bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use and Outcomes of Epoetin Alfa and Darbepoetin Alfa for Anemic Cancer Patients in Outpatient Community Practice Settings.
Authors: Fahrbach Kyle R. , Frame Diana , Sercus Brian , Schenkel Brad 
Published: October 2019

Abstract
Objective: To assess the treatment patterns and hematologic outcomes associated with epoetin alfa (EPO) and darbepoetin alfa (DARB) for the treatment of anemic cancer patients in the community practice setting.
Methods: A retrospective observational study design was used. De-identified data from patients receiving care in community oncology practice settings were obtained from an electronic medical record system. Eligible patients were >= 18 years of age, had a cancer diagnosis, and were treated with an erythropoiesis stimulating agent (ESA: EPO or DARB) during the period July 2002 – July 2004, with baseline anemia (Hb<=11 g/dL) and at least one follow-up Hb value. No other selection criteria were applied (e.g. ESA dose, tumor type, chemotherapy treatment) in keeping with the objective of characterizing outcomes in a real-world setting. Data were summarized by treatment overall and by using a multivariate model adjusting for age, gender, baseline Hb, clinic site, ECOG performance score, type of cancer (solid vs hematologic) and chemotherapy (platinum vs non-platinum vs. none). Patient selection criteria and analytic methods were determined prospectively. The cost for each ESA was calculated based on 2004 average wholesale prices ($13.36 per EPO 1,000 U; $4.99 per 1 mcg DARB).
Results: 2382 EPO and 1399 DARB patients were eligible for analysis. The two groups were comparable in terms of baseline characteristics (62% female, 75% solid tumors, mean baseline Hb 9.9 g/dL). Only about two-thirds of patients were treated with standard dosing regimens of the two agents in the US (EPO 40,000 U qw, DARB 200 mcg q2w). Hematologic outcomes observed in patients receiving EPO were consistently better than those in patients receiving DARB.
Table 1. Hematologic outcomes by ESA treatment EPO DARB p value Week 4 Hb change (g/dL) 0.79 0.59 <0.001 % Early Hb response (Hb change >=1 g/dL at 4 weeks) 61.5 55.2 0.004 % Hb response (Hb change >=2 g/dL by end of treatment episode) 41.4 34.7 <0.001 % Hematopoietic response (Hb change >= 2 g/dL or reaching 12 g/dL by end of treatment episode) 52.3 44.6 <0.001
The mean treatment durations for patients receiving EPO and DARB were 55.3 and 62.5 days, respectively. Mean cumulative doses were 231,211 U for EPO and 857 mcg for DARB. These doses resulted in an average cost per patient of $3,089 for those receiving EPO and $4,276 for those receiving DARB.
Conclusion: These results, based on over 3000 community-treated cancer patients, reinforce previous findings of earlier and greater overall hematologic response for EPO vs. DARB in this setting. Additionally, based on mean cumulative doses, the cost of DARB per patient was substantially greater than that of EPO. Additional studies of variations in dosing regimens used in the community setting are warranted, as are well-powered, randomized, controlled trials to further confirm the clinical results observed here.
Rituximab vs Observation after High-Dose Consolidative First-Line Chemotherapy (HDC) with Autologous Stem Cell Transplantation in Poor Risk Diffuse Large B-Cell Lymphoma. Final Analysis of the LNH98-B3 GELA Study.
Authors: Haioun Corinne , Mounier Nicolas , Emile Jean François , Feugier Pierre , Coiffier Bertrand , Tilly Hervé , Recher Christian , Fermé Christophe , Gabarre Jean , Herbrecht Raoul , Morschhauser12 Frank , Gisselbrecht Christian 
Published: October 2019

Abstract
We have shown (Haioun, JCO 2000) that consolidative HDC provides a better survival for patients (pts) with aggressive non-Hodgkin’s lymphoma presenting with 2 or 3 adverse age-adjusted International-Prognostic-Index (aa-IPI) factors in complete remission after induction treatment. In the same time, rituximab had been evaluated as a single therapeutic agent in aggressive lymphomas with promising efficacy (Coiffier, Blood 1998). More recently, rituximab maintenance therapy has been successfully used after chemotherapy or after ASCT to keep responding patients in remission.
