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First Year VICTORY CELEBRATION after Successful Double Cord Blood Transplant

27 Aug 2007

A very spirited teenager at the height of her youth, Candy was devastated when she was diagnosed with a very aggressive acute leukaemia (Philadelphia positive acute leukaemia) in March 2006. She underwent the double cord blood transplant on 25 August 2006 after receiving intensive chemotherapy and radiotherapy. The transplant was a success and Candy is now in complete remission, off all immuno-suppressants and is back at school.

Philadelphia positive acute lymphoblastic leukaemia is widely acknowledged to be one of the worst, if not the worst type of leukaemia known to have very few long-term survivors. Standard treatment with chemotherapy has been known not to cure the disease. The only chance of cure is with an allogeneic stem cell transplant. Unfortunately, Candy’s only sibling was not a suitable match and extensive search for unrelated adult donors around the world was not fruitful. The search with the cord blood registry, both in Singapore and overseas found no single and suitably matched sample.

It was therefore decided to opt for a relatively novel way of performing the transplant – by combining two different cord blood units. After extensive discussion with Candy and her parents it was decided that this would be the only way of potentially curing Candy

“Double cord blood transplants are still not commonly practised. One cord blood unit may not contain enough stem cells for an adult patient. The rationale of combining two units together is the novel concept of applying cord blood in adults. In this rare instance, not just one but two cord blood units were available from an overseas cord blood bank. This gave Candy a second chance in life. The double cord blood units provided sufficient stem cells dose for engraftment to occur and prevent rejection and helped Candy achieved remission”, said Dr Mickey Koh, Consultant Haematologist, Department of Haematology, SGH and Deputy Director, Centre for Transfusion Medicine, Health Sciences Authority.
Double cord blood transplant

The actual mechanistic and biology of a double cord transplant are fascinating. Although still not completely understood, they contribute to our continual scientific understanding of how donor stem cells engraft in a patient.

For example, it is difficult to predict which of the two cord blood units will eventually dominate in the patient. This does not seem to be wholly dependent on either the size or the number of stem cells in each respective unit, which would have been the intuitive approach. Often, one sees initial engraftment of both units but one unit quickly dominates and often becomes the only unit left; and this may be the smaller unit with less stem cell. We are also learning how these two units may cooperate in other areas like killing off the leukaemia cells.

Engraftment and Chimerism


Candy’s long-term outlook is promising.

She demonstrates 100% engraftment with one of the units (CBU #2) while there are no longer any traces of CBU #1. This means that her entire bone marrow has now been replaced by another healthy one, derived from the 2nd cord blood unit. The 1st cord blood unit did initially engraft and so for a while: there were three different stem cells co-existing in Candy (Candy’s herself and the two cord blood units). However, CBU#1 soon disappeared over the course of one month in the “friendly competition” between both cord blood units. It did however enable her to recover faster from the intensive chemotherapy and radiotherapy that we had administered to her just prior to the transplant. In fact, it was also suggested that it (CBU #1) may have played a role in helping to eradicate any residual leukaemia.

Very sensitive molecular testing to try to detect any residual leukaemia cells have also been negative and this is a good indicator that the transplant has been very successful.

Candy is well and back at school and is no longer on medication. She also shows no evidence of graft-versus-host disease, which is a potentially very serious complication of stem cell transplantation. This is a situation where the donor cord blood recognises Candy’s body tissue as being “foreign” and therefore attacks it.

This “victory celebration” with the team who look after her signifies one year since the successful double cord blood transplant.

About SGH’s Department of Haematology


The SGH’s Department was established in 1985 providing a comprehensive range of clinical and laboratory services for the diagnosis and treatment of all blood and blood related disorders.

The Department plays an importance role in the development of haematology and bone marrow transplant in Singapore with its successful bone marrow transplant programme that dated back to 1985. It has become the major referral centre for most haematological disorders in the region.

The opening of the Haematology Centre in 1999 marked another milestones in the development of the department bring all haematology-related services under one roof, offering patients a one-stop, seamless service.

To-date, the department has performed more than 800 cases of haemopoietic stem cell transplants.

In 2001, the Department of Haematology and the NUH’s Department of Paediatrics set a milestone in the medical history. The team performed the successful cord blood transplant from an unrelated donor for Thalassaemia Major. This breakthrough has proven cord blood transplant to be a valid alternative to bone marrow transplant from a sibling, giving Thalassaemia Major patients from all over the world a new lease of hope.

