Symptoms:

The disease does not have specific symptoms. Acute lymphoblastic leukemia leads to the following conditions:

• general intoxication of the body (weakness, fever, fatigue);
• anemia (pale skin, increased heart rate, shortness of breath);
• blood-clotting disorders (nasal hemorrhage, prolonged hemorrhage from the slightest scratches, bruises on the body for no reason).

All patients have reduced immunity due to a decrease in the number of normal white blood cells. Although their total number is large, it is mainly lymphoblasts that are not able to perform their function.

Diagnosis confirmation:

Early diagnostics is complicated due to the absence of specific symptoms. Therefore, if any of the manifestations listed above appear, you should visit a doctor, undergo an examination and blood test. The doctor will analyze the patient's medical history, look at the data from previous tests, perform an examination and prescribe the necessary tests.

Only one complete blood count often allows the doctor to detect leukemia in a child. The number of erythrocytes and platelets in the blood is reduced. The doctor can detect many immature white blood cells, called lymphoblasts. These are precursor cells, which are normally detected only in the red bone marrow. They should not be in the blood at all. They are immature and cannot function as normal white blood cells.

However, the complete blood count is not sufficient to confirm the diagnosis. It is necessary to carry out the aspiration and biopsy of the red bone marrow. Both types of tests can be taken simultaneously.

At first, the doctor carries out aspiration. For this purpose, he uses an aspirator – a syringe with a thin needle. He inserts it into the pelvic bone and using negative pressure extracts a small amount of red bone marrow. The second stage is the biopsy. The doctor uses a thicker needle. It allows him to obtain a column of tissue, which is sent for histological examination.

The doctors perform the following test with these samples:

• examination under the microscope.
• cytochemical analysis.
• immunohistochemical examination.
• Immunophenotyping.
• cytogenetic tests, fluorescence in situ hybridization, and PCR for detection of chromosomal and genetic abnormalities.

The diagnosis can be determined after microscopy. The criterion for leukemia is the detection of blast cells in the red bone marrow in an amount of more than 20%. Normally, they should be less than 5%. Further examinations can be required only to clarify the diagnosis. The subtype of leukemia, genetics and other changes are prognostic factors and allow to carry out a better planning of treatment for the child.

A bone marrow biopsy is performed repeatedly during the treatment process. The analysis is used to assess its results, detect a relapse, and determine the optimal treatment options.

Occasionally, lumbar puncture can be carried out as well. It can be required in the case of signs of the spread of lymphoblastic leukemia to the organs of the central nervous system. The needle is inserted into the space between the lumbar vertebrae and cerebrospinal fluid is extracted for analysis.

A sentinel lymph node biopsy can be required in rare cases. It serves for the differential diagnostics of acute lymphoblastic leukemia and lymphoma. As a rule, the entire node is removed and sent for histological examination.

Medical imaging tests are not performed at all or have limited diagnostic value. As a rule, the doctors use the following examination techniques:

• chest x-ray – to detect signs of infectious processes in the lungs, which often occur due to the decrease in immunity.
• CT – allows the doctor to detect enlarged lymph nodes or tumor foci in the spleen.
• MRI – can be prescribed for the detection of malignant cells in the cerebrospinal fluid after lumbar puncture.
• Ultrasound examination – can detect enlarged liver, spleen, lesion of the kidneys or testicles.

The protocol does not require medical imaging tests for all patients. These methods can be used only according to the indications.

Treatment:

Chemotherapy

While surgery is considered the primary treatment for most cancers, acute lymphoblastic leukemia can be cured with chemotherapy. The participation of surgeons is usually not required, except in cases of emergency, when a tumor mass is so large that it compresses the vital organs.

Blood cancer treatment is carried out in three stages:

Induction is aggressive chemotherapy that aims to achieve cancer remission. Remission means that leukemia cells are absent in bone marrow samples. Remission does not yet mean a cure, since a small number of leukemia cells still remain in a patient's body. It is for this reason that treatment continues after induction. The starting stage of chemotherapy for acute lymphoblastic leukemia lasts about 1 month, while the total duration of treatment for blood cancer reaches 2-3 years.

Conventional cancer chemotherapy regimens are effective in more than 90% of patients. The younger the age, the better the results. Remission of acute lymphoblastic leukemia in children can be achieved in more than 95% of cases.

Since a chemotherapy regimen during this period is quite intense and may cause side effects, patients at this stage of treatment for acute lymphoblastic leukemia stay at the hospital all the time. Chemotherapy blocks the division of not only cancer cells, but also other cells that are rapidly dividing. The function of the bone marrow is almost always affected. As a result, the production of blood cells decreases. To overcome side effects, patients frequently require antibiotics, as well as red blood cell and platelet transfusions.

