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Controversy surrounds the question of whether clinical trial participants have better outcomes than comparable patients who are not treated on a trial. We explored this question using a recent large, randomized, multicenter study comparing peripheral blood (PB) with bone marrow transplantation from unrelated donors, conducted by the Blood and Marrow Transplant Clinical Trials Network (BMT CTN). We compared characteristics and outcomes of study participants (n = 494) and nonparticipants (n = 1384) who appeared eligible and received similar treatment without enrolling on the BMT CTN trial at participating centers during the study time period. Data were obtained from the Center for International Blood and Marrow Transplant Research. Outcomes were compared between the 2 groups using Cox proportional hazards regression models. No significant differences in age, sex, disease distribution, race/ethnicity, HLA matching, comorbidities, and interval from diagnosis to hematopoietic cell transplantation were seen between the participants and nonparticipants. Nonparticipants were more likely to have lower performance status, lower risk disease, and older donors, and to receive myeloablative conditioning and antithymocyte globulin. Nonparticipants were also more likely to receive PB grafts, the intervention tested in the trial (66% versus 50%, P < .001). Overall survival, transplantation-related mortality, and incidences of acute or chronic graft-versus-host disease were comparable between the 2 groups though relapse was higher (hazard ratio, 1.22; 95% confidence interval, 1.02 to 1.46; P = .028) in nonparticipants. Despite differences in certain baseline characteristics, survival was comparable between study participants and nonparticipants. The results of the BMT CTN trial appear generalizable to the population of trial-eligible patients., (Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Central nervous system complications (CNSC) can be the cause of morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aimed to determine the incidence of CNSC and its impact on survival., Patients and Methods: This retrospective cohort study included patients with hematologic disorders who received allo-HSCT between 2002 and 2011 at the University of Nebraska Medical Center., Results: Of the 351 patients identified, 45 developed CNSC (12.8%). The 100-day cumulative incidence of CNSC was 8% (95% confidence interval, 8-15). The most common CNSC included posterior reversible encephalopathy syndrome (40%), stroke or transient ischemic attack (24%), seizures (20%), and infection (9%). The 5-year overall survival was significantly lower among patients with versus without CNSC (14% vs. 44%, P = .0004). In multivariate analysis, the risk of mortality for patients with versus without CNSC was significantly higher (hazard ratio, 1.56; 95% confidence interval, 1.03-2.36; P = .04)., Conclusion: The occurrence of CNSC after allo-HSCT was associated with reduced survival. Identifying patients at risk, monitoring, early detection, and management of CNSC after allo-HSCT are needed to improve outcomes., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Understanding the mortality patterns of patients with lymphoma and myeloma, who have undergone autologous hematopoietic stem cell transplantation (ASCT) might identify improvement opportunities., Patients and Methods: The present retrospective study included patients with lymphoma and myeloma, aged ≥ 18 years, who had undergone ASCT from 1983 to 2010 at the University of Nebraska Medical Center. Of the 2284 patients, 972 had died within first 5 years after ASCT. The