The primary objective of the present study was to evaluate the potential benefit, as randomly compared to observation, of rituximab - 375 mg/m2/week for 4 weeks - 2 months after HDC, in decreasing the relapse rate (second randomization: R2). A secondary objective was to improve the response rate before HDC treatment using the intensified ACE chemotherapy regimen (doxorubicin 75mg/m2 d1, cyclophosphamide 1g/m2 d1-d2, etoposide 150mg/m2 d1–d3) as compared to the standard GELA ACVBP induction regimen (first randomization: R1). Induction regimens were delivered every 15 days for 4 cycles. In responding pts, peripheral blood stem cell (PBSC) collection was performed after the third or fourth cycle. HDC (mitoxantrone 45 mg/m2, cyclophosphamide 1500 mg/m2 x 4d, etoposide 250 mg/m2 x 4d and carmustine 300 mg/m2) was started between d80 and d90 after one or two courses of high-dose methotrexate.
From 10/99 to 05/03 (closing date), 476 pts younger than 60 years with diffuse large B-cell lymphoma and aa-IPI 2 or 3 (aa-IPI 3: 29%). were enrolled. We here present the results of the final analysis, performed in July 2005 with 235 pts assigned to receive ACE and 241 to ACVBP. Complete response (CR+CRu) rates to induction treatment did not significantly differ between the 2 regimens (65% and 63%, respectively, p=0.71) and toxic death rates were similar (2% and 3%, respectively) despite higher NCIC grade 3–4 infectious toxicity with the ACE regimen. Among the 331 pts who received HDC, 269 were randomized (R2) to receive either rituximab (n=139) or observation (n=130). 545 infusions of rituximab were administered with no clinically relevant infectious toxicity except two resolutive VZV infections. With a median follow-up of 3 years after R2, a trend toward a better 3y-EFS was observed in the rituximab group (80% vs 72%, p=0.10).
Early and brief rituximab maintenance is feasible after HDC. We hypothesize that prolongation of treatment may improve the results as well as selection of patients more likely to respond to rituximab therapy.
New Transplant Strategies Utilizing Radioimmunotherapy (RIT) Based Regimens To Reduce Relapse in High Risk Mantle Cell Lymphoma (MCL).
Authors: Krishnan Amrita , Raubitschek Andrew , Forman Stephen J. , Fung Henry , Molina Arturo , Yamauchi David , Falk Peter , Spielberger Ricardo , Popplewell Leslie , Rodriguez Roberto , Parker Pablo , Chow Warren , Nakamura Ryoto , Nademanee Auayporn 
Published: October 2019

Abstract
The treatment of high-risk MCL remains a challenge. High dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT) has been used for some of these patients (pts). However, relapse rates remain high. RIT with single agent 90Yttrium(90Y) ibritumomab tiuxetan (Zevalin®) has demonstrated activity in pts with relapsed MCL. Therefore, we postulated that the combination of 90Y with HDC and ASCT may reduce relapse rates of pts with high- risk MCL. Between 5/00 and 9/04 eighteen pts with MCL were enrolled on one of two RIT ASCT trials. The first was a phase I/II dose escalation trial of high-dose 90Y + cyclophosphamide 100mg/kg (day -4) and etoposide 60mg/kg(day-2). Pts underwent dosimetry day-21 with 5mCi Indium111 followed a week later by 90Y to deliver a maximum target dose of 1000cGy to normal organs. The second study was a phase I/II trial of standard dose 90Y (0.4mCi/kg) administered day-14 and BEAM (day-8 to day-2, BCNU300mg/m2, cytarabine 800mg/m2, etoposide 800mg/m2, melphalan 140mg/m2). Ten pts who were>60yrs or had received prior dose-limiting radiation were placed on the 90Y BEAM trial while the other 8 received high-dose 90Y. The median age at ASCT was 58 years (range 44–72). Disease status at ASCT included 1st CR -9(high or high intermediate IPI score), 1st PR-4, 1st relapse -4, 2nd CR-1. Fifty percent had received HyperCEVAD chemotherapy and 56% had Rituximab prior to ASCT. Thirteen pts had stage IV disease, 5 had stage III disease. The median 90Y dose administered was 40mCi (range 27–100). Treatment was well tolerated. Engraftment to anc>500 occurred at a median of 10 days (range 9–26). Reversible grade 3 pulmonary toxicity occurred in 5 pts. This included steroid responsive pneumonitis in four and acute respiratory distress related to sepsis in one. One pt with a prior history of heavy alcohol use died of liver failure at four months post ASCT. Four pts have relapsed and two have died of disease progression. With a median follow up of 19 months (range 6–60), the estimated overall survival and disease free survival at two years are 79% (CI 55–91) and 59% (CI 43–73) respectively. By univariate analysis 90Y dose did not correlate with risk of relapse. To date, no relapses were seen beyond the first twelve months (see figure). In conclusion 90Y based transplant conditioning regimens are well tolerated, even in older pts. The apparent plateau in the relapse rate is encouraging and suggests that this approach may lead to durable remissions in pts with high-risk MCL.
