Chronic myeloid leukemia (CML)

Description

Chronic myeloid leukemia, also called chronic myelosis, is a malignant disease. The basis for CML is the development of cancer cells from blood stem monoclonal cells, with an abnormal increase in leukocytes (white blood cells).

It is divided into 3 stages: "Chronic stage" develops slowly and, if left untreated, progresses to the "Acceleration stage", which progresses more rapidly and is more dangerous. Finally, the "blast crisis" occurs, which resembles acute leukemia.

CML occurs comparatively rarely and accounts for approximately 15 -20% of all adult leukemias. It affects only 1 person out of 100,000 annually. Most of the patients are middle-aged (50 - 60 years).

The lifespan of blood cells is limited, so they must be constantly replenished in the bone marrow. A few stem or progenitor cells divide and mature until countless blood cells are formed. Fully formed, they are then released into the bloodstream.

Degeneration of monoclonal stem cells leads to chronic myelosis.

Risk factors include:

• Chemicals (e.g. benzene)
• Ionising radiation (e.g. radioactivity)

Approx. 90 % of all patients have changes in chromosome 22 ("Philadelphia" chromosome). Erroneous addition of genetic information from chromosome 9, resulting in the formation of an altered tyrosine kinase (special protein). This leads to the degeneration of blood cells.

Chronic myelosis is often discovered late, as symptoms are initially absent. It is not uncommon for years to pass between the onset of the disease and diagnosis. Experts divide it into 3 stages:

Chronic-stable phase

The number of white blood cells increases and splenomegaly (enlargement of the spleen) occurs. Due to the enlarged spleen, pressure may be felt in the left upper abdomen. There is also a decrease in performance and fatigue.

Acceleration phase

The blood count shows leukocytosis (increase in white blood cells) and a decrease in red blood cells and platelets.

Characteristic of this phase are bleeding gums and nose, pallor, palpitations and shortness of breath. Less frequently, there are night sweats and fever. In addition to the spleen, the liver also enlarges.

Blast crisis / blast spurt

Finally, immature blood cell precursors (myeloblasts, promyelocytes) enter the blood from the bone marrow. The course now resembles acute leukaemia and usually results quickly in death.

The diagnosis of chronic myeloid leukaemia is often just a coincidence. Fatigue or pressure in the upper abdomen can be the reason for a visit to the doctor. The blood count shows an increased number of white blood cells (leukocytosis). A bone marrow puncture can confirm the diagnosis, while the detection of the Philadelphia chromosome (by means of chromosome analysis) provides further evidence of the disease.

Once the diagnosis is made, treatment is started. Usually, treatment is started with the tyrosine kinase inhibitor imatinib. If the therapy remains unsuccessful, interferon-alpha and chemotherapy are also available. The last options are stem cell transplantation (SCT) or bone marrow transplantation (BMT).

Imatinib

This is a tyrosine kinase inhibitor. Degenerated blood cells are prevented from multiplying and die more quickly.

If treatment is started early, the success rate is about 95%. If there is an intolerance to imatinib, similar preparations such as dasatinib can be used.

Interferon-alpha

In the chronic phase, interferon-alpha treatment has a good success rate of 70-80%.

In the majority of patients, the blood findings normalise afterwards. The strong side effects prove to be a drawback, which is why many patients discontinue the therapy prematurely.

Chemotherapy

Chronic myelosis cannot be cured by chemotherapy, but the symptoms of the disease regress. Sometimes it is combined with interferon therapy, but it can also cause severe side effects.

Bone marrow and stem cell transplantation

Until today, the only chance for a cure is offered by BMT and SCT. However, they carry high risks, which is why patients must be under 55 years of age and the decision should be well-considered.

The good success rates of therapy with tyrosine kinase inhibitors give reason for hope. The majority of patients respond well to treatment and the disease can be contained almost beyond recognition. However, long-term studies are still pending.

Interferon-alpha and chemotherapy also offer good prospects.

A real cure can so far only be achieved with the help of a transplantation of stem cells or bone marrow.