patients were divided into 3 cohorts according to the time of transplantation: 1983 to 1990 (cohort I), 1991 to 2000 (cohort II), and 2001 to 2010 (cohort III). Using Cox proportional hazards regression analysis, the risk of cause-specific mortality was compared across the 3 cohorts., Results: Of a total of 1215 deaths, 972 (80%) occurred within the first 5 years after ASCT. Disease relapse (73.4%), organ failure (7.8%), infection (4.7%), and secondary malignancy (4.2%) accounted for most of the deaths. The risk of death from infection (P < .0001), but not from relapse (P = .26), organ failure (P = .68), or secondary malignancy (P = .15), had declined in the more recent cohorts., Conclusion: The 5-year overall survival of patients undergoing ASCT has improved significantly owing to a decline in infectious mortality. Our results highlight that the mortality from relapse remains the most common cause of death, warranting investigation of different strategies to reduce the incidence of relapse and improve the therapy for relapse after ASCT., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The creation of new cancer immunotherapies represents 1 of the most exciting advances taking place this decade. Although clinical studies continue to indicate improvement in clinical outcomes, the speed of its diffusion into actual practice is not known. It is important to understand practice variation in the use of recommended immunotherapies as new and more effective immunotherapies are developed. Additionally, as the field continues to grow, immunotherapy will encounter new barriers that will hinder its rapid adoption into clinical practice. This review aims to present a brief summary of the mechanisms and uses of antibody-based immunotherapies used to treat lymphoma and to present available practice variation data, including factors associated with variation. Review of the available data implicated patient characteristics and health care systems as being associated with practice variation; however, in several instances, ease of use, cost, toxicity, and physician knowledge contributed to variation, regardless of efficacy. As new immunotherapies are developed, these factors must be considered to increase the rapid diffusion of effective immunotherapies into wide clinical use., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Although a well-established risk factor for lung cancer, the impact of smoking on the survival of non-small cell lung cancer (NSCLC) is not well known. We performed a retrospective analysis of the Veteran's Affairs Comprehensive Cancer Registry of NSCLC patients. Smoking status was categorized as never smoker, past smoker and current smoker based on self-reported history. Multivariate analysis was performed to evaluate the impact of smoking on overall survival (OS) from NSCLC. The study population (n = 61,440) comprised predominantly of males (98 %) and Caucasians (81 %). The median age at diagnosis was 68 years (range 22-108 years). Current smokers were diagnosed with NSCLC at a younger age (65 years) compared to never smokers (71 years) and past smokers (72 years) (p < 0.001). On multivariate analysis, current smokers (n = 34,613) [Hazard ratio (HR) 1.059; 95 % confidence interval (CI) 1.012-1.108], but not past smokers (n = 23,864) (HR 1.008; 95 % CI 0.962-1.056), had worse OS for Stage III and IV NSCLC, compared to never smokers (n = 2,963). Smoking status was not prognostic in stages I and II NSCLC. Current smokers were diagnosed with NSCLC at a younger age than never smokers. Although current smoking was associated with worse prognosis, especially in stages III and IV, the impact of smoking status on OS was modest.

