5 November 2009

Double Unit Unrelated Cord Blood Transplantation Sheds New Hopes for Children with Leukaemia



Bone marrow transplantation (BMT) is a well-established treatment for children with various severe blood or hereditary diseases and cancers. However, BMT is limited by a lack of suitable donors. In communities with nuclear-sized families, it has become more difficult to find an identically matched sibling for transplantation. Unrelated donor BMT is associated with much higher complications rate, especially graft-versus-host disease (GVHD). Furthermore, the time required to search for compatible donors can be lengthy and it usually takes three months or longer.

Umbilical cord blood, like bone marrow, also contains a rich source of blood producing stem cells. The use of cord blood transplantation (CBT) in children has witnessed important progress. With the first successful CBT from a compatible sibling in a child with Fanconi anaemia in 1989 and the establishment of the first public unrelated cord blood bank in the United States in 1991, the number of CBT from related and unrelated donors has increased dramatically to more than 10,000. While representing less than 5% in year 2000, 40% of children worldwide received cord blood as the stem cell source for unrelated stem cell transplantation in 2008. CBT has a number of advantages over BMT. Since cord blood units have already been stored in cord blood bank, they are readily available within 4 weeks. This time factor is especially important for patients who require urgent transplantation for serious diseases such as acute leukaemia. Furthermore, cord blood cells are naive cells, and strict matching is not required as the risk of GVHD is not as severe as in BMT.

The Hong Kong Red Cross Blood Transfusion Service (HKRCBTS) established its public unrelated cord blood bank in 1998 and soon started to deliver cord blood units for transplant. However, before 2006, usage of unrelated cord blood had been modest. During an eight-year-period between 1998 and 2005, only 15 (29%) patients among a total of 52 paediatric unrelated transplants in Prince of Wales Hospital were transplanted with cord blood units from HKRCBTS. There are only a finite number of stem cells in each unit of cord blood collected, and depending on the weight of the patient, a unit of cord blood might not be adequate to secure an engraftment and to restore adequate marrow function for the patient. This had limited the usage of cord blood transplant in early years.

In 2006, Department of Paediatrics at The Chinese University of Hong Kong (CUHK) and HKRCBTS jointly launched a three-year programme on using double unit unrelated cord blood transplantation for patients who require BMT but without compatible related or unrelated bone marrow donors. Each of the compatible cord blood units alone contains inadequate cell doses to be used alone. The rationale of combining two units of cord blood was to increase the total number of cells infused which in turn to enhance the chance of engraftment.

During this period, 23 unrelated transplants were performed in this Centre, three (13%) were from unrelated bone marrow donor, three (13%) were from single unit unrelated cord blood, and the remaining 17 (74%) were from double-unit unrelated cord blood. Eleven of these 17 patients were transplanted for acute leukaemia, 10 patients (91%) had achieved successful engraftment. There is no increase in complications after transplantation. Up to now, 8 patients are alive with no evidence of leukaemia. These data support a very favourable outcome as compared to unrelated BMT or single unit CBT. Without utilization of double unit CBT, these high risk patients might not have a change to go through stem cell transplantation and receive cure.

Public cord blood banks provide an alternative source of stem cell for transplantation that achieve an outcome similar to unrelated bone marrow in children. Usage of double unit cord blood for transplant saves the long search time for a suitable unrelated bone marrow donor and overcomes the obstacle of limited number of stem cells available in each cord blood unit. This has increased the chance of finding suitable cord blood units for early transplant and as a result, more patients can now benefit from umbilical cord blood transplantation.

(Left) Dr Wai Chiu TSOI, Associate Consultant, Hong Kong Red Cross Blood Transfusion Services; 
Professor Chi Kong LI, Honorary Clinical Professor, Department of Paediatrics, Faculty of Medicine, CUHK; 
Professor Pak Cheung NG, Chairman, Department of Paediatrics, Faculty of Medicine, CUHK; 
Dr Vincent LEE, Clinical Assistant Professor (honorary), Department of Paediatrics, Faculty of Medicine, CUHK
(Left) Dr Wai Chiu TSOI, Associate Consultant, Hong Kong Red Cross Blood Transfusion Services;
Professor Chi Kong LI, Honorary Clinical Professor, Department of Paediatrics, Faculty of Medicine, CUHK;
Professor Pak Cheung NG, Chairman, Department of Paediatrics, Faculty of Medicine, CUHK;
Dr Vincent LEE, Clinical Assistant Professor (honorary), Department of Paediatrics, Faculty of Medicine, CUHK

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