Public Cord Blood Bank


The establishment of public cord blood banks worldwide has improved the likelihood of finding suitably matched stem cells for needy patients, leading to an upsurge in the number of cord blood transplants from unrelated donors.

Singapore’s only public cord blood bank was established in 2005, which serve as a national repository of stem cell rich umbilical cord blood, and it is available to anyone who requires a suitable match for stem cell transplants.

Singapore has done more than 40 cord blood transplants. Majority are single cord unit transplant in paediatric patients performed in public hospitals.

Annexe

Cord Blood Transplantation


Like bone marrow, the umbilical cord is rich in haemopoietic stem cells, the same cells found in bone marrow that are the primitive cells from which all types of blood cells evolve.

Cord blood offers an opportunity as an alternative transplant source, besides bone marrow and peripheral blood stem cells, which will give new life to patients suffering from blood disorders and cancers.

Cord blood transplantation is increasingly becoming the treatment of choice as bone marrow transplant, which requires the donor and recipient to be perfectly matched, pose a great challenge. This is because cord blood stem cells are more immunologically trainable and have the ability to adapt to another person’s body more easily, allowing for an easier match and a significantly lower risk of Graft-vs-Host Disease (GVHD).

The Advantages of Cord Blood Transplants


Cord blood transplants offer some potential advantages over unrelated bone marrow transplants.

Patients transplanted with cord blood have a lower risk of severe graft-versus-host disease than those of unrelated bone marrow transplants, as the umbilical cord blood has not been exposed to outside antigens so the chance of graft-versus-host disease is reduced. Graft-versus-host disease is caused by the incompatibility between the transplanted cells and their new host where the grafted cells reject their new host, causing a number of complications, including death.

Cord blood transplant allows a mismatch, as the degree of histo-incompatibility that can be tolerated is greater with cord blood than with bone marrow. In unrelated bone marrow transplants, a full tissue match is crucial. Unfortunately, most tissue typing has racial significance. It is very difficult to find any unrelated donor for an Indian patient for example, from the registries in Asia, which are pre-dominantly Chinese, or the USA, which are pre-dominantly Caucasian. In cord blood transplants, two or even three mismatched antigens are acceptable. Significantly, cord blood transplant allows racial disparity.

Rapid availability – The preparation time for cord blood transplants is faster as the cord blood has been immunologically typed and is frozen, ready and available. Once a match is found, the cord blood only needs to be thawed and it can be used immediately, compared with the two to three months of preparation required for a normal marrow transplant

Ease - harvesting cord blood is a painless, non-invasive procedure with no risk to the newborn or the mother.

In addition, there is no donor attrition and no donor risk as no donor is involved. For ordinary transplants, the selected matched donor may refuse donation or be unavailable. There is also a small risk to the donor e.g. from general anaesthesia required during marrow harvest. In contrast, when cord blood donation is required, the blood is simply taken out from the cord blood bank, processed in the laboratory and given to the donor.



Dr Mickey Koh

Consultant Haematologist

 

许文才医生

血液科顾问医生

Candy Yeow

姚甜甜

Department of Haematology

血液科部门

Cord blood bank

脐带血库

 

 

Medical Terms

 

Cord Blood Transplant

脐带血移植

Pooled Cord Blood Transplant

混合脐带血移植

Allogeneic Stem Cell transplant (transplant of tissues from another person)

异体干细胞移植

Acute lymphoblastic leukaemia

急性淋巴母细胞性白血病

Immuno-suppressants

免疫抑制剂 / 抗排斥药物

Engraftment

植入成功 (嫁接)

Chimerism (co-existence of two or more cells types in the same body)

嵌合体

Graft-versus-Host disease

移植体对抗宿主病

Haemopoietic stem cell

造血干细胞

Bone marrow

骨髓

Human Leukocytes Antigens *(HLA) System

人白细胞抗原系

Chemotherapy

化疗

Radiotherapy

电疗

Unrelated donor

非亲属捐献者

Rejection

排斥

Mismatch

不完全相配

Thalassaemia Major

严重地中海贫血症


  

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Last Modified Date :04 Jan 2010