Thursday, March 13, 2008

A chimeric cure: donor takeover

A unique medical case reported in the New England Journal of Medicine in January is seen as an example of chimerism: that is, one body with genetic components of two distinct entities.

Around 2002, a nine-year-old girl from south of Sydney "contracted a virus that destroyed her liver". With less than two days to live, she was given a replacement liver. Normally, it would be expected that she would need to take immunosuppresant drugs for the rest of her life - which would leave her susceptible to opportunistic illnesses.

Nine month later, when she fell ill, it was discovered that her blood type had changed from O negative to O positive - that of her donor.

Effectively, the blood stem cells of the donor's liver penetrated the bone marrow, performing a bone marrow transplant. As a result the new liver was no longer treated as foreign. The girl's immune system had been almost totally replaced.

The story from Westmead Hospital's haematology head (Julie Curtin) was that the patient's remaining white blood cells (responsible for immunity) started breaking down the new O positive red blood cells, a process called haemolysis. This resulted in the patient being very sick for a while. The medical staff, in trying to recover the situation, tried the risky step of stopping the course of immunosurpressant (anti-rejection) drugs. The situation stabilised, and the patient recovered. Blood tests also showed she no longer had immunity to measles or mump, despite immunisation as a baby.

There is no recorded precedent for this, and no easy explanation. Some factors mooted include that the donor was young (12 years old), the recipient having a low white blood cell count, the original type of liver failure - and the original virus, cytomegalovirus, which can suppress the immune system.

Four years down the track, the situation appears to be permanent and stable; anti-rejection drugs are not needed.

Interesting to note some irony between the mythic history of chimeras and this actual outcome: this is a complete reversal of the traditional, perjorative depiction of monsters.

Knowing the answers would be a giant boon to medical treatment. I note that there is some research into inducing chimerism to achieve just such an outcome. However, as it stands I suspect most doctors would be extremely reluctant to replicate some of the risky situations involved.

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