bluuebunny/crossref_metadata_2025_split huggingface dataset:
Younger Patients with CLL/SLL Are Less Frequent and Have Favorable Survival in a Canadian Population Based Study: The Manitoba Cohort.
Authors: Banerji Versha , Demers Alain , Johnston James B. , Pitz Marshall W. , Nugent Zoanne , Morales Carmen , Mahmud Salah , Hewitt Donna , Gibson Spencer B. , Seftel Matthew D. 
Published: October 2019

Abstract
Background: Detailed population-based clinical characteristics and outcomes of chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL) are scarce. We have previously demonstrated in the province of Manitoba that by combining population-based sources of a cancer registry and a centralized flow cytometry database, the incidence of CLL/SLL is much higher than previously reported. We have now examined the clinical characteristics of this large and well defined patient group. We hypothesized that the clinical features of these patients (pts) may differ from previous studies where data was obtained from referral centers.
Methods: All pts from the Manitoba Cancer Registry with ICD codes 9 & 10 for CLL or SLL from 01/01/1998 to 12/31/2003 were identified. Pts from the flow cytometry database during this time period with a diagnosis of CLL/SLL were also identified. A retrospective electronic chart review was conducted. The two databases were compared and analyzed.
Results: 715 pts with CLL were identified. 358 pts were identified from the cancer registry alone, 136 pts by the flow cytometry database, and 221 pts in both datasets. Overall, the age-adjusted annual incidence rate of CLL/SLL in Manitoba was 10.5/105 (95% C.I. 9.4–12.7/105). Median age of all pts was 72yrs (19–101). Only 71 pts (9.9%) were aged <55 and 212 pts (29.6) were <65. The Male: Female ratio was identical in the age<55 and >55 categories (1.33). Median follow-up of living pts is 6.6 years (range 2.0–8.0). The Cox regression model was used to evaluate the significance of prognostic factors including age at diagnosis and gender. Older cases (>55 years) had significantly higher risk of dying (HR: 4.0, 95%CI: 1.23–13.1) than younger pts. Women had a slightly lower risk of dying (HR: 0.78, 95%CI: 0.40–1.50) than men. For the 136 pts for whom accurate Rai staging was available, estimated median survival has not been reached in stage 0 patients, while it was 7.2 years in stage I–II cases and 4.5 years in stage III–IV patients. Cause specific mortality and complete survival according to Rai stage for all pts will be presented at the meeting.
Conclusions: In this population-based CLL/SLL cohort, clinical presentation and outcomes appear to differ from previously reported studies. Specifically, (1) there are fewer younger pts, (2) the male: female ratio is similar amongst all ages, (3) older pts have a significantly poorer survival, (4) pts with advanced Rai stages appear to live longer than previously reported. This has important implications for treatment and counseling of pts, as well as for resource allocation for this common hematological malignancy.
Cost-Effectiveness of Rituximab Maintenance Treatment Versus Autologous Stem Cell Transplantation (ASCT) in Patients with Relapsed Follicular Lymphoma (FL).
Authors: Leppä Sirpa , Linna Miika , Nyman Heidi , Taimela Eeva 
Published: October 2019

Abstract
PURPOSE: High dose chemotherapy followed by ASCT is commonly used in responding patients with FL as consolidation treatment in first relapse. Recently, rituximab maintenance treatment has shown to improve both progression free (PFS) and overall survival (OS) in the same patient population. The objective of this analysis was to estimate the incremental cost-effectiveness of rituximab maintenance compared to ASCT in patients with FL in first relapse.
METHODS: Efficacy data for rituximab maintenance treatment was derived from the EORTC 20981 trial (van Oers et al, ASH 2005). FL patients (n=334) were randomized to observation or rituximab maintenance treatment in first relapse. Rituximab maintenance treatment consisted of eight infusions during two years. The reported PFS for R-CHOP induction followed by maintenance arm was 51.9 mo, in comparison to 23.1 mo for observation arm. Efficacy data on ASCT and immunochemotherapy were derived from local experience during 1994–2005. Twelve patients with relapsed FL received ASCT, and had median PFS of 34.1 mo. In comparison, fifty patients who received immunochemotherapy without neither ASCT nor rituximab maintenance had a PFS of 21.8 mo, which is comparable to the outcome of R-CHOP treated patients in the observation arm of the EORTC 20981 study. To estimate the incremental resources involved we included therapy associated costs, and visit costs during the first two years. Rituximab maintenance costs included eight infusion visits, in addition to drug costs. Costs for ASCT were based on real data of individual patients, collected from hospital’s accounting systems. These costs are also used as prices charged by Helsinki University Hospital (HUCH) in Finland. The costs included only direct medical costs for hospital services and were calculated in 2004 prices.
