bluuebunny/crossref_metadata_2025_split huggingface dataset:
High Dose Therapy and Autologous Hematopoietic Cell Transplantation for Primary Refractory Diffuse Large Cell Non-Hodgkin’s Lymphoma.
Authors: Cao Thai M. , Stockerl-Goldstein Keith E. , Cao Paul D. , Laport Ginna G. , Sheehan Kevin , Shizuru Judith A. , Johnston Laura J. , Negrin Robert S. , Lowsky Robert 
Published: October 2019

Abstract
The efficacy of high dose therapy (HDT) and autologous hematopoietic cell transplantation (AHCT) for patients with diffuse large cell non-Hodgkin’s lymphoma (NHL) who never achieve a first complete remission (CR) with conventional chemotherapy have been addressed by few published studies. We retrospectively analyzed outcomes for 43 consecutive patients with chemotherapy-sensitive primary refractory diffuse large cell NHL treated with HDT and AHCT at our center between November 1988 and January 2002. The median age at transplant was 43 years (range: 18 – 64). At diagnosis 26 patients (60%) had stage IV disease, 28 patients (65%) had extranodal involvement, and bulky disease was present in 17 patients (40%). The age-adjusted NHL international prognostic index (IPI) score was low in 4 patients (9%), low-intermediate in 18 patients (42%), high or high-intermediate in 12 patients (28%), and not available in 9 patients (21%). All patients failed to achieve a first CR following CHOP (n = 31, 72%), R-CHOP (n = 6, 14%), and other anthracycline-containing regimens (n = 6, 14%). Fourteen patients (33%) did not receive additional conventional chemotherapy before proceeding to HDT and AHCT. The remaining 29 patients (67%) received in addition between 1 – 6 cycles of salvage chemotherapy. None of the 43 patients had achieved a CR at any time point before HDT and AHCT and all patients had measurable disease at the start of the HDT regimen. The median interval from diagnosis to HDT was 8.9 months (range: 2.4 – 15.5). The HDT regimen consisted of total body irradiation, etoposide, and cyclophosphamide in 15 patients (35%); BCNU, etoposide, and cyclophosphamide in 26 patients (60%); and CCNU, etoposide, and cyclophosphamide in 2 patients (5%). All but three patients (7%) were rescued with peripheral blood stem cells mobilized with cyclophosphamide 4 gm/m2 plus G-CSF and purged with monoclonal antibodies and complement. With a median follow-up of 5.8 years (range: 0.2 – 15.8) among surviving patients, the 5-year Kaplan-Meier estimates for overall survival was 67.4% (95% CI: 52.4 – 82.4), freedom from progression was 60.1% (95% CI: 43.7 – 76.6), and event-free survival was 55.8% (95% CI: 39.2 – 72.4). Two patients with relapse post-AHCT proceeded to non-myeloablative allogeneic HCT and were censored at the time of second transplant. By univariate analyses the following characteristics were not prognostically significant for overall survival: disease stage at diagnosis (I–II versus III–IV), prior radiotherapy, age-adjusted IPI score (low versus high) in evaluable patients, and the HDT regimen (TBI versus non-TBI). These results demonstrate that HDT and AHCT is effective treatment for chemotherapy-sensitive primary refractory diffuse large cell NHL.
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Efficient Viral Transduction of Murine Hematopoietic Stem Cells Using HIV-1 Gag-Pol Cross Packaged Simian Immunodeficiency Viral Backbone.
Authors: Lin Yuan , Gerson Stanton L. 
