Donors' health state the year after peripheral haematopoietic progenitor cell collection: A prospective follow-up study in related and unrelated donors compared to first-time platelet donors.

Granulocyte colony-stimulating factor (G-CSF) mobilized peripheral haematopoietic progenitor cells collected by apheresis (HPC-A) are the most common source used for allogeneic hematopoietic stem cell transplantation (HSCT). Retrospective short and long-term donor follow-up studies show very low risks of serious complications and do not report compelling evidence of increased cancer occurrence. Some studies reported a prolonged period of leucopenia without an obvious association with infectious complications. However, beyond the first few weeks after the procedure a relationship between events is elusive. We therefore evaluated medical service utilization by prospectively recruited HPC-A donors and first-time platelet apheresis donors for comparison for 1 year after donation. Data were prospectively collected using questionnaires and by medical record review. A total of 215 HPC-A donors (111 unrelated donors and 104 related donors) and 96 first-time platelet donors consented to participation in the study. Follow-up was available for 202 (96%): questionnaires were returned by 74% and records from nonstudy contacts were available for 94% of donors. During the 1-year follow-up, 94 of the donors who returned questionnaires sought medical attention for diagnostic evaluation and/or treatment: 41% of HPC-A donors and 40% of platelet donors. Medical service utilization the first year after HPC-A donation is similar to that after first-time platelet donation. The occurrence of serious medical conditions in both related and unrelated HPC-A donors underscores the importance of participation in long-term follow-up in large cohorts. The findings in this relatively small cohort contribute to evidence on the safety of G-CSF mobilization and HPC-A. J. Clin. Apheresis 31:523-528, 2016. © 2015 Wiley Periodicals, Inc.

Prediction of nucleated cells in bone marrow stem cell products by donor characteristics: a retrospective single centre analysis.

BACKGROUND AND OBJECTIVES: Number of total nucleated cells is an important prognostic factor of unrelated bone marrow transplantation. The objective of our study was to further optimize donor selection by finding donor characteristics which predict the total nucleated cell concentration in unrelated bone marrow products. MATERIAL AND METHODS: Data were collected retrospectively from the pre-donation medical records. The outcome variable was concentration of total nucleated cells in the final products. We investigated several candidate predictors, including demographic variables and peripheral blood counts. A backward selection procedure was performed, using multivariable multilevel analysis. RESULTS: A total of 471 donations were included. Significant predictors were increase of age (ratio per 5 years 0.971), cytomegalovirus (ratio 0.947 if positive), smoking (ratio 1.079 if yes), higher haemoglobin (ratio 1.052 per mmol/l), higher mono-nuclear cells (ratio 1.169 when mono-nuclear cells >2.69 compared to mono-nuclear cells <1.89 x 10E9/l), increasing number of whole blood donations (ratio 1.115 when blood donations >4 compared to blood donation <1), and larger body surface area (ratio 1.179 when body surface area >2.07 compared to body surface area <1.82 m(2)). The model was adjusted for collection volume. CONCLUSION: Presence of all favourable factors was associated with a twofold higher concentration of total nucleated cells in the bone marrow harvest.

Related hematopoietic cell donor care: is there a role for unrelated donor registries?

In almost half of allogeneic hematopoietic progenitor cell (HPC) transplants, a related donor (RD) is used, yet a lack of standardized guidelines means that their care is heterogeneous. Changes to regulatory standards aim to improve uniformity, but adherence to these regulations can prove logistically difficult for the transplant centers (TCs) managing RDs. Discussion has ensued around possible alternative models of related donor care and a session at the European Society for Blood and Marrow Transplantation (EBMT) annual meeting in 2013 debated the question of whether a role exists for unrelated donor registries in the management of 'related' donors. In this overview, we discuss the issues raised at this debate and the pros and cons of donor registry involvement in various aspects of RD management. By examining existing models of related donor care that have been adopted by members of the World Marrow Donor Association (WMDA), we look for ways to enhance and homogenize RD care, while also enabling transplant centers to meet standards required for mandatory accreditation.

