Childhood acute myeloid leukemia

Summarize

1. General

● OVERVIEW: Childhood acute myeloid leukemia is a type of acute leukemia in children. The bone marrow of these children produces large numbers of abnormal white, red, or megakaryocytes. If left untreated, it tends to deteriorate rapidly.

● Manifestations: Common symptoms of acute myeloid leukemia in children include fever, pallor, malaise, bleeding, bone and joint pain and enlargement of liver, spleen and lymph nodes.

● TREATMENT: Common treatment modalities for childhood AML (except acute promyelocytic leukemia) include chemotherapy and hematopoietic stem cell transplantation. Treatments for childhood AML include all-trans retinoic acid, arsenic, and chemotherapy. Hematopoietic stem cell transplantation is also considered for AML with signs of relapse.

● Prognosis: Reports show that the five-year survival rate for children with AML under 15 years of age is approximately 68%, and 57% for children aged 15-19 years. Of these, survival rates for childhood acute promyelocytic leukemia are better, with the vast majority of studies showing five-year survival rates of 90% or more.

2. Definition of disease

Childhood acute myeloid leukemia (AML), also known as childhood acute myeloid leukemia, childhood acute granulocytic leukemia, or childhood acute nonlymphoblastic leukemia, and commonly referred to as childhood acute myeloid or childhood acute nonlymphoblastic leukemia, is a type of childhood acute leukemia. The bone marrow of these children produces large numbers of abnormal red blood cells, or white blood cells, or megakaryocytes. If left untreated, it tends to deteriorate rapidly.

Epidemiological

epidemiological

The overall incidence rate of childhood leukemia is about 3 to 5 per 100,000 persons. Some domestic data show that the incidence rate of leukemia among children under 5 years of age in China is 11.81 per 100,000, among children between 5 and 10 years of age is 4.61 per 100,000, among those between 10 and 15 years of age is 4.50 per 100,000, and among those between 15 and 20 years of age is 4.75 per 100,000.

Among them, the incidence of childhood acute myeloid leukemia is second only to childhood acute lymphoblastic leukemia, accounting for about 20% of childhood acute leukemias. Among them, acute promyelocytic leukemia (APL) accounts for about 10% of childhood AML.

Etiolog & Risk factors

1. General

The cause of childhood AML is usually related to chromosomal and genetic variants, and many children are born with disease-related variants. However, childhood AML is not a hereditary disease, and the associated variants are basically due to abnormalities during development. Because childhood AML is a multigene, multifactorial disease, the exact cause of the disease is not known, although certain environmental and genetic factors are known to be associated with the risk of childhood AML.

2. Underlying causes

The cause of acute myeloid leukemia in children is that a large number of hematopoietic cells in the bone marrow do not undergo the normal maturation process and multiply rapidly, forming leukemia cells and crowding out the space for normal cells to live, and also reaching other parts of the body through the bloodstream, such as lymph nodes, the spleen, the liver, the central nervous system (the brain and the spinal cord), the testes, or other organs, forming infiltrations and affecting the normal functioning of the other cells, leading to the leukemia's Various symptoms.

Childhood acute myeloid leukemia occurs when the associated chromosomes and genes are mutated during the child's development. Acute promyelocytic leukemia is known to be associated with the PML-RARα fusion gene, but the development of other types of childhood AML is usually not a result of a single genetic variant, but rather a multigene, multifactorial change, and therefore the exact cause of most childhood AML is unclear.

3. Predisposing factors

Certain environmental, genetic and disease factors are known to be associated with the risk of childhood AML:

● Significant exposure to ionizing radiation, such as nuclear radiation (e.g., atomic bomb blasts, nuclear accidents, etc.), X-rays, etc. However, ionizing radiation increases the risk of leukemia only when the cumulative dose is high. Medical examinations involving ionizing radiation, such as X-rays and CTs, which are usually performed in hospitals, do not usually accumulate to a cancer-causing dose and are therefore safe for the general population. In addition, everyday radiation such as cell phones, microwave ovens, and WIFI are not ionizing radiation, and there is no evidence that they are associated with leukemia risk.

● Certain carcinogens in the environment, such as benzene and its derivatives and formaldehyde, have also been linked to an elevated risk of leukemia.