RESULTS: The cost of rituximab maintenance treatment was estimated to be approximately EUR 19.700. The actual cost of ASCT was approximately EUR 38.600. In terms of health benefits, rituximab maintenance seems to provide longer PFS after first relapse, with incremental difference of 17.8 mo, based on these early results reported. In the base case, therapy associated costs were lower in the rituximab maintenance treatment group. After sensitivity analysis without follow-up visit costs, this difference remained. Thus, rituximab maintenance treatment was the dominant choice in treating FL patients at first relapse, when compared to ASCT.
CONCLUSIONS: This analysis cloncludes that new treatment approaches may lead to improved PFS combined with cost savings in those FL patients where ASCT previously has been the preferred treatment option. The potential impact of these findings on the whole FL patient population will be discussed.
Experience of Respect and Pain Management among Adult Patients with Sickle Cell Disease during Vaso-Occlusive Crisis.
Authors: Beach Mary Catherine , Duggan Patrick , Lanzkron Sophie 
Published: October 2019

Abstract
BACKGROUND. Adults with sickle cell disease (SCD) have reported adversarial relationships with health professionals in qualitative studies, but there are no quantitative data. We sought to examine experiences of respect among patients with SCD seeking acute care for vaso-occlusive crisis (VOC), and to relate these experiences to quality of pain management.
METHODS. We surveyed 54 adult patients upon discharge from the Emergency Department (ED) at an urban academic medical center. We measured patient experience of respect using items from the Interpersonal Processes of Care Instrument and summed responses to form a ‘respect’ scale from 0–100 (alpha 0.89). We measured pain management quality by asking patients whether doctors and nurses brought them their pain medicines as soon as they needed them and changed their pain medicines if they were not working (‘all’ and ‘most’ of the time were considered favorable responses while ‘some’ or ‘none’ of the time were considered unfavorable).
RESULTS. Patients generally reported low levels of respect and poor pain management. A small proportion of patients reported (‘all of the time’) that doctors and nurses seemed to care about them as a person (19%), listened carefully to what they had to say (17%), and took their concerns seriously (13%). A substantial proportion reported (‘all, ‘most’ or ‘some of the time’) that their doctors and nurses had a negative attitude towards them (63%), made them feel inferior (74%), made them feel as if they weren’t welcome (65%) and behaved rudely towards them (50%). Only 34% of patients reported timely receipt of pain medication and 48% reported that ineffective medication was changed. Patient experience of respect and pain management quality were not significantly related to patient age, sex, or employment status; however patients seen more frequently in the ED reported less respect (mean respect scores 74.1, 62.7, and 54.6 for patients seen <5 times/year, 5–15 times/year, and >15 times per year respectively, p=0.04). Patients who experienced lower respect also reported poorer pain management quality. Compared to patients who reported timely receipt of and changes in ineffective medication, patients who reported delays in receipt and no change in ineffective medication had lower respect scores (mean 71.9 vs. 53.9, p=0.001 for timely vs. delayed; 65.6 vs. 53.7 for change vs. no change).
CONCLUSION. Interventions are needed to improve the experiences of adult patients with SCD who present to the ED with VOC. Further research is needed to determine the causes of poor experiences of respect and pain management, and to determine their further consequences.
Cost of Current Iron Chelation Infusion Therapy and Cost-Effectiveness of Once-Daily Oral Deferasirox in Transfusion-Dependent Thalassemia Patients in Canada.
Authors: Delea T.E. , El Ouagari K. , Sofrygin O. 
Published: October 2019

Abstract
Background: Deferasirox (Exjade®) is a recently approved once-daily oral chelator that has been shown to produce reductions in liver iron concentrations and serum ferritin similar to those with infusional deferoxamine (Desferal®), in patients with β-thalassemia major or sickle cell disease (SCD) and chronic iron overload from blood transfusions. The objective of this study was to estimate the cost of deferoxamine administration in Canada and evaluate the cost-effectiveness of deferasirox versus deferoxamine for chronic iron overload from blood transfusions from the Ontario provincial healthcare system.
