Improving the Informed Consent Process in Hematopoietic Cell Transplantation: Patient, Caregiver, and Provider Perspectives.

One of the significant modifications to the Common Rule is the requirement that prospective participants be given information sufficient for a "reasonable person." However, research is limited on what types of information patients, caregivers, and providers consider "key information." Although certain aspects of informed consent (IC) may be considered standard, considering the individualized needs and preferences of patients is necessary for patient-centered consent. In this study, we qualitatively examined the specific types of information that patients and caregivers involved in hematopoietic cell transplantation (HCT), as well as their providers, believe to be important and necessary as part of the IC process to make a decision about participating in clinical research; and further, how these perspectives are aligned. Our findings suggest opportunities for improving the IC document and process by emphasizing information of importance to patients, such as the benefits to others and contributions to science that are associated with participation in clinical research. Furthermore, increasing patient engagement during the IC process may allow providers to streamline information that is aligned with patient information needs and preferences.

Research involving pediatric stem cell donors: A way forward.

The most suitable donor for younger patients who undergo hematopoietic stem cell transplantation in the research setting is frequently a minor sibling. These cases raise the question of whether minors who serve as stem cell donors for research subjects should be regarded as research subjects themselves. Regarding pediatric donors as research subjects ensures that an Institutional Review Boards reviews their involvement and determines whether it is appropriate. Yet, Institutional Review Boards must follow the US regulations for pediatric research, which were designed for patients and healthy volunteers, not for healthy donors. As a result, regarding pediatric donors as research subjects also can pose unnecessary obstacles to appropriate and potentially life-saving research. This article considers a new way to address this dilemma. The federal research regulations allow for waiver of some or all of the included requirements when they are unnecessary for a study or a class of studies. We argue that this option offers a way to ensure that the involvement of pediatric donors receives sufficient review and approval without inadvertently undermining valuable and potentially life-saving research.

[Authorization of tissue and blood stem cell preparations for hematopoietic reconstitution: Documentation of clinical and nonclinical data in a central expert report]. / Genehmigungsverfahren für Gewebezubereitungen und Blutstammzellzubereitungen zur hämatopoetischen Rekonstitution: Dokumentation klinischer und nicht klinischer Daten mittels eines Zentralgutachtens.

In order to address the European Directive 2004/23 on human tissues and cells, the authorization obligation for tissue and blood stem cell preparations was introduced (§ 21a AMG) in the year 2007 in the German medicinal products act. Stem cell transplantation for hematopoietic reconstitution has been in use for decades and is well established for the treatment of many malignancies. The manufacture of stem cell preparations varies, but in terms of hematopoietic reconstitution, different products are intended for the same indication. Taking these aspects into account, it was considered inappropriate that every single applicant should provide their own documentation, including an expert report on clinical and nonclinical data. Consequently, the idea came up to create a central expert report, to which all applicants could refer and would include relevant clinical and nonclinical data according to current knowledge. A central expert report was therefore generated, called the "Gemeinsame Stellungnahme der Fachgesellschaften Deutsche Gesellschaft für Transfusionsmedizin und Immunhämatologie (DGTI), Deutsche Gesellschaft für Hämatologie und Onkologie (DGH) und Gesellschaft für Pädiatrische Onkologie und Hämatologie (GPOH)". Applicants are allowed to refer to this central expert report provided their stem cell product is comparable with the cell preparations included in the report. In order to represent current knowledge, the content of the central expert report was already reworked once, but should be updated regularly.

A policy for the disposal of autologous hematopoietic progenitor cells: report from an Italian consensus panel.