Figure Figure
Application of FASTTM Fragment-Based Lead Discovery and Structure-Guided Design to Discovery of Small Molecule Inhibitors of BCR-ABL Tyrosine Kinase Active Against the T315I Imatinib-Resistant Mutant.
Authors: Burley Stephen K. 
Published: October 2019

Abstract
The Philadelphia chromosome translocation creates a BCR-ABL fusion gene that encodes a constitutively active BCR-ABL tyrosine kinase, which gives rise to chronic myelogenous leukemia (CML). The clinical success of imatinib (Gleevec) demonstrated that BCR-ABL tyrosine kinase inhibitors can provide effective treatment for CML. However, some CML patients treated with imatinib develop resistance leading to disease progression. The majority of resistance is due to point mutations in BCR-ABL, which give rise to active mutant enzymes that are insensitive to imatinib. In all, ~30 imatinib-resistant BCR-ABL mutants have been identified in clinical isolates. The T315I mutant represents ~20% of clinically observed mutations, making it one of the most common causes of resistance. Second-generation BCR-ABL inhibitors, including AMN-107 and BMS-354825, inhibit many of the clinically relevant mutants but not T315I. Mutant T315I BCR-ABL is, therefore, an important and challenging target for discovery of CML therapeutics. We have applied a proprietary X-ray crystallographic fragment-based lead discovery platform (FASTTM) and structure-guided lead optimization to identify potent inhibitors of wild-type BCR-ABL and the four most common mutants, including T315I. Our lead discovery efforts yielded five chemical series that inhibit both wild-type (WT) and T315I BCR-ABL. Compounds in our most advanced lead series potently inhibit proliferation of K562 cells and Ba/F3 cells with WT BCR-ABL and the four major clinically relevant BCR-ABL mutations (T315I, E255K, M351T, Y253F; see below). Further details describing in vitro and in vivo profiling of these novel BCR-ABL T315I inhibitors will be presented.
Ba/F3 cell proliferation for BCR-ABL Inhibitors (EC50, nM) BCR-ABL Form Imatinib AMN-107 BMS-354825 SGX-70430 WT 790 33 12 11 T315I > 10000 > 10000 > 10000 21 Y253F 5700 370 8 334 E255K 8300 350 7 77 M351T 2000 38 28 15 Control Assay Ba/F3 (T315I) + IL3 > 10000 > 10000 > 10000 > 10000
Outpatient Management of Pulmonary Embolism: Results from the National Multicentre PE Study.
Authors: Rhodes Susan , Bond Sarah , Green Sarah , Wimperis Jennie Z. , Pendry Kate , Davies Christopher W.H. , Medhi Ijaz , Killen Jeremy 
Published: October 2019

Abstract
Pulmonary embolism (PE) is a common complication of deep vein thrombosis(DVT). It has been shown that low molecular weight heparin (LMWH) may be used to treat PE and DVT and that home treatment of DVT with LMWH is safe and effective. A study published in 2000 suggested that outpatient management of PE is feasible and safe for the majority of patients. Phase 1 of this study showed that 44% of patients fulfilled criteria for theoretical outpatient management and that there were no bleeding or theomboembolic complications in the LMWH treatment phase in this group suggesting that these patients could safely have been discharged early.
In Phase 2 of the study all patients with a confirmed PE (high probability VQ scan, positive CT pulmonary angiogarm or clincal features of PE plus radiologically confirmed DVT) were entered into the early discharge scheme if they fulfilled criteria validated in phase 1, patients consented and they were discharged within 72 hours of presentation. Patients were treated with 175 Anti-Xa IU/kg tinzaparin (Innohep®) daily (for a minimum of 6 days) and oral anticoagulant therapy. Patients were excluded if: age < 18, admission for additional monitoring or treatment, active bleeding or bleeding disorder, poor compliance or morbidity, pregnant, previous PE, co-existing major DVT and patient preference. Outcome data were collected at 3 and 6 months including mortality and thromboembolic or bleeding events (early, whilst receiving LMWH, and late, after cessation of LMWH). Patients were asked to complete a satisfaction score using 10-point visual analogue score at the end of LMWH treatment phase and to indicate their preference for inpatient or outpatient management for any future episodes of PE.
