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Treatment of CML - chronic myeloid leukemia in Assuta

treatment of CMLIn the treatment of chronic myeloid leukemia in clinic Assuta used several methods - targeted therapy, chemotherapy, irradiation, and stem cell transplantation. The choice of treatment options due to the phase CML.

Targeted therapy

Target therapy is a basic method in the treatment of this disease.

Pathological cells have oncogene BCR-ABL, which produces a protein (a kind of tyrosine kinase) that promotes the growth and development of the disease. Known as with the tyrosine Drugs kinase inhibitors to a suppress activity of the protein, as with the the standard treatment ofmyeloid leukemia chronic :

  • Imatinib (Glivec)
  • Dasatinib (Spraysel®)
  • Tasigna (Nilotinib) 
  • Bosutinib (Bosulif®)
  • Ponatinib (Iclusig)

All of them can lead to serious and even fatal consequences when interacting with some biological supplements or even foods (grapefruit or pomegranate). For this reason, the doctor should have a list of medications and dietary supplements, which are accepted by the patient.

In addition, tyrosine kinase inhibitors can cause harm to the fetus if the treatment is administered during pregnancy. These preparations demonstrate greater efficacy in the treatment of myelogenous leukemia in chronic phase, but they also can help patients in the later stages of the disease for some time.

Imatinib (Glivec)

It was the first drug aimed at the suppression of activity of the protein BCR-ABL, and quickly became the standard treatment for patients with CML. Imatinib is a tyrosine kinase inhibitor known as the first generation.

Almost all patients with CML body responds to the treatment of Gleevec for many years. Get rid of the disease is a medicine can not, so patients need to take it indefinitely or until it ceases to have an impact. Receiving Imatinib made orally, usually once daily with food.

Common adverse effects of therapy include digestive disorders (diarrhea, nausea) muscle pain and fatigue. Basically, they are quite soft. In 30% of people observed skin rash with itching. If necessary, the majority of these symptoms can be treated effectively.

Another common side effect is the accumulation of fluid around the eyes, in the legs or abdomen, in rare cases - in the lungs or around the heart, which can cause breathing problems. Some studies suggest that accumulation of fluid provoked the influence of imatinib on the heart, though rarely observed. It is unclear how serious it is, and whether side effects go away when treatment is stopped. If the patient is taking imatinib and notes sudden weight gain or fluid accumulation in any point of the body, shortness of breath, be sure to tell your doctor.

Another possible unintended consequence of reception - reduction in the number of white blood cells and platelets. If this happens at the beginning of treatment, the reason may lie in the development of malignancy. In this case the blood parameters over time will come to normal. When tests show very low levels of blood cells, the physician for a short time may recommend to stop the therapy. In the past, a lack of red blood cell growth factor used to foster the development of - erythropoietin (Procrit®) or darbepoetin (Aranesp °), but now these drugs involve less and less. Instead, it can lower the imatinib dose to improve blood parameters.

In some patients, imatinib is no longer cause effects. This is called resistance. It is believed that the cause is a mutation in the genes of CML cells. Sometimes it is overcome by increasing the dose of the drug. But in some cases there is a need for a change of medication.

dasatinib

Another anti-cancer drug aimed at action BCR-ABL protein. It is called a second-generation, as Dasatinib after Imatinib emerged. Admission is by mouth, usually one tablet per day. Indications:

  1. Initial treatment of myeloid leukemia.
  2. Intolerance to the side effects of imatinib.
  3. Treatment failure with imatinib.

Potential side effects:

  • accumulation of fluid;
  • reducing the number of blood cells;
  • Gastrointestinal disorders;
  • skin rash;
  • effusion - fluid accumulation around the lungs - a serious complication. It is most commonly seen in patients who take the drug twice a day. The liquid may be drained through the needle, and also reduce the dose of the drug.

nilotinib

Anticancer agent from the class of tyrosine kinase inhibitors, it also refers to the second generation. Indications for use:

  • The initial or starting myeloid leukemia treatment.
  • Contraindications or resistance to gleevek.

Side effects are mild, but, nevertheless, can develop accumulation of fluid, reduced blood cell disorders in the digestive tract (nausea, diarrhea). Nilotinib also can affect the heart rate, causing long QT syndrome. Usually, it does not show any symptoms, but the effects can be serious and even fatal end. Therefore, patients should be done prior to receiving the cardiogram nilotinib, and then in the course of treatment. The problem with the heart rhythm sometimes arises from the interaction of the drug with other medicines or supplements that it is important that the doctor is aware of the reception of various medical and non-pharmaceutical products.