A phase I/II trial was designed to evaluate the safety and efficacy of adding bortezomib to standard BEAM (BCNU, etoposide, cytarabine, melphalan) and autologous hematopoietic stem cell transplantation (ASCT). Eligible patients had relapsed/refractory indolent or transformed non-Hodgkin lymphoma or mantle cell lymphoma (MCL) that was relapsed/refractory or in first partial (PR) or complete remission (CR). Patients received bortezomib on days -11, -8, -5, and -2 before ASCT. Phase I had 4 dose cohorts (.8, 1, 1.3, and 1.5 mg/m(2)) and 3 patients were accrued to each. Any nonhematological ASCT-related toxicity >2 on the Bearman scale occurring between day -11 and engraftment defined the maximum tolerated dose (MTD). After the MTD has been reached, another 20 patients were enrolled at this dose to determine a preliminary overall response rate (ORR). Patients who were in CR or PR at day +100 were considered responders. The study enrolled 42 patients through August 14, 2009. The median age was 58 (range, 34 to 73) years, with 33 males and 9 females. The most common diagnoses were MCL (23 patients) and follicular lymphoma (7 patients). The median number of prior therapies was 1 (range, 0 to 6). The median follow-up was 4.88 (range, 1.07 to 6.98) years. Thirteen patients were treated in phase I and 29 patients were treated in phase II. The MTD was initially determined to be 1.5 mg/m(2) but it was later decreased to 1 mg/m(2) because of excessive gastrointestinal toxicity and peripheral neuropathy. The ORR was 95% at 100 days and 87% at 1 year. For all 38 evaluable patients at 1 year, responses were CR 84%, PR 1%, and progressive disease 13%. Progression-free survival (PFS) was 83% (95% CI, 68% to 92%) at 1 year, and 32% (15% to 51%) at 5 years. Overall survival (OS) was 91% (95% CI, 79% to 96%) at 1 year and 67% (50% to 79%) at 5 years. The most common National Cancer Institute grade 3 toxicities were neutropenic fever (59%), anorexia (21%), peripheral neuropathy (19%), orthostatic hypotension/vasovagal syncope (16%), and 1 patient failed to engraft. Compared with 26 MCL in CR1 historic controls treated with BEAM and ASCT, PFS was 85% and 43% for the BEAM group versus 87% and 57% for those who received bortezomib in addition to standard BEAM (V-BEAM) at 1 and 5 years, respectively (log-rank P = .37). OS was 88% and 50% for the BEAM group versus 96% and 72% for V-BEAM at 1 and 5 years, respectively (log-rank P = .78). In conclusion, V-BEAM and ASCT is feasible. The toxicities were manageable and we did not observe any treatment-related mortalities; however, we did observe an excess of autonomic dysfunction and ileus, which is concerning for overlapping toxicity with BEAM conditioning. Determining relative efficacy of V-BEAM compared to BEAM would require a randomized trial., (Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Racial disparities in outcomes of non-small-cell lung cancer (NSCLC) patients in the United States are well documented. A retrospective analysis of patients in the Veterans Affairs Central Cancer Registry was conducted to determine whether similar disparities exist in a population with a single-payer, accessible health care system., Patients and Methods: Demographic data of patients diagnosed with NSCLC between January 1995 and February 2009 were analyzed using Kruskal-Wallis test or the χ(2) test. Multivariate Cox proportional hazards regression analysis was used to compare survival among races., Results: Of the 82,414 patients, 98% were male, 82% had a smoking history, and 81% were Caucasian. Caucasian individuals had better prognostic features compared with African-American individuals (stage I/II [24% vs. 21%]; Grade I/II [21% vs. 17%]). A larger proportion of Caucasian compared with African-American individuals received stage-appropriate treatment (surgery for stage I [48% vs. 41%; P < .001]; chemotherapy for stage IV [18% vs. 16%; P = .003]). African-American individuals had a lower risk of mortality compared with Caucasian individuals (hazard ratio, 0.94; 95% confidence interval, 0.92-0.96)., Conclusion: Although African-American patients had a higher stage and grade of NSCLC, they had a better overall survival than Caucasian patients. In a single-payer system with accessible health care, previously described racial differences in lung cancer outcomes were not observed., (Published by Elsevier Inc.)

