bluuebunny/crossref_metadata_2025_split huggingface dataset:
Limits of HLA mismatching in unrelated hematopoietic cell transplantation
Authors: Petersdorf Effie W. , Anasetti Claudio , Martin Paul J. , Gooley Ted , Radich Jerald , Malkki Mari , Woolfrey Ann , Smith Anajane , Mickelson Eric , Hansen John A. 
Published: July 2004

Abstract
HLA matching between the donor and recipient improves the success of unrelated hematopoietic cell transplantation (HCT). Matched donors are available for only a minority of patients. Further information is needed to evaluate the limits of HLA mismatching. We examined the association of mortality with HLA-A, -B, -C, -DRB1, and -DQB1 mismatching in 948 patients who received a T-replete unrelated HCT for treatment of a marrow disorder. A single HLA allele or antigen mismatch was associated with increased mortality among patients with chronic myeloid leukemia (CML) within 2 years after diagnosis compared to patients with no HLA mismatch, but not among those with more advanced malignancy. In particular, a single HLA-C mismatch conferred increased risk of mortality compared to matches. There was a suggestion for increased mortality with multiple mismatches involving HLA-DQB1 compared to multiple mismatches not involving HLA-DQB1. Donors with a single HLA allele or antigen mismatch may be used for HCT when a fully matched donor is not available for patients with diseases that do not permit time for a lengthy search. Whenever possible, HLA-C mismatches should be avoided for patients with early stage CML, and HLA-DQB1 mismatches should be avoided for patients with multiple mismatches.
Anti-CD20 monoclonal antibody treatment in 6 patients with therapy-refractory chronic graft-versus-host disease
Authors: Canninga-van Dijk Marijke R. , van der Straaten Hanneke M. , Fijnheer Rob , Sanders Cornelus J. , van den Tweel Jan G. , Verdonck Leo F. 
Published: July 2004

AbstractChronic graft-versus-host disease (cGVHD) is an important determinant of long-term morbidity and mortality in allogeneic stem cell transplantation patients. Because cGVHD has clinical, histologic, and laboratory findings of autoimmune diseases and anti–B-cell therapy has shown efficacy in autoimmune diseases, we hypothesized that monoclonal anti-CD20 antibody therapy might improve patients with cGVHD. We treated 5 men and 1 woman with therapy-refractory extensive cGVHD with anti-CD20 monoclonal antibody. Intravenous infusion was given at a weekly dose of 375 mg/m2 for 4 weeks. In case of incomplete clinical response, additional courses of 4 weeks were given. Five patients responded to treatment with marked clinical, biochemical, and histologic improvement. One patient failed to respond. Anti-CD20 monoclonal antibody seems to be effective in cGVHD. A controlled trial is mandatory to confirm these results. The outcome of this study suggests a participating role of B cells in the pathogenesis of cGVHD.
Research methodology: cancer cachexia syndrome
Authors: Dahele Max , Fearon Kch 
Published: July 2004

Cachexia is a syndrome and therefore does not have a specific definition. Patients are characterized by the presence of anorexia, early satiety, weight loss, weakness, anaemia and oedema. These features occur to a variable extent in different patients and may change in severity during the course of a patient's illness. The multifactorial origin of cachexia precludes a uniform pathophysiological definition. Taken together these factors have hindered clinical studies both at a fundamental level and in terms of the introduction of effective therapy. The advent of novel therapeutic targets (e.g., ubiquitin-proteasome pathway) and biological response modifiers has opened possibilities for new clinical trials in cachexia. Regulatory authorities feel it is important not only to demonstrate efficacy in terms of patients' nutritional status (e.g., lean body mass) but also functional status (e.g., performance status). This article reviews current methods to assess the latter. Methods focused on measuring physical activity level (e.g., doubly labelled water technique or physical activity meters) promise objective data which can be readily interpreted in terms of clinically meaningful benefit.
Post-Treatment Change in Serum Estrone Predicts Mammographic Percent Density Changes in Women Who Received Combination Estrogen and Progestin in the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial
Authors: Ursin Giske , Palla Shana L. , Reboussin Beth A. , Slone Stacey , Wasilauskas Carol , Pike Malcolm C. , Greendale Gail A. 
Published: July 2004

