The principal limitations of allegoric bone marrow transplantation (ABMT) are the lack of suitable HLA-matched donors for the majority of patients and the complication of graft-versus-host disease (GvHD). The lack of sibling donors in some cases has been overcome through the establishment of large panels of potential marrow donors but these panels are restricted in terms of HLA polymorphism and of their ethnic diversity. This is most marked in Europe where each nation has its own ethnic diversity. Limitation is also related to the fact that results of allegoric bone marrow transplantation from normal bone marrow donor are dependent of HLA-A, B, C, DR, DP, DQ identity between donor and recipient. Umbilical cords from full-term pregnancies have been shown to be a source of haematopoetic progenitors (1,2,3,5,6). Banks of cord blood samples are being established in a number of EU member states (47). A number of cord blood transplants have been performed with encouraging results (3,39,40,41,42,43,44). Preliminary evidence suggests that these transplants are associated with less GvHD than comparable unrelated BMT.
The purpose of the research is to advance our understanding of cord blood transplantation and to establish common criteria and protocols for the handling of cord blood samples.
- to standardise the methods of collection, testing and cryopreservation of cord blood
- to study the properties of haematopoietic progenitors present in cord blood
- to study the immune function of cord blood lymphocytes
- to co-ordinate and facilitate the exchange of sera and cells from regional cord blood depositories held in member states
- to establish a European Registry of patients treated by cord blood transplantation and design protocols comparing cord blood transplants with alternative conventional blood and bone marrow haematopoietic stem cell transplants.
The concerted action (CA) will : 1) compare methods of collection, banking and testing of cord blood collected for clinical use across different European countries. This will need communication between obstetricians, blood banks and laboratories involved in cellular biology, microbiology, immunology and the detection of genetic disease ; 2) study the properties of haematopoietic stem cells present in cord blood with regard to their selection and expansion for the purpose of improving their long term capacity for engraftment ; 3) study the immune reactivity of cord blood lymphocytes. The T lymphocytes and natural killer cell subsets present in cord blood samples will be characterised. Their in vitro responses to mitogenic and antigenic stimulation will be measured to determine functional maturity as will their reactivity to allegoric stimulation (GvHD) and to leukaemia cells (GvL) ; 4) co-ordinate the exchange of cells and DNA from cord blood samples between different expert groups to perfect the detection and enumeration of contaminating maternal cells ; study transmission of infectious diseases from the mother to the child and perform studies of transmission of genetic diseases ; 5) establish a central registry of all European cord blood transplants to facilitate the analysis of results. Subsequently to design trans-European clinical studies in the light of these analyses.
The significance of this application is that the research planned herein is beyond the capability of any single EU member state. This research will be done within the European Blood and Marrow transplant group. All members of the project are active members of this group. This project has been approved by the board of the EBMT (March, 13 1995) Co-operation and exchange of ideas, material and personnel for training will allow the successful completion of these studies and the transfer of many expert techniques to EU states with less well-developed medical research facilities.