BACKGROUND: Autologous stem cell transplantation (ASCT) requires collection and cryopreservation of hematopoietic progenitor cells (HPCs), which in turn may be partially or never reinfused. Thus, HPC storage has become a logistic, ethical, and economic issue. SIDEM, GITMO, and CNT/ISS endorsed a project aimed to define national criteria for HPC disposal aimed to guarantee appropriateness and equity. STUDY DESIGN AND METHODS: A multidisciplinary panel was convened including HPC harvest and manipulation experts from apheresis units, hematologists with clinical expertise in ASCT, a representative of the national health authority, and a bioethicist. An analytic hierarchy process (AHP) was carried out to select disposal criteria. RESULTS: The AHP selected two criteria for prompt disposal of freshly collected HPCs: an abnormal freezing procedure causing highly reduced viability or major microbiology contamination. Moreover, AHP selected six major criteria, each one of them allowing for the disposal of stored HPC units: patient death, withdrawal of consent to ASCT, contraindications or loss of indications to ASCT, a damaged label that prevents correct identification of the unit, and time elapsed since harvest longer than 10 years. Three minor criteria were additionally identified that allowed to anticipate disposal only provided that viability levels are below the limit of acceptance: a documented cold chain interruption, loss of bag integrity, and total amount of stored CD34+ cells lower than 1 × 10(6) /kg or lower than 2 × 10(6)/kg in patients with a successfully completed stem cell transplantation program. CONCLUSIONS: A formal consensus process allowed SIDEM and GITMO to propose a policy for autologous HPC disposal that fulfills clinical, ethical, and economic criteria.

Haematopoietic stem cell transplantation: a comparison between the accreditation process performed by competent authorities and JACIE in Italy.

There have been great advances over the last decades in haematopoietic stem cell (HSC) transplantation, using either bone marrow, peripheral blood or cord blood-derived stem cells. The coming into force of the European legislation on tissues and cells and the consequent transposition of Directives into national laws have required the health authorities in the Member States (MS) and the scientific societies to review the transplantation activities to ensure the circulation of safe HSC products. Here, the regulatory inspection process performed by the Competent Authorities and the professional voluntary accreditation process of the Transplant Programmes active in Italy is compared.

Ethical and legal issues raised by cord blood banking - the challenges of the new bioeconomy.

• Cord blood banking raises ethical and legal issues which highlight the need for careful regulatory approaches to the emerging bioeconomy. • Consent processes for both private and public banking should be inclusive and representative of the different familial interests in the cord blood. • Property law is a potentially useful way of understanding the mechanisms for donation to both public and private banks. • Increasing tensions between public and private models of banking may require the adoption of hybrid forms of banking.

Research using autologous cord blood - time for a policy change.

• Type 1 diabetes results from the loss of normal immunological self-tolerance, which may be attributable to the failure of Foxp3+ regulatory T cells (Tregs). Umbilical cord blood is rich in Tregs and therefore has the potential to prevent or delay the onset of type 1 diabetes. A pilot trial is currently underway in Australia to examine whether infusion of autologous cord blood can prevent type 1 diabetes in high-risk children with serum antibodies to multiple ß-cell antigens. • A number of other potential therapeutic indications for autologous cord blood have been proposed, including cerebral palsy and hypoxic-ischaemic encephalopathy. • Recruitment to clinical trials using cord blood is influenced by divergent public and private cord blood banking policy in Australia. The burgeoning consumer demand for storage of cord blood highlights the need for regulatory bodies to develop and adapt policies to facilitate research that may extend the use of cord blood beyond currently recognised indications. • Consumers, researchers and policymakers must also recognise specific ethical issues associated with collection and storage of cord blood, including storage in public and private banks, informed consent, ownership, access and the principle of beneficence.

The policy statement of the American Academy of Pediatrics -- children as hematopoietic stem cell donors -- a proposal of modifications for application in the UK.

BACKGROUND: With a view to addressing the moral concerns about the use of donor siblings, the Policy Statement of the American Academy of Pediatrics - Children as Hematopoietic Stem Cell Donors (the Policy) has laid out the criteria upon which tissue harvest from a minor would be permissible. DISCUSSION: Although tissue harvest serves the best interests of recipient siblings, parents are also obliged to act in the best interests of the donor sibling in the UK. Tissue harvest should proceed if and only if it serves the best interests of both the donor and recipient. Parents should be forbidden, and they are by UK law, to consent to tissue harvest unless there are substantial benefits for an incompetent minor that can outweigh the potential harm. There is no basis to subject a minor to the medical risks of tissue harvest if the recipient sibling can wait without significant risks of complications until the donor becomes Gillick competent. We also argue that the Policy fails to take into account recent advances in haematopoietic transplantation from haploidentical donors or related tissue-matched donors. SUMMARY: Unless a recipient sibling will suffer from serious complications or die without the transplantation and no other medically equivalent donors are available, there is no moral or legal basis to violate the donor sibling's right to bodily integrity. Accordingly, we propose that the Policy should be modified in order to fully satisfy the legal requirements for application in the UK and other commonwealth jurisdictions with similar statute laws protecting minors.

