The procedure of mini-transplants, or reduced intensity conditioning, is very, very interesting, being able to manipulate the body’s immune abilities to combat cancer. Can you tell me what you’ve been doing? You’ve been looking at a very interesting possibility with acute myeloid leukaemia but acute myeloid leukaemia is very difficult to treat, isn’t it?

Very true. We know that both myelodysplastic syndrome and acute myeloid leukaemia in the elderly have got poor long-term outcomes. This was the population that was the basis for the study. We also know that conditioning regimens including busulfan have the potential for toxicity and therefore of late there is a move towards defining the pharmacokinetics of the drug and giving a targeted dose of the drug. What we did in this study was look at a test dose to first define in the conditioning regimen the actual dose of busulfan to administer. What we targeted was, instead of the 50% dose that is used traditionally in reduced intensity conditioning regimens, a 75% dose hoping that we could strike the right balance between efficacy and toxicity.

And where does azacitidine come in?

Azacitidine is introduced at about six weeks to three months after the stem cell transplant is done to reduce the chances of the disease relapsing. We know that with AML and MDS a lot of the mortality is due to the disease coming back despite the initial eradication in the early days post-transplant. Also the drug has the potential to modify the immune system to potentially abrogate graft versus host disease so it has got a multi-pronged attack potential on the diseases that we studied.

Now, mini-transplants are essentially a balancing act. You’ve been trying targeting as a means of getting that balance right.

Correct.

What did you achieve?

What we saw was that in 80% of patients we got within our target dose of the drug and so that validated our initial assumption that we could, with a test dose, define an appropriate targeted dose.

What do you think might be the impact on outcomes of doing that?

The study is a little early to know for sure as to how the long-term impact of the patients is going to turn out. We will need longer term follow-up to see if this entire strategy led to superior outcomes. It was a phase II study so once again the data that emerges will be hypothesis generating. The true answer would lie in a randomised trial to conclusively prove that a conditioning regiment or post-transplant modifications are beneficial.

Could there be a benefit in treatment related mortality?

Very true, that is one of the potentials with the targeting to reduce treatment related mortality.

So overall what would you draw doctors attention to this finding in terms of focussing perhaps the future use of mini-transplants in this setting for acute myeloid leukaemia.

This trial gives us validation of a test dose strategy to target a specific dose of busulfan. It also tells us that azacitidine can be delivered to a majority of patients in the post-transplant setting and longer follow-up will tell us if we’ve made an impact in the long-term progression free and overall survival of these patients.