Sunday, September 29, 2002

Cord Blood Transplants

SGH scores another first in stem cell transplants

Singapore General Hospital, in collaboration with the National University Hospital, has chalked up another world-class achievement in stem cell therapy. Doctors in the team treating a 5 year old boy with Thalassaemia Major have successfully performed the first case of cord blood transplant from an unrelated donor.

This is the first known case in the world of such a transplant conducted successfully for a patient with Thalassaemia Major. It marks yet another significant milestone in the development of leading edge stem cell therapy conducted at SGH. In 1995, SGH successfully performed the world's first recorded case of peripheral blood stem cell transplant from an unrelated donor for a patient with Thalassaemia Major. In that case, the stem cells were extracted through the blood instead of the conventional method of extraction from the bone marrow, making the ground breaking transplant the first of its kind in the world. Today, the patient is a healthy 10 year old boy attending primary school.

A lifeline for child with Thalassaemia Major
This current medical breakthrough involves a 5 year old Malaysian Chinese boy, born with Thalassaemia Major, a hereditary blood disorder where the body is unable to produce enough haemoglobin leaving the patient persistently and severely anaemic, requiring frequent and regular blood transfusions. Frequent blood transfusions often leave sufferers of Thalassaemia Major at risk of infections like hepatitis and possible iron overloading resulting in multiple organ failure. There is also a general immune suppressive effect. The majority of patients die of heart failure and do not have a life expectancy beyond 15 to 20 years. In this particular case, there were no matched sibling donors for either a bone marrow transplant or a cord blood transplant. When the boy was first referred to Associate Professor Patrick Tan, Head of the SGH Department of Haematology, a search with the Singapore Bone Marrow Donor Programme found no matched donor then. A/Prof Tan reviewed the case again this year, for consideration for a cord blood transplant and a new search was activated. Fortunately, a good cord blood sample was found and the cord blood transplant took place on 3 July 2001, at the National University Hospital, where the patient is being co-managed by the Department of Paediatrics.

Success factor - good sample of cord blood
One of the success factors attributed to the transplant was the availablity of a good sample of cord blood. The cord blood was collected from a Chinese baby delivered in SGH in 1998. The exceedingly high cell dose in the sample and the fact that it fully matched in the direction of rejection ensures a high chance of engraftment - a critical issue in all transplants for Thalassaemia Major. The cord blood sample contains 60-million cell dose per kilogram. Cell dose refers to the number of cells per kilogram of the patient's body weight and is a critical factor in predicting the patient's survival. The success of the cord blood transplant depends directly on the dose of stem cells received in the transplant - the larger the cell dose, the better the outcome. In this case, the cell dose contained in the sample is four times higher than the international recommended cell dose of 15-million cell dose per kilogram for cord blood transplant, which means that it has excellent potential for a successful transplant.


All signs pointing to complete recovery
Since the transplantation, the patient has not required any red cell transfusions. Preliminary blood studies show that he no longer has Thalassaemia Major and the
stem cells are functioning properly within his marrow by producing various kinds of blood cells. He is now producing normal red cell corpuscles unlike those seen in Thalassaemia Major, which are small and pale. The patient was discharged on 8 August, 36 days after the transplant. However he will still require to be monitored at the specialist clinic twice a week for 100 days.

Cord blood transplantation is a viable option
With the results indicating that the patient has been cured of Thalassaemia Major, cord blood transplantation from an unrelated donor has now been proven to be a valid alternative to bone marrow transplant from a sibling. This breakthrough achievement not only sets a milestone in the medical history of Singapore, it also highlights the successful outcome that arose from the close collaboration and teamwork between the SingHealth and the National Healthcare Group, the two healthcare clusters to which SGH and NUH belong to.


Article reproduced from Singapore General Hospital website

Bone Marrow Transplants v/s Cord Blood Transplants

what are the differences and what are the advantages of each ?

BONE MARROW TRANSPLANTATION
Bone marrow transplant is curative for Thalassaemia Major patients. When successful, it is an absolute cure.

Bone marrow allograft from matched siblings have been carried out extensively for Thalassaemia Major patients. Allograft refers to transplantation of tissue from another person, be it a sibling or an unrelated donor. There have been approximately 2,000 cases world-wide. In a good risk patient, the success rate is 90% . However, bone marrow allograft from matched unrelated donors for Thalassaemia Major patients is uncommon.

In general, there is a one-in-four chance of receiving a bone marrow transplant from a matched sibling. However, with decreasing family size, many patients are unable to find a matched sibling for bone marrow transplant.


CORD BLOOD TRANSPLANTATION
The umbilical cord provides a lifeline between mother and child during pregnancy. Like bone marrow, the umbilical cord is rich in haemopoietic stem cells, the same cells found in bone marrow which are the primitive cells from which all types of blood cells evolve.

Cord blood an opportunity for an alternative transplant source, besides bone marrow and peripheral blood stem cells, which will give new life to patients suffering from leukaemia, and other fatal blood disorders (Thalassaemia Major included).


Advantages of Cord Blood Transplants
Cord blood transplants offer some potential advantages over unrelated bone marrow transplants :

Lower risk of rejection - 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 transplanted cells and their new host where the grafted cells reject their new host, causing a number of complications, including death.

Greater match tolerance - Cord blood transplant allows a mismatch, as the degree of histoincompatibility 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 predominantly Chinese, or the USA, which are predominantly 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 of the mother.
No donor risk - 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, eg. from the general anaesthesia required during the marrow harvest. In constrast, when cord blood donation is required, the blood is simply taken out from the cord bank, processed in the laboratory and given to the donor.

Collecting cord blood
After the baby has been delivered, the umbilical cord is clamped, cut and separated from the baby. While waiting for the placenta to be delivered, the physician will collect the cord blood by inserting a needle into the umbilical vein after cleansing the cord. The entire process is non-invasive, painless and does not interfere with the birthing process.

Success factor - good sample of cord blood
A critical issue in all transplants for Thalassaemia Major is the availability of a good sample of cord blood. The exceedingly high cell dose in the sample collected for this transplant and the fact that it fully matched in the direction of rejection ensured a high chance of engraftment.

The cell dose in the cord blood is important to the success of the transplant because the larger the cell dose, the better the coutcome. In this case, the cell dose contained in the sample was 60-million cell dose per kilogram, four times higher than the international recommended cell dose of 15-million cell dose per kilogram.


Our local Cord Blood Registry - the first in Asia
Singapore is the first country in Asia to set up a functional cord blood bank. The SGH Department of Haematology, in collaboration with Singapore's Bone Marrow Donor Programme, started the cord blood collection programme in August 1997.

The Obstetrics and Gynaecology departments of SGH, NUH and a few private hospitals have been actively supporting the programme. There are now about 1,000 cord blood units stored at the cord blood bank.

As placentas and cords do not contain a set volume of blood, the stem cells contained most cord blood collection are usually sufficient for a small child. As a result, cord blood transplants are for now limited for paediatric patients.

© Singapore General Hospital 15 August 2001

Article reproduced from Singapore General Hospital website