Methods: Cost of chelation therapy with deferoxamine was estimated from five major treatment centers in Canada. Costs comprised the material used and the time spent by hospital pharmacists in preparing deferoxamine infusions. Cost-effectiveness of the new oral iron chelator, deferasirox, which could replace deferoxamine, was estimated using a Markov model. The model estimates and compares the total lifetime costs and quality-adjusted life years (QALYs) related to the use of deferasirox or deferoxamine in patients with β-thalassemia major at risk of chronic iron overload from blood transfusions. Dosages of deferasirox and deferoxamine used in the model were those that have been shown to be similarly effective in such patients. Compliance with deferoxamine was based on analyses of health-insurance claims data from transfusion-dependent thalassemia patients. Probabilities of complications of iron overload and death by compliance with chelation were estimated from published studies. Because data on compliance with deferasirox in typical clinical practice are unavailable, we used published data on compliance with the oral chelator deferiprone versus deferoxamine. Costs of deferasirox, deferoxamine, and drugs used in the treatment of complications of iron overload were based on publicly available data sources. Utilities were based on a study of patient preferences for oral versus infusional chelation therapy, as well as published literature and assumption. Future costs and QALYs were discounted at 5% annually. Costs were adjusted to 2004 Canadian dollars.
Results: Cost of yearly infusion therapy in Canada was estimated at $6,000 per patient, excluding deferoxamine drug cost. Cost-effectiveness of deferasirox compared to deferoxamine was estimated at $45,054 per QALY gained resulting mainly from a gain in 2.9 QALYs obtained at an expected lifetime cost of $130,058 per patient. Cost-effectiveness is sensitive to the estimated costs of deferoxamine and infusional therapy, as well as the quality of life benefit associated with oral versus infusional therapy, and is more favorable in younger patients.
Conclusion: In patients with transfusion-dependent β-thalassemia, the cost-effectiveness of deferasirox versus deferoxamine is within the range generally considered acceptable in Canada.
Screening for Iron Deficiency: Can We Continue To Avoid Ferritin?.
Authors: Montoya Maria E. , Van Delden Peter R. , Elghetany M. Tarek , Bessman J. David 
Published: October 2019

Abstract
Detection of iron deficiency remains poorly understood and costly due to inappropriate screening. Low ferritin is a definitive diagnosis of iron deficiency, but screening with ferritin is not allowed. Therefore surrogates in the blood count have been used to justify obtaining the serum ferritin. The purpose of this research was to analyze the role of Hemoglobin (Hgb), Mean Corpuscular Volume (MCV), and RBC Distribution Width (RDW) as surrogates in screening for iron deficiency. All 2,563 patients with serum ferritin levels gathered over 12 months were reviewed. The relative utility of Hgb, MCV, and RDW in screening for low ferritin levels was shown through multiple Receiver Operator Characteristic (ROC) curves. 264 patients had a ferritin less than 10 ng/ml and 210 between 11 to 20 ng/ml. Results indicate that when viewed independently MCV correlates most closely to low ferritin as seen in Figure 1. RDW and Hgb in both males and females demonstrate a weaker association though remains of value. Table1 lists the values at which the three screening tools were 95% and 100% sensitive for detecting ferritin levels of 10 ng/ml and below. In contrast the data indicate that for ferritin levels from 11 to 20 ng/ml all three screening variables have poor sensitivity and specificity. This is demonstrated clearly in Figure 2. The data suggest that the most severe iron deficiency (ferritin under 10 ng/ml) can be well predicted by abnormalities in the blood count; however less severe iron deficiency (ferritin 10 to 20 ng/ml) cannot be anticipated from the blood count. The blood count does not appear to be a practical alternative to ferritin for screening for iron deficiency.
Table 1: Sreening Variable Sensitivities* 100% Sensitivity 95% Sensitivity *values for ferritin less than 11 ng/ml MCV >98.2 >90.0 RDW <12.2 <13.1 Hgb Males >15.0 >13.7 Hgb Females >14.2 >12.6 Figure 1 Figure 1. Figure 2 Figure 2.
