Therapy Of Chronic Leukemia (CLL, CML)

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Therapy Of Chronic Leukemia (CLL, CML)
Therapy Of Chronic Leukemia (CLL, CML)
Video: Therapy Of Chronic Leukemia (CLL, CML)
Video: Chronic Lymphocytic Leukemia (CLL) 2023, February
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Chronic leukemia: therapy

Chronic leukemia develops slowly over months and years. The therapy is usually less aggressive than for acute leukemia, but accompanies those affected permanently. Even without complete healing, the majority of patients can lead a symptom-free life for years.

The course of the disease and the prognosis depend in detail on the respective subtype of the disease as well as the age and general health of the person affected.

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  • How is chronic myeloid leukemia (CML) treated?
  • How is the success of the therapy assessed?
  • How long does the treatment for CML take?
  • What do tumor board and clinical study mean?

The chronic lymphocytic leukemia (CLL) makes the affected initially usually no symptoms and is often discovered only by chance. In this case, it is possible to first wait and see how the disease develops. Therapy is only started if the blood values ​​worsen or symptoms occur. CLL is also counted among the malignant diseases of the lymphatic system (lymphoma). More on the topic: Lymphomas: Therapy

For chronic myeloid leukemia (CML), treatment is started after diagnosis, because the earlier treatment for CML is initiated, the better the chance of a favorable course of the disease. Chronic myeloid leukemia is generally well treatable today. With the development of modern drugs, the life expectancy of those affected has improved significantly in recent years.

How is chronic myeloid leukemia (CML) treated?

Treatment for CML depends on what stage the patient is in at the time of diagnosis. More on the topic: Types and symptoms of leukemia.

Chronic phase of CML

The diagnosis of CML is usually made in the chronic phase. In these cases, the molecular genetic characteristics of the leukemia cells are used for therapy: A special genetic change, the so-called Philadelphia chromosome, is typical of CML. This changed chromosome results in the creation of a new gene (BCR-ABL) and the formation of a new protein (from the group of protein kinases). Both the BCR-ABL gene and the resulting protein do not occur in healthy individuals; they stimulate the leukocytes to constantly, uncontrolled division and are known today as the mechanism of the formation of CML. The modern treatment of CML starts with this: Oral (swallowable) drugs are available (so-called tyrosine kinase inhibitors), which are directed against this protein and can thereby stop the disease.

Tyrosine kinase inhibitors are among the so-called targeted therapies, and several preparations have now been approved. They are the standard therapy for CML today. The success of the treatment is therefore very good; depending on the preparation, normalization of the blood count can be achieved in up to 95 percent of cases (complete remission, see below).

The tyrosine kinase inhibitors are relatively well tolerated compared to immunotherapy and chemotherapy (which used to be the standard of CML treatment), so those affected can lead a largely normal everyday life. However, a complete cure is usually not possible with tyrosine kinase inhibitors. The medication must be taken permanently, otherwise the symptoms of the disease may recur.

More on the topic: Therapy for cancer

Accelerated phase of the CML

If the general condition or the blood values ​​of those affected worsen, this is a sign that the disease is entering the accelerated phase. In this case, those affected initially receive another preparation from the group of active substances called tyrosine kinase inhibitors; this can lead to a renewed regression of the leukemia cells and an improvement in the symptoms. The goal is to bring the disease back into the chronic phase.

If the tyrosine kinase inhibitors are insufficient or no longer work, a stem cell transplant may be an option. In the process, healthy stem cells are transferred to the patient, with the help of which the blood-forming system can build up again. In the best case scenario, permanent healing can even be achieved. However, a stem cell transplant is a very intensive treatment that comes with various risks. It is not an option for all those affected, in particular age and general condition play a decisive role. More on the topic: stem cell transplantation.

If a stem cell transplant is not possible, newer tyrosine kinase inhibitors, chemotherapy or immunotherapy with interferon alpha or a combination of both can be used. Immunotherapy stimulates the body's immune system to target the wrong proteins. The rate of side effects of cytostatics and interferons is relatively high. Today, further developed interferons (pegylated interferons), which have to be administered less often and are better tolerated, are used in clinical studies.

