Acute myeloid leukemia (AML) is a malignant disease of blood system in which a large number of defective myeloid tumor cells multiply in peripheral blood and bone marrow. AML accounts for up to 25% of all childhood leukemias and ranks second in prevalence after acute lymphoblastic leukemia. Children of all age groups are affected, but most often pathology occurs in children under 2 years of age and in teenagers.
Tumor cells in AML develop from myeloid stem cells, which are normally precursors of erythrocytes, platelets and granulocytes (monocytes, basophils, neutrophils). As the disease progresses, the main part of normal bone marrow cells are replaced by tumor cells (blast cells of the myeloid series) and all functions of blood system are affected.
Acute myeloid leukemia is a serious disease with a serious prognosis, but with timely diagnosis and the correct, modern approach to therapy, it is completely curable.
It is very important that a child with such a diagnosis receive medical care in specialized Pediatric Hematology Oncology Departments, where the best doctors with extensive practical experience in caring for such patients work. Pediatric Hematology Oncology Department at Tel Aviv Medical Clinic is just such a medical institution.
Our department has a unique multidisciplinary team of specialists who have completed training and internships in the best children’s oncology hospitals in the world. Each individual case of the disease is considered by doctors individually, the approach to treatment is comprehensive – using world protocols and treatment standards, as well as the rich practical experience of hematologists. Patient and his family members must receive all the necessary support from psychologists, social workers, and other specialists.
Causes of acute myeloblastic leukemia
Unfortunately, to date, the true causes of acute myeloblastic leukemia development have not been established, but there are risk factors that significantly increase the chances of this pathology developing.
Risk factors for AML:
- Age. The older a person gets, the more likely they are to develop AML.
- Gender. This type of leukemia occurs much more often in male patients than in female patients.
- Presence of acute myeloblastic leukemia cases in family relatives.
- Smoking.
- Constant contact with certain chemicals, for example, benzene, formaldehyde.
- Exposure to ionizing radiation, such as a history of radiation therapy.
- Underlying blood diseases (polycythemia vera, idiopathic myelofibrosis, essential thrombocythemia).
- Genetic diseases or syndromes, for example, trisomy 21 pairs of chromosomes (Down syndrome), trisomy 8 pairs of chromosomes (Varkani syndrome), Diamond-Blackfan anemia, Fanconi anemia, Li-Fraumeni syndrome, neurofibromatosis type 1, Noonan syndrome, Shwachman-Diamond syndrome.
Symptoms of AML in children
In most cases, symptoms of the disease appear several days or weeks before diagnosis. Most of them are associated with disruption of normal bone marrow function. Due to its infiltration by malignant defective leukemia cells, the hematopoietic function is significantly affected. Bone marrow cannot provide normal amount of red blood cells, platelets, and lymphocytes in peripheral blood, which becomes the cause of striking clinical manifestations.
Among them:
- Anemia (decrease in red blood cells and hemoglobin), which is manifested by weakness, pale skin, breath shortness, and rapid heartbeat.
- Thrombocytopenia (decrease in blood platelets), which is manifested by bleeding into mucous membranes, small bruises appearance, hemorrhagic rash, bleeding from nose, gums, and heavy menstrual flow.
- Granulocytopenia (most often a decrease in neutrophils), which is manifested by frequent and severe infectious diseases.
- Skin manifestations may include various types of rashes that are resistant to any standard treatment.
- Enlargement of liver and spleen, peripheral and internal lymph nodes and symptoms associated with this.
- Pain in bones and joints. Neurological manifestations of damage to the central nervous system (headache, paralysis, paresis, sensory disturbances, changes in mental state, visual and auditory disturbances, stroke and transient ischemic attack).
Important! If one or more of described clinical symptoms appears, do not hesitate! Seek medical help, because every lost hour can cost your child his life.
Modern diagnostic methods
An undeniable advantage of examining children with suspected AML in Pediatric Hematology Oncology Department of TAMC is a comprehensive and rapid diagnostic program. All examinations take 3-5 working days and are carried out directly on site.
At the first stage of diagnostics, child and his parents are consulted by the leading specialist of the department. Doctor conducts a thorough physical examination, reviews your medical history, and identifies risk factors for AML. If patient already has any medical documents with diagnostic results, specialist must review them. Next, hematologist develops an individual examination plan for child, which includes all the necessary tests and instrumental diagnostic methods.
It is mandatory to carry out a general and biochemical blood test, where specific changes are identified, and then, using a bone marrow puncture procedure, biological material is taken for cytological analysis. Doctors use a bone marrow puncture (or biopsy) to confirm the diagnosis of acute myeloid leukemia. This procedure is invasive and painful, so in children it is performed only under general anesthesia, in accordance with international standards for providing medical care to children, so that during the examination child does not feel pain or fear.
