Incidence

• Acute lymphoblastic leukemia (ALL) is a cancer of the blood and bone marrow. It is the most common form of childhood cancer.
• ALL affects white blood cells called lymphocytes. These cells fight infection and help protect the body against disease.
• There are 2 types of lymphocytes: B lymphocytes and T lymphocytes. ALL may arise from either type of lymphocyte. Cases of ALL are known as either B cell or T cell ALL. B cell ALL is more common.
• ALL occurs most often in children ages 2–5. It is also found in older children and teens.

Symptoms of Acute Lymphoblastic Leukemia

• Pain or fullness below the ribs (enlarged liver and/or spleen)
• Lumps in the neck, underarm, stomach, or groin · Fever · Fatigue · Easy bruising and bleeding that is hard to stop
• Pale skin
• Bone or joint pain
• Frequent infections
• Tiny, flat, dark red skin spots (petechiae)
• Loss of appetite
• Shortness of breath

Risk factors for acute lymphoblastic leukemia

Most cases of ALL have no known cause. Certain inherited syndromes are linked to an increased risk of ALL:

• Down syndrome
• Neurofibromatosis type 1
• Bloom syndrome
• Ataxia-telangiectasia · Li-Fraumeni syndrome
• Certain forms of Fanconi anemia
• Constitutional mismatch repair deficiency
• Diamond-Blackfan anemia
• Familial PAX5 syndrome
• Familial ETV6 syndrome
• Familial SH2B3 syndrome

Diagnosis of acute lymphoblastic leukemia

Physical exam and health history

During the exam and history, the provider will:

• Check general signs of health, including signs of disease, such as lumps or other unusual symptoms.
• Examine the eyes, mouth, skin, and ears. The provider will feel the belly for signs of an enlarged spleen or liver. In boys, the provider may also examine the testes.
• Ask about other health conditions, including illnesses that relatives such as parents, siblings, and grandparents have had. The provider is looking for inherited conditions that may increase cancer risk.

Blood and bone marrow tests

A provider will draw blood to run tests. These tests include: · Complete blood count – This test checks the counts of different types of blood cells. In ALL, the blood may have too many white blood cells. Many of these cells will be cancer cells. · Blood chemistry studies – This test checks the amounts of certain substances in the blood. An unusual level (either higher or lower than normal) can be a sign of disease.

• Liver function tests
• Coagulation test – This test measures the blood’s ability to clot. Bone marrow aspiration and biopsy are 2 tests that will confirm a diagnosis of cancer. Patients usually have these procedures at the same time. They will either be sedated or receive pain medicine.

Tests after ALL diagnosis

If leukemia is found, the care team will run more tests.

These include lab tests to identify specific genes, proteins, and other factors involved in the leukemia.

This is important because cancer is caused by mistakes (mutations) in the cell’s genes. Identifying these mistakes may help diagnose the specific subtype of leukemia.

Doctors use these details to choose treatment options tailored to your child’s case.

The care team also will run tests to find out if cancer is in other parts of the body:

Lumbar puncture A lumbar puncture will show if leukemia has spread to the brain and spinal cord. The test is also called an LP or spinal tap.

Patients may get chemotherapy at the same time this is done. This is called prophylactic intrathecal chemotherapy. It is given to prevent ALL from spreading to the cerebrospinal fluid.

Chest x-ray A chest x-ray will show if leukemia cells have formed a mass in the middle of the chest.

Other imaging tests and laboratory tests Other imaging studies and laboratory tests may be used if patients have certain signs and symptoms.

A female patient of childbearing age may have a pregnancy test.

A male patient may have an ultrasound to check for testicle involvement. This is rare in ALL. It happens in 1–2% of males.

Fertility counseling

The care team may discuss fertility with you and/or your child

Phases of treatment

Week 1

Treatment prep

Doctors gather information to help plan treatment. · Blood tests

• Physical exam and history · Chest x-ray · Bone marrow aspirate and/or biopsy · Lumbar puncture

Next 4–6 weeks (Induction phase)

• The goal of this phase is to kill leukemia cells in the blood and bone marrow and bring the disease into remission. This phase is intense and may require hospital stays.
• Central nervous system (CNS) sanctuary therapy may be given to destroy leukemia cells in the spinal fluid.

Doctors will look at several factors to plan next steps:

• Doctors will consider age of the patient and white blood cell counts, one of the risk factors of relapse.
• By the end of induction phase, doctor will know the results of genetic testing. This is another important factor to determine the risk.
• Many pediatric centers use highly sensitive tests to measure for minimal residual disease (MRD). Positive MRD indicates a greater risk of relapse and need for more intense therapy. · Doctors will decide if a stem cell transplant (bone marrow transplant) is needed. Patients who have Philadelphia chromosome-positive ALL may receive imatinib, dasatinib, or ponatinib during this phase.