Blast phase of the CML

If the disease worsens acutely and the number of leukemia cells in the blood and bone marrow increases sharply within a short period of time, it is called a blast crisis or blast phase. In this phase, the disease is similar to acute myeolic leukemia and is treated accordingly: Intensive chemotherapy is started immediately, which takes place in the hospital.

As soon as the condition of those affected improves, it will be checked whether a stem cell transplant can be carried out in the next step.

More on the topic: Therapy of acute leukemia

How is the success of the therapy assessed?

Regular blood and bone marrow check-ups are carried out to assess the success of the therapy. When the symptoms have receded, it is called remission. A distinction is made between different levels:

Haematological remission

If leukemia cells can no longer be detected in the blood using normal examination methods, one speaks of complete haematological remission. The blood count has normalized and the patients are largely symptom-free. If the leukemia cells are still detectable but greatly reduced, one speaks of hematological partial remission. However, a haematological remission does not automatically mean that the body is completely free of leukemia cells; individual pathologically altered cells cannot be detected in normal blood tests. The examination of the blood alone is therefore not sufficient to assess the success of the treatment.

The aim of therapy is to achieve a complete haematological remission after three months.

Cytogenetic remission

A chromosome analysis is also carried out on the basis of a bone marrow sample: If the Philadelphia chromosome can no longer be detected using special cytogenetic examination methods, one speaks of complete cytogenetic remission. If the Philadelphia chromosome is detectable in less than 35 percent of all examined leukocytes, one speaks of partial cytogenetic remission.

Ideally, a partial cytogenetic remission should be achieved three months after the start of therapy and a complete cytogenetic remission six months after the start of therapy.

Molecular Remission

In addition, the so-called molecular remission can now also be determined. The proportion of leukemia cells in the blood that carry the pathological BCR-ABL gene is determined using highly sensitive methods. An optimal response to therapy is achieved when:

  • the BCR-ABL values ​​have fallen below ten percent after three months of therapy,
  • the BCR-ABL values ​​have fallen below 0.1 percent after twelve months of therapy (good molecular remission),
  • the BCR-ABL values ​​fall below 0.01 percent in the further course (deep molecular remission).

The regular determination of the remission is crucial in order to assess the course of the CML and the likelihood of a relapse and to adjust the therapy accordingly.

How long does the treatment for CML take?

Even if a molecular remission is achieved using a tyrosine kinase inhibitor and the BCR-ABL gene is no longer detectable, it is unclear whether one can speak of a permanent cure. There is still a residual risk that isolated leukemia cells are dormant in the body. It is therefore currently common practice to continue drug therapy for life.

Clinical studies are currently investigating whether it is possible to interrupt the intake without causing the disease to relapse. In these studies, drug discontinuation is very controlled; close-knit examinations are carried out in order to identify possible recurrence of symptoms at an early stage. The treating physicians can inform you in individual cases whether participation in such a study is possible and what advantages it may bring.

The only way to permanently cure CML is through a stem cell transplant. As long as tyrosine kinase inhibitors bring the desired therapeutic success, however, it is not carried out due to the numerous risks.

What do tumor board and clinical study mean?

Leukemia is not a uniform clinical picture; numerous factors influence the course and severity. Accordingly, there are no generally applicable treatment strategies for all those affected; which therapy is best in each individual case is determined individually. Therefore, so-called tumor boards are held regularly as part of the care and therapy planning for leukemia. A tumor board is a kind of conference at which experts from various disciplines work together to determine the best individual treatment strategy for each patient based on the latest scientific findings.

Those affected may also be given the opportunity to take part in a clinical study. This does not mean that the treatment is experimental; clinical studies enable access to the latest treatment approaches and drugs. The participants receive very intensive and close-knit support and follow-up checks. Many patients with leukemia can benefit enormously from this.

The attending physicians provide individual information on whether participation in a clinical study is possible and how it will proceed.

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