The most common treatment regimen involves chemotherapy with three drugs. In high-risk patients, four drugs can be used at once. In Philadelphia-positive acute lymphoblastic leukemia, targeted therapy can be additionally prescribed.

At the stage of induction, patients receive not only systemic, but also intrathecal chemotherapy. This involves injecting drugs into the cerebrospinal fluid. This necessity is due to the fact that blood cancer often spreads to the central nervous system. However, most drugs cannot cross the blood-brain barrier, so leukemic cells remain in the brain. Doctors perform a lumbar puncture to destroy them. The procedure involves the injection of drugs into the spinal canal, just below the point where the spinal cord ends. In total, 2 injections are required in the first month, and then several more injections 1 time in the next 2 months. In high-risk acute lymphoblastic leukemia, drugs can be injected into the cerebrospinal fluid even more often.

Consolidation begins after achieving remission and lasts for several months. This phase of treatment for acute leukemia destroys any remaining cancer cells in the body. Doctors use combinations of several drugs to avoid the formation of resistance in cells to chemotherapy agents. Intrathecal chemotherapy is still going on, although injections are becoming rarer.

As a rule, during the consolidation phase, treatment is not as intense as during induction. However, some patients still have leukemic cells. In this case, minor residual disease is diagnosed. These patients require more aggressive drug treatment for cancer. Doctors can also repeat the course of induction chemotherapy, which is called "delayed intensification".

Maintenance therapy lasts about 2 years. The task of this stage of treatment is to prevent the recurrence of the disease and destroy the remaining cancer cells to cure acute lymphoblastic leukemia completely. Patients take several drugs. Some of them are taken constantly, and others in short courses.

Targeted therapy and immunotherapy

Other drugs that are effective in the treatment of some forms of acute lymphoblastic leukemia are as follows:

BCR-ABL inhibitors can be used in the presence of the Philadelphia chromosome in cancer cells. This is more common in myelogenous leukemia but can also be found in some patients with lymphoblastic leukemia. BCR-ABL inhibitors are combined with chemotherapy.

CD19/CD3 monoclonal antibodies can be used for B-cell lymphoblastic leukemia. The drug is used after chemotherapy. The course of treatment is 4 weeks, and a patient spends all this time at the hospital, so the infusions are carried out continuously. In addition, immunotherapy with monoclonal antibodies may cause complications, and, in this case, a person should be provided with timely medical care. The course of treatment with antibodies can sometimes be repeated after 2 weeks.

 

 

Radiation therapy

Radiation therapy is highly effective for acute lymphoblastic leukemia, but not all patients require this treatment option. As a rule, cancer can only be cured with chemotherapy. Irradiation can be required in the following cases:

• a large number of leukemia cells were detected in the cerebrospinal fluid.
• preparation for a bone marrow transplant.

In recent years, more and more new drugs have appeared, and drug therapy regimens for blood cancer have improved, so even in these two cases, radiation therapy is used less and less frequently. This is due to the fact that most patients with acute lymphoblastic leukemia are children, and irradiation of the brain and spinal cord may cause a developmental delay with impaired cognitive functions. For this reason, even in high-risk acute lymphoblastic leukemia, doctors are more likely to prefer more intensive chemotherapy but try to avoid radiation therapy.

Recurrence treatment

If cancer has recurred after treatment, the further treatment tactics depend on how aggressive acute lymphoblastic leukemia was, what the previous treatment was, how successful it was, and how much time has passed from remission to recurrence.

As a rule, doctors prescribe chemotherapy to treat cancer recurrence. If the time before the onset of recurrence of acute lymphoblastic leukemia turns out to be significant, it is possible to use the same regimen as for the first time, or one that is similar to it. A short remission requires the use of other drugs, and the treatment regimen becomes more aggressive. Even in cancer recurrence, acute lymphoblastic leukemia can still be cured in many patients.

Recurrence can be extramedullary. This is when cancer recurs outside of the bone marrow. Most often, this is a recurrence from the central nervous system, and, in boys, a tumor may recur in the testicles. This form of the disease can be treated with chemotherapy in combination with radiation therapy.

Stem cell transplant

A bone marrow transplant is the most effective treatment for acute lymphoblastic leukemia. This can be resorted to in the most severe cases, when it is not possible to cure cancer with another method.

A stem cell transplant can be:

• autologous – transplantation of a patient's own cells.
• allogeneic – transplantation of donor cells.