Bosutinib (bosutinib) 

Bosutinib (bosutinib) - preparation inhibiting tyrosine kinase activity.

Adverse effects are usually mild reception. These include gastrointestinal disorders (diarrhea, pain, vomiting, nausea), rash, weakness and fatigue, low blood blood cells. Less bosutinib able to cause accumulation of liquid, severe allergic reactions and the difficulties in the liver. Constantly performed blood tests that check liver function and blood counts.

Ponatinib (Iclusig)

This drug is a new generation of inhibitors categories, suppresses the activity of tyrosine kinase. Capable of provoking serious complications, however recommended in patients with CML in cases when other drugs in this group have no effect, or the malignant cells have a genetic mutation T315I, developing inhibitors for the treatment and creating resistance to their action.

The bulk of the unwanted effects of treatment rather poorly expressed - fatigue, rash, headaches, pain in the abdomen. Often there is high blood pressure, you may need to prescribing. There is considerable likelihood of thrombosis that can cause strokes and heart attacks, blockage of arteries (in rare cases there is a need of amputation). surgery or other procedures may be necessary in the treatment of thrombosis. This risk is higher in elderly patients, when there is high blood pressure, high cholesterol, or diabetes, and after a heart attack, stroke or circulatory disorders.

In rare cases ponatinib able to damage the heart, triggering chronic heart failure, worsen the liver (hepatic failure), pancreas (pancreatitis).

Treatment of chronic myeloid leukemia with interferon

Interferons are a family of substances (glycoproteins-proteins), are produced naturally by the immune system. Interferon-alpha is most commonly used in the treatment of chronic myeloid leukemia (CML). This substance reduces the growth and division of the leukemic cells. Interferon was once considered the best tool in CML but imatinib (Glivec) has proved more effective. Now, tyrosine kinase inhibitors are the mainstay of treatment, interferon, and is rarely used.

Typically, it is administered in the form of daily subcutaneous injections. In the treatment of chronic myeloid leukemia interferon given for several years.

The drug may cause some side effects. They include a "flu-like" symptoms - pain in the muscles and bones, fever, headaches, fatigue, nausea and vomiting. There may be problems with thinking and concentration. May reduce the level of blood cells. These effects last as long as the drug is used, with the condition is normalized over time. However, some patients can be hard to cope with these unwanted effects of treatment, which may require discontinuation of therapy.

Chemotherapy is the treatment of chronic myeloid leukemia in Assuta

Chemotherapy uses anticancer drugs that enter the body orally or intravenously. These drugs enter the bloodstream and reach all areas of the body, so this method is useful for leukemia because it affects the entire body. Any drug that is used for the treatment of cancer (including tyrosine kinase inhibitors) can be referred to chemotherapeutic drugs, but in this aspect, chemotherapy is considered as the use of conventional cytotoxic agents which kill rapidly growing and rapidly dividing cells.

Chemotherapy was once one of the main methods of treatment of chronic myeloid leukemia, today it is used much less often because available tyrosine kinase inhibitors such as imatinib (Glivec). It is recommended in cases where the targeted therapy is ineffective. Moreover, cytostatic agents used as part of treatment in the transplantation of stem cells.

Hydroxycarbamide (hydroxyurea) is taken in pill form, can help reduce the very high level of white blood cells and reduce the size of enlarged spleen. Other cytostatic drugs in CML include cytarabine (Ara-C), busulfan, cyclophosphamide (tsitoksan®) and vincristine (Oncovin).

Omacetaxine (Synribo®) was approved for the treatment of chronic myeloid leukemia resistant to the use of tyrosine kinase inhibitors. It may help some patients with the T315I mutation.

Adverse effects of treatment with cytostatics

In addition to the destruction of malignant cells chemotherapy affects healthy cells in the body that divide rapidly and grow. This leads to such negative phenomena as digestive disturbances (vomiting, nausea, loss of appetite), ulcerous lesion of the oral cavity, hair loss; reduced levels of leukocyte (risk of infection), red blood cells (anemia), platelets (thrombocytopenia).

The severity and number of side effects caused by the type and dose of cytostatics, the duration of their admission.

