Chronic lymphocytic leukemia/small lymphocytic lymphoma

CLL is a cancer of lymphocytes, a kind of white blood cell. The bone marrow — the spongy tissue inside bones where blood is made — produces too many of them, and they are not the working kind.

CLL and SLL are the same disease with two different addresses. When most of the abnormal cells are in the blood and marrow, doctors call it leukemia. When they are mainly in the lymph nodes, the small immune glands in the neck, armpit and groin, they call it lymphoma. Cancer Research UK states plainly that the treatment for the two is the same.

It is usually slow. The NCI says CLL usually gets worse slowly, and the EBMT Handbook describes it as following an indolent course that does not require treatment in the majority of patients. “Indolent” is the clinical word for slow-growing.

It is a disease of later life. The NHS notes it is very rare in people under 40, and the median age at diagnosis in US registry data is 71.

It is not clear what causes CLL. That is the NHS’s own wording, and it is the honest headline.

Age is the dominant risk factor. It is more common in men than in women. Having a close relative who has had it may mean a slightly higher risk — a small increase, not a condition that is passed down predictably.

There is a related finding called monoclonal B-cell lymphocytosis, where a small population of identical abnormal B cells shows up in the blood below the count that would define CLL. It is common, becomes more common with age, and the low-count form rarely progresses to CLL.

Often, at first, nothing a person can feel. That is why CLL is so frequently found while it is still causing no symptoms — a routine blood test comes back with a high lymphocyte count.

When symptoms do come, the NCI lists painless swelling of the lymph nodes, weakness or tiredness, pain or a feeling of fullness below the ribs from an enlarged spleen, fever, easy bruising, pinpoint red spots under the skin, unexplained weight loss and drenching night sweats.

The mechanism behind most of that is straightforward to picture. Abnormal lymphocytes accumulate in the marrow and crowd out normal blood production — which is why the staging system marks its more advanced stages by a low red cell count, causing the tiredness and breathlessness, and a low platelet count, causing the bruising and the pinpoint spots. Cells also build up in the lymph nodes and spleen, which is the swelling and the fullness.

There is one uncommon but serious event to know the name of. In a minority of people, CLL transforms into a more aggressive lymphoma. It is called Richter transformation, and it is the point at which the disease stops being slow.

The main pathway starts by not treating. It is called watchful waiting, or watch and wait, and it means monitoring closely without giving treatment until signs or symptoms appear or change. For someone who has just been told they have cancer, this can sound like being abandoned. It is the opposite, and the evidence for it is unusually good.

The older evidence was a meta-analysis finding no difference in overall survival at ten years between treating early-stage disease immediately and waiting. The obvious question was whether the modern targeted drugs would change that answer — so it was tested. The CLL12 trial randomised 363 people with symptom-free early-stage CLL to ibrutinib or a placebo. The drug clearly delayed the disease progressing. It did not help people live longer, and the authors concluded that watch and wait should remain the standard of care.

Treatment starts when the disease gives a reason: symptoms, anemia or a falling platelet count, bulky nodes or spleen, or a lymphocyte count that is doubling in under six months. Until then, monitoring is check-ups and blood tests.

When treatment does begin, it is usually tablets rather than chemotherapy. The common first treatments are targeted drugs — acalabrutinib, ibrutinib and zanubrutinib, which block a signal called Bruton’s tyrosine kinase that CLL cells depend on, and venetoclax, which removes a survival signal keeping the cells from dying. These are often paired with an antibody such as rituximab or obinutuzumab. Chemotherapy is now usually only used when targeted drugs cannot be given.

A transplant is not a common treatment for CLL. Cancer Research UK says so directly, and the EBMT Handbook calls CLL a rare indication for transplant, precisely because most people never follow a course that needs one.

The defining experience at diagnosis is being told you have a cancer and that nobody is going to treat it. Readers are less prepared for that than for almost anything else in this library.

Both common reactions are normal, and Cancer Research UK names both: some people find watch and wait makes them anxious, and other people feel relieved that they do not need treatment yet and can carry on with work and plans. Neither reaction is the wrong one.

How long it lasts is genuinely open-ended. Some people wait years before they need treatment. Some never need any at all.

The monitoring itself is light — outpatient appointments and blood tests. No admission, no infusions, no hair loss. Most of life continues. When treatment does start, the targeted drugs are usually daily tablets taken continuously, though some venetoclax-based regimens run for a fixed period.

For the small number of people who reach a transplant, it is a different order of experience entirely: conditioning treatment, a hospital stay, and a long recovery with the risk of graft-versus-host disease. Cancer Research UK notes it is intensive enough that a person needs to be relatively young and well to have one.

Rarely. For most people diagnosed with CLL or SLL, no donor is ever involved, and it would be misleading to suggest otherwise on a page most people reading it will never need.

Two specific situations bring a donor into the picture. The first is Richter transformation, where the 2025 EBMT recommendations rate an allogeneic transplant as standard of care. The second is poor-risk CLL that has relapsed or stopped responding after both main drug classes — the BTK inhibitors and venetoclax. That situation is sometimes called double-refractory, and EBMT rates transplant a clinical option there.

For those people the donor question is entirely real and often urgent. For everybody else with CLL, it is not the question at all.