A: It's paradoxic in a sense that a stem cell transplant is absolutely capable of curing CML. There's no question about it — the disease can be cured with transplant. But in order to have an opportunity for cure, there is a risk for early death. Untreated, the disease can go five or six years on average [while the disease is in the chronic phase] and things are OK. But with a transplant, you run about a one or two out of 10 chance of not surviving six months after the transplant. That's because the incoming marrow — the incoming immune system — rejects the recipient (not the recipient rejecting the marrow).
Plus, if a patient survives the transplant, there is the potential for a long-term immune reaction called graft versus host disease that never goes away. That's a high price to pay even if you're cured. That's why transplant has been relegated to second-line therapy - the toxicities of it are far greater than the potential benefit.
Q: The advances in this field have been quite remarkable in the last 10 years.
A: Absolutely. It's changed my practice. When I came in as a stem cell transplanter in 1994, when I had a patient with CML, I would transplant them. I had a clinic full of patients with chronic graft versus host disease. But since about 2001, when Gleevec was first introduced, the number of patients I've transplanted for CML has gone to almost zero and my clinic is full of people taking pills. It's completely changed the way we deal with CML. And I don't see as many patients anymore because the local doctors can take care of them on their own. They don't need to send them to see me to get pills. Whereas, they had to send them to me to get a transplant once upon a time.
Q: What new treatments do you foresee in the treatment of leukemia? Will there be better drugs than the ones we have now?
A: I wouldn't necessarily say better, but they are at least as good. The class of drugs that includes Gleevec is called tyrosine kinase inhibitors. There are other tyrosine kinase inhibitors under development. And there are other agents under development that work in a complementary fashion to the tyrosine kinase inhibitors. And perhaps most exciting, there are vaccines under development.
Q: Wow, a cancer vaccine? How does it work and who would be a candidate for vaccination?
A: These vaccines work by getting your own immune system to recognize the BCR-ABL protein as a foreign body and reject it. It would be a secondary vaccination. So you would be diagnosed with CML, then your immune system would be "vaccinated," for lack of a better word, and the disease would go away. So it's not primary prevention, it's secondary treatment. Because it is still immunologically-based we call it a vaccine.
The purpose of the vaccine is to stop the medicine, because otherwise you're on the pills forever. The problem with this is that, let's say you're on Gleevec and you're doing great, responding well to treatment, and you know that your long-term survival looks good. But in order to get the vaccine, you've got to stop the Gleevec. Who's willing to do that? That's the problem.
Q: In a field where there's not usually a lot of good news, is there a message of hope you give your patients?
A: I try to convince them that, yes they've got leukemia, and yes, untreated it's fatal, but with treatment, there's every expectation that their life span will be just as long as everybody else's. Now I can't say that with certainty because the drug hasn't been around long enough to say that with certainty.
And what do we mean by cure? If a pill keeps you in remission forever, you're cured. But if you stop taking the medicine, the disease comes back, so you're not really cured. We can't cure high blood pressure either, but if you take your medicine, you don't die of a stroke. Much like CML, where if you take your medicine, you won't die of the leukemia.