate Disodium for the Palliation of Bone Pain in Men With Metastatic Prostate Cancer
Authors: Small Eric J. , Smith Matthew R. , Seaman John J. , Petrone Stephanie , Kowalski Mildred Ortu 
Published: October 2003

Purpose: Bone metastases occur in approximately 80% of patients with advanced prostate cancer. Pain is common in these patients. The purpose of this study was to evaluate the effect of an intravenous bisphosphonate, pamidronate disodium, on pain control in metastatic prostate cancer patients. Patients and Methods: Two multicenter, double-blind, randomized, placebo-controlled trials were conducted in patients with bone pain due to metastatic prostate cancer, with disease progression after first-line hormonal therapy. Intravenous pamidronate disodium (90 mg) or placebo was administered every 3 weeks for 27 weeks. Efficacy was measured via self-reported pain score (Brief Pain Inventory), analgesic use, the proportion of patients with a skeletal-related event (SRE; defined as pathologic fracture, radiation or surgery to bone, spinal cord compression, or hypercalcemia), and a pilot quantitative measurement of mobility. Laboratory evaluations included serum prostate-specific antigen, interleukin-6, bone alkaline phosphatase, and urinary bone resorption markers. Results: Results of the two trials were pooled. There were no sustained significant differences between the pamidronate and placebo groups in self-reported pain measurements, analgesic use, proportion of patients with an SRE, or mobility at week 9 or 27. Urinary bone resorption markers were suppressed in the pamidronate group compared with placebo. Conclusion: Pamidronate disodium failed to demonstrate a significant overall treatment benefit compared with placebo in palliation of bone pain or reduction of SREs. Evaluation of more potent bisphosphonates in patients with prostate cancer is warranted.
Adjuvant Chemotherapy for Breast Cancer: How Presentation of Recurrence Risk Influences Decision-Making
Authors: Chao Celia , Studts Jamie L. , Abell Troy , Hadley Terence , Roetzer Lynne , Dineen Sean , Lorenz Doug , YoussefAgha Ahmed , McMasters Kelly M. 
Published: October 2003

Purpose: The purpose of this study was to examine the impact of four methods of communicating survival benefits on chemotherapy decisions. We hypothesized that the four methods of communicating mathematically equivalent risk information would lead to different chemotherapy decisions. Methods: Each participant received two hypothetical scenarios regarding their mother (a postmenopausal woman with an invasive, lymph node-negative, hormone receptor-positive breast cancer) and was asked to decide whether they would encourage their mother to take chemotherapy in addition to surgery and tamoxifen. In the part 1, participants received one of four methods of describing the chemotherapy survival benefit: (1) relative risk reduction, (2) absolute risk reduction, (3) absolute survival benefit, or (4) number needed to treat. In part 2, each participant received all four methods. Following each decision, participants were asked to rate their confidence and confusion regarding their decision. Results: Participants included 203 preclinical medical students. In part 1, participants who received relative risk reduction information were significantly more likely to endorse chemotherapy. In part 2, there were no treatment decision differences when participants received all four methods of communicating survival benefits of chemotherapy. However, receiving all four methods led to significantly higher ratings of confusion. In deciding on endorsing chemotherapy, participants understood the information best when presented with data in the absolute survival benefit format. Conclusion: These results support the hypothesis that the method used to present information about chemotherapy influences treatment decisions. Absolute survival benefit is the most easily understood method of conveying the information regarding benefit of treatment.