Background: Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is often associated with concurrent or subsequent development of T-cell/histiocyte-rich large B-cell lymphoma (THR-LBCL). Distinguishing the two is important because their therapies are different. Functional imaging with PET/CT is used to stage both Hodgkin and non-Hodgkin lymphomas. Aggressive lymphomas are usually more PET avid than the indolent subtypes. Therefore, it is possible that PET/CT may help distinguish NLPHL from THR-LBCL., Patients and Methods: Herein, we retrospectively describe the clinical and PET/CT findings of 12 patients with NLPHL or THR-LBCL seen from 2004-2010., Results and Conclusions: Six patients each were identified and the average SUVmax was 6.9 (range, 5.7-7.3) in NLPHL and 16.6 (range, 4-29) in THR-LBCL (p = 0.055). Bone and extranodal involvement was found in one patient with NLPHL compared to four patients with THR-LBCL. This patient failed to respond to ABVD and was subsequently found to have THR-LBCL. We suggest that patients with NLPHL and THR-LBCL have different clinical and PET/CT characteristics. NLPHL patients had lower SUVmax on PET/CT compared to those with THR-LBCL. The presence of bone or extranodal involvement is more common in patients with THR-LBCL. Patients with NLPHL and an uncharacteristically higher SUVmax on PET/CT, or those with bone or extranodal involvement, should alert the clinician to consider the presence of THR-LBCL., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Autologous stem cell transplantation is the standard of care for patients with relapsed HL and the long-term outcomes for survivors 2 years after ASCT have not been well described. No prospective trials have compared the effect of different conditioning regimens on outcomes., Patients and Methods: We searched the Nebraska Lymphoma Study Group database to identify patients with HL who received ASCT from 1984 to 2007. Patients were conditioned with either CBV (cyclophosphamide, carmustine, and etoposide) or BEAM (carmustine, etoposide, cytarabine, and melphalan)., Results: At a median follow-up of 8 (range, 2-26) years, 225 patients were alive and disease-free 2 years after ASCT. Analysis was limited to these patients. At 5 years, the progression-free survival (PFS) was 92% for BEAM and 73% for CBV (P = .002) and the overall survival (OS) was 95% for BEAM and 87% for CBV (P = .07). At 10 years, the PFS was 79% for BEAM and 59% for CBV (P = .01) and the OS was 84% for BEAM and 66% for CBV (P = .02)., Conclusion: Patients with HL who are disease-free and alive 2 years after ASCT have favorable outcomes. We observed lower risk of progression and longer survival associated with use of BEAM vs. CBV. Patients in the BEAM group received a transplant in more recent years so we cannot exclude the possibility that the superior outcomes seen in the BEAM group are because of better supportive care, use of peripheral blood stem cell grafts, or improvements in salvage therapies before transplantation., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The purpose of this study was to evaluate the standard outpatient dose of 131-Iodine tositumomab (75 cGy) combined with high-dose carmustine, etoposide, cytarabine, and melphalan (BEAM) followed by autologous stem cell rescue for the treatment of chemotherapy-sensitive relapsed or refractory, or high-risk first complete remission (CR) patients with diffuse large B cell non-Hodgkin's lymphoma (DLBCL). Forty patients with chemotherapy-sensitive persistent or relapsed or high/intermediate or high international prognostic index DLCBL were treated in a phase II trial combining 75 cGy 131-Iodine tositumomab with high-dose BEAM followed by autologous stem cell transplantation. The CR rate after transplantation was 78%, and the overall response rate was 80%. Short-term and long-term toxicities were similar to historical control patients treated with BEAM alone. With a median follow-up of 6 years (range, 3-10 years), the 5-year overall survival (OS) was 72% (95% confidence interval [CI], 55%-83%), and the 5-year progression-free survival (PFS) rate was 70% (95% CI, 53%-82%). The PFS and OS were encouraging in this group of chemotherapy-sensitive persistent, relapsed, or high-risk patients with DLBCL. A follow-up phase III trial with 131-Iodine tositumomab/BEAM vs rituximab/BEAM was planned based on this information., (Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