107 patients with confirmed PE across 6 centres were discharged early. All patients completed the acute treatment phase with Innohep® and outcome data for this period were available for 100% patients. 3 month outcome data were available in 93 (86%) patients. There were no bleeding, thromboemblic complications, deaths or related readmissions in the early treatment phase. 1 patient experienced an anxiety episode in the early treatment phase and required reassessment but not readmission. Patients received a mean of 7.6 days of Innohep® and this was continued for a mean of 5.5 days after discharge, indicating that outpatient management of PE saved up to 5.5 inpatient bed days. 79.5% of patients completed the satisfaction score - the mean score was 9.3 indicating that patients were highly satisfied with outpatient treatment. 98% of patients expressed a preference for outpatient management. There were no significant adverse events in the acute LMWH treatment phase indicating that selected patients with a confirmed PE can safely be managed as outpatients in schemes similar to outpatient management of DVT and that this is highly acceptable to patients.
Sequential Treatment with the Anti-CD 20 Antibody Rituximab and CHOP+GCSF Chemotherapy in Patients with Post-Transplant Lymphoproliferative Disorder (PTLD): First Interim Analysis of a Multicenter Phase II Study.
Authors: Trappe Ralf , Oertel Stephan , Choquet Sylvain , LeBlond Vernoique , Papp-Vary Matthias , Riess Hanno 
Published: October 2019

Abstract
Post-transplant lymphoproliferative disorders (PTLD) are a main causative factor for mortality after organ transplantation. In January 2003 we started a multicenter phase II trial investigating a sequential treatment of the anti-CD 20 antibody rituximab and CHOP + GCSF chemotherapy. 29 patients have been enrolled so far. 14 patients were renal transplant recipients, 5 were heart transplant recipients, 7 were liver transplant recipients, 1 was a combined heart/lung transplant recipient, one was a combined kidney/pancreas transplant recipient and one patient was after bone marrow transplantation. Patients were treated with four weekly doses of 375mg/m2 of rituximab as a single therapeutic agent at days 1, 8, 15 and 22. CHOP chemotherapy had been administered at days 50, 72, 94 and 116 and was followed by GCSF starting at day 3 of each chemotherapy cycle. In case of disease progression during administration of rituximab or during the 4-week interval between antibody therapy and CHOP administration the patients directly entered chemotherapy. Histology divided in 21 diffuse large cell-, 2 marginal zone-, 1 Burkitt lymphoma and 3 polymorphic lymphoproliferations. 18 patients had stage III or stage IV disease. Patient age ranged from 16 to 80 years with a median age of 55 years and a mean age of 50.9 years. Time from transplantation to diagnosis divided the patients into two groups. The first group is defined by a median time from transplantation to diagnosis of 6 months (range 1 to 11 months, 11 patients, early PTLD), and a second one is defined by a median time from transplantation to diagnosis of 90 months (range 19 to 204 months, 16 patients, late PTLD). EBV-status was available for 19 patients with 10 EBV-associated PTLD and 9 non-EBV associated PTLD. In August 2005 24 patients were evaluable for treatment response, 25 were evaluable for treatment toxicity. In 84 applied chemotherapy cycles WHO 3°–4° leucopenia occurred in 29 cycles. 9 patients suffered from WHO 3°–4° infections. There were 3 early deaths due to therapy-associated complications. 15 patients (62.5%) achieved complete remission. Partial remission was observed in 5 patients (20.8%). 5 patients experienced progressive disease. With a mean follow up of 10.7 months four patients relapsed. There was no difference in response to rituximab therapy and in response to the sequential treatment of rituximab followed by CHOP chemotherapy for EBV-positive and EBV-negative PTLD. In summary sequential treatment of PTLD with rituximab and CHOP+GCSF is associated with an acceptable toxicity profile and is highly effective with a overall response rate of 83.3%.
PRTX-100 Inhibits Platelet Phagocytosis In Vitro.
Authors: Yatko Chris , Herrem Christopher , Siddiqui Samia , Sloan Victor S. 
Published: October 2019

Abstract
Background: In idiopathic thrombocytopenic purpura (ITP), autoantibodies bind to platelets which are then phagocytosed by monocytes/macrophages and removed by the reticuloendothelial system. PRTX-100 (Staphylococcal protein A) is being investigated for the treatment of ITP.
Objective: To assess the effect of PRTX-100 on phagocytosis of platelets in an in vitro assay.
