Internal Medicine

Chronic myeloid leukemia (CML)

Synonyms in a broader sense

Leukemia, white blood cancer, Philadelphia chromosome

definition

The CML (chronic myeloid leukemia) shows a chronic, i.e. rather slowly progressing course of the disease. This leads to the degeneration of a stem cell, which is a precursor of the granulocytes, i.e. for the defense of v.a. Bacteria important cells.

frequency

There are 3 / 100,000 new cases per year. People around the age of 60 are particularly affected.

CML in children

The average age of onset is 65 years of age. In principle, all age groups can get the disease, but children are rarely affected. In Germany, for example, only 1-2 children per 1 million population develop chronic myeloid leukemia every year.
Due to the rarity of the disease in childhood, it is therefore not surprising that there are currently few meaningful studies and data on this topic. However, there is evidence that childhood CML may be more aggressive in its course. Under certain circumstances, the disease in children even represents a separate clinical picture.
Therapeutically, roughly the same goals can be formulated as with adult patients. However, since children are much more susceptible and sensitive to the side effects of modern therapies, therapy decisions must be considered very carefully. The children often need decades of treatment. Avoiding lifelong therapy with modern tyrosine kinase inhibitors is therefore often an important goal. Current studies also deal with the possibility of “stopping therapy”.

Read more on the subject at: Leukemia in children

The tyrosine kinase inhibitors belong to the targeted chemotherapeutic agents and are mainly used in CML. Find out more about the effects and side effects of this therapy at: Targeted chemotherapy with tyrosine kinase inhibitors

causes

It is currently relatively unclear why this disease occurs, but radiation (as in a nuclear reactor accident) or certain substances (benzene) are factors that could lead to the disease.

However, the Philadelphia chromosome is found in about 90% of cases, which is the result of a chromosome mutation. A reciprocal translocation of fragments of chromosomes 9 and 22 takes place.

Symptoms

There are three typical phases in this disease:

Stable phase: Often only a performance kink can be seen, as is weight loss. Symptoms are relatively atypical at this stage.

Transition phase: There is often a rapid enlargement of the spleen (Splenomegaly), e.g. can lead to abdominal pain. Fever is also relatively common here. The weight loss and the drop in performance can increase.

Blast blow: The so-called blasts are early precursors of the granulocytes. In this phase, the body is flooded with the degenerated cells. So the symptoms are increasing rapidly. It can Anemia (anemia) and increased Bleeding added (through the suppression of platelet formation).

These symptoms can tell you whether you have a leukemia may be ill and should have this checked by a doctor.

How do you recognize chronic myeloid leukemia?

In contrast to the acute forms of leukemia, chronic leukemia can run unnoticed for many years. Especially in the early stages, if at all, rather unspecific symptoms such as chronic fatigue, fever, or unwanted weight loss. So it is not that easy to recognize the CML easily.
Only in the two advanced phases (acceleration phase and blast crisis) do those affected suffer from more serious complaints.
The family doctor often recognizes changes in the blood count by chance. These include e.g. a strong increase in white blood cells (Leukocytosis) in different forms. In addition, leukemia cells, the so-called "blasts", can often be detected in the blood.
Often fall at one Ultrasound examination of the belly a partly massively enlarged spleen.
When the evidence of chronic myeloid leukemia increases, a detailed diagnosis is usually carried out in the hospital. Special examinations of the blood and bone marrow can be carried out here.

General information on the topic can be found at: How do you recognize leukemia?