The outcomes for 162 patients with diffuse large B-cell lymphoma treated with a CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone)-like regimen who obtained a complete remission and who subsequently relapsed after ≥5 years of remission (late relapse, N=30), or <5 years of remission (early relapse, N=132), were compared. The late relapsing patients had better prognostic characteristics at diagnosis, such as stage I/II disease (73% vs. 49%, P=0·04), a normal lactic dehydrogenase (77% vs. 48%, P=0·01), and a Karnofsky performance score of ≥80 (100% vs. 86%, P=0·01). The 3-year survival after relapse was better in late relapsing patients (48% vs. 25%, P=0·03), but the survival at 5 years (32% vs. 20%) and 10 years (13% vs. 14%) after relapse was not different. A multivariate analysis of factors predicting survival after relapse found age (P<0·0001) and presence of B-symptoms (P=0·03) to predict survival, but not early versus late relapse. A small percentage of the late relapsing patients can have a prolonged second remission. However, the overall survival from the time of relapse was not different between early and late relapsing patients with most succumbing to lymphoma., (© 2010 Blackwell Publishing Ltd.)

Background: Despite accounting for more than half of the patients diagnosed with non-small cell lung cancer (NSCLC), only 20% of elderly patients receive chemotherapy. One reason for withholding systemic therapy is the concern for an increased incidence of side-effects, especially cytopenia from bone marrow toxicity. Limited data exist regarding specific factors that affect blood count nadirs following chemotherapy., Patients and Methods: A retrospective chart review was conducted of chemotherapy-naïve patients who had received standard doses of carboplatin and paclitaxel for NSCLC. Hemoglobin levels, total white blood cell counts (WBC) and platelet counts before each chemotherapy cycle and nadir counts following each cycle were obtained. Wilcoxon test and Chi-square test were used for univariate comparisons of patient characteristics and unpaired t-test for hematological parameters. Multivariate analyses of change over time in the hematological parameters by age groups were performed using mixed models while adjusting for other clinical factors., Results: Of the 91 consecutive patients identified from the medical records between 1992 and 2007, 37 (41%) were <60 years old at diagnosis. Pre-chemotherapy and nadir values for hemoglobin, WBC and platelet counts did not vary by age over time. The nadir values correlated with the corresponding pre-chemotherapy values. Both the pre-chemotherapy and nadir values showed a decreasing trend with increasing numbers of chemotherapy cycles administered., Conclusion: Age does not affect the nadir counts of hemoglobin, WBC and platelets following administration of carboplatin and paclitaxel for NSCLC. Pre-chemotherapy blood counts are more important determinants of hematologic toxicity following administration of carboplatin and paclitaxel for advanced NSCLC.

Studies suggest that patients who live in rural areas may have worse clinical outcomes compared with patients living in urban areas. We studied whether place of residence (rural versus urban) is associated with clinical outcomes of patients with leukemia or myelodysplastic syndrome (MDS) who received an unrelated donor hematopoietic cell transplantation (HCT). Patients' residential ZIP code at the time of transplant was used to determine rural or urban designation based on the Rural Urban Commuting Codes. The study included 6140 patients reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) from 121 U.S. HCT centers: 1179 (19%) came from rural areas, whereas 4961 (81%) came from urban areas. Rural and urban patients were similar in patient-, disease-, and transplant-related characteristics aside from household income and distance traveled to the HCT center. After adjusting for income and other significant patient, disease, and transplant-related variables, the risk of overall mortality between patients residing in rural and urban areas were not statistically significant (relative risk 1.01, 95% confidence intervals 0.93-1.10, P = .74). Similar outcomes were noted for treatment-related mortality (TRM), disease-free survival (DFS), and relapse. Patient's income, derived from the U.S. Census and based on their residential ZIP code, was independently associated with outcomes. In summary, our study showed no differences in the clinical outcomes of patients from rural or urban areas after unrelated donor HCT., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Outcome disparity associated with race or ethnicity in the United States has been observed in hematopoietic cell transplantation (HCT). The underlying reasons for such disparity are not known. In the United States, an optimal study of health care disparity by race or ethnicity involves consideration of both biologic and psychosocial determinants, which requires an adequately powered, prospective cohort study design. To better characterize the nature and quantify the magnitude of the many impediments relevant to conducting a successful prospective study involving racial or ethnic minorities in HCT, we conducted a feasibility study to help guide planning of a larger scale outcome and disparity study in HCT. The primary questions to be addressed in the study were: (1) can we establish a racially or ethnically diverse patient sample that will respond to a survey focused on sociodemographic, economic, health insurance, cultural, spiritual, and religious well-being, and social support information? (2) What is the retention rate in the study over time? (3) What is the quality of the data collected from the patients over time? The challenges we faced in conducting this multicenter feasibility study are summarized in this report. Despite the difficulty in conducting disparity studies in racial and ethnic minorities, such studies are essential to ensure that people of all ethnic and racial backgrounds have the best chance possible of benefiting from HCT.

