T Cell Therapy for Leukaemia - Why is this news?

In a recent report in The New England Journal of Medicine, the authors explain how two child patients were treated with a new technique. In both, their leukaemia was cleared and one of them remains in remission. The technique has previously had some success on a small group of adults.

News of medical research does not usually cover successes in just one or two patients - so why did the researchers go public on this?

In solid cancers you can never be sure that there are no cancer cells left in the body but in leukaemia you can be much more certain. It is no longer a case of looking at slides through a microscope - the latest techniques and equipment can scrutinise large numbers of blood cells and detect the presence - or absence - of cancerous cells.

There are many different kinds of leukaemia, each relating to a particular kind of blood cell. The nursery for blood cells is the red bone marrow and it is here that leukaemia cells are produced before they are released into the circulation. This red bone marrow is essential to life. It not only replaces red blood cells but all the white blood cells that make up the immune system. Without it, fatal anaemia and infection are inevitable.

Doctors can categorise the various leukaemias very accurately these days. For some patients the prognosis is good. For others, the only hope is a stem cell (bone marrow) transplant. These two young patients were suffering from relapsed Acute Lymphoblastic Leukaemia (ALL).

A stem cell transplant is usually the treatment of last resort. It uses brutal chemotherapy to kill all the red bone marrow, diseased and healthy. Then there is an infusion of blood stem cells, gathered from a closely matched donor. These then set up home in the bone marrow cavities and rebuild the blood producing tissue. It is a risky and arduous process. For some it fails to work and for others the treatment itself proves fatal.

Medical researchers sometimes use what they call translational research, which they also refer to as "bench to bedside research". Scientific advances in the lab are tried out on small groups of volunteers. These are patients who have little to lose - maybe a stem cell transplant has already failed - and they are willing to take the risk of acting as guinea pigs.

Translational research is quite different to a controlled trial - it is, literally, trying out something that they think should work to see what happens. This paper is an example of translational research - hence the tiny numbers. The progress of research like this is slow. Suitable patients are rare. By publishing this early success, researchers can share knowledge and perhaps find other patients who would benefit.

 We have long had the tantalising knowledge that immune cells known as T cells (or T lymphocytes) can destroy cancer cells in the lab - but often fail to do so in the body. One of the reasons for this failure is that the immune cells cannot recognise the cancer cells as something alien to the body. Store detectives deal with a similar problem: shoplifters tend to look like honest shoppers.

In the experimental treatment two child patients were treated with a kind of gene therapy in which T cells were genetically altered in the lab and put into the patient's body. The technique teaches the T cells the exact molecular pattern they need to attack and harnesses their killing power. It's like giving store detectives a photograph of a professional shoplifter.

There was a serious reaction to the treatment - the children's immune systems reacted violently to the rapid dying-off of cancer cells (tumour lysis syndrome). But both went into remission with no trace of the ALL cells. One of them subsequently started producing a slightly different kind of leukaemia cell but the other seemed to be remaining clear.

Such new forms of treatment may in time prove to be less dangerous and more effective than the current approach, which involves strong chemotherapy drugs. For sick children and their parents in particular, a shorter and less arduous course of treatment would be a great step forward.

Chimeric Antigen Receptor-Modified T Cells for Acute Lymphoid Leukemia," New England Journal of Medicine, Online March 25, 2013. To appear in print April 18, 2013.

Science Daily article: http://bit.ly/ZoAuE6

Stem Cell Transplants to Cure AIDS?

I am always concerned when the press run stories of cures. The science may well be interesting but I feel compassion for those who have hopes raised.

There was much publicity recently about the man who was "cured of HIV" by a stem cell transplant. He was unfortunate enough to have leukaemia. And he was HIV positive. In the process of treating his leukaemia in 2007, with a procedure known as a stem cell transplant, it appears that the AIDS virus was cleared from his immune system and he remains healthy. It is possible though that HIV still lurks in his brain, beyond the reach of his immune cells.

So does this news offer hope for those who have to take a daily cocktail of antivirals to keep their HIV infection in check?

The stem cells that make up the red bone marrow produce the full range of "white blood cells" that, in turn, make up the immune system. Leukaemia is a disease of the bone marrow - one type of stem cell turns cancerous and the mix of immune cells is thrown wildly off balance, with fatal consequences. Stem cell transplants have superceded "bone marrow transplants". These days the stem cells can be harvested from the donor's blood using a process similar to a single session of dialysis.

If normal chemotherapy fails to cure a case of leukaemia, the only solution is to use stronger drugs to kill off the bone marrow. Then the patient is given a transplant of healthy stem cells from a donor. This rebuilds the immune system with cells that are genetically matched to the donor.

There are many risks and difficulties. While waiting for the transplant to start working, the patient's immune system dwindles to almost nothing for a few weeks, leaving them highly vulnerable to infection. Any pre-existing infections would run riot - so that probably excludes anyone suffering from AIDS. The other problem is finding a suitable donor. We have all heard of people who need a bone marrow transplant but cannot find a suitably matched donor. The problem is the huge variety of possible tissue types. The tissue types of patient and donor need to be very similar if they transplant is to work. Rejection can bring life-threatening complications. So a stem cell transplant is a risky, expensive, treatment-of-last-resort, that is only used in a minority of cases of leukaemia.

 In this remarkable case the patient was able to receive a transplant from another unusual person - someone who had a natural immunity to HIV. These people are extremely rare. So it was not necessarily the transplant that cleared the virus - it might have been the particular genetic makeup of the donated cells.

 So to use this as a treatment for HIV you would need a reasonably healthy patient who has not succumbed to any AIDS-related infections and a matched donor, with a very special, very rare immune system.  

This was not an experiment. An imaginative doctor identifying an opportunity and tried something new. It could well turn out to be a one-off case, thought provoking for scientists, but for the time being (sadly) a million miles away from being a realistic prospect as a treatment for HIV. A cure for HIV may someday be found, but it will result from painstaking research and not from stem cell transplants as we know them today.