Methods: Human monocytes were isolated from whole blood peripheral blood mononuclear cells (PBMCs) by adherence and cultured for 6 days in RPMI + 5% human serum. 48 hours prior to phagocytosis assay, PRTX-100 was added at 250, 25, and 2.5ng/ml. Human platelets were labeled with a fluorescent (PerCP) lipophilic dye and opsonized with an antibody to MHC Class I (W632). 2×10−5 monocytes were co-cultured with 2×10−7 labeled platelets for 1 hour at 37 ° C. All conditions were performed in triplicate. After an hour, phycoerythrin (PE) labeled anti-CD61 antibody was added to assess surface bound platelets versus ingested platelets. Phagocytosis was determined by flow cytometric analysis. The monocyte population was gated upon by forward and side scatter properties, then verified by staining with CD14-FITC. Percent phagocytosis was calculated as the fraction of ingested platelets (PerCP +/CD61−) to the total PerCP population (PerCP +/CD61−) + ( PerCP+/CD61+) within the gated monocyte population.
Results: PRTX-100 inhibits the phagocytosis of W632 opsonized platelets by human monocytes. Phagocytosis of W632 opsonized platelets was 40%, while phagocytosis in the presence of PRTX-100 at concentrations of 250, 25, and 2.5ng/ml was 18.3%, 23%, and 24.3%, respectively. Phagocytosis at 250ng/ml and 25ng/ml was significantly different from control phagocytosis with p values of 0.014 and 0.001 respectively by Student’s t test.
Conclusions: PRTX-100 inhibits the phagocytosis of platelets by monocytes, the effector limb of ITP. Prevention of platelet phagocytosis is an important treatment goal in ITP. PRTX-100 has been shown to be generally safe and well-tolerated in a phase I study in healthy volunteers (J Clin Pharmacol, in press). PRTX -100 is a promising therapeutic option for ITP and deserves further study.
Effect of PRTX-100 on In Vitro Phagocytosis of Opsonized Human Platelets Effect of PRTX-100 on In Vitro Phagocytosis of Opsonized Human Platelets
Prevalence and Clinical Significance of Elevated Antiphospholipid Antibodies in Adults with Immune Thrombocytopenic Purpura.
Authors: Pierrot-Deseilligny Carole , Khellaf Mehdi , Gouault Michele , Intrator Liliane , Michel Marc , Bierling Philippe , Godeau Bertrand 
Published: October 2019

Abstract
Background: The clinical and pathogenic significances of the presence of antiphospholipid antibodies (APA) [anticardiolipin antibodies (aCL) and lupus-like anticoagulant (LA)] in patients with immune thrombocytopenic purpura (ITP) remain controversial.
Objective: To determine the prevalence and clinical significance of positive APA in a large monocentric cohort of adults with newly diagnosed ITP.
Methods: aCL (IgG and IgM) and LA were searched at time of diagnosis in 260 adults with ITP and a platelet count < 50×109/L over a 15 years period. Thirty-five patients with definite systemic lupus, 5 with primary antiphospholipid syndrome and 4 with HIV infection were excluded and the analysis was performed on 216 patients.
Results: APA (aCL and LA) were detected at ITP diagnosis in 55 patients (25%) including: IgG-aCL in 43 patients (20%) with a level between 15-39 UI/L in 31 and ≥40UI/l in 12; IgM-aCL in 11 patients (5%); and LA in 16 patients (7%). LA was associated with IgG-aCL in 14 patients, IgM-aCL in 1 patient, and was isolated in 1 patient. Positive test for LA was correlated with the presence of highly positive IgG-aCL (≥40UI/L) (p=0.001). Age, gender, initial platelet count, acute or chronic outcome of ITP were not associated with the presence of APA (aCL and LA), aCL and LA status except for age which was lower in LA positive group (mean age 22 years vs 42 years in LA negative group, p=0.002). After a median follow-up of 31 months (range: 1 to 185 months), 15/216 (7%) patients experienced a thrombosis (arterial = 3, deep venous thrombosis and/or pulmonary embolism = 12); 5 of whom (33%) had positive aCL (with a level ≥ 40 UI/L in 4). In 4 of these 5 patients, aCL were associated with positive LA. In multivariate analysis, thrombosis events were associated with age [Hazard ratio = 1.5 (IC95% : 1.1–2.0], presence of LA [Hazard ratio = 6.5 (IC95% : 1.7–25.5] or presence of IgG-aCL at high level (≥40UI/L) [Hazard ratio = 6.1 (IC95% : 1.6–23.7]. In contrast, there was no association of thrombosis events with sex, platelet count at diagnosis, acute or chronic evolution (≥ 6 months), antinuclear antibodies or treatments used.
Conclusions: Prevalence of APA (25%) in adults with newly diagnosed ITP is lower in our cohort than previously observed in other studies. Though the incidence of thrombosis is significantly increased in patients with LA and/or highly positive aCL, this risk seems too low to recommend a systematic testing in patients with ITP and no previous history of thrombosis.