An allogeneic transplant is mostly used for acute lymphoblastic leukemia. Before it is carried out, doctors destroy all cancer cells in the body with high-dose chemotherapy, sometimes combined with irradiation. A successful transplant results in the activation of the graft-versus-tumor immune response. Immune cells are formed, and they completely cure acute lymphoblastic leukemia.

Indications for a stem cell transplant include:

• a high risk of cancer recurrence.
• unsuccessful attempts to achieve remission at the stage of induction.
• cancer recurrence, especially up to 6 months after successful chemotherapy.
• Philadelphia chromosome-positive acute leukemia.

In acute myeloblastic leukemia, the need for a stem cell transplant is less common than in lymphoblastic leukemia because this type of cancer is less likely to recur after its initial treatment, and the response rate to chemotherapy is higher.

CAR T-cell therapy

CAR T-cell therapy is used to treat leukemia that has recurred and is not responding to any other treatment.

Doctors take immune cells from a patient's body. Their genotype is then changed. Once modified, leukocytes are able to attack cells containing CD19 receptors. Therefore, they destroy the tumor, but do not damage healthy tissue. The modified cells are cultured to increase their numbers and then injected into the body after several days of chemotherapy. The whole process, from obtaining cells to their injection, takes several weeks.

Although CAR T-cell therapy is expensive and sometimes causes complications, this treatment for acute lymphoblastic leukemia is very effective. Even the most aggressive and advanced forms of cancer can be cured with its help. The most dangerous complication is cytokine release syndrome. This is a very severe inflammation that leads to fever, nausea, muscle and joint pain, as well as breathing difficulties. Doctors are usually able to manage these symptoms, but additional medical procedures and drugs are required for the treatment of complications.

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1-Diagnosis:

The program includes:

• Initial presentation in the clinic
• clinical history taking
• review of medical records
• physical examination
• laboratory tests:
  • complete blood count
  • biochemical blood test
  • inflammation markers (CRP, ESR)
  • blood coagulation analysis (aPTT, PT, INR)
  • differential blood count
• ultrasound of the abdomen, CT/MRI / PET scans (if clinically indicated)
• bone marrow aspiration and biopsy (if clinically indicated)
  • histological study
  • immunohistochemical study
  • cytogenetic analysis (Philadelphia chromosome detection)
• biopsy and histological examination of CSF (if clinically indicated)
• biopsy of lymphatic nodes with histopathology and immunohistochemistry (if indicated clinically)
• tumor board: consultation of medical oncology, radiology and radiation therapy specialists
• examination by related specialists (if clinically indicated):
  • cardiologist
  • otolaryngologist
  • immunologist
  • infectious diseases.
• nursing services
• explanation of future recommendations

Required documents

• Medical records
• MRI/CT scan (not older than 3 months)
• Bone marrow biopsy results (if available)

Price from: on request 

Type of program: Inpatient

Expected duration of the program: 6 days

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2-Chemotherapy:

The program includes:

• Initial presentation in the clinic
• case history collection
• general clinical examination
• laboratory tests:
  • complete blood count
  • biochemical analysis of blood
  • TSH-basal, fT3, fT4
  • differential blood count
  • inflammation indicators (CRP, ESR)
  • indicators blood coagulation
• CT/MRI / PET scans (if indicated clinically)
• bone marrow aspiration and biopsy (if clinically indicated)
• biopsy and histological examination of CSF
• examination by experts of:
  • cardiology
  • otolaryngology
  • immunology
  • ophthalmology
• one cycle of chemotherapy
• symptomatic treatment
• control examinations
• the cost of essential medicines and materials
• nursing services
• tumor board: consultation of medical oncology, radiology and radiation therapy specialists
• full hospital accommodation
• explanation of future recommendations

Required documents

• Medical records
• MRI/CT scan, PET scan (not older than 3 months)
• Lymph node or Bone marrow biopsy results (if available)

Price from: on request

Type of program: Inpatient or outpatient (related to your diagnosis and treatment protocol).

Expected duration of the program: may differ and be related to your diagnosis and treatment protocol.

