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.

Adverse reactions and events related to musculoskeletal allografts: reviewed by the World Health Organisation Project NOTIFY.

PURPOSE: The use of bone and connective tissue allografts has grown rapidly and surpassed the use of autografts in many countries. Being of human origin, bone and tendon allografts carry the risk of disease transmission and complications have been reported. As part of the Project NOTIFY led by the World Health Organisation, an effort to improve recognition, reporting, tracking and investigation of adverse outcomes of allografts was initiated, achieving a comprehensive review of associated disease transmission and failures. Those involving the use of musculoskeletal allografts are reported here. A major objective is to involve orthopaedic surgeons in the improvement of the safe use of the musculoskeletal allografts. METHODS: We reviewed the medical literature, requested reports from surgeons in selected professional organisations and informally surveyed tissue bank organisations and selected tissue bank professionals to discover reported and unreported cases of adverse outcomes. We analysed each case to decide the likelihood that the complication was truly allograft related. RESULTS: The efficiency of the procedures involved in bone banking and bone and tendon allograft has improved significantly during the last three decades. The evolution of the incidence of reported adverse reactions and events reflects positively on the safety of transplanted tissues. Cases of bacterial and viral transmission by bone and tendon allografts occurred mainly with those that contained viable cells, were not processed to remove cells, or were not disinfected or sterilised. We documented cases of transmission of human immunodeficiency virus (HIV), hepatitis C virus (HCV), human T-lymphotropic virus (HTLV), unspecified hepatitis, tuberculosis and other bacteria. Reporting of these adverse outcomes has led to corrective actions and has significantly improved the safety of allograft use. However, it is probable that not all cases have been reported and investigated. CONCLUSIONS: Considering the high quality standards achieved in many countries, the best approach for further improvement in the safety of allografts is through a systematic reporting of all serious adverse reactions and events in the context of a global biovigilance programme.

West Nile virus: the Italian national transplant network reaction to an alert in the north-eastern region, Italy 2011.

We report four cases of West Nile virus (WNV) transmission following a single multiorgan donation in north-eastern Italy. The transmissions were promptly detected by local transplant centres. The donor had been tested for WNV by nucleic acid amplification test (NAT) prior to transplantation and was negative. There were no detected errors in the nationally implemented WNV safety protocols.

Cord blood banking in London: the first 1000 collections.

The London Cord Blood Bank was established with the aim of collecting, processing and storing 10000 unrelated stem cell donations for the significant number of children in the UK requiring transplantation, for whom a matched unrelated bone marrow donor cannot be found. Collection is performed at two hospitals by dedicated cord blood bank staff after delivery of the placenta. Mothers are interviewed regarding medical, ethnic and behavioural history by nurse counsellors and sign a detailed consent form. Donations are returned to the bank for processing. Volume reduction is undertaken by a simple, closed, semi-automated blood processing system, with excellent recovery of progenitor cells. Units are cryopreserved and stored in the vapour phase of liquid nitrogen. Blood samples from mothers and cord blood donations are tested for the UK mandatory red cell and microbiology markers for blood donors. Donations are typed for HLA-A, B and DR at medium resolution (antigen split) level using sequence-specific oligonucleotide probing and sequence-specific priming techniques. The selection of collection hospitals on the basis of ethnic mix has proven effective, with 41.5% of donations derived from non-European caucasoid donors. Bacterial contamination of collections has been dramatically reduced by implementation of improved umbilical cord decontamination protocols.

The London Cord Blood Bank.

Cord blood (CB) contains a sufficient number of haemopoietic progenitor cells and can be used as an alternative to bone marrow transplantation. To date, a number of transplants using cord blood-derived stem cells from HLA-identical siblings and unrelated donors have been successfully performed. However, only approximately 30% of patients have an HLA-identical sibling while the rest are reliant on finding an HLA-compatible unrelated donor. This is particularly difficult for patients from ethnic minorities since the majority of unrelated bone marrow donor volunteers are from Caucasoid ancestry. The London Cord Blood Bank was established to provide an additional source of stem cells for all patients requiring bone marrow transplantation.

Cord blood banking: volume reduction of cord blood units using a semi-automated closed system.

Clinical evidence indicates that placental/umbilical cord blood (CB) is an alternative source of haematopoietic stem cells for bone marrow reconstitution. To establish a CB bank large panels of frozen, HLA-typed CB units need to be stored. Cryopreserved, unprocessed CB units require vast storage space. This study describes a method, using the Optipress II Automated Blood Component Extractor (Opti II) from Baxter Healthcare Corporation, to reduce the volume of the CB collection, preserving the quantity and quality of the progenitor cells, in a closed system. The CB collection was transferred to a triple bag system, centrifuged to produce a buffy coat layer and processed using a standard Opti II protocol to separate the whole blood into three components: plasma, buffy coat and buffy coat-depleted red cell concentrate. The buffy coat volume was standardised to 25 ml; mean reduced volume of 24.5 ml (s.d. 1.5 ml) with 53% red cell depletion. Good recovery of cells was observed: 92%, 98%, 96% and 106% recovery of nucleated, mononuclear, CD34+ and total colony-forming cells, respectively. Using this method for processing CB units reduces storage requirement by two-thirds but preserves the quantity and quality of the progenitor cells.

