Comment on the concept of saviour sibling as discussed in the HFE Bill 2008.

This explanation prepared by Peter Braude and Ruth Warwick, does not take a view as to whether the technique should or should not be performed or allowed, but seeks to provide background information about its use in comparison to other avenues of treatment available.

‘Saviour sibling’ is the term applied to the selection of an embryo at an IVF procedure with the deliberate purpose of establishing a pregnancy, where the tissue type of the child born will be a match for another child already born into the family, who suffers from a life-threatening disease which may be curable by a haemopoietic (blood cell producing) stem cell graft derived from umbilical cord blood stem cells.

We should also differentiate two different situations where this technique may be considered useful.

I. PGD (preimplantation genetic diagnosis) and tissue typing. This may be employed where the couple carry a serious genetic disease which they have passed on to one of their children and where that child’s life may be threatened by the disease. Generally these are blood diseases or serious metabolic diseases which could be cured by a suitable cord blood or bone marrow transplant. E.g. Sickle cell disease, Fanconi anaemia, thalassaemia.This couple may wish to have another child unaffected by the disorder. They are not prepared to risk another affected pregnancy, nor undertake a pregnancy with prenatal diagnosis and the possibility of abortion of an affected child. They prefer to undertake PGD, but also wish to help their sick child as well, as no suitable cord blood or bone marrow donor can be found after trawling the international volunteer unrelated bone marrow or cord blood registers.

The procedure to have a child unaffected by the disease and who is also a tissue type match involves undergoing IVF, despite the couple being normally fertile, and where embryos generated have a cell removed on day 3 in vitro (8-cell stage) as a biopsy, which can be tested for the disease, so that only embryos unaffected by the genetic disorder are suitable to be returned to the uterus in the hope of establishing a pregnancy. However in addition to the test to avoid the genetic disease, the biopsied cell is also tested to see whether the embryo would be a tissue type match for the sick child. In this case any umbilical cord blood collected after the birth of the new child could contain haemopoietic stem cells suitable for transplantation to cure the disorder for the sick child, in those circumstances where the doctors looking after the sick child were to decide that such a transplant is warranted.

II. Embryo biopsy for tissue typing. The couple do not carry a genetic disorder, but have a child affected by a serious, usually life-threatening disorder, such as acute leukaemia which may be unresponsive to usual chemotherapy but which may be curable by a matched cord blood or bone marrow transplant, but where no matched donor can be found. Although acute lymphoblastic leukaemia (ALL) is the commonest childhood malignant condition, the success of treating the disease has been so great that over 80% of children who develop the disease are cured by chemotherapy alone. In this case, should they wish to have another child, they could have this by IVF where a biopsy is taken as above, but only tested to see which embryos are a tissue match to the sick child. Umbilical

cord from the child resulting after embryo transfer, could be stored for use as transplant to save the first child’s life.

In discussing this concept it is important to appreciate:

1. The IVF is not undertaken because of infertility, but to access early embryos for this purpose2. The embryos in vitro are tested by removing a single cell on day 3 of development, when the

embryo is only 8-cells (1/10th mm in diameter).3. There is as yet no evidence that removal of a cell causes any damage to the child which may

be born following the procedure. However, absence of evidence at the moment, does not mean absence of risk as there have been relatively few children conceived in this way.

4. A number of embryos need to be generated as only a few, if any, will be a match.(i) where PGD is needed to exclude a genetic disease as well; only 3 out of 16 embryos will be a full match(ii) where only a tissue match is required; 1 in 4 embryos will be a matchBecause of these figures, IVF/PGD for a sibling match is often unsuccessful and may need multiple attempts to achieve a matched result and a successful pregnancy.

5. Should umbilical cord blood collection fail or if the dose collected is too small, or should it be deemed that it need not be used immediately, then the alternative of a bone marrow donation from the same matching individual can be used for transplant at a later stage when the children are older. The same rules for decision would have to be applied as would if a child in the family was fortuitously found to be a suitable match for the sick child. The rules for donation of bone marrow are given in the Human Tissue Authority’s Codes of Practice.

6. Bone marrow can provide larger numbers of stem cells as a source for of stem cell transplantation than cord blood, as the volume that can be collected is more. Sometimes cord blood and bone marrow from the same individual can be used together to supplement the stem cell dose.

7. Umbilical cord blood from international unrelated cord blood banks could be an alternative to the need for saviour sibling umbilical cord blood but would not overcome the need in the case where PGD to exclude a genetic disorder is needed as well (case I). However finding matches varies between ethnic groups both for cord blood and bone marrow registries as the probability of finding a match depends on the ethnic ancestry of those represented amongst the donors. A saviour sibling match can be perfect in both aspects and results of cord blood and bone marrow transplantation are superior when the matches come from a family member, but the practicalities are such that many individuals do not have a family match or an unrelated match.

Professor Peter Braude PhD FRCOG FMedSci Dr Ruth Warwick FRCP FRCPath

Head of Department of Women’s Health Consultant Specialist for Tissue Services,

King’s College London. NHSBT

rw2008publs saviour sibsPB/RW16th May 08