Chronic myeloid leukaemia

This illness usually starts not with a complaint but with a line on a routine blood test: the white cell count comes back several times higher than it should be in someone who felt fine, or who was blaming the tiredness on work. Chronic myeloid leukaemia is a rare tumour of the blood-forming tissue, and in twenty years its outlook has changed more than that of almost any other cancer. Where a bone marrow transplant was once the only real chance, the conversation today is about tablets taken for years on end and a life expectancy close to normal. But it has a handful of situations where the clock runs in hours, and those are worth knowing in advance.

What actually breaks in the bone marrow

Inside a single blood-forming stem cell, chromosomes nine and twenty-two swap pieces. At the join sits a gene that does not exist in nature, and it makes a protein: an enzyme from the tyrosine kinase family with its off-switch broken. That enzyme tells the cell to divide around the clock. The marrow starts pushing granulocytes, a kind of white cell, into the blood, mature and immature ones mixed together, until there are so many that the blood thickens and the spleen, left to filter all of it, grows.

The fault arises in one single cell of an already adult body. It is not passed on to children, so leukaemia is not inherited in the everyday sense of the word. It cannot be caught from anyone either. And — this has to be repeated to almost every patient — it is not brought on by diet, stress, past colds or household appliances.

How it shows itself

More than half of cases turn up by accident: bloods taken before an operation, at a check-up, or because of something else entirely. When there are signs, they come from three things at once — too many white cells, too few red ones, and an enlarged spleen:

• tiredness that a weekend does not fix, and breathlessness on effort that used to be easy;
• pallor, easiest to spot on brown and dark skin at the palms, the lips and the inner surface of the eyelids;
• heaviness or fullness under the left ribs, and feeling full after a few spoonfuls;
• drenching night sweats that mean changing the bedding;
• weight coming off without dieting, and loss of appetite;
• a slight temperature that hangs about for weeks with no cold behind it;
• a dull ache in the bones, most often the pelvis and the ribs;
• bruises from the lightest knock, bleeding gums, nosebleeds that go on and on;
• frequent infections and a long haul back afterwards;
• itchy skin with no rash.

Swollen lymph nodes, by contrast, are not typical here at all, and if they appear they point to a shift into a more aggressive phase. Everything else on the list turns up in a dozen ordinary conditions, from anaemia to a thyroid problem, so there is no cause to panic — and none to ignore it either: a full blood count with a differential costs very little, comes back within a day and settles the question.

Signs that cannot wait

Here there is nothing to weigh up and no appointment to book — this needs an ambulance or the nearest emergency department:

• an erection lasting more than two hours that hurts. Thickened blood is stuck in the vessels of the penis; without treatment within a few hours the tissue is lost for good;
• vision that drops or clouds over suddenly, severe headache, confused speech and thinking, ringing in the ears, breathlessness at rest. That is blockage of the small vessels of the brain and lungs by the mass of white cells;
• sudden severe pain under the left ribs, sometimes spreading to the left shoulder — the enlarged spleen may have infarcted or ruptured;
• a temperature above 38 °C with shivering in someone already on treatment;
• bleeding that will not stop, vomiting blood, or black tarry stools;
• weakness, bone pain and a swelling abdomen all building up over a few weeks — that is what the move into blast phase looks like.

Who gets it more often

The disease is rare: one or two new cases per hundred thousand people a year. It can begin at any age, childhood included, but most diagnoses fall in the second half of life, and it is slightly more common in men than in women.

The one proven outside factor is a large dose of ionising radiation: nuclear accidents, radiotherapy given for another tumour. None of that applies to background radiation or to an X-ray or scan at the clinic. Smoking, alcohol, contact with chemicals, family history and chronic illness are not accepted as causes. Which is why the disease has neither prevention nor screening: it cannot be headed off, only picked up in time on a blood test.

How the diagnosis is confirmed and the phase worked out

A raised white cell count on its own proves nothing — an ordinary infection does the same. A haematologist takes it from there, and the work-up usually includes:

• a full blood count with a differential and a look at the film under the microscope;
• a bone marrow aspirate and biopsy — marrow is drawn with a needle from the pelvic bone under local anaesthetic, with a sedative if you prefer;
• a chromosome study of the marrow cells, looking for that swap between nine and twenty-two;
• a molecular blood test that finds the abnormal gene and measures how much of it there is. The diagnosis is not made without it, and it later becomes the main way of tracking treatment;
• an abdominal ultrasound to measure the spleen.

The share of immature cells in blood and marrow sets the phase: chronic, where nine people in ten are caught, accelerated, and blast. Treatment and outlook both hang on it, so this is no formality. Results sometimes take two or three weeks; the wait in itself means nothing bad, and you may ask the clinic at any point how long it will be.

What treatment looks like today

The backbone is the tyrosine kinase inhibitors, the drugs that shut down the broken enzyme. They are tablets, taken at home, daily, for a long time. There are several generations by now, so if one is poorly tolerated or stops working, your doctor moves you to another. Side effects are usually moderate: nausea, puffy eyelids and ankles, rash, aching muscles, changes on blood tests; a few of the drugs act on the blood vessels, so they are picked with the heart in mind.

The rest plays a supporting role. In the first days, when the white count is very high, drugs are given that bring it down quickly, and in severe cases the blood is run through a machine that separates the cells out mechanically. Not everyone needs chemotherapy — mainly it is for blast phase and the run-up to a transplant. A stem cell transplant from a donor remains the only method capable of curing outright, but it carries serious risks, and these days it is held back for people the tablets have failed and for aggressive phases. Supportive care runs alongside: vaccinations, treating infections, transfusions when anaemia is deep.

Progress is measured not by how you feel but by that same molecular test, usually every three months. There are checkpoints: how far the figure should have dropped, and by when. If after years of treatment the abnormal gene stops being detectable and stays that way for a long stretch, some patients come off the drug under frequent lab monitoring. That is a separate, planned procedure, not a decision anyone makes alone.

What is down to you

A short list, but it matters. First and foremost, take the drug every day and do not skip doses: irregular dosing lies behind most lost responses and most resistance. After that:

• tell your haematologist about every medicine, vitamin and herbal remedy you take — some shift the drug level in your blood sharply;
• grapefruit and grapefruit juice are off the table while you are on these tablets;
• do not quietly stop treatment because of side effects — almost always the dosing can be adjusted or the drug swapped;
• reliable contraception is essential: these medicines are dangerous to a developing baby. Pregnancy is possible, but only when planned with your doctor;
• do not miss the monitoring tests, even when you feel perfectly well — the disease comes back before any symptoms do;
• smoking and excess weight do not cause leukaemia, but they clearly worsen how treatment is tolerated and add vascular risk.

Online consultation

Two things are best sorted out remotely. The first is what to do with a blood test you cannot make sense of: the doctor goes through the figures, explains which genuinely call for a haematologist and which are down to a recent infection, and suggests what is worth having done before a face-to-face appointment. The second is living with a diagnosis already made: working through side effects, checking new medicines for interactions, understanding the latest monitoring result, putting together questions for your haematologist. The urgent signs listed above are not handled through a screen — with those you go straight to emergency care.

This material is for information only and does not replace medical advice.