Historical perspectives and the future of adverse reactions associated with haemopoietic stem cells cryopreserved with dimethyl sulfoxide.

A retrospective review of the published literature identified several hundred adverse reactions (e.g. nausea, chills, cardiac arrhythmias, neurological symptoms and respiratory arrest) associated with the transplantation of stem cells cryopreserved with dimethyl sulfoxide. The occurrences of these are generally accepted as commonplace, as the majority of reactions are transient, whilst a few patients may require clinical treatment. This exploratory study is a collation of the historical data and the expectations for the notification of serious adverse reactions. Outline information is presented on the development of related European Directives, some technical aspects of dimethyl sulfoxide and the sequential stages of preservation and administration.

[Organ and tissue harvesting in children: comparison of the legal framework in Tunisia and France]. / Le prélèvement d'organes et de tissus chez l'enfant : comparaison du cadre juridique en Tunisie et en France.

In Tunisia as in France, the legislator recognized the organ harvesting as of public health priority. To promote it, cells of coordination are created, and controlled by regulatory texts. There are differences in the strategy of organ harvesting in minor but whether he is alive or dead, he is well protected by law. Organ harvesting in alive child is prohibited in both Tunisia and France but the haematopoietic cells one is authorized. In the minor deceased organ harvesting obeys common principles, appearing in the bioethical law (France) and the law n°91-22 of March 25, 1991 (Tunisia) with a difference in the procedure of the assent of the legal guardian.

[Report on notifications pursuant to Section 21 of the German Transfusion Act for the years 2008 and 2009]. / Bericht zur Meldung nach § 21 TFG für die Jahre 2008 und 2009.

This report contains the data collected in 2008 and 2009, pursuant to Section 21 of the German Transfusion Act (Transfusionsgesetz), as well as an overview of the supply situation during the last 10 years. In 2009, blood donation services reported a total of 7.5 million donations--the largest amount since 2000. At the same time, more than 4.7 million red blood cell concentrates and more than 500,000 platelet concentrates were available. The number of therapeutic single plasma units decreased to 1.1 million units in 2009. The loss rate for red blood cell concentrates is still between 3% and 4% for the users, while for the manufacturers, it has decreased slightly to 1.4%. The loss rate, for platelet concentrates, on the other hand, increased in 2009, and--what is noteworthy--especially for manufacturers of pooled platelet concentrates. The loss rate for apheresis platelet concentrates accounted for 5.2% compared to 17.5% for pooled platelet concentrates. As far as the users were concerned, loss rates for platelet concentrates largely remained unchanged with rates between 5% and 6%. Based on the data collected, the supply of blood components for transfusion can be regarded as assured. Nearly 2.9 million liters of plasma for fractionation were collected in Germany in 2009. According to reports from the pharmaceutical industry, of these, 2.6 million liters remained on the German market, of which only 56% were fractionated in this country; no statement can be made on the use of the remaining amount. Many plasma derivatives are not manufactured in Germany, despite the large amount of plasma collected. The supply with these products, however, is assured by imports. Overall, 16,409 autologous and 9,435 allogeneic hematopoietic stem cell preparations were manufactured in 2009, of which 3,382 allogeneic preparations were exported. A total of 3,181 autologous and 2,374 allogeneic preparations were transplanted; 187 of these products from imports. The large number of exported stem cells and the small number of imported stem cells suggest that no serious shortages are to be expected for the supply with these products.