For example, vincristine can cause nerve damage (neuropathy), which results in tingling, numbness, pain sensations in the extremities. Busulfan rarely able to provoke damage to the lungs. Before starting treatment with a team of doctors, working with the patient talks about drugs and their side effects. For the most symptoms occur within a short time, but sometimes they become permanent. When these signs occur, it is important to inform the experts as they may apply measures to reduce or prevent side effects. 

If myeloid leukemia after treatment with chemotherapy reduces the number of leukocytes to the critical, doctors may designate drugs, known as growth factors - Neupogen and GM-CSF (Leukine®), contributing to an increase in white blood cells and reduce the likelihood of infection .

At low platelet content corresponding formulations are assigned and can be carried out red blood cell transfusions.

Radiation therapy in the treatment of chronic myeloid leukemia in Assuta

Radiotherapy - a treatment of malignant diseases with high-energy rays or particles. Typically, radiation therapy is not part of the primary treatment of chronic myeloid leukemia, but is used in certain situations.

When an internal organ tumors develop symptoms, eg, if increases spleen. It caused pressure on other organs may have an impact on appetite. If in order to reduce the data attributes ineffective chemotherapy is considered as an option for the irradiation of the spleen.

Radiation therapy will benefit in the treatment of bone pain caused by the growth of leukemia cells in the bone marrow.

Sometimes before stem cell transplantation radiotherapy given in small doses to the organism as a whole.

The main short-term side effects of radiation therapy depend in part on whether the area was processed:

  • Fatigue - a common undesirable effects of treatment of chronic myeloid leukemia.
  • Changes in skin care range from mild redness to blistering and peeling.
  • If the radiation is directed to the head or the neck area may mucositis of the oral cavity and throat.
  • Irradiation of the abdomen or pelvis may cause nausea, vomiting and / or diarrhea.
  • When radiotherapy exposed large areas of the body, the bone marrow may be damaged and, consequently, reduced blood counts.

Surgery in the treatment of chronic myeloid leukemia in Assuta

Leukemia cells tend to be widespread throughout the bone marrow and other organs, so surgery is not used in the treatment of myeloid leukemia. In the process of diagnostics and rarely plays any role as a blood or bone marrow aspirate and biopsy, usually give the necessary information to confirm the diagnosis.

If leukemia spreads to the spleen, an organ may become large enough and put pressure on nearby organs, causing symptoms. When chemotherapy or radiation does not help to reduce spleen size, it can be surgically removed. This operation is called a splenectomy.

Also, splenectomy may increase the level of blood cells and reduce the need for blood donations. One of the functions of the body - the removal of old blood cells from the bloodstream. Leukemia or other diseases can cause excessive activity of the spleen, resulting in a lack of red blood cells or platelets. In some patients, organ resection increases the number of red blood cells and platelets in the blood.

Most people do not have problems after the removal of the spleen. It increases the risk of certain bacterial infections, so doctors often recommend a special vaccine.

Stem cell transplantation for the treatment of chronic myeloid leukemia

The usual dose of cytotoxic drugs cause bone marrow damage, because its cells also divide rapidly, as well as malignant. Although high-dose chemotherapy is more effective in the treatment of leukemia, it is not recommended, as this will cause a critical shortage of blood cells.

When transplanting stem cells higher doses of cytotoxic agents given to destroy the abnormal cells. Sometimes it assigned irradiation of the whole body. This treatment eliminates the myeloid leukemia tumor cells, but also damage healthy bone marrow cells. transplantation procedure restores the body.

Hematopoietic stem cells are obtained from peripheral blood or bone marrow. Bone marrow transplantation has been increasingly common in the past, now it is increasingly replaced by transplantation of stem cells from peripheral blood.

  1. Autologous transplantation involves the use of their own hematopoietic stem cells from blood or bone marrow. The difficulty is that the abnormal cells can be removed along with the rest.
  2. Allogeneic transplant uses donor stem cells. The donor must have similar genetic structure. A good option is a close relative - a sister or brother. A rare opportunity to find a compatible donor who is not a relative.

The second procedure is a major in the treatment of chronic myeloid leukemia. However, it can cause serious adverse effects, therefore, not be considered for older patients or those with other serious illnesses.

In these modern drugs such as imatinib, stem cell transplantation in the treatment of chronic myelogenous leukemia is less and less. Doctors recommend it for young patients, especially children. The advantage is the availability of a compatible donor - a brother or sister. Transplantation also advise when the CML does not respond to targeted therapies.

APPLICATION FOR TREATMENT

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