HISTORY OF CORD BLOOD TRANSPLANTS

  

 

The first allogeneic umbilical cord blood transplant (CBT) was successfully performed in 1988 to treat a child with Fanconi anemia, the umbilical cord blood donor was his HLA identical sister. Fourteen years later, this patient is doing well with full donor haematopoietic and lymphoid reconstitution. This first success opened the way to an entire new field in the domain of allogeneic haematopoietic stem cell transplant as it showed that a single umbilical cord blood contained sufficient numbers of haematopoietic stem cells to reconstitute definitively the host lymph haematopoietic compartment, that an umbilical cord blood unit could be collected at birth without any harm to the newborn infant and finally that umbilical cord blood haematopoietic stem cells could be cryopreserved and transplanted to a myeloablated host after thawing without losing their repopulating ability. Since then, our knowledge of the biological characteristics of umbilical cord blood cells has increased emphasizing the advantages of using umbilical cord blood stem cells for transplantation. Simultaneously, umbilical cord blood banks have been established for related or unrelated umbilical cord blood transplants with more than 300,000 units currently available and more than 6,000 umbilical cord blood transplants having been performed in children and increasing numbers in adults with malignant and non malignant diseases.

 

Summary of chronological aspects of the clinical use of cord blood as a source of allogeneic hematopoietic stem cells for transplantation
Period	Events
1988	First Cord blood transplant.
1989 -1992	Clinical observation that GvHD was reduced even in HLA incompatible CBT.
1992 - 1993	Establishment of Cord Blood Banks.  (New York, Paris, Milan and Düsseldorf)
1993 - 1996	Feasibility of HLA incompatible unrelated Cord blood transplants.
1995	Establishment of Eurocord group program sponsored by European Union.
1997	Nucleated cell dose - more important factor for engraftment and survival and influence of HLA on engraftment after CBT (Eurocord group study).
1998	Large series of UCBT = confirmation of the impact of cell dose and HLA.
1998	Foundation of the NETCORD organization in order to control the quality of cord blood units.
2000	Retrospective comparisons between UBMT and UCBT.
2002	Use of cord blood cells in adults with promising results.
2003	Criteria of cord blood choice and indications.
2004	Use of double cord blood transplants  and reduced intensity conditioning in adults.
2004	Isolation of USSC from umbilical cor blood.
2004	Comparable results between unrelated CBT and UBMT in adults.
2006	More adults than children transplanted with cord blood cells.
2007-2008	Allele matched UBMT compared to UCBT.

Cord blood as an alternative source of stem cells for transplantation

    

The principal limitations of allogeneic bone marrow transplantation are the lack of suitable HLA-matched donors and the complications due to graft-versus-host disease (GVHD) that are more severe with increasing HLA disparities. In the absence of a suitable HLA identical sibling donor, alternative donors such as mismatched related or matched unrelated donors are sought. Results have been disappointing in the past because major and minor histocompatibility differences often were not detected due to the inadequacy of standard typing techniques, explaining the relatively high frequency of post transplant complications, graft failure, GVHD and delayed immune reconstitution.  Despite the increasing number of bone marrow donor registries, which now contain more than 7 million bone marrow donors worldwide, some patients cannot be transplanted because of the lack of an HLA identical unrelated donor. In these cases, alternative approaches have been used with HLA mismatched cord blood cells, T cell depletion in unrelated matched or partially matched donors or related haploidentical donors.

 

The main practical advantages of using umbilical cord blood as an alternative source of stem cells are: 

• Relative ease of procurement (the units are readily available, having been previously tested and cryopreserved).
• Absence of risks to donors.
• Reduced risk of transmitting infection.
• Prompt availability of cryopreserved samples to transplant centers.
• Darge donor pool.
• Decreased risk of viral transmission.
• Low incidence of GVHD due to the immune immaturity of the newborn.   

 

Establishment of Eurocord group and objectives 

     

In order to develop and evaluate cord blood transplant, the European Blood and Marrow Transplantation group (EBMT) has organized a concerted action the EUROCORD group in 1996. The objectives of EUROCORD are: 

1) To study the properties of haematopoietic progenitors and gene transfer in cord blood.

2) To study the immune function of cord blood lymphocytes. 

3) To establish a European Registry of patients treated by cord blood transplants and design protocols comparing cord blood transplants with alternative conventional blood and bone marrow haematopoietic stem cell transplants. 

4) To control the quality of cord blood units delivered from Netcord and European Banks.  

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