So with chronic lymphocytic leukaemia the patient’s condition can vary hugely in that this can be present as a very, very slow growing and relatively benign condition, and sometimes it can be more aggressive than that. And in many cases no treatment is required initially so that one can just watch and wait until treatment becomes necessary. In some people this may never happen or it may take many years to happen. And there’s no advantage in starting the treatment early, and that can introduce complications of the treatment without actually offering any extra benefit.

The sorts of treatment that you need for CLL are again chemotherapy type drugs but these are of a relatively low intensity type so that they can be delivered as an outpatient. You don’t normally need to be admitted to hospital for them. And there are some newer treatments coming through which are being incorporated also with monoclonal antibodies that, again, are more specifically targeted to the CLL cells.

So what determines when someone with CLL needs treatment?

There may be a number of things. It depends if the patient has significant symptoms. Sometimes with CLL this can also make the lymph glands in the body enlarge because the CLL cells can track their way into the lymph glands. So sometimes there are symptoms from having very large lymph glands that people can find uncomfortable or painful. CLL can affect the normal bone marrow function if the level of the leukaemia rises, so that the patient may become anaemic or start to get a lower platelet count than normal. And that would be another reason to start treatment, to reverse that balance, to try and restore some normality to the bone marrow. Also sometimes the CLL can get to a stage where the patient may be losing weight or has fevers or is generally becoming more poorly, and again that would be a reason to start treatment.

So one of the complications that can occur with an allogeneic stem cell transplant is this condition called graft-versus-host-disease. And this arises because when the new stem cells seed and take root in the patient a new immune system develops. Immune systems are there to recognise things that are foreign to them and to attack them, and because the new immune system doesn’t recognise some of the other parts of the patient’s body as belonging to the same immune system, they can attack those. And this can give complications such as liver damage, problems with the gut and with the skin. This is a complication that can be treated but it requires further immune suppression drugs to be given.

Now, there is a flip side to graft-versus-host-disease which is potentially of benefit, which is that any leukaemia cells that are left in the patient that weren’t killed off by the chemotherapy and the radiotherapy, these may also be recognised as foreign by the new immune system. So the new immune system recognises the leukaemia cells as not belonging to them and therefore can attack them and kill them. And in some kinds of leukaemia, for example for chronic myeloid leukaemia, this is a very powerful effect and it is sometimes called graft-versus-leukaemia-effect.

So for chronic myeloid leukaemia the treatment now involves most commonly taking a new type of drug which has become available over the last few years, and this is a drug called imatinib or Glivec. And this is a new type of drug in that it specifically is targeted towards a genetic abnormality that’s found only in the CML cells. So the CML cells are growing out of control because they’ve got a hyperactive molecule in them and what the Glivec does is it binds to this particular molecule and stops it working normally, and that puts the patient back into remission and restores normality in their blood. With the Glivec we at the moment don’t know how long we need to keep treatment going for and it’s likely that it would need to be life long. it’s a relatively simple treatment to take. it’s in the form of a tablet which needs to be taken daily over, as I say, probably many years.

You were talking about the chromosomal abnormality in CML. Is that the Philadelphia chromosome?

That’s right.

Is that unique to CML?

it’s not completely unique to CML. it’s also found in certain types of ALL, acute lymphoblastic leukaemia, but everybody who has CML has that abnormality in their leukaemia cells only. Not in other cells in the body but purely in the leukaemia cells. So the Glivec, the imatinib is also being used for treatment of those types of ALL where the Philadelphia chromosome may be present. But for those conditions it needs to be combined with intensive chemotherapy to get a remission, whereas in CML the Glivec alone is sufficient usually to induce the remission.

There’s two main types of leukaemia. There is acute leukaemia and chronic leukaemia. And then within the acute leukaemias there’s two types’ acute myeloid leukaemia and acute lymphoid leukaemia, and the same applies to the chronic leukaemias. And the definition of acute leukaemia comes from the fact that it normally is a very rapidly growing cancer and if left untreated would result in relatively short survival of the patient, but with effective treatment that can be reversed.

And the symptoms that one normally gets with acute leukaemia are a consequence of the fact that the leukaemia takes over the bone marrow and therefore you can’t make your normal blood cells anymore. So the patient may become tired and breathless because they’re not making red blood cells which carry the oxygen around the body. They may notice that they’re having frequent infections because the normal white blood cells are not being produced. And also sometimes you get bruising or inappropriate bleeding because the blood cells that stop you doing that, platelets, are also reduced in number.