Cadaveric Tissue Supply to the Commercial Sector For Research: Collaboration between NHS Pathology and NBS Tissue Services in the U.K., Extending the Options for Donors.

The Peterborough Hospital Human Tissue Bank (PHHTB) and National Blood Service Tissue Services (London and South East Zone) (NBSTS) operate within the U.K. National Health Service (NHS) and have a system in place to retrieve cadaveric tissues for commercial sector research. The collaboration meets the aims of PHHTB and NBSTS and is legal, ethical and safe. This paper presents the results of the first 20 successful retrievals referred from NBSTS to PHHTB. Cadaveric retrieval of tissue for research extends the options for donors and their relatives. The research option is particularly welcomed in cases where clinical retrieval for tissue transplantation is contraindicated. We believe the system is applicable to other centres.

Ensuring safety and quality of tissues in Italy: application of European directives.

Three European Directives published in 2004 and 2006 require Member States to take a series of regulatory actions to ensure appropriate quality and safety of tissues and cells. These directives define responsibilities to inspect and certify centers, to put vigilance systems in place and to publish information on certified centers and their activities. A European-funded project led by the Italian National Transplant Centre has supported Member States in the development of common guidelines for inspection, tools for vigilance, and training for inspectors. In Italy, inspections are conducted every 2 years at each tissue bank, and a vigilance system has been launched. Information on Italian centers and their activity is published in the Eurocet Registry.

Role of the blood transfusion service in tissue banking.

Tissue transplantation and banking are rapidly growing services throughout the world reflecting the widening availability of transplantable cadaver tissue and the mounting clinical indications particularly in orthopaedic, plastic and cardiovascular surgery. In the US tissue banking is more established, yet continues to show a rapid growth profile. In the UK it is currently organised in a variety of different ways and by a number of different organisations. The risks of disease transmission by tissue transplantation are similar to those for blood transfusion and the majority of tissues are grafted during procedures that are not life saving. The danger of disease transmission has resulted in the introduction of legislation in the US which allows the FDA to inspect tissue banks and to recall and destroy tissues. In the UK, there is currently no regulation or inspection of tissue banks to demonstrate that donor selection, tissue processing and tracking are conducted to acceptable standards. Blood transfusion services in the UK, US, New Zealand, Australia and possibly other countries have extended their roles to include organ and tissue donation to varying degrees, with the collection, processing and distribution of bone and tendon allografts most commonly undertaken. They have readily available special capabilities and experience with an established infrastructure, compliant with Good Manufacturing Practice, placing them in an ideal position to provide this service safely and cost-effectively.

Redistribution of plasma zinc between albumin and alpha 2-macroglobulin in pregnancy.

A cross sectional study involving 12 non-pregnant and 71 pregnant women was undertaken to determine the effect of pregnancy on the concentration in the plasma of zinc and copper and the binding of zinc to plasma proteins. The results confirmed the relationship observed by others between reduced zinc and increased copper concentrations in the plasma of pregnant women. These changes occurred during the first and second trimesters of pregnancy. The concentrations of plasma albumin-bound zinc and alpha 2-macroglobulin-bound zinc were observed to decrease 27.5% and 52.1%, respectively, during the second and third trimesters of pregnancy. During the second and third trimesters of pregnancy a redistribution of zinc occurred within the total plasma zinc pool between albumin and alpha 2-macroglobulin. In the process, the contribution of albumin-bound plasma zinc pool was increased 16.2%, whereas the contribution of alpha 2-macroglobulin-bound plasma zinc was decreased 31.6%. The former is considered more "dynamic" than the latter and the observed shift of zinc within the plasma pool to the albumin-bound state, during pregnancy, may represent an adaptive response designed to offset any adverse effects of reduced maternal plasma zinc concentrations on the developing fetus.

Association of fetal growth with elevated maternal plasma zinc concentration in human pregnancy.

This report consists of two separate studies. Study I was a prospective one in which 23 pregnant women ultrasonically diagnosed as having small fetuses were compared with 22 women with large fetuses. Maternal plasma zinc concentrations pre- and post-35 weeks gestation were significantly higher in mothers of small than in mothers of large infants. Twelve women with normal pregnancies participated in study II. Biochemical data obtained in maternal plasma during the third trimester of pregnancy, including total, albumin-bound and alpha 2-macroglobulin-bound plasma zinc concentrations and plasma copper concentration were compared with infant anthropometric data at birth. The results indicated significant negative correlations between maternal plasma zinc and albumin-bound zinc concentrations and plasma copper concentration in the third trimester of pregnancy and mid-arm circumference and ponderal index. The results of these studies, in the light of other data reported for primates and humans, suggest the need for a more extensive investigation of the relationship between maternal circulating zinc and copper concentrations and fetal growth.

An international survey of unrelated umbilical cord blood banking.

OBJECTIVES: To investigate operational and technical practices within the field of cord blood banking. MATERIALS AND METHODS: Cord blood banks world-wide were invited to participate in a survey of collection, processing and testing. The survey covered a 12-month period up to August 1998. RESULTS: Replies were received from 18 cord blood banks. Analysis of the survey responses demonstrated wide variations in many aspects of cord blood banking. CONCLUSION: There is a need for standardization to ensure adoption of best practice.