Purpose Postmenopausal estrogen and progestin therapy (EPT) increases mammographic percent density and breast cancer risk substantially more than does estrogen therapy alone. We determined whether increases in serum estrone as a function of treatment predict increases in mammographic percent density. Methods We measured mammographic percent density and serum estrone levels in participants in the Postmenopausal Estrogen/Progestin Interventions Trial who were randomly assigned to receive conjugated equine estrogens (CEE) 0.625 mg/d; CEE and medroxyprogesterone acetate (MPA) 10 mg on days 1 to 12 per 28-day cycle; CEE and MPA 2.5 mg/d; or CEE and micronized progesterone (MP) 200 mg on days 1 to 12 per 28-day cycle. We used linear regression to determine whether serum estrone changes predicted mammographic percent density changes from baseline to 1 year. Results Mammographic percent density increased with increasing change in estrone level in the EPT groups, but not in the CEE group. Combined, the mammographic percent density in the three EPT groups demonstrated an absolute increase of 2.95% per 100 pg/mL increase in serum estrone level (P = .0003). The absolute increases were 4.09% (P = .0018) in the CEE + MPA continuous group, 2.79% (P = .0292) in the CEE + MPA cyclical group, and 1.40% (P = .36) in the CEE + MP group, but the differences among the EPT groups were not statistically significant. Conclusion Greater increase in serum estrone level as a function of treatment is a significant predictor of increase in mammographic percent density in women randomly assigned to the combination of estrogen and progestin.
Gene Expression Alterations in Prostate Cancer Predicting Tumor Aggression and Preceding Development of Malignancy
Authors: Yu Yan Ping , Landsittel Douglas , Jing Ling , Nelson Joel , Ren Baoguo , Liu Lijun , McDonald Courtney , Thomas Ryan , Dhir Rajiv , Finkelstein Sydney , Michalopoulos George , Becich Michael , Luo Jian-Hua 
Published: July 2004

Purpose The incidence of prostate cancer is frequent, occurring in almost one-third of men older than 45 years. Only a fraction of the cases reach the stages displaying clinical significance. Despite the advances in our understanding of prostate carcinogenesis and disease progression, our knowledge of this disease is still fragmented. Identification of the genes and patterns of gene expression will provide a more cohesive picture of prostate cancer biology. Patients and Methods In this study, we performed a comprehensive gene expression analysis on 152 human samples including prostate cancer tissues, prostate tissues adjacent to tumor, and organ donor prostate tissues, obtained from men of various ages, using the Affymetrix (Santa Clara, CA) U95a, U95b, and U95c chip sets (37,777 genes and expression sequence tags). Results Our results confirm an alteration of gene expression in prostate cancer when comparing with nontumor adjacent prostate tissues. However, our study also indicates that the gene expression pattern in tissues adjacent to cancer is so substantially altered that it resembles a cancer field effect. Conclusion We also found that gene expression patterns can be used to predict the aggressiveness of prostate cancer using a novel model.
Central Nervous System Atypical Teratoid/Rhabdoid Tumor: Results of Therapy in Children Enrolled in a Registry
Authors: Hilden Joanne M. , Meerbaum Sharon , Burger Peter , Finlay Jonathan , Janss Anna , Scheithauer Bernd W. , Walter Andrew W. , Rorke Lucy B. , Biegel Jaclyn A. 
Published: July 2004

Purpose Atypical teratoid/rhabdoid tumor (AT/RT) of the CNS is an extremely rare and aggressive tumor of early childhood. The poor outcome with conventional infant brain tumor therapy has resulted in a lack of clear treatment guidelines. A registry has been established to create an outcomes database and to facilitate biology studies for this tumor. Materials and Methods A standardized data sheet was provided to treating physicians listing the reports that were to be sent to the registry for abstraction. Follow-up information was sought twice yearly. Results Information was complete for 42 patients. Median age at diagnosis was 24 months. Nine patients (21%) had disseminated disease at diagnosis. Sixteen tumors were infratentorial; 26 were supratentorial. Twenty patients (48%) received a primary complete resection. Primary therapy included chemotherapy in all patients, radiotherapy in 13 patients (31%), stem-cell rescue in 13 patients (31%), and intrathecal chemotherapy in 16 patients (38%). Recurrent or progressive disease was reported in nine and 19 patients, respectively. Twenty-seven patients (64%) are dead of disease (3 to 62 months from diagnosis) and one patient died of toxicity. Fourteen patients (33%) show no evidence of disease (9.5 to 96 months from diagnosis). The median survival is 16.75 months and the median event-free survival is 10 months. Conclusion Aggressive therapy has prolonged the natural history in a subset of children. Prospective multi-institutional and national clinical trials designed specifically for AT/RT are needed. Enrollment onto the AT/RT registry should be continued.
Outcome of Allogeneic Hematopoietic Stem-Cell Transplantation in Adult Patients With Acute Lymphoblastic Leukemia: No Difference in Related Compared With Unrelated Transplant in First Complete Remission
Authors: Kiehl Michael G. , Kraut Ludwig , Schwerdtfeger Rainer , Hertenstein Bernd , Remberger Mats , Kroeger Nicolaus , Stelljes Mathias , Bornhaeuser Martin , Martin Hans , Scheid Christoph , Ganser Arnold , Zander Axel R. , Kienast Joachim , Ehninger Gerhard , Hoelzer Dieter , Diehl Volker , Fauser Axel A. , Ringden Olle 
Published: July 2004