Chronic leukaemias are normally much more slow growing. And in fact before we had treatments for leukaemias people could have certain types of chronic leukaemia for many, many years without requiring any treatment or coming to any harm from it. And with these more commonly the symptoms are to do, again patients can complain of fatigue and tiredness and weight loss but it doesn’t normally affect the bone marrow function the way that the acute leukaemias do.

So there are, in the acute leukaemias there are two types, the myeloid type and the lymphoblastic type. And similarly in the chronic leukaemias there is a myeloid and a lymphoid type. The difference between these two is that they develop from slightly different types of white blood cells. So normally in our circulation we have white blood cells called neutrophils, which are the myeloid type of cells. These are very important in fighting bacterial infection in particular. And then the other main type of white blood cell we have is the lymphocyte, and this is important, especially important in fighting viral infections. So in chronic or acute myeloid leukaemia the cancer is developed in a cell that would normally have become a neutrophil, it would have become a normal myeloid cell but has become damaged in some way and is now growing out of control. And in the lymphoid types of leukaemias, what has happened is that a cell normally destined to become a lymphocyte has started to grow out of control and that’s what the lymphoid leukaemias are.

So myelodysplasia or myelodysplastic syndrome, MDS, this a group of related conditions where you have poor production of your normal blood cells, but in contrastto acute leukaemia there isn’t an excess of malignant cells. So instead of the blood cells developing normally in the bone marrow, they develop in an abnormal way and they tend to die prematurely in the bone marrow and don’t find their way into the blood. So typically what this means is the patient usually is anaemic and needs regular red blood cells transfused to them. And sometimes there can be a reduction in the other blood cells as well, the platelets and the white blood cells. So the treatment in most instances requires regular transfusions and chemotherapy type treatments are not commonly used.

Now, as I said at the beginning, it’s a range of conditions some of which behave in a very indolent and slow way in that, although the patient requires regular transfusions, the disease doesn’t progress in any sinister way. In other individuals the myelodysplastic syndrome can convert to an acute myeloid leukaemia, and at that stage it would require treatment with chemotherapy. At the point at which the MDS is diagnosed there are certain tests including the chromosomal make-up of the bone marrow cells that will help the clinicians to decide whether it’s the type of MDS that is less likely or more likely to develop into leukaemia.

So with acute leukaemias the growth of the cancer cells is very rapid and therefore we need to get treatment started urgently, normally in a matter of days. And the treatment consists of chemotherapy. So these are drugs that damage the leukaemia cells and we hope cause them to die. Because the leukaemia cells can travel throughout the body and are found throughout the bone marrow the treatment has to be in a form that travels throughout the body, so you can’t have an operation. We need to give chemotherapy drugs that travel throughout the blood stream. And these are normally given in short intensive bursts of treatment, so this is sometimes called intensive chemotherapy. So there are combinations of drugs. You normally get at least two, sometimes three, and these are given daily over of a period of about a week to ten days.

This sort of treatment needs to be given in hospital because one of the consequences of the chemotherapy is that there is damage to normal blood cells and normal bone marrow cells, and temporarily the patient has very low levels of these cells. So we have to support them through that period. they’re very likely to need blood transfusions, platelet transfusions and also treatment for infection. So this is a period when because of low immunity and the patient is very susceptible to getting serious infections and has to spend time in hospital.

What we’re hoping with this intensive course of treatment is to induce what is called a remission, which means that we can’t detect the leukaemia cells anymore. However, we know that if we were to stop treatment at that stage the leukaemia would inevitably come back because although we can’t detect them there are still some left behind. So once the first course of treatment is completed, which normally for acute leukaemias takes about a month to six weeks, you usually have a short break of a week to two weeks, and then have further courses of treatment. And for acute myeloid leukaemia that normally takes about four courses of intensive chemotherapy which, with the intervals in between, requires about a six month period to complete your treatment. And normally that’s when the treatment stops, all being well. And then after that there’s monitoring usually as an outpatient to make sure that things stay in remission.

For acute lymphoblastic leukaemia the treatment is very similar in the initial phases with intensive chemotherapy but then, once that’s been completed and you’re an outpatient again there is a more protracted period of about eighteen months after that where you have low doses of outpatient type chemotherapy. So these are doses not sufficient to reduce your normal blood cells right down, so you don’t need to be in hospital for them, but they’re a very effective and a very important part of the treatment.