The synthesis of chiral cyanohydrins by oxynitrilases.

Enantiomerically pure cyanohydrins are important synthetic intermediates for pharmaceuticals and agrochemicals. They are produced by enzyme-catalysed synthesis using oxynitrilases. Sufficient quantities of enzyme are available via cheap natural sources and there have been recent advances in overexpression production of cyanohydrins on an industrial scale.

[Pediatric scaphoid fractures--treatment and prognosis]. / Kindliche Skaphoidfrakturen--Behandlung und Prognose.

From 1990 to 1994, we treated 28 children aged eight to fourteen years, with a scaphoid fracture. In eight of them, the initially suspected fracture could not be verified by X-ray earlier than two weeks after the injury. Eleven more patients--after false initial suspect of fracture--were discharged after two weeks without any complaints and negative X-ray control. These were not included in the series. Patients with radiologically evident fracture or clinically typical history and symptoms of scaphoid fracture--even without positive X-ray--were treated by below-elbow-thumb spica-cast for two weeks. After that period, all patients went for repeated clinical and radiological examination. All children with radiologically visible fracture or continuous, typical complaints underwent cast fixation for another four weeks. Symptom-free patients without radiological evidence of fracture were discharged. One displaced fracture was reduced and stabilized with a screw. In follow-up examination after six to forty months, all fractures showed good radiological consolidation, four patients reported occasional pain on straining the wrist. Scaphoid fractures in children seem to be more difficult to diagnose than to treat. Nondisplaced or slightly displaced fractures can be treated easily with plaster cast. Fractures that show dislocation of more than 1 mm should undergo open reduction and stabilization by a screw.

[Effect of the mode of delivery on the newborn infant with gastroschisis. With data from the Styrian Malformation Register]. / Die Auswirkungen des Geburtsmodus auf Neugeborene mit Gastroschisis. Mit Daten des Steirischen Fehlbildungsregisters.

OBJECTIVE: Our purpose was to investigate the influence of the mode of delivery on the outcome of children with gastroschisis. METHODS: 38 children were born and treated at the University Hospital of Graz between 1977 and 1995. The perinatal and surgical data were analyzed retrospectively. Furthermore, we compared the prevalence of gastroschisis in Styria to international data. RESULTS: The mode of delivery did not influence the fetal outcome. The higher rate of acidosis and shorter interval from rupture of the membranes to delivery in cases of cesarean section may be attributable to the obstetric decision for an operative delivery. The prevalence of gastroschisis is high as compared to European data. CONCLUSIONS: Our data and the majority of publications do not show a benefit of cesarean section for children with gastroschisis. A randomized prospective trial is still lacking to end controversies.

Unrelated adult stem cell donor medical suitability: recommendations from the World Marrow Donor Association Clinical Working Group Committee.

The World Marrow Donor Association (WMDA) fosters collaboration between international registries to facilitate the exchange of hematopoietic stem cell products for unrelated stem cell donor transplantation. As indications for hematopoietic SCT grow, the movement of products across the world will increase. Although competent authorities may regulate products within their country, there is a need to protect the best interests of donors and recipients by identifying universal donor medical suitability criteria. Within this report the WMDA provides a background to unrelated adult donor and recipient safety, recommends a common framework for assessing the health of unrelated adult donors at each stage of the donation pathway and presents a novel mechanism for sharing international consensus criteria for individual medical and lifestyle conditions. Wherever possible, these criteria are evidence-based. By establishing a donor medical suitability working group, the WMDA has developed a process through which donor centers and registries may request a consensus opinion on conditions not already listed, as well as challenge existing criteria. Guidance from the WMDA is intended to complement, not supersede, guidance from national competent authorities and international regulatory bodies.

Towards a global system of vigilance and surveillance in unrelated donors of haematopoietic progenitor cells for transplantation.