Long Term Follow-Up of Patients with Chronic Myeloid Leukemia Receiving BuCy2 as Preparation for Allotransplantation.
Authors: Copelan Edward A. , Dodds Anthony J. , Bolwell Brian J. , Crilley Pamela Ann , Elder Patrick , Pant Shubham , Kalaycio Matt , Sobecks Ronald , Topolsky David , Nivison-Smith Ian , Avalos Belinda R. , Szer Jeffrey 
Published: October 2019

Abstract
In 1992, we published the results of the first multi-institutional study of BuCy2 (busulfan 4mg/kg daily for four days and cyclophosphamide 60mg/kg on each of two days) preparation for allogeneic transplantation using related HLA-identical donors in chronic myeloid leukemia (CML). Median follow-up was 3 years. This report updates outcomes to July 1, 2006 for a total of 294 patients, including the original cohort, who underwent allogeneic transplantation with the BuCy2 regimen at 7 centers between March 1984 and December 1995. The median follow-up of surviving patients is 13 years. Two hundred patients underwent transplantation in chronic phase, 58 in accelerated phase and 36 in blastic phase. One hundred thirty two patients (45%) remain alive. Seventy-nine percent of patients surviving 3 years after transplantation are estimated survivors 13 years after transplantation. The estimated survivals at 3 and 13 years are 69% (95% CI: 57–81%) and 56% (42–70%) for chronic phase patients, 38% (14–62%) and 25% (1–49%) for accelerated phase patients, and 17% (0–41%) and 4% (0–16%) for those in blastic phase. Estimated relapse rates, according to stage of disease, are 6% (0–14%), 21% (1–49%), and 55% (7–100%) respectively at 3 years and 22% (6–38%), 42% (0–84%) and 74% (20–100%) respectively at 13 years. Of 51 patients who developed hematologic or persistent cytogenetic relapse, 28 relapsed within 3 years of transplantation and 23 (45%) relapsed more than 3 years from transplantation (longest: 15 years) Twenty-five of the 28 patients who relapsed within 3 years have died. Of the 23 who relapsed beyond 3 years, 7 have died. Death occurred more frequently (P<0.001) and the interval from relapse to death was shorter (P=0.02) for those who relapsed within 3 years. Of 162 patients who have died, 34 died beyond 3 years, most commonly from chronic GVHD (10), relapse (9), or new malignancies (6). Advanced stage was a risk factor for late failure (death or relapse beyond 3 years, P=0.003), as it was for early failure (P=0.001). Older age (P=0.03) and chronic GVHD (P=0.05) were also risk factors for late failure. For chronic phase patients, risk of late failure was not increased in those who underwent transplantation at longer intervals from diagnosis (P=0.5), in contrast to early failure (P=0.002). In conclusion, approximately four of five patients with CML who underwent allo-transplantation using BuCy2, and were alive 3 years following transplantation, are survivors at 13 years. Late relapse was associated with a significantly better outcome than early relapse. Late deaths occurred most frequently due to chronic GVHD, relapse or new malignancies.
A Novel Role for Thrombin in Hematopoietic Stem/Progenitor Cell Homing.