After confirming AML diagnosis, hematologists perform additional tests to accurately determine the type of acute myeloid leukemia, since the treatment program and prognosis depend on this. The following studies are used:
- Immunophenotyping, which at TAMC is carried out using 2 modern methods – flow cytometry and immunohistochemical analysis. With the help of these tests, it is possible to recognize certain subtypes of leukemia cells and then select more effective therapy.
- Molecular genetic analysis is carried out using modern FISH analysis technique (fluorescent in situ hybridization). This study helps to identify specific points on the surface of malignant cells (for example, receptors or specific mutations), which can then be used to select targeted therapy for AML.
To determine tumor spread in the body and the stage of acute myeloblastic leukemia, each comprehensive diagnostic program contains imaging research methods: ultrasound, CT, MSCT, MRI, PET-CT, PET-MRI, bone scintigraphy, digital radiography, etc. A lumbar puncture with a study of cellular composition of cerebrospinal fluid is used to determine the spread of leukemia cells to organs of central nervous system.
Prognosis for acute myeloid leukemia in children
The 5-year survival rate for children with acute myeloid leukemia is about 70%.
90% of children with AML no longer have malignant cells in their blood after the first treatment course. Unfortunately, in approximately 30% of pediatric patients, pathology relapses or disease initially turns out to be resistant to treatment.
The prognosis for AML in children depends on the following factors:
- Subtype of acute myeloblastic leukemia.
- Child’s age.
- The results of laboratory tests – the number of leukemia cells in bone marrow, concomitant damage to central nervous system, the presence of certain genetic mutations of malignant cells, etc.
- Response to the first treatment course.
- An underlying blood disorder, such as myelodysplastic syndrome or Fanconi anemia.
Modern treatment of AML
The team of specialists at of Pediatric Hematology Oncology Department at TAMC has extensive and successful experience in treating children with acute myeloid leukemia. Each patient who turns to us for help takes advantage of an individual treatment program, which is developed by highly qualified specialists in accordance with global protocols for AML treatment and personal successful experience of department’s doctors.
The main treatment for acute myeloid leukemia is chemotherapy with or without allogeneic hematopoietic stem cell transplantation. Chemotherapy is the mainstay of treatment for AML and is used in all patients. Chemotherapy for children with acute myeloid leukemia has 3 phases:
- Remission induction phase. The goal is to destroy as many malignant cells as possible in peripheral blood and bone marrow. For this purpose, high-dose intensive polychemotherapy is used for 1 week. Induction therapy regimens usually include a combination of the following chemotherapy drugs – cytarabine, daunorubicin, etoposide, thioguanine.
- Consolidation phase of remission. The goal is to destroy all malignant cells in the body that might remain after the first phase of treatment. Now chemotherapy courses last for 4-6 months. During treatment, chemotherapy regimens are used, which include both drugs to induce remission and other drugs, for example, cytarabine.
- Maintenance phase. It is not always used; only some subtypes of AML require maintenance chemotherapy to prevent relapse of the disease. In this case, chemotherapy drugs are administered in courses over several months and even years after the main treatment. Maintenance therapy is carried out using the drug azacitidine in oral form.
Allogeneic hematopoietic stem cell transplantation is prescribed for children with a high risk of relapse of the pathology or in presence of resistance to chemotherapy. In this case, donor can be a relative or another person who meets all the necessary parameters. Before bone marrow transplantation procedure, the child is given a course of high-dose chemotherapy or radiation to destroy all malignant cells. After this, hematopoietic cells donor are directly transplanted. The latter take root in a new place and begin to produce healthy blood cells.
Radiation therapy is generally not used to treat children with AML. Radiation can be used only in cases where the patient is preparing for a bone marrow transplantation or in presence of damage to internal organs for palliative purposes.
Targeted therapy has advantages over classical chemotherapy drugs. Such drugs specifically destroy only malignant cells, without affecting healthy cells of the body, which is associated with fewer side effects of such treatment. The following targeted drugs are currently used to treat AML: FLT3 inhibitors (gilteritinib), gemtuzumab ozogamicin (Mylotarg), isocitrate dehydrogenase-1 inhibitors (ivosidenib), venetoclax (Venclexta), HH signaling pathway inhibitors (glasdegib).
Clinical trials are currently researching the effectiveness of CAR-T therapy – chimeric antigen receptor T (CAR-T) cells targeting the cancer cell receptors CD123 or CD33. All our patients can participate in such trials. For some of them, this is the only and real chance for recovery.