Published: October 2019

Abstract
Lentiviral vectors have been shown to infect non-dividing cells, including hematopoietic stem cell [HSC], and HIV lentiviral vector has been studied extensively in preclinical models. However low HIV lentiviral vector transduction efficiency compared to retroviral vectors, is seen in murine HSC, hampering transplantation and long-term expression of transgene in the recipients. Furthermore, concerns remain regarding the safety of HIV based vectors. Simian Immunodeficiency Viral [SIV] vectors could be safer since the parent virus does not cause disease in humans. However, to model this approach has been difficult because native SIV vectors do not transduce murine cells. We have generated a bicistronic SIV lentiviral SIN vector, containing MGMT and firefly luciferase genes linked by a self-cleavage FMDV 2A sequence. The SIV backbone was kindly provided by Dr. Donald Kohn (University of Southern California). The transgenes are controlled by the MND promoter, which has been shown to express well in murine hematopoietic stem cells. The vector was generated by cross-packaging SIV RNA with HIV-1 ΔR8.91 packaging plasmid and VSVG pseudotyped envelope (Ref. Retrovirology2005, 2:55). Unconcentrated viruses had an average titer of 1E+06 iu/ml, which was similar to HIV-1 lentiviral vectors. In vitro, HIV-1 cross-packaged SIV-mnd-MGMT-2A-Luc vector was able to transduce both human and murine cell lines with no reduction of expression for 10 weeks. In addition, this cross-packaged SIV vector was also able to transduce primary murine bone marrow cells from Balb/C mice with low MOI of 0.5 to 1. Transduced primary murine bone marrow cells maintained transgene expression during a 4 week culture. To analyze in vivo expression, Balb/C bone marrow cells were transduced for 48 hrs in cytokines with the HIV-1 packaged SIV vector and transplanted into irradiated recipients. We used bioluminescent imaging (BLI) to monitor the transgene expression and the dynamic engraftment of transduced murine bone marrow cells. At MOI of 0.5 or 5, transduction efficiencies in murine progenitor cells were 24.4% and 46.7% respectively by PCR of transgene from CFU colonies. Bioluminescent imaging indicated similar engraftment patterns of transduced bone marrow cells by HIV-1 lentiviral vector or cross-packaged SIV lentiviral vector, as early as day 5. Consistent BLI signals indicated sustained expression of transgene in SIV vector transduced bone marrow cells beyond 30 days. With this study, cross-packaged SIV SIN vector could be used as a potential gene transfer vector in both preclinical murine studies and perhaps in clinical trials.
HemoBase: A Multidisciplinary Registration Systeem in Hemato-Oncology.
Authors: Joosten Peter , Hoogendoorn Mels , Storm Huib , Kibbelaar Robby E. 
Published: October 2019

Abstract
HemoBase is a patient oriented prospective hemato-oncology database using three central concepts:
Report periods; Integrated Diagnosis; Multidisciplinary discussion of patient data.
The disease history of a patient is divided in report periods. Each containing an integrated diagnosis, a treatment plan and a therapy evaluation. The integrated diagnosis is composed of an overall diagnosis, the topography of the primary tumor and the prognostic factors. A new integrated diagnosis or new treatment strategy leads to a next report period. Relevant clinical and diagnostic data and conclusions leading to the integrated diagnosis are registered according to the (mandatory) international guidelines and coding systems (anamnesis, physical examination, clinical chemistry, blood and bonemarrow cytology, flowcytometry, histology, genetic analysis (i.e karyotyping, PCR, FISH), imaging studies (i.e. CT including perpendicular diameter calculation, MRI, PET). Microscopic or other images may be imported. Furthermore, it is possible to record general medication and make follow up notes during patient visits or hospital stay. HemoBase contains algorithms to determine prognostic factors and a diagnostic multiple myeloma algorithm. HemoBase registers chemo-, radio-, surgical- or transplantation therapy, including (inter)national trials and registration of toxicity and infections. Dose regimens and dose reduction are calculated automatically. Therapy evaluation includes response evaluation and registration of cause of death. Plenary discussion of patients is facilitated by providing on screen the list of patients to be discussed with a direct link to individual data. Essential items of patient status are shown in a nutshell on a visual time axis. Using the query module one can evaluate patient data for quality, research and management purposes, i.e. patient outcome for diagnosis X with therapy Y, or more complicated queries. The housekeeping part of the system contains a personal task list and an internal mail module. Using the management module fields, forms and thesauri may be configured by the user according to the latest standards, i.e. a new therapeutic trial, a new translocation, a new WHO diagnosis etc. Access to Hemobase and to the separate datasets is linked to hospital function (account name) and password protected.