Authors: Shirvaikar Neeta , Jalili Ali , Ratajczak Mariusz Z. , Janowska-Wieczorek Anna 
Published: October 2019

Abstract
Thrombin, an important serine protease, not only plays a pivotal role in platelet aggregation and coagulation, but also through activation of its receptor, seven transmembrane, G-protein-coupled receptor PAR-1, elicits numerous cellular responses in platelets and endothelial cells such as induction of adhesion molecules, production of chemokines, activation of matrix metalloproteinase (MMP)-2, cytoskeletal reorganization and migration. Thrombin is also one of the inflammatory molecules elevated during G-CSF mobilization of hematopoietic stem/progenitor cells (HSPC) and their collection by leukapheresis. We recently reported that components of leukapheresis products including thrombin enhance in vitro chemotaxis of CD34+ cells towards an SDF-1 gradient and in vivo homing to bone marrow (BM) niches in a murine model (Blood2005; 105:40). In this study we investigated whether thrombin enhances the homing-related responses of human HSPC (CD34+ cells) through MMPs, especially membrane-type (MT)1-MMP which is known to be localized on the leading edge of migrating cells and both activates latent proMMPs (MMP-2, -9) and itself has strong pericellular proteolytic activity. We found that stimulation of CD34+ cells with thrombin upregulates mRNA for MT1-MMP and MMP-9 as well as MT1-MMP protein expression (Western blot, flow cytometry) and proMMP-2 and proMMP-9 secretion (zymography). Thrombin was also found to (i) prime trans-Matrigel chemoinvasion of CD34+ cells towards a low SDF-1 gradient (20 ng/mL), which was inhibited by epigallocatechin-3-gallate, a potent inhibitor of MT1-MMP, and (ii) activate MMP-2 in of co-cultures of CD34+ cells with stromal cells (BM fibroblasts and HUVEC) which secrete proMMP-2. We also found that SDF-1 upregulates mRNA and protein expression of MT1-MMP. Moreover, using confocal microscopy we demonstrate for the first time that in CD34+ cells, PAR-1, like CXCR4, is localized in the GM1 fraction of lipid rafts and stimulation of these cells with thrombin as well as SDF-1 increases incorporation of MT1-MMP into membrane lipid rafts. Furthermore, disruption of lipid raft formation by the cholesterol-depleting agent methyl-b-cyclodextrin inhibits MT1-MMP incorporation into membrane lipid rafts and also trans-Matrigel chemoinvasion of CD34+ cells towards SDF-1. Thus we conclude that thrombin, through PAR-1 signalling and the SDF-1-CXCR4 axis, upregulates the incorporation of MT1-MMP into membrane lipid rafts and the interaction of these axes enhances the homing-related responses of HSPC towards SDF-1.
Kinetics of Autologous Stem Cell Mobilization Failure: Comparison of AMD3100/G-CSF, G-CSF, GM-/G-CSF, and Chemotherapy/G-CSF on Remobilization Success.
Authors: DiPersio John F. , Smith Angela , Sempek Dianne , Baker Albert , Jiang Steven , Vij Ravi , Cashen Amanda , Westervelt Peter 
Published: October 2019

Abstract
Background: No standard approach for the mobilization of peripheral hematologic stem and progenitor cells (HSPCs) has been established. High levels of circulating CD34+ cells, a surrogate marker for mobilization efficiency, are associated with less apheresis days. A higher dose of CD34+ cell transfused after high-dose chemotherapy decreases time to hematologic recovery. Consequently, a better understanding of variables associated with mobilization kinetics may further optimize stem cell collection and reduce complications associated with autologous stem cell transplants.
Methods: The Washington University (St. Louis, MO) transplantation database includes clinical parameters from 407 multiple myeloma (MM), 567 non-Hodgkin’s Lymphoma (NHL), and 164 Hodgkin’s disease (HD) pts who received an ASCT between 1995 and 2006. A retrospective analysis of this large pt population was conducted to determine factors associated with the mobilization kinetics of CD34+ cells.
Results: Figure 1 summarizes the mobilization kinetics as defined by number of days to reach a target of 2 × 10^6 CD34+ cells/kg. Overall, the median number of aphereses to reach the target were 1, 2, and 2 in MM, NHL, and HD, respectively. Daily median CD34+ yields in MM pts were 3.8, 1.2, and 0.5 × 10^6 on day 1–3, respectively. In NHL pts, yields were 1.4, 0.8, and 0.4 × 10^6 on day 1–3. In HD pts, yields were 1.8, 0.8, and 0.3 × 10^6 on day 1–3, respectively. The addition of chemotherapy increased the % of pts requiring only a single apheresis to reach the mobilization target. Figure 2 summarizes the mobilization kinetics for each re-mobilization regimen. In general, a limited number of cells was collected with each aphereses; >70% of pts failed to mobilize 2 × 10^6 CD34+ cells/kg. In contrast, remobilization with AMD3100 allowed the collection of sufficient CD34+ cells in 67% of pts; median number of apheresis to reach the target was 3.
Conclusions: Factors associated with mobilization kinetics of CD34+ cells include disease state and mobilization regimen. Re-mobilization is associated with high failure rates, re-mobilization regimens including AMD3100 are more successful.
Figure 1: Mobilization kinetics by disease state Figure 1:. Mobilization kinetics by disease state Figure 2: Mobilization kinetics by re-mobilization regimen Figure 2:. Mobilization kinetics by re-mobilization regimen