Purpose The role of unrelated allogeneic stem-cell transplantation in acute lymphoblastic leukemia (ALL) patients is still not clear, and only limited data are available from the literature. We analyzed factors affecting clinical outcome of ALL patients receiving a related or unrelated stem-cell graft from matched donors. Patients and Methods The total study population was 264 adult patients receiving a myeloablative allogeneic stem-cell transplant for ALL at nine bone marrow transplantation centers between 1990 and 2002. Of these, 221 patients receiving a matched related or unrelated graft were analyzed. One hundred forty-eight patients received transplantation in complete remission; 62 patients were in relapse; and 11 patients were refractory to chemotherapy before transplant. Fifty percent of patients received bone marrow, and 50% received peripheral blood stem cell from a human leukocyte antigen–identical related (n = 103), or matched unrelated (n = 118) donor. Results Disease-free survival (DFS) at 5 years was 28%, with 76 patients (34%) still alive (2.2 to 103 months post-transplantation), and 145 deceased (65 relapses, transplant-related mortality, 45%). We observed an advantage regarding DFS in favor of patients receiving transplantation during their first complete remission (CR) in comparison with patients receiving transplantation in or after second CR (P = .014) or who relapsed (P < .001). We observed a clear trend toward improved survival in favor of B-lineage ALL patients compared with T-lineage ALL patients (P = .052), and Philadelphia chromosome–positive patients had no poorer outcome than Philadelphia chromosome–negative patients. Total-body irradiation–based conditioning improved DFS in comparison with busulfan (P = .041). Conclusion Myeloablative matched related or matched unrelated allogeneic hematopoietic stem-cell transplantation in ALL patients should be performed in first CR.
Gabapentin for Neuropathic Cancer Pain: A Randomized Controlled Trial From the Gabapentin Cancer Pain Study Group
Authors: Caraceni Augusto , Zecca Ernesto , Bonezzi Cesare , Arcuri Edoardo , Tur Ricardo Yaya , Maltoni Marco , Visentin Marco , Gorni Giovanna , Martini Cinzia , Tirelli Walter , Barbieri Massimo , De Conno Franco 
Published: July 2004

Purpose To determine the analgesic effect of the addition of gabapentin to opioids in the management of neuropathic cancer pain. Patients and Methods One hundred twenty-one consecutive patients with neuropathic pain due to cancer, partially controlled with systemic opioids, participated in a multicenter, randomized, double-blind, placebo-controlled, parallel-design, 10-day trial from August 1999 to May 2002. Gabapentin was titrated from 600 mg/d to 1,800 mg/d in addition to stable opioid dose. Extra opioid doses were available as needed. Zero to 10 numerical scale was used to rate average daily pain. The average pain score over the whole follow-up period was used as main outcome measure. Secondary outcome measures were: intensity of burning pain, shooting/lancinating pain, dysesthesias (also scored on 0 to 10 numerical scale), number of daily episodes of lancinating pain, presence of allodynia, and daily extra doses of opiod analgesics. Results Overall, 79 patients received gabapentin and 58 (73%) completed the study; 41 patients received placebo and 31 (76%) completed the study. Analysis of covariance (ANCOVA) on the intent-to-treat population showed a significant difference of average pain intensity between gabapentin (pain score, 4.6) and placebo group (pain score, 5.4; P = .0250). Among secondary outcome measures, dysesthesia score showed a statistically significant difference (P = .0077; ANCOVA on modified intent-to-treat population = 115 patients with at least 3 days of pain assessments). Reasons for withdrawing patients from the trial were adverse events in six patients (7.6%) receiving gabapentin and in three patients receiving placebo (7.3%). Conclusion Gabapentin is effective in improving analgesia in patients with neuropathic cancer pain already treated with opioids.
Clinical and Immunologic Effects of Subcutaneously Administered Interleukin-12 and Interferon Alfa-2b: Phase I Trial of Patients With Metastatic Renal Cell Carcinoma or Malignant Melanoma
Authors: Alatrash Gheath , Hutson Thomas E. , Molto Luis , Richmond Amy , Nemec Cheryl , Mekhail Tarek , Elson Paul , Tannenbaum Charles , Olencki Thomas , Finke James , Bukowski Ronald M. 
Published: July 2004