________________________________________________________________________________

3-Radiotherapy:

The program includes:

• Initial presentation in the clinic
• clinical history taking
• review of medical records
• physical examination
• CT /MRI (if indicated clinically)  
• laboratory tests:
  • complete blood count
  • general urine analysis
  • biochemical analysis of blood
  • indicators of inflammation (CRP, ESR)
  • indicators of blood coagulation
• CT simulation and planning of radiation therapy
• Physics calculation
• full course of radiation therapy with different modalities (3D, IMRT, VMAT) according to your treatment plan.
• individual plan of the chemotherapy, the cost of medicines is included
• symptomatic treatment (for side effects of radiotherapy that may developed).
• cost of essential medicines and materials
• nursing services
• control examinations
• consultations of related specialists
• explanation of future recommendations

How program is carried out

During the first visit, the doctor will conduct a clinical examination and go through the results of previous laboratory tests and instrumental examinations. After that, you will undergo an additional examination, including complete blood count, laboratory assessment of liver and kidney function. Based on the received results, the physician will conduct radiotherapy planning with the help of CT or MRI, make the permanent tattoo marks on the skin and conduct CT simulation to assess the accuracy of the rays and the radiation dose. If necessary, related medical specialists will be involved in the elaboration of a treatment regimen (tumor board).

Radiation therapy is carried out as an inpatient procedure, with mandatory admission to the hospital. Before each session the physician will assess your general condition and the marks on the skin. After that, you will be placed in a shielded radiation therapy room, on a special table.

Each radiation therapy session lasts less than half an hour (including preparation). All this time, doctors and nurses are monitoring your condition, you can communicate with them through a loudspeaker. The procedure is completely painless. Depending on the planned course of treatment, you will have from 1 to 3-5 sessions of radiation therapy a week.

After the completion of the radiation therapy course, you will undergo control examinations aimed at assessing your condition and efficacy of treatment. After that you will receive the medical report with detailed recommendations regarding further follow-up and treatment. In the future, you will be able to have a distant consultation with your attending physician and schedule the next course of treatment, if necessary.

Required documents

• Medical records
• MRI/CT scan, PET scan (if available)

Price from: on request

Type of program: Inpatient

Expected duration of the program: 30 days

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4-Bone marrow transplantation:

The program includes:

• Initial presentation in the clinic
• case history collection
• general clinical examination
• laboratory tests:
  • complete blood count
  • general urine analysis
  • biochemical analysis of blood
  • TSH-basal, fT3, fT4
  • tumor markers
  • indicators of inflammation
  • indicators of blood coagulation
• CT/MRI scans of the whole body
• needle biopsy of the bone marrow
• biopsy and histological examination of CSF (if indicated clinically)
• examination by experts of:
  • Cardiology
  • Otolaryngology
  • Immunology
  • Ophthalmology
  • Infectious disease
• conducting high-dose chemotherapy or radiotherapy (for destruction of all marrow cells).
• CT simulation and Physics calculations
• autologous bone marrow transplantation
• isolation by neutropenic precautions in transplantation unit
• symptomatic treatment
• the cost of essential medicines and blood products
• nursing services
• stay in the hospital with full board
• elaboration of further recommendations

How program is carried out

During the first visit, the doctor will conduct a clinical examination and go through the results of the available diagnostic tests. After that, you will undergo the necessary additional examination, such as the assessment of liver and kidney function, ultrasound scan, CT scan and MRI.

Also, the doctor will conduct a bone marrow biopsy followed by cytological examination of the harvested material. This will help him to determine the histological features of your bone marrow (in particular, identify HLA system antigens) and the use of a person’s own stem cells. They typically involve harvesting your cells before beginning a damaging therapy to cells like chemotherapy or radiation. After the treatment is done, your own cells are returned to your body.

This type of transplant isn’t always available. It can only be used if you have a healthy bone marrow. However, it reduces the risk of some serious complications, including GVHD.

 

Before the procedure, you will receive chemotherapy, if necessary, in combination with radiation therapy. The course of chemo- or chemoradiation therapy lasts from 2 to 8 days.

The bone marrow transplant procedure is an intravenous infusion, i.e. the healthy bone marrow will be injected through a catheter, intravenously. You will stay in your room during the procedure. A bone marrow transplant is completely painless and does not require anesthesia.

 

During the period of healthy bone marrow engraftment, you will stay in a sterile ward. This is a necessary precaution because during this time your immune system is very weak and cannot withstand environmental pathogens. The risk of bleeding is also quite high, so you will be advised to avoid mechanical damage.

 

A relative or other close person may stay in the ward with you. You will not be allowed to go outside the department and leave your ward often. The rehabilitation period can last from 1 to 2 months.

When your complete blood count returns to normal, your doctor will schedule your discharge from the department. You will receive information about the rules that you will need to follow at home, the frequency and type of control examinations, and subsequent treatment measures. You will also receive a detailed medical report, which will reflect the entire course of treatment.

 

Required documents

• Medical records
• MRI/CT scan (not older than 3 months)
• Bone marrow biopsy results (if available)

Price from: on request

Type of program: Inpatient

Expected duration of the program: 57 days