● The vast majority of childhood leukemias are not inherited. However, in identical twins, if one child is diagnosed with childhood leukemia before the age of one, the other child may also be at higher risk of developing the disease.

● There are also a number of congenital factors that have been associated with the risk of AML in children, such as Down syndrome, familial chromosome 7 monozygosity, Fanconi anemia, congenital dyskeratosis, Bloom's syndrome, neurofibromatosis type 1, congenital midget dementia syndrome (also known as Noonan's syndrome), and severe congenital neutropenia (Kostmann's syndrome), Shwachman-Diamond syndrome, congenital erythrocyte-only aplastic anemia (Diamond-Blackfan anemia), congenital absence of megakaryocyte thrombocytopenia, CBL syndrome, Leigh-Fraumeni syndrome (Leigh-Fraumeni syndrome), hereditary RUNX1 gene mutations in the presence of a familial platelet disorders, myelodysplastic syndromes (MDS) with inherited mutations in the GATA2 or CEBPA genes, and specific mutations in the TERC and TERT genes.

● Certain acquired diseases may also increase the risk of developing AML, such as severe aplastic anemia, paroxysmal sleep hemoglobinuria, and thrombocytopenia.

Classification & Stage

Type of disease

1) Disease typing

Based on cell morphology, AML can be classified as M0, M1 to M7 according to FAB typing criteria.

In addition, clinicians usually perform MICM typing for acute lymphoblastic leukemia, which involves testing the child's bone marrow and blood samples in the four areas of morphology (M), immunophenotype (I), cytogenetics (C), and molecular biology. Blood and bone marrow samples are tested for accurate diagnostic typing to help determine the subsequent treatment plan.

It is important to note that AML in children includes about 10% of acute promyelocytic leukemia. Acute promyelocytic leukemia is usually accompanied by severe coagulation abnormalities, manifested by varying degrees of bleeding, and progresses very rapidly, so there are special treatment considerations. Acute promyelocytic leukemia is classified as acute myeloid leukemia type M3 according to FAB typing, with the characteristic chromosomal translocation t(15;17) of chromosomes 15 and 17, which can be detected as a positive PML-RARα fusion gene due to this chromosomal translocation.

2) Disease Grouping

Acute myeloid leukemia in children is usually treated with risk groupings, which are listed below for acute myeloid leukemia in children (excluding acute promyelocytic leukemia):

● low-risk group

Children with childhood acute promyelocytic leukemia (FAB typed as M3), and children with FAB typed as M2b, M4Eo, or other children carrying an inversion of chromosome 16.

● medium risk group

Not in the low-risk group and not having any of the following risk factors:

● The child was no more than one year old at the time of diagnosis of AML.

● White blood cell count greater than or equal to 100 X 109/L at diagnosis.

● Chromosome 7 is missing.

● myelodysplastic syndrome (medicine)

● One course of the standard regimen does not provide relief.

● high risk group

Presence of any of the five risk factors listed above.

Acute promyelocytic leukemia in children (M3 childhood acute myeloid leukemia) has an independent method of risk grouping as follows:

● Low-risk group: white blood cell count <10×109/L.

● High-risk group: white blood cell count ≥ 10 × 109/L, or presence of FLT3-ITD mutation, or molecular biology remission not achieved before maintenance therapy in the low-risk group.

Clinical manifestations

1. General

Common symptoms of acute myeloid leukemia in children include fever, pallor, malaise, bleeding, bone and joint pain and enlargement of the liver, spleen and lymph nodes.

2. Typical symptoms

● Fever: The fever is mainly due to the leukemia itself, which is usually low to moderate around 38°C, is not treated with antibiotics and resolves within 72 hours of induction therapy. However, it can also be accompanied by infections due to the immunocompromised nature of children with leukemia due to the decrease in the number of white blood cells and the abnormalities in their functioning, in particular the decrease in the number of neutrophils. The most common infections are respiratory infections such as tonsillitis, bronchitis and pneumonia, but also oral mucosal infections or gastrointestinal infections (e.g. gastroenteritis). A small number of children develop more serious infections, such as septicemia. The source of infection may be almost any pathogen, and co-infections are likely to occur.