HemoBase an application based on internet technology, currently implemented in the Dutch language and running on a central server. For access to the application Internet Explorer 6.0 is minimally required. At present, HemoBase is being used for a year in 6 different hospitals and laboratory locations in one region of the Netherlands (pop. 600.000) connected by secure intranet technology. This will be increased gradually and a HemoBase board will be developed for agreement and monitoring of registration protocols.
Burden of Visits for Treating Side Effects of Chemotherapy or Radiotherapy in Cancer Patients.
Authors: Henry David H. , Wade Shawn M. , Servin Mariana , Hershfield William 
Published: October 2019

Abstract
INTRODUCTION: The time incurred in seeking care for the treatment of side effects of chemotherapy (CT) or radiotherapy (RT) can result in lost productivity and resulting lost wages for cancer patients (pts) and their caregivers. The purpose of this study was to assess the amount of time spent by pts and caregivers to seek treatment for side effects of CT/RT and to examine productivity losses associated with such visits.
METHODS: A cross-sectional survey was conducted from April to May 2006 using a random sample of pts from a chronic illness panel of 550,233 pts. Inclusion criteria were being at least 18 years of age, diagnosed with cancer, and receiving CT and/or RT either currently or during the 12 months prior to participating in the study. Percentages and means were used to calculate descriptive statistics.
RESULTS: A total of 1,569 cancer pts were surveyed: 1,302 pts online and 267 pts by telephone. No significant differences were found between phone and online respondents. Of the pts currently receiving CT and/or RT (N=814), a total of 249 pts received treatment for side effects of CT/RT. The total time spent per visit to receive treatment for side-effects of CT/RT was approximately 5 hrs/visit including preparation time, travel time, and time spent at the clinic. Approximately one-half (54%) of the 249 patients currently receiving treatment for side effects of CT/RT were employed full-time (44%) or part-time (10%). Among employed patients currently receiving treatment for side effects of CT/RT, the mean number of work days missed as a result of visits for the treatment of CT/RT related side effects was 20 days per year. The primary reason for continuing to work during cancer treatment was financial need, reported by 59% of patients. Approximately 83% of all patients indicated that a caregiver generally accompanied them on their visits to the doctor’s office, clinic, or hospital to receive treatment for side effects of CT/RT. Seven out of ten caregivers (68%) were reported as being employed either full-time (62%) or part-time (6%).
CONCLUSIONS: Time related burden for patients receiving treatment for side effects of CT/RT and their caregivers is significant. Reduction in frequency of such visits is important from the standpoint of patients’ economic livelihood and can stand to benefit employers and society.
Table 1. Time Spent on Healthcare Provider Visits for Treatment of Side Effects Related to Chemotherapy and/or Radiation (N=249) Activity (per visit) Minutes Spent (mean) Standard Deviation Minutes Spent (median) Preparing to go to the doctor’s office, clinic or hospital 81 127 55 Travel to and from the doctor’s office, clinic, or hospital 102 188 58 Waiting at the doctor’s office, clinic, or hospital to see the doctor or another healthcare professional 64 72 39 Seeing the doctor or another healthcare professional 64 75 43 Total 311 380 210
Integrated Diagnosis Treatment Combinations To Improve Cure.
Authors: Van Hoef Marlies E.H.M. 
Published: October 2019

A diagnosis treatment combination is defined as a combination of compounds or treatment modalities that is prescribed at diagnosis of a disease or disease condition. Combinations are administered when a synergistic or additive effect is known or a protection can be anticipated.
In hematological malignancies the highest probability of disease free survival can be obtained by a fast remission-induction and consolidation of complete response at diagnosis followed by an allogeneic transplant in first complete remission to eradicate residual malignant cells. Effects of treatment that induce side effects are to be controlled to reduce treatment risks. Therefore, ablative allogeneic transplants are more and more replaced by non-myeloablative reduced intensity conditioning transplants. In acute leukemia these transplants have a much more dramatic course than in more indolent hematological malignancies and solid tumors.