Safety of living donors is critical to the success of blood, tissue and organ transplantation. Structured and robust vigilance and surveillance systems exist as part of some national entities, but historically no global systems are in place to ensure conformity, harmonisation and the recognition of rare adverse events (AEs). The World Health Assembly has recently resolved to require AE/reaction (AE/R) reporting both nationally and globally. The World Marrow Donor Association (WMDA) is an international organisation promoting the safety of unrelated donors and progenitor cell products for use in haematopoietic progenitor cell (HPC) transplantation. To address this issue, we established a system for collecting, collating, analysing, distributing and reacting to serious adverse events and reactions (SAE/R) in unrelated HPC donors. The WMDA successfully instituted this reporting system with 203 SAE/R reported in 2011. The committee generated two rapid reports, reacting to specific SAE/R, resulting in practice changing policies. The system has a robust governance structure, formal feedback to the WMDA membership and transparent information flows to other agencies, specialist physicians and transplant programs and the general public.

Allogeneic hematopoietic stem cell donation-standardized assessment of donor outcome data: a consensus statement from the Worldwide Network for Blood and Marrow Transplantation (WBMT).

The number of allogeneic hematopoietic SCTs performed globally each year continues to increase, paralleled by an increased demand for donors of therapeutic cells. Donor characteristics and collection procedures have undergone major changes during recent decades, and further changes are foreseen. Information on short- and long-term donor outcomes is of crucial importance to ensure maximal donor safety and availability. Current data, predominantly from unrelated donors, give reliable information on the frequent early events associated with donation-most of them of mild-to-moderate intensity. Information on the type and relative risk of serious adverse reactions is more limited. Moreover, only few data exist on long-term donor outcome. On the basis of this need, recommendations for a minimum data set for prospective donor follow-up were developed in a workshop with the participation of an international group of investigators actively involved in allogeneic stem cell donation under the auspices of and approved by the Worldwide Network for Blood and Marrow Transplantation. Establishment of a standardized global follow-up for both, related and unrelated, donors will enable monitoring of the short- and long-term safety profiles of hematopoietic cell donation and form a solid basis for future donor selection and counseling.

Donor safety: the role of the WMDA in ensuring the safety of volunteer unrelated donors: clinical and ethical considerations.

Since the beginning of hematopoietic stem cell harvesting from volunteer unrelated donors, ensuring donor safety has been a necessary goal of all parties involved in the process. As donation of BM or PBSCs is not in the interest of the donor's own physical health, donor registries and transplantation centers must take into account both medical and ethical aspects involved in the donation procedure. One of the principal goals leading to the formation of the World Marrow Donor Association (WMDA) was to establish internationally acceptable standards for all aspects of unrelated donor care.

Experimental eosinophilia and inflammation--the effect of various inflammatory mediators and chemoattractants.

An experimental subcutaneous inflammation was produced in guinea pigs with peripheral blood eosinophilia. The eosinophilia resulted from two subsequent infections with Trichinella spiralis larvae. One group of guinea pigs served as non-infected control. Inflammation was induced by carrageenan, bradykinin, histamine, platelet activating factor and eosinophilotactic factors of lymphocytic or neutrophilic origin. Whereas in the control group no eosinophil granulocytic response was observed, this response was seen in the group with peripheral blood eosinophilia. The inflammatory substances and mediators (carrageenan, bradykinin, histamine, platelet activating factor) did not attract eosinophils alone, but also neutrophils. Under peripheral blood eosinophilia within the time course of the inflammatory reaction a second emigration with a shifted neutrophil/eosinophil ratio in favour of eosinophils was found. This could be due to a generation of chemoattractants by the injected substances themselves or more probably, by already emigrated granulocytes. Neither histamine, bradykinin, carrageenan, nor the eosinophilotactic factors (ECF's) in the concentrations used did release the cytotoxic major basic protein from eosinophils. Platelet activating factor exhibited a release of major basic protein from some eosinophils but no release of the peroxidase under our experimental conditions. The immigration of sufficient numbers of eosinophils into inflammatory areas might be one cause of the reduction of the inflammatory edema found in a previous investigation under similar conditions.