● Anemia: is one of the earlier symptoms and worsens with the progression of the disease. It usually occurs gradually and is characterized by pallor, weakness, shortness of breath after activity, drowsiness, etc. The nails and the conjunctiva of the eyelids may also appear to varying degrees of pallor.

● Bleeding: Most of the time, bleeding or ecchymosis of the skin and mucous membranes (e.g., bruising of the skin) is present, as well as unexplained nosebleeds or bleeding from the gums. Some children may have gastrointestinal bleeding or hematuria, but this is very rare.

● Infiltration of leukemia cells: usually presenting with enlarged lymph nodes in different areas and/or hepatosplenomegaly. If the leukemia cells proliferate rapidly in the bone marrow for a short period of time or infiltrate the epiphyses of the bones, the child may develop bone and joint pain. In some children, arthralgia may be the first symptom, and blood counts may be completely normal, with temporary relief with hormonal therapy. Leukemia cells may also invade the brain, resulting in central nervous system leukemia (also called meningeal leukemia). Leukemia cells may also infiltrate the eyes, gums, or skin.

3. Accompanying symptoms

When a child is weak due to anemia, it may show up as needing to be held by an adult (especially in younger children). Joint pain may manifest as a reluctance to walk. If the mediastinal lymph nodes are severely enlarged, they may compress the organs and cause the child to have difficulty breathing.

Clinical Department

1. General

Acute myeloid leukemia in children is diagnosed and typed with reference to clinical symptoms, signs, myeloid cytology results, immunophenotyping, genetic features and molecular biology tests. This information is important for the diagnosis, risk grouping and prognosis of the disease. Other ancillary tests, such as ultrasound, chest X-ray, blood biochemistry, etc., will also be performed to assess the physical condition of the child and the specific disease.

2. Consultation room

Hematology, Pediatrics, Hematology-Oncology.

Examination & Diagnosis

1. Diagnostic basis

The main basis for confirming the diagnosis of childhood acute myeloid leukemia is changes in bone marrow morphology. Children with childhood acute myeloid leukemia show characteristic myeloid hyperplasia on bone marrow smears. Typically, bone marrow smears show primitive granulocytes + early juvenile granulocytes (or primitive monocytes . + young monocytes) ≥20% is required to confirm the diagnosis of AML.

2. Relevant inspections

1) Routine physical examination and history taking

Routine physical examination, including physical condition, manifestations of disease, other abnormal signs such as painless lumps. The doctor will also ask about the history of previous illnesses, family history and treatment.

2) Bone marrow biopsy

The doctor will perform a bone marrow aspiration, which is a puncture using a special hollow needle in the iliac bone area to extract a small amount of bone marrow, which will then be sent to the laboratory for relevant tests in cytomorphology, immunology, cytogenetics, and molecular biology in order to confirm the diagnosis and further typing.

3) Cerebrospinal fluid examination

Cerebrospinal fluid is a bodily fluid found in the body's central nervous system. The purpose of a cerebrospinal fluid test is to check whether a child has central nervous system leukemia (also known as meningeal leukemia, in which leukemia cells have infiltrated the central nervous system). Cerebrospinal fluid is sampled through a lumbar puncture, where a special lumbar puncture needle is used to draw the child's cerebrospinal fluid for cytology and other tests.

4) Laboratory tests

● Bone marrow cytomorphometry: FAB typing based on the morphology of the cells in the sample.

● Immunophenotyping: analysis of cell types by immunological markers on the cell surface.

● Cytogenetic and molecular biology analysis: The chromosomes and disease-related fusion genes of the cells in the sample are examined to determine whether there is chromosome damage, loss, or recombination, or whether there are extra chromosomes, and whether there are disease-related fusion genes.

5) Blood tests

● Routine blood tests: platelet count, counts of all types of white blood cells, hemoglobin levels, red blood cell ratios. In addition to automated routine blood tests, a blood smear should be done for manual classification.

● Blood biochemistry tests: Routine blood biochemicals are checked to determine if any are outside the normal range. Liver and kidney function, lactate dehydrogenase levels, and electrolytes are mandatory. Patients with a high leukocyte load may have increased blood uric acid and lactate dehydrogenase levels.