Next 8–16 weeks

Consolidation/intensification phase

This phase uses a different combination of drugs to destroy any remaining cells. It may require hospital stays.

Next 2–3 years

Maintenance/continuation phase

If the leukemia stays in remission, maintenance therapy can begin. Its goal is to destroy any leukemia cell that might remain after the first 2 phases.

Patients will likely have weekly chemotherapy and blood tests with periods of high-dose chemotherapy known as reinduction.

The first 6–9 months of this phase is usually intense. Often patients can return to school after 6–9 months.

Follow-up schedule

Year 1

The patient will return for follow-up visits once every 1–4 months.

These visits may include:

• Physical exam and medical history
• Blood tests and other lab tests

Year 2

Follow-up visits may change to once every 6 months.

Years 3-5

Follow-up visits may change to once a year.

Stem cell (bone marrow) transplant for acute lymphoblastic leukemia A stem cell transplant may be recommended for children who are at high risk for relapse or whose treatment does not work. Patients must be medically able and have a suitable donor.

Doctors sometimes look at how well induction chemotherapy worked to decide whether a transplant is needed.

Radiation therapy for acute lymphoblastic leukemia

Radiation is rarely used in ALL treatment. It may be given in cases where ALL has spread to the brain, spinal cord, or testicles.

Radiation may also be given to prepare patients to receive a stem cell transplant.

Minimal residual disease and ALL

Minimal residual disease (MRD) is a term used when there are so few leukemia cells in the bone marrow that they cannot be seen under a microscope.

Highly sensitive tests can detect 1 leukemia cell in 10,000–1 million normal cells in the bone marrow.

Children who have positive MRD (more than 1 cell in 10,000) after induction therapy are at the greatest risk of relapse. The timing of MRD measurement varies depending on the center.

Acute Lymphoblastic Leukemia Diagnosis Program

The program includes:

• Initial presentation in the clinic
• clinical history taking
• review of medical records
• physical examination
• laboratory tests:

o complete blood count

o biochemical blood test

o inflammation markers (CRP, ESR)

o blood coagulation analysis (aPTT, PT, INR)

o differential blood count

o Hepatitis & HIV markers

• ultrasound of the abdomen
• CT/MRI scan (if clinically indicated)
• bone marrow aspirate +/- biopsy

o histological study

o immunohistochemical study

o molecular & cytogenetic analysis (karyotyping, t(12;21), t(9:22), MLL gene re-arrangement, t(1;19) )

• Lumbar Puncture & CSF examination
• Echocardiography
• examination by related specialists (if clinically indicated):

o cardiologist

o otolaryngologist

o immunologist

• nursing services
• explanation of future recommendations

Required documents

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

Type of program : Inpatient

Expected duration of the program: 7 days

High-intensity induction chemotherapy of acute lymphoblastic leukemia with complications

• Initial presentation in the clinic
• clinical history taking
• physical examination
• laboratory tests:

o complete blood count

o general urine analysis

o biochemical analysis of blood

o differential blood count

o indicators of inflammation

o indicators blood coagulation

• two blocks of induction chemotherapy
• symptomatic treatment
• blood products
• control examinations
• cost of essential medicines and materials
• nursing services
• full hospital accommodation
• explanation of future recommendations

Required documents

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

Expected duration of the program: 42 days

Consolidation treatment for acute lymphoblastic leukemia

The program includes:

• Initial presentation in the clinic
• case history collection
• general clinical examination
• laboratory tests:

o complete blood count

o biochemical analysis of blood

o TSH-basal, fT3, fT4

o differential blood count

o inflammation indicators (CRP, ESR)

o indicators blood coagulation

• CT/MRI scanners of the complete organism
• needle biopsy of the bone marrow
• biopsy and histological examination of CSF
• examination by experts of:

o cardiology

o otolaryngology

o immunology

o ophthalmology

• consolidation treatment
• symptomatic treatment
• control examinations
• the cost of essential medicines and materials
• nursing services
• full hospital accommodation
• explanation of future recommendations

Required documents

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

Type of program : Inpatient

Expected duration of the program: 60 days

Radiation therapy of brain in acute lymphoblastic leukemia (ALL) with brain damage

The program includes:

• Initial presentation in the clinic
• case history collection
• general clinical examination
• laboratory tests:

o complete blood count

o biochemical analysis of blood

o TSH-basal, fT3, fT4

o differential blood count

o inflammation indicators (CRP, ESR)

o indicators of blood coagulation

• CT/MRI scans of the whole body
• needle biopsy of the bone marrow
• spinal tap and examination of CSF
• examination by experts in:

o cardiology

o otolaryngology

o immunology

o ophthalmology

• radiation therapy of brain
• symptomatic treatment
• control examinations
• cost of essential medicines and materials
• nursing services
• full hospital accommodation
• 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 in order 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).

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 (not older than 3 months)
• Bone marrow biopsy results (if available)

Type of program : Inpatient

Expected duration of the program: 31 day