[Report on notifications pursuant to Section 21 German Transfusion Act for 2007]. / Bericht zur Meldung nach section sign 21 TFG für das Jahr 2007.

The present report contains the data collected in 2007, pursuant to Section 21 Transfusionsgesetz (German Transfusion Act), and an analysis of the supply situation over the past eight years. The recording of the data by online reporting is in the meantime well established and generally accepted. As in previous years, all blood donation centers located in Germany transmitted data on the collection, manufacture, import and export of blood components for transfusion, so that meaningful data are available. According to these data, a total of 6.7 million blood collections were performed in 2007. The number of whole blood donations was at the level of previous years, with 4.7 million, whereas the number of apheresis donations rose again, to 1.9 million. The portion of autologous blood collections accounts for only 1.1% and thus continues to decline. Since 2003, the number of red blood cell concentrates prepared has been a constant 4.5 million transfusion units. The decrease in the portion of decay of red blood cell concentrates on the user side is particularly good news. In 2000, it accounted for 5% and in 2007, it was just above 3%, referred to the total quantity of data reported as transfused and decayed. The manufacture of platelet concentrates rose from 366,000 to 480,000 transfusion units between 2003 and 2007. The production of therapeutic single plasmas also markedly increased in 2007 compared with previous years, accounting for 1.2 million transfusion units. In 2007, 2.2 million liters of plasma for fractionation were collected in Germany. This trend went hand in hand with the increasing number of apheresis donations that year. In addition, 1.0 million liters were imported, and, at the same time, 1.8 million liters were exported. The quantity available in Germany from a pure arithmetic point of view of 1.4 million liters was almost entirely allocated to basic fractionation, so that a sufficient plasma supply can be assumed. The assessment of the degree of self-sufficiency is made difficult because of the influence of imports and exports; however, the results show no deficit for plasma derivatives. Due to the fact that manufacturing capacities are still lacking in Germany, recombinant factors need to be imported in their entirety. Since 2003, Germany has by far been the leader in Europe with more than 20 liters of fractionation plasma collected per 1,000 inhabitants. Furthermore, regarding the manufacturing figures of red blood cell concentrates, platelet concentrates, and therapeutic single plasma, Germany is in the top third for all these products compared with other European countries. The manufacture of allogeneic stem cell products for hematopoietic reconstitution, obtained by apheresis, has continuously risen to 4,700 in the reporting year. A large portion of this, 1,810 transplants could be exported while only a small number, 179 preparations, had to be imported. The manufacture of autologous stem cell preparations from cord blood also rose drastically compared with 2006, to more than 10,000 in 2007. It must be emphasized that these products were entirely placed into stock; none were transplanted in the reporting year. The interest in the figures collected in compliance with Section 21, Transfusion Act remains high both in Germany and at the international level. Reliable data are available thanks to the evaluations of trends over years, above all on the availability of blood components for transfusion. In addition, the Paul Ehrlich Institute will continue to strive to meet the demands for high-quality information on the supply situation in the future.

[Graft reinjection: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]. / Réinjection du greffon : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC).

JACIE (Joint Accreditation Committee ISTC EBMT) regulations and standards impose a quality and safety requirement for graft reinjection by nurses. However, the standards do not provide a step-by-step graft reinjection procedure. Because of high medical team turnover, the opening of new transplant centers, and continual questions from colleagues trying to decipher the JACIE standards, the need for a specific procedure goes without saying. We collected graft reinjection procedures from each SFGM-TC center that participated in our survey, thus creating an inventory of the different steps that make up graft reinjection. In addition to reviewing the main regulatory texts and JACIE standards, we sought advice from medical and cellular therapy experts. We observed that most centers use a mix of practices and some unjustified practices. In some transplant units, it is still standard practice to defrost cell therapy products in the transplant unit. Caregivers are aware of the need for a rigorous application of the regulatory requirements and are willing to administer a procedure that provides specific steps for each stage of the process. In this workshop, we questioned each stage of the graft reinjection procedure, which helped us define clear methods of implementation. In the form of a checklist, we offer bone marrow and stem cell transplant units a step-by-step procedure.