PurposeInterleukin-12 (IL-12) and interferon alfa-2b (IFN-α-2b) are pleiotropic cytokines with activity in renal cell carcinoma (RCC) and malignant melanoma (MM) as single agents. Preclinical studies suggest concurrent administration may have synergistic antitumor effects. We conducted a phase I trial of concurrent subcutaneous (SC) administration of IL-12 and IFN-α-2b in patients with metastatic RCC or MM to determine toxicity, maximum-tolerated dose, preliminary efficacy, and effects on chemokine/cytokine gene expression in peripheral blood mononuclear cells (PBMCs).Patients and MethodsCohorts of three to six patients were treated with escalating doses of IL-12 (dose I, 100 ng/kg; dose II, 300 ng/kg; dose III, 500 ng/kg; dose IV, 500 ng/kg SC) given twice weekly and IFN-α-2b (dose I, 1.0 MU/m2; dose II, 1.0 MU/m2; dose III, 1.0 MU/m2; dose IV, 3.0 MU/m2SC) three times weekly in 4-week cycles. Effects on gene expression were assessed by reverse transcriptase polymerase chain reaction.ResultsTwenty-six patients (19 with RCC, seven with MM) were accrued at dose levels I (n = 3), II (n = 3), III (n = 13), and IV (n = 7). Dose-limiting toxicity included grades 3 and 4 hepatotoxicity and neutropenia/leukopenia. Patients received a median of three cycles of treatment. Two patients with RCC and one patient with MM had partial responses. Median survival was 13.8 months. Reverse transcriptase polymerase chain reaction on PBMCs revealed induction of IP-10, Mig, B7.1 (CD80), interleukin-5, and interferon gamma in selected patients.ConclusionConcurrent SC administration of IL-12 and IFN-α-2b is possible at the dose levels utilized. Recommended doses for phase II trials are 500 ng/kg IL-12 and 1.0 MU/m2IFN-α-2b. Consistent induction of IP-10 and Mig, as well as variable induction of B7.1, interleukin-5, and interferon gamma expression was noted in PBMCs.
Randomized Phase II Study of Two Irinotecan Schedules for Patients With Metastatic Breast Cancer Refractory to an Anthracycline, a Taxane, or Both
Authors: Perez Edith A. , Hillman David W. , Mailliard James A. , Ingle James N. , Ryan J. Michael , Fitch Tom R. , Rowland Kendrith M. , Kardinal Carl G. , Krook James E. , Kugler John W. , Dakhil Shaker R. 
Published: July 2004

Purpose A pressing need exists for agents active against anthracycline- or taxane-refractory metastatic breast cancer (MBC), or both. Previous clinical trials suggested that irinotecan might have such activity. We conducted this multicenter phase II study to assess efficacy and tolerability of two irinotecan schedules. Patients and Methods MBC patients who experienced disease progression after one to three chemotherapy regimens, including at least one anthracycline- or taxane-based regimen, were randomly assigned to irinotecan in 6-week cycles comprising 100 mg/m2 weekly for 4 weeks, then a 2-week rest (weekly) or 240 mg/m2 every 3 weeks. Results The weekly arm had 52 assessable patients; the every-3-weeks arm had 51 assessable patients. In the weekly arm, the objective response (complete regression [CR] + partial regression [PR]) rate was 23% (one CR, 11 PR; 95% CI, 13% to 37%). Median response duration was 4.9 months (range, 1.9 to 15.9 months), and median overall survival was 9.7 months (95% CI, 8.0 to 14.2 months). In the every-3-weeks arm, the objective response rate was 14% (nine PR; 95% CI, 6% to 26%), median response duration was 4.2 months (range, 3.1 to 13.9 months), and median overall survival was 8.6 months (95% CI, 7.0 to 12.3 months). Treatment generally was well tolerated, especially in the weekly arm. Grade 3 to 4 adverse events with ≥ 10% incidence included neutropenia (29%) and diarrhea (17%) in the weekly arm and neutropenia (36%), vomiting (20%), dyspnea (18%), nausea (16%), and diarrhea (12%) in the every-3-weeks arm. Conclusion Irinotecan is active with good tolerability in refractory MBC. Irinotecan (especially weekly) warrants additional study as monotherapy and in combination regimens in this setting.
Incidence Proportions of Brain Metastases in Patients Diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System
Authors: Barnholtz-Sloan Jill S. , Sloan Andrew E. , Davis Faith G. , Vigneau Fawn D. , Lai Ping , Sawaya Raymond E. 
Published: July 2004