● Coagulation tests: including prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (FIB), D-dimer (DD), fibrin degradation products (FDP).

6) Imaging

Chest X-rays, abdominal ultrasound, and, depending on the condition, ultrasound (in order to understand cardiac function and abdominal organs), CT (to assess for head or chest and abdominal occupations, bleeding, or inflammation), or Magnetic Resonance Imaging (MRI, to assess for occupations and bleeding and vascularity).

3. Differential diagnosis

1) Central nervous system leukemia

CNS leukemia often lacks clinical symptoms at the time of onset or during the course of treatment, and abnormalities are only detected during routine testing of cerebrospinal fluid, but need to be differentiated from bacterial infections and drug-induced chemical meningitis.

2) Leukemia-like reactions

There may be hepatosplenomegaly, thrombocytopenia, and occasional mid to late juvenile and nucleated erythrocytes in the terminal blood picture, but the leukemia-like reaction often has an infectious trigger, and the blood picture recovers when the primary disease is controlled.

3) Infectious mononucleosis

Infectious mononucleosis is caused by EBV infection, with enlarged liver, spleen and lymph nodes, fever, positive serum heterophilic agglutination reaction, positive EBV antibody, elevated leukocytes and presence of anisotropic lymphocytes, but normal hemoglobin and platelet counts, and no leukemic changes on bone marrow examination.

4) Aplastic anemia

Bleeding, anemia, fever, and pancytopenia have similarities to the hypoproliferative manifestations of leukemia, but the disease is not accompanied by enlargement of the liver, spleen, or lymph nodes, and hypoproliferative bone marrow cells without naïve cell proliferation.

5) Rheumatism and rheumatoid arthritis

Some children with acute myeloid leukemia have joint pain as the first symptom, and the hematological examination may be completely normal, so it is easy to be misdiagnosed as rheumatoid or rheumatoid arthritis, and in atypical cases, bone marrow examination should be carried out as early as possible in order to confirm the diagnosis.

Clinical Management

1. General

The common treatment modalities for childhood AML (except acute promyelocytic leukemia) include chemotherapy and hematopoietic stem cell transplantation. The disease of AML in children progresses rapidly, and once the diagnosis is confirmed, induction chemotherapy should be carried out immediately to reduce the tumor load and alleviate the clinical symptoms caused by the tumor within a short period of time. After the success of induction chemotherapy, according to the grading of the risk level, the appropriate intensity and dose of treatment will be carried out. The treatment of AML in children is usually divided into three phases: induction, consolidation, and intensification, with some AML regimens having a maintenance phase after the intensification. Hematopoietic stem cell transplantation needs to be considered for some children at intermediate to high risk of relapse.

Treatment for acute promyelocytic leukemia in children is primarily all-trans retinoic acid and arsenic. Hematopoietic stem cell transplantation also needs to be considered for acute promyelocytic leukemia with signs of relapse.

2. Chemotherapy

1) Chemotherapy regimen

Chemotherapy is the mainstay of treatment for childhood AML and is divided into the following stages:

● induction therapy period

Intermediate-risk, and low-risk myeloid leukemias other than childhood promyelocytic leukemia: the DAE regimen (Zoerythromycin (DNR) + Cytarabine (also known as Ara-C) + Etoposide (VP16)) or the HAD regimen (Hauteric Triglyceride (HRT) + Cytarabine + Etoposide) are currently the preferred choices.

Children with high-risk myeloid leukemia are preferred to be treated with IA regimen [desmethoxylated erythromycin (IDA) + cytarabine] or DAE regimen. Alternatively, chemotherapy with novel antitumor agents may be chosen based on the physician's recommendation. If the child's white blood cell count is greater than 100 X 109/L before induction therapy, small doses of cytotoxic drugs can be used to reduce the leukemic cell load and prevent tumor lysis syndrome, and combination chemotherapy can be given after the white blood cell count is less than 50 X 109/L.

Children with hypoproliferative AML or co-infections should be treated with moderate chemotherapy in conjunction with infection control, and then enter induction chemotherapy as described above when their general condition improves.

● consolidation period

Those in complete remission with induction chemotherapy were given another course of the original regimen.