Background: Previous meta-analysis on three drugs combination for treatment of advanced non-small cell lung cancer (NSCLC) did not demonstrate an improvement in survival, however many of the trials included in this meta-analysis used older and less effective cytotoxic drugs. We conducted this analysis to compare the relative efficacy of third generation triplet therapy with that of standard double therapy in the treatment of advanced NSCLC., Methods: A MEDLINE search was performed using the search terms "lung cancer" and "randomized trials". Trials not utilizing a third generation cytotoxic chemotherapeutic agent (paclitaxel, docetaxel, vinorelbine, gemcitabine) were excluded. Pooled odds ratios (OR) for the objective response and toxicity rates were calculated using the Mantel-Haenszel estimate. Pooled median ratios for median survival were calculated using the weighted sum of the log-ratio of median ratios of individual study., Results: We analyzed six randomized comparative trials involving 1932 patients. Patients receiving triplet therapy had a significantly higher response rate (OR: 1.33; 95% CI, 1.50-2.23; P<0.001). Incidence of grade III/IV hematological toxicity was higher with triplet therapy. Non-hematological toxicities, with the exception of neuropathy, were similar. Median survival of triplet therapy was not significantly different from doublet (MR: 1.10; 95% CI: 0.91-1.35; P=0.059)., Conclusions: Triplet therapy with third generation cytotoxic drugs is associated with higher tumor response rate at the expense of increased toxicity. Although triplet therapy had a better overall survival compared to doublet therapy, this did not reach statistical significance.

Background: Risk factors for development of lung cancer include a family history of the disease. The effect of family history on lung cancer outcomes is unknown. A study was conducted to investigate this., Methods: The medical records of all patients with lung cancer seen in an academic medical oncology lung cancer clinic between 1999 and 2006 were reviewed for outcomes and family history of lung cancer. chi(2)-test and Wilcoxon test were used for univariate comparisons, while Cox Proportional Hazards regression analysis was used to evaluate the adjusted risk of death. Univariate probability of survival was computed using Kaplan-Meier estimate and compared using the log-rank test., Results: Of the 560 patients evaluated, 289 (51%) were male and 519 (93%) had a smoking history. Of the 148 patients (26%) with a family history of lung cancer, 115 had an affected first-degree relative. No association between family history and histology or stage at diagnosis was detected. Median survival in patients with a family history of lung cancer was 53 months compared to 58 months in patients without such a history (p=0.06). Patients with a positive family history had an adjusted relative risk of death of 1.65 (95% CI: 1.07-2.56; p=0.02) compared to those without a family history. This risk was especially increased in those with an affected first-degree relative (RR: 1.72; 95% CI: 1.08-2.75, p=0.02)., Conclusions: Lung cancer patients with a first-degree relative with lung cancer have a poorer outcome than those without such a history.

To compare the clinical outcomes of older (age > or =55 years) non-Hodgkin lymphoma (NHL) patients with younger NHL patients (<55 years) receiving autologous hematopoietic cell transplantation (HCT) while adjusting for patient-, disease-, and treatment-related variables, we compared autologous HCT outcomes in 805 NHL patients aged > or =55 years to 1949 NHL patients <55 years during the years 1990-2000 using data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). In multivariate analysis, older patients with aggressive histologies were 1.86 times (95% confidence interval [CI] 1.43-2.43, P < .001) more likely than younger patients to experience treatment-related mortality (TRM). Relative death risks were 1.33 times (CI 1.04-1.71, P = .024) and 1.50 times (CI 1.33-16.9, P < .001) higher in older compared to younger patients with follicular grade I/II and aggressive histologies, respectively. Autologous HCT in older NHL patients is feasible, but most disease-related outcomes are statistically inferior to younger patients. Studies addressing supportive care particular to older patients, who are most likely to benefit from this approach, are recommended.

Although results of autologous stem cell transplantation (SCT) for recurrent follicular non-Hodgkin lymphoma (NHL) have been previously reported, the long-term results and evaluation of prognostic factors in a large patient population receiving this therapy are difficult to find in the literature. To address these issues, we evaluated 248 patients with recurrent follicular NHL treated with high-dose chemotherapy and autologous SCT between 7/87 and 6/03. According to the World Health Organization (WHO) classification system, 64 patients (26%) had follicular NHL grade 1 (FL 1), 98 (40%) had FL 2, and 86 (35%) had FL 3. At the time of transplantation, 88 of the patients (35%) had a Follicular Lymphoma International Prognostic Index (FLIPI) score of low risk, 87 (35%) had an intermediate-risk FLIPI score, 37 (15%) had a high-risk FLIPI score, and 36 (15%) had at least 1 missing value, preventing calculation of the FLIPI score. The 5-year overall survival (OS) for all patients was 63%, and the 5-year progression-free survival (PFS) was 44%. In a multivariate analysis, a histological grade of FL 3, a high-risk FLIPI score at the time of transplantation, and having received 3 or more previous chemotherapy regimens were significant factors for predicting a worse OS. In addition, the use of a transplantation regimen including a monoclonal antibody decreased the relative risk of progressive lymphoma. These data suggest that transplantation earlier in the course of the disease for patients with follicular lymphoma with use of a monoclonal antibody-based regimen may lead to improved outcomes.