Chronic phase

Most often, chronic myeloid leukemia is discovered during the chronic phase. It corresponds to that Initial stage of the disease and can last up to ten years. It often runs without symptoms, so that the initial diagnosis is not infrequently more incidental, e.g. as part of a routine blood test at the family doctor.
At this stage there is a gradual displacement of healthy blood-forming cells in the bone marrow. In order to still be able to produce enough blood cells, the body switches to other organs for blood formation. In this context one speaks of extramedullary blood formation.
This primarily affects the spleen, so that the organ can become extremely enlarged. Due to the massive increase in size, there is even a risk of life-threatening Ruptured spleen. Occasionally, those affected previously report problems on the left upper abdomen.
There are hardly any characteristic symptoms of the chronic phase. Often patients complain unspecific complaints, such as. Weight loss, fatigue, or night sweats.

diagnosis

Blood sampling: Here the number of white blood cells in the blood is determined. With this disease, especially in the blast episode, an increased number of white blood cells is to be expected (leukocytosis). Parameters such as the so-called ALP (alkaline leukocyte phosphatase) in the serum are also determined. This value is lowered in CML (chronic myeloid leukemia) and distinguishes this disease from other similar diseases in which this value is increased. In addition, other parameters are determined that indicate an increased cell turnover in the body (uric acid, for example). The values are determined each time a blood cancer is suspected.

Bone marrow tissue removal (bone marrow biopsy) and blood smear: After analyzing the tissue removal from the bone marrow with the aid of the microscope, the cells in the bone marrow can be assessed and their origin can be determined. In addition, a sample of blood drawn from the vein can also be examined and assessed under the microscope.

Read more on the topic: Bone marrow puncture

Cytogenetics: The already described examination of the genetic material of the degenerate cells is crucial for both therapy and prognosis, because the cells of the CML (chronic myeloid leukemia) have an extremely high proportion of the Philadelphia chromosome (approx. 95% of the Cells have this atypical connection between chromosomes 9 and 22).

Computed tomography (slice x-ray) and ultrasound: the enlargements of the liver and the spleen can be assessed with this imaging.

therapy

Bone marrow transplant: With this disease, it is especially important to find bone marrow donors, because this makes this type of leukemia curable.

Chemotherapy: This type of cancer is also used chemotherapy treated.

Leucopheresis: This method removes the very numerous cells from the blood due to the uncontrolled growth, otherwise it would lead to a thickening of the blood due to the increase in the viscosity of the blood. The consequence would be Strokes, Heart attacks or Thrombosis, because the blood would remain in smaller vessels and clog these vessels.

Imatinib: The active ingredient is particularly important in this disease Imatinib plays a very important role, as 95% of the degenerated cells have the Philadelphia chromosome.

Prognosis / life expectancy / chances of recovery

According to the current state of science, chronic myeloid leukemia cannot be cured with drugs. In the case of advanced disease or a lack of response to therapy, a principally curative (i.e., promising cure), but risky bone marrow transplant can be considered. Accordingly, it is not so easy to make general statements about the individual prognosis or life expectancy.
Basically, in chronic myeloid leukemia, massively increased cell counts in the blood cause complications and complaints. The aim of therapy is therefore to reduce the number of leukemia cells so that potentially fatal complications can be avoided.
So-called "tyrosine kinase inhibitors" such as imatinib, nilotinib or dasatinib have been approved in Germany since 2001. Behind these complicated names are novel drugs that can, in simple terms, suppress the malignant leukemia cells. In contrast to conventional chemotherapy, these drugs intervene directly at the site of the CML and thus prevent the development of degenerate cancer cells.
The introduction of tyrosine kinase inhibitors can now be described as a real medical revolution, because before that, chronic myeloid leukemia was considered a poorly treatable disease that led to death within a few years.
In contrast, patients today can lead a largely normal life. With early, optimal and consistent therapy, an almost normal life expectancy can now be achieved.
In addition to a timely diagnosis, the strict and continuous use of medication is of great importance for the prognosis. The attending physicians check meaningful laboratory parameters at regular intervals so that they can intervene quickly in an emergency.
Current studies also deal with the question of whether it is even possible to “suppress” the disease completely. Then those affected could, at least for a certain point in time, stop taking the medication completely.
If modern therapies still do not work and the CML progresses, a bone marrow transplant may bring the prospect of a cure. Nevertheless, the risk of this dangerous intervention should not be underestimated.

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