● intensive treatment period

Intensive treatment is mainly chemotherapy with medium- and high-dose cytarabine in combination with other chemotherapeutic agents to prevent recurrence and improve long-term disease-free survival.

● Maintenance therapy or hematopoietic stem cell transplantation

Currently, maintenance therapy is not advocated for children with acute myeloid leukemia in the low-risk group after induction of remission and consolidation and intensification. Children with childhood acute myeloid leukemia in the intermediate- and high-risk groups are prone to relapse with chemotherapy alone; therefore, hematopoietic stem cell transplantation is aggressively pursued after induced remission with a suitable donor.

● intrathecal chemotherapy

Subtypes of acute myeloid leukemia other than acute promyelocytic leukemia require intrathecal injection for prophylaxis or treatment of CNS leukemia.

2) Adverse Reactions

i) Cardiotoxicity

Anthracyclines may cause acute myocardial injury and chronic cardiac impairment. The former is transient and reversible localized myocardial ischemia, which may be manifested by panic, shortness of breath, chest tightness and precordial discomfort. The latter is irreversible congestive heart failure and is related to the cumulative dose of the drug. If cardiac function tests suggest abnormal cardiac function and are not due to infection, anthracyclines need to be suspended until cardiac function recovers. If myocardial injury occurs, drugs such as dexpropylenetramine (Zinecard) may be selected for treatment according to the condition.

ii) Hepatotoxicity

Some chemotherapeutic agents are toxic to the liver, as evidenced by elevated aminotransferases or bilirubin. Therefore, liver function tests are usually required before each course of treatment to determine whether chemotherapy can be given on time, and every 4-8 weeks during maintenance treatment, or every 12 weeks if there are no special circumstances.

If the direct bilirubin is elevated during chemotherapy and it is determined that it is due to leukemic cell infiltration, then chemotherapy is given as usual; if it is not due to leukemic infiltration, then the dose of chemotherapy is adjusted according to the condition. In children with acute promyelocytic leukemia, when elevated direct bilirubin occurs, the cause of differentiation syndrome should also be excluded; if it is indeed due to differentiation syndrome, treatment should be based on differentiation syndrome. Prior to the start of chemotherapy, if the direct bilirubin is too high, chemotherapy can be delayed for 1 week; if the bilirubin is still high after 1 week, the dose is adjusted and chemotherapy is started. When direct bilirubin is too high, care should be taken to adjust the dose of Zoerythromycin.

At present, there are some "liver-protecting drugs" on the market, but their role is not clear, the international major clinical programs do not routinely use "liver-protecting drugs", and there is no "liver-protecting drugs" to increase the safety of chemotherapy. There are no reports that "liver-protecting drugs" increase the safety of chemotherapy. In addition, hepatoprotective drugs may interact with chemotherapeutic drugs and increase the complexity of chemotherapeutic drug metabolism, so the use of adjuvant hepatoprotective drugs is not recommended.

iii) Neurotoxicity

The chemotherapeutic drug cytarabine is neurotoxic. The dose of cytarabine in the treatment regimen needs to be adjusted when the symptoms of cytarabine-associated neurotoxicity are so pronounced that they interfere with the normal life of the child.

iv) Acute Respiratory Distress Syndrome (ARDS)

Cytarabine is toxic to the lungs and may cause acute respiratory distress syndrome, which manifests as, for example, dyspnea, hypoxemia (SpO2 < 92%), and a chest line suggestive of infiltrates in both lungs. Children with such symptoms need to first rule out the possibility of pulmonary infection and cardiotoxicity of other chemotherapeutic agents by chest CT and cardiac ultrasound. If acute respiratory distress syndrome due to cytarabine is identified, it can be treated with glucocorticoids, with methylprednisolone recommended. A pediatric pulmonologist may be invited to consult if available.

v) Hematological toxicity

Chemotherapeutic agents remove leukemia cells while also affecting normal hematopoiesis. Before chemotherapy with anthracyclines, the blood picture should meet the following criteria: white blood cell count (WBC) ≥ 2.0 × 109 /L, absolute neutrophil count (ANC) ≥ 0.8 × 109 /L, platelet (PLT) ≥ 80 × 109 /L.