In the Netherlands reimbursement for treatment components such as remission induction chemotherapy, an autologous transplant and an allogeneic transplant are currently reimbursed as independent diagnosis treatment combinations. Review of epidemiological data of cancer incidence and death in the Netherlands reveal that treatment of hematological malignancies are poor compared to projections in the United States. In the period 1997 to 2003 treatment results in the Netherlands are more or less stable except for Hodgkin’s disease; allogeneic transplantation has mainly been reserved for hematological malignancies (figure 1). Epidemiological data show that no improvement was achieved. In particular leukemia’s do poor. American Cancer Society projections show that there is a trend towards improvement in the USA for leukemias, non-Hodgkin lymphoma and in myeloma in the period 1997–2005 (figure 2).
Non-myeloablative reduced intensity conditioning autologous and/or allogeneic transplants are the curative element for transplantable diseases not curable by standard or intensified cytotoxic cytoreductive therapy. Critical also is rapid remission induction. Delay of transplantation to later stage than first complete remission only increases costs and risk of treatment or disease related mortality. We will present our protocol full of treatment plans to support in improving cure internationally. (www.transplantcreations.com).
Death/incidence ratio per 100.000/annum Netherlands Death/incidence ratio per 100.000/annum Netherlands Death/incidence ratio per 100.000/annum USA Death/incidence ratio per 100.000/annum USA
Health Economic Review of Recombinant Activated Factor VII (Novoseven®) for Treatment of Bleeding Episodes in Hemophilia Patients with Inhibitors.
Authors: Stephens Jennifer M. , Botteman Marc F. , Joshi Ashish V. , Sumner Michael 
Published: October 2019

Abstract
OBJECTIVE: Severe hemophilia with inhibitors is a rare disease with substantial clinical, humanistic, and economic consequences. Within the past few years, a number of formal economic analyses have emerged which examined the cost of treating bleeding episodes with recombinant activated factor VII (rFVIIa) versus plasma-derived agents. Thus the objective was to review the recent health economic analyses of rFVIIa in the management of patients with hemophilia and inhibitors.
DATA SOURCES: Published, English-language medical literature on the economics of rFVIIa was searched from January 1996 through July 2006 using: the MEDLINE/PubMed database, PubMed related articles feature, company knowledge of published medical literature for rFVIIa that was not indexed by MEDLINE/PubMed, and a thorough review of retrieved article bibliographies.
STUDY SELECTION AND DATA ABSTRACTION: Abstracts selected for full article retrieval/review were those that specifically mentioned (or implied that the full article would address) cost impact, cost of treatment, or cost-effectiveness for rFVIIa in patients with hemophilia and inhibitors. Of 70 abstracts reviewed, 30 articles were selected for retrieval, and from those, thirteen economic analyses (6 burden of illness and 7 comparative studies) met inclusion criteria for data abstraction and synthesis. Seventeen articles were excluded for the following reasons: reports of basic drug acquisition costs without formal economic analysis, single case reports, studies without inhibitor patients, or studies of immune tolerance therapy.
DATA SYNTHESIS: The economic impact of rFVIIa on hospitals and treatment centers occurs primarily during hospitalization to manage major bleeding episodes and allow for elective orthopedic surgeries that would not have been attempted without availability of rFVIIa. Six out of seven comparative analyses for on-demand treatment suggest that total cost of treating a bleeding episode with rFVIIa may be lower than that of using plasma-based agents due to faster bleeding resolution, higher initial efficacy rates, and avoidance of second and third lines of treatment. Dosing assumptions for the various agents compared in the economic analyses were the most sensitive variables.
CONCLUSIONS: The currently available literature suggests that rFVIIa is a cost-effective treatment option and may ultimately lead to improvement in clinical outcomes for patients with hemophilia and inhibitors.
Once Weekly Subcutaneous Idraparinux Versus Placebo in the Extended Treatment of Deep-Vein Thrombosis or Pulmonary Embolism. The van Gogh Investigators.
Authors: Buller Harry R. ,   on Behalf of the Van Gogh Investigators
Published: October 2019

Abstract
Background. Although vitamin K antagonists are effective for treatment of venous thrombo-embolism, in many patients their extended use is constrained by limitations of risk-benefit and inconvenience. We evaluated whether an extended six-month treatment with idraparinux would be effective and safe in patients with venous thrombo-embolism who had received an initial 6-month anticoagulant treatment.