Purpose Population-based estimates of the incidence of brain metastases are not generally available. The purpose of this study was to calculate population-based incidence proportions (IPs) of brain metastases from single primary lung, melanoma, breast, renal, or colorectal cancer. Patients and Methods Patients diagnosed with single primary lung, melanoma, breast, renal, or colorectal cancer (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System (MDCSS) were used for analysis. IP of brain metastases by primary site and variable of interest (race, sex, age at diagnosis of primary cancer, and Surveillance, Epidemiology, and End Results [SEER] stage of primary cancer) was calculated with 95% CIs. Results Total IP percentage (IP%) of brain metastases was 9.6% for all primary sites combined, and highest for lung (19.9%), followed by melanoma (6.9%), renal (6.5%), breast (5.1%), and colorectal (1.8%) cancers. Racial differences were seen with African Americans demonstrating higher IP% of brain metastases compared with other racial groups for most primary sites. IP% was significantly higher for female patients with lung cancer, and significantly higher for male patients with melanoma. The highest IP% of brain metastases occurred at different ages at diagnoses: age 40 to 49 years for primary lung cancer; age 50 to 59 years for primary melanoma, renal, or colorectal cancers; and age 20 to 39 for primary breast cancer. IP% significantly increased as SEER stage of primary cancer advanced for all primary sites. Conclusion Total IP% of brain metastases was lower than previously reported, and it varied by primary site, race, sex, age at diagnosis of primary cancer, and SEER stage of primary cancer.
On Blue Tongues, Undergraduates, and Science: An Interview with Linda M. Bartoshuk
Authors: King Camille Tessitore 
Published: July 2004

Camille Tessitore King is an Assistant Professor in the Department of Psychology at Stetson University in DeLand, Florida, where she teaches Introduction to Psychology, Great Experiments in Psychology, Biological Psychology, as well as other advanced topic courses such as Drugs and Behavior. She received her BA, MA, and PhD from the University of Virginia where her research career began as an undergraduate student. King's research focus is on identifying the neural circuits involved in taste-related behaviors. Linda M. Bartoshuk is a Professor in the Departments of Surgery and Psychology at Yale University School of Medicine, New Haven, Connecticut. She does psychophysical research on genetic variation in taste as well as with patients with taste disorders. She received her BA from Carleton College and her PhD from Brown University. She has been President of the Association for Chemoreception Sciences, the Eastern Psychological Association, and Divisions 1 (General Psychology) and 6 (Behavioral Neuroscience and Comparative Psychology) of the American Psychological Association.
Evidence-based priority-setting: what do the decision-makers think?
Authors: Mitton Craig , Patten San 
Published: July 2004

Objectives: Resource scarcity dictates the need for health organisations to set priorities. Although such activity should be based, at least in part, on evidence, there are limited examples in the literature of decision-makers reflecting on their use of evidence in priority-setting. Methods: A participatory action-research project was conducted in a single health authority in Alberta. It included in-depth interviews and focus groups with senior decision-makers both before and after development and implementation of a macro-level priority-setting framework (programme budgeting and marginal analysis, PBMA). Data were thematically coded and information on the use of evidence in priority-setting is reported. Results: Barriers to the use of evidence in priority-setting identified by decision-makers included crisis-orientated management, time constraints and a lack of skills. Decision-makers suggested using a mix of 'soft' and 'hard' forms of evidence in priority-setting. Following PBMA implementation, decision-makers wanted better information on capacity to benefit, but preferred to do this pragmatically from multiple sources of information rather than using a single metric. Conclusion: In examining the perspectives of decision-makers in using evidence to support priority-setting, valuable information was derived which should provide insight for such processes in other jurisdictions. The main finding of a desire for pragmatic assessment of benefit is informative for those involved in both decision-making and research.