Often in biomedical research the aim of a study is to compare the outcomes of several treatment arms while adjusting for multiple clinical prognostic factors. In this paper we focus on computation of the direct adjusted survival curves for different treatment groups based on an unstratified or a stratified Cox model. The estimators are constructed by taking the average of the individual predicted survival curves. The method of direct adjustment controls for possible confounders due to an imbalance of patient characteristics between treatment groups. This adjustment is especially useful for non-randomized studies. We have written a SAS macro to estimate and compare the direct adjusted survival curves. We illustrate the SAS macro through the examples analyzing stem cell transplant data and Ewing's sarcoma data.

High-dose therapy with autologous hematopoietic cell transplantation (auto-HCT) is frequently used to improve outcomes in lymphoma. However, small studies suggest a survival disadvantage among obese patients. Using a retrospective cohort analysis, we studied the outcomes of 4681 patients undergoing auto-HCT for Hodgkin or non-Hodgkin lymphoma between 1990 and 2000 according to body mass index (BMI). Four groups categorized by BMI were compared by using Cox proportional hazards regression to adjust for other prognostic factors. A total of 1909 patients were categorized as normal weight (BMI 18-25 kg/m2), 121 as underweight (BMI<18 kg/m2), 1725 as overweight (BMI>25-30 kg/m2), and 926 as obese (BMI>30 kg/m2) at the time of HCT. Outcomes evaluated included overall survival, relapse, transplantation-related mortality (TRM), and lymphoma-free survival. TRM was similar among the normal, overweight, and obese groups; the underweight group had a higher risk of TRM (relative risk [RR], 2.46; 95% confidence interval [CI], 1.59-3.82; P<0.0001) compared with the normal-BMI group. No differences in relapse were noted. Overall mortality was higher in the underweight group (RR, 1.48; 95% CI, 1.17-1.88; P=.001) and lower in the overweight (RR, 0.87; 95% CI, 0.79-0.96; P=.004) and obese (RR, 0.76; 95% CI, 0.67-0.86; P<.0001) groups compared with the normal-BMI group. In light of our inability to find differences in survival among overweight, obese, and normal-weight patients, obesity alone should not be viewed as a contraindication to proceeding with auto-HCT for lymphoma when it is otherwise indicated.

Adenosine is a key myocardial metabolite that elicits coronary vasodilation in a variety of pathophysiological conditions. We examined the mechanism of adenosine-induced vasodilation in coronary arterioles from patients with heart disease. Human coronary arterioles (HCAs) were dissected from pieces of the atrial appendage obtained at the time of cardiac surgery and cannulated for the measurement of internal diameter with videomicroscopy. Adenosine-induced vasodilation was not inhibited by endothelial denudation, but A(2) receptor antagonism with 3,7-dimethyl-1-propargylxanthine and adenylate cyclase (AC) inhibition with SQ22536 significantly attenuated the dilation. In contrast, A(1) receptor antagonism with 8-cyclopentyl-1,3-dipropylxanthine significantly augmented the sensitivity to adenosine. Moreover, dilation to A(2a) receptor activation with 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamido-adenosine hydrochloride was reduced by the A(1) receptor agonist (2S)-N(6)-(2-endo-norbornyl)adenosine. The nonspecific calcium-activated potassium (K(Ca)) channel blocker tetrabutylammonium attenuated adenosine-induced dilation, as did the intermediate-conductance K(Ca) blocker clotrimazole. Neither the large-conductance K(Ca) blocker iberiotoxin nor small-conductance K(Ca) blocker apamin altered the dilation. In conclusion, adenosine endothelium independently dilates HCAs from patients with heart disease through a receptor-mediated mechanism that involves the activation of intermediate-conductance K(Ca) channels via an AC signaling pathway. The roles of A(1) and A(2) receptor subtypes are opposing, with the former being inhibitory to AC-mediated dilator actions of the latter. These observations identify unique fundamental physiological characteristics of the human coronary circulation and may help to target the use of novel adenosine analogs for vasodilation in perfusion imaging or suggest new strategies for myocardial preconditioning.

