Mobilization of hematopoietic stem cells with the novel CXCR4 antagonist POL6326 (balixafortide) in healthy volunteers—Results of a dose escalation trial

Background: Certain disadvantages of the standard hematopoietic stem and progenitor cell (HSPC) mobilizing agent G-CSF fuel the quest for alternatives. We herein report results of a Phase I dose escalation trial comparing mobilization with a peptidic CXCR4 antagonist POL6326 (balixafortide) vs. G-CSF. Methods: Healthy male volunteer donors with a documented average mobilization response to G-CSF received, following ≥6 weeks wash-out, a 1–2 h infusion of 500–2500 µg/kg of balixafortide. Safety, tolerability, pharmacokinetics and pharmacodynamics were assessed. Results: Balixafortide was well tolerated and rated favorably over G-CSF by subjects. At all doses tested balixafortide mobilized HSPC. In the dose range between 1500 and 2500 µg/kg mobilization was similar, reaching 38.2 ± 2.8 CD34 + cells/µL (mean ± SEM). Balixafortide caused mixed leukocytosis in the mid-20 K/µL range. B-lymphocytosis was more pronounced, whereas neutrophilia and monocytosis were markedly less accentuated with balixafortide compared to G-CSF. At the 24 h time point, leukocytes had largely normalized. Conclusions: Balixafortide is safe, well tolerated, and induces efficient mobilization of HSPCs in healthy male volunteers. Based on experience with current apheresis technology, the observed mobilization at doses ≥1500 µg/kg of balixafortide is predicted to yield in a single apheresis a standard dose of 4× 10E6 CD34+ cells/kg from most individuals donating for an approximately weight-matched recipient. Exploration of alternative dosing regimens may provide even higher mobilization responses. Trial Registration European Medicines Agency (EudraCT-Nr. 2011-003316-23) and clinicaltrials.gov (NCT01841476

Superior physical and mental health of healthy volunteers before and five years after mobilized stem cell donation

Background: Safety, tolerability and efficacy of granulocyte colony-stimulating factor (G-CSF) for mobilization of hematopoietic stem and progenitor cells (HSPCs) from healthy donors have been conclusively demonstrated. This explicitly includes, albeit for smaller cohorts and shorter observation periods, biosimilar G-CSFs. HSPC donation is non-remunerated, its sole reward being “warm glow”, hence harm to donors must be avoided with maximal certitude. To ascertain, therefore, long-term physical and mental health effects of HSPC donation, a cohort of G-CSF mobilized donors was followed longitudinally. Methods: We enrolled 245 healthy volunteers in this bi-centric long-term surveillance study. 244 healthy volunteers began mobilization with twice-daily Sandoz biosimilar filgrastim and 242 underwent apheresis after G-CSF mobilization. Physical and mental health were followed up over a period of 5-years using the validated SF-12 health questionnaire. Results: Baseline physical and mental health of HSPC donors was markedly better than in a healthy reference population matched for ethnicity, sex and age. Physical, but not mental health was sharply diminished at the time of apheresis, likely due to side effects of biosimilar G-CSF, however had returned to pre-apheresis values by the next follow-up appointment after 6 months. Physical and mental health slightly deteriorated over time with kinetics reflecting the known effects of aging. Hence, superior physical and mental health compared to the general healthy non-donor population was maintained over time. Conclusions: HSPC donors are of better overall physical and mental health than the average healthy non-donor. Superior well-being is maintained over time, supporting the favorable risk–benefit assessment of volunteer HSPC donation. Trial registration National Clinical Trial NCT0176693

Zeitschriftenrankings für die Wirtschaftswissenschaften - Konstruktion eines umfassenden Metaindexes

This article constructs several meta-indexes of journal rankings from existing journal rankings which all have limited coverage. It is applicable both for researchers in the field of economics and business administration (including their respective subfields) and includes also journals which are published in German. We discuss the relative merits of meta-indexes based on peer assessment and on citations. Copyright 2008 der Autoren Journal compilation 2008, Verein für Socialpolitik und Blackwell Publishing Ltd.

Zur Aussagekraft von Idealpunktschätzungen in parlamentarischen Systemen. Eine Analyse potentieller Auswahlverzerrungen

Die Idealpunktschätzung auf Grundlage namentlicher Abstimmungen zur Ermittlung politischer Positionen von Parteien und Abgeordneten ist eine auch außerhalb der Forschung zum U.S.-Kongress zunehmend häufig genutzte Technik. Unser Beitrag setzt sich mit den handlungstheoretischen und methodischen Herausforderungen dieser Technik in parlamentarischen Systemen auseinander. Dabei argumentieren wir, dass das Problem der Auswahlverzerrung der Stichprobe namentlicher Abstimmungen auch bei der Idealpunktschätzung berücksichtigt werden muss. Konkret zeigen wir, dass der Dualismus von Regierung und Opposition je nach Abstimmungsvorlage die politischen Positionen von Parteien unterschiedlich stark überdeckt. Darüber hinaus demonstrieren wir, dass die Präsenz extremer Parteien zu einer Unterschätzung der politischen Distanz gemäßigter Parteien führt. Grundlage unserer Untersuchung sind 2305 namentliche Abstimmungen aus insgesamt 46 Wahlperioden in allen 16 deutschen Länderparlamenten