Methods. We randomly assigned patients warranting consideration of extending anticoagulation, and who had completed 6-months of either idraparinux or vitamin K antagonist treatment, to once weekly injections of either 2.5 mg of idraparinux without monitoring or placebo for 6 months. Recurrent venous thrombo-embolism and major bleeding were assessed during this period as the primary efficacy and safety outcomes.
Results. Of 1215 patients, 6 (1.0 percent) idraparinux and 23 (3.7 percent) placebo recipients had recurrent venous thrombo-embolism (p=0.002). Eleven (1.9 percent) idraparinux, but no placebo recipients, had major bleeding (p=0.0007), including 3 fatal intracranial bleeds. The patients previously treated with idraparinux (versus a vitamin K antagonist) had a lower incidence of recurrent thrombo-embolism among those randomized to placebo (0.7 versus 5.9 percent, respectively P=0.003), and a higher incidence of major bleeding among those randomized to idraparinux. (3.1 versus 0.9 percent, respectively, P=0.1647).
Conclusion: This placebo controlled trial demonstrated the effectiveness of idraparinux during a 6-month extended treatment, at the expense of an increased risk of bleeding. Previous administration of idraparinux was associated with extended anti thrombotic activity in the placebo recipients.
Potential Tolerizing Capacity of Human Dendritic Cells Featuring High Levels of Expression and Activity of the Tryptophan Metabolizing Enzyme Indoleamine 2,3 Dioxygenase.
Authors: Heitger Andreas , Juergens Birgit , Hainz Ursula , Fuchs Dietmar 
Published: October 2019

Abstract
An enhanced tryptophan metabolism mediated by the enzymatic activity of indoleamine 2,3 dioxygenase (IDO) has recently been demonstrated to profoundly affect T cell responses. By the present study we explored whether human dendritic cells (DCs) displaying high IDO expression and activity, down-regulate allogeneic T cell responses. A comparison of lipopolysaccaride (LPS), interferon-γ (IFN-γ), and CD40L as DC maturation agents showed that most abundant IDO expression and activity in DCs was observed when immature DCs were exposed to a combination of LPS and IFN-γ for 48 hours. This time period of maturation was associated with the development of a mature DC phenotype. In contrast, semi-mature DCs, i.e. DCs matured for 4 hours only, were IDO negative. In co-cultures with allogeneic T cells both types of DCs began to metabolize tryptophan, as determined by decreasing concentrations of tryptophan and increasing concentrations of kynurenines in cell culture supernatants, but mature IDO positive DCs did so at a faster rate (complete consumption of tryptophan within 16 hours of co-culture) than semi-mature DCs. A comparison of the allo-stimulatory capacity of semi-mature IDO negative DCs and mature IDO positive DCs showed that at a high DC/T cell ratio (1:1) IDO positive DCs had a significantly reduced capacity to stimulate allogeneic T cells (median 63% reduction, n=5). The reduction of the allogeneic T cell response induced by IDO positive DCs was reversed upon the addition of the IDO inhibitor methylhydantoin-tryptophan to the co-cultures, suggesting an IDO dependent mechanism. Furthermore, allogeneic T cells exposed to IDO positive DCs had
an increased rate of apoptosis in the activated cell fraction and after 8 days of co-culture contained a cell fraction (~30%) displaying a CD4+CD25+highFOXP3+ phenotype.
These latter cells, when enriched by fluorescent activated cell sorting (FACS), were able to suppress the proliferative response of naive T cells to anti-CD3 mediated stimulation, which indicates the generation of a regulatory T cell population by IDO positive DCs. Together, these findings suggest that the amount of IDO expression and activity by DCs is one feature to govern the type of response of stimulated T cells. Human DCs can be induced to display high levels of IDO expression and activity and, thereby, acquire the ability to effectivley modulate allogeneic T cell responses towards tolerance by
eliminating allo-reactive T cells through apoptosis and augmentation of their regulatory rather than their effector potential.
Our current approaches address whether this property can be employed to use DCs for the generation of allo-antigen specific tolerance in the setting of hematopoietic cell transplantation.