Abstract Hematopoietic stem cell transplantation (HSCT) as a field of medicine has been subject to rapid development and evolution since its inception. Traditionally, HSCT has been used for therapy of a diverse group of malignancies, bone marrow failure states, and inherited disorders. The rapid evolution of transplantation technology coupled with the diverse outcomes associated with a heterogeneous group of patients has stymied the development of consensus over objective programmatic indicators of quality, especially as they pertain to outcomes. In some regard, the lack of consensus has caused transplant programs to respond to a more consumer-driven paradigm of evaluation. The community of providers of transplantation therapies has responded by establishing standards for accreditation of facilities and uniform presentation of programmatic data. Rapid acceptance of the need for meaningful quality programs to address all aspects of the transplant facility has moved HSCT to the forefront of implementing standards for medical practice. Because definition of optimal outcomes in HSCT is likely to remain elusive, it is imperative that providers involved with HSCT continue to take a leadership role in defining program quality through further research.

The effect of the organization and delivery of health care at medical centers, referred to as "center effects," with clinical outcomes after hematopoietic stem cell transplantation (HSCT) is not clear. We examined the association between center and treatment provider factors and mortality after HSCT. We surveyed 163 (87% response rate) United States transplantation centers that performed HLA-identical sibling HSCT for leukemia or autologous HSCT for lymphoma between 1998 and 2000 among patients at least 18 years old. One hundred thirteen (69%) centers performed HLA-identical sibling transplantations, whereas 162 (99%) performed autologous transplantations. Factors associated with decreased 100-day mortality in the allogeneic setting include a higher patient-per-physician ratio (P = .003) and centers where physicians answer calls after office hours (P = .03). Medical school affiliation was not associated with increased 100-day mortality except in centers where students/residents are present without fellows (P = .02). Center effects were weaker in autologous HSCT at 1 year. Differences in 100-day mortality in patients receiving transplants in centers with favorable versus unfavorable factors were greater in allogeneic than autologous HSCT. Greater physician involvement in patient care is important in producing favorable outcomes after HSCT. To more clearly establish the role of the factors we identified, further studies are recommended.

The association of ethnicity with the incidence of graft-versus-host disease (GVHD) and other clinical outcomes after transplantation is controversial. We compared the results of HLA-identical sibling bone marrow transplantations for leukemia, performed between 1990 and 1999, among different ethnic populations, including 562 Japanese, 829 white Americans, 71 African Americans, 195 Scandinavians, and 95 Irish. Results for adults and children were analyzed separately. Multivariate analyses of adult patients showed that white Americans, African Americans, and Irish cohorts were at significantly higher risk for acute GVHD than Japanese or Scandinavian cohorts (relative risk [RR] = 1.77, P < .001; RR = 1.84, P < .006; RR = 2.22, P < .001, respectively). White Americans, African Americans, and Irish, but not Scandinavians, were at significantly higher risk for early (within 3 months of transplantation) transplant-related mortality (TRM) compared with Japanese (RR = 2.99, P < .001; RR = 5.88, P < .001; RR = 2.66, P < .009, respectively). No differences in the risk for chronic GVHD, relapse, and overall survival were noted. In the pediatric cohort (limited to Japanese and white Americans), white Americans were at significantly higher risk for acute (RR = 1.93; P = .04) and chronic (RR = 3.16; P = .002) GVHD. No differences in other clinical outcomes were noted. Our findings suggest that ethnicity may influence the risk for GVHD, though overall survival rates after transplantation remain similar.