Granulocyte colony-stimulating factor (commonly known as leukapheresis) may be used if the child's neutropenia persists for 2-4 weeks without recovery or if it is anticipated that the child may have a prolonged period of neutrophil deficiency. Platelets should be transfused if the platelet count is less than 20×109 /L. The indication for transfusion may be relaxed if the child has significant bleeding symptoms or manifestations of infection.

3. Drug treatment

1) Treatment Programs

Acute promyelocytic leukemia in children is usually treated with all-trans retinoic acid and arsenic. Because acute promyelocytic leukemia can cause significant coagulation abnormalities, all-trans retinoic acid therapy should be started as soon as acute promyelocytic leukemia is suspected, even if all laboratory tests have not been completed.

2) Adverse Reactions

i) Differentiation syndrome

In children with acute promyelocytic leukemia, differentiation syndrome is a common complication that occurs after the use of all-trans retinoids or arsenicals, usually 2-3 days after administration, and may be life-threatening in severe cases.

A child may have differentiation syndrome if three or more of the following clinical signs are present at the same time: increased peripheral blood leukocytes, dyspnea, respiratory distress, fever, pulmonary edema, pulmonary infiltrates, pleural or pericardial effusion, peripheral edema, short-term weight gain (10% or more over the concomitant basal body weight), bone pain, headache, hypotension, congestive heart failure, acute renal function insufficiency, and abnormal liver function. If a child develops differentiation syndrome, it may be treated with steroid hormones and other symptom-relieving medications, and the dosage of all-trans retinoic acid and arsenic may be adjusted according to the child's condition.

ii) Cardiotoxicity

Arsenic agents can cause cardiac arrhythmias. Therefore, ECGs also need to be checked before each course of arsenicals and reviewed every 1-2 weeks. Once the risk of arrhythmia is detected, close observation is needed to correct electrolyte disturbances, discontinue suspected medications that may be causing the associated symptoms (e.g., macrolide antibiotics, azole antifungals, and antiarrhythmics), and review the ECGs at least once a week. If symptoms are severe, the arsenic will need to be tapered or discontinued. If torsion tachycardia occurs, arsenic should be permanently disabled.

4. Hematopoietic stem cell transplantation

In general, children with high-risk or relapsed AML (not acute promyelocytic leukemia) require HSCT. Chemotherapy is an option for intermediate-risk children, but chemotherapy alone is prone to relapse, so HSCT may also be an option.

Treatment by chemotherapy is recommended in principle for low-risk children, and allogeneic HSCT is generally not required. However, in some cases, some patients may undergo autologous HSCT to avoid recurrence.

For children with acute myeloid leukemia, due to the current advances in transplantation technology, both unrelated donors and HLA hemi-compatible donors (i.e., donors with half of their HLA matches, also known as haploidentical donors, and relatives such as fathers, mothers, siblings, and other relatives who are related to the child, have a higher likelihood of being hemi-compatible donors) are transplanted to achieve relatively good results. Therefore, the main thing that needs to be chosen for allogeneic hematopoietic stem cell transplantation in children with acute myeloid leukemia is the timing of the transplantation.

Allogeneic hematopoietic stem cell transplantation is also recommended for children with acute promyelocytic leukemia who develop a negative-to-positive PML-RARa fusion that persists for more than 2 episodes after discontinuation of the drug.

5. Cutting-edge treatment

The targeted drug gitumumab is approved in the United States for the treatment of childhood acute myeloid leukemia, and has been shown to be effective in children with high expression of the CD33 molecule on leukemia cells.

Prognosis

1. General

According to the National Cancer Institute (NCI), the five-year survival rate for children under 15 years of age with acute myeloid leukemia is approximately 68%, and 57% for children 15-19 years of age. Certain treatment centers in the country have outcomes similar to international ones. The prognosis of children depends on their molecular biology subtype. Survival rates for childhood acute promyelocytic leukemia are better, with the vast majority of studies showing a five-year survival rate of more than 90%.

2. Sequelae

Children with acute myeloid leukemia who have received chemotherapy are at risk for long-term side effects and secondary tumors, which may occur even many years later. Therefore, attention needs to be paid to review and follow-up, as well as tumor screening after a certain age.

3. Complications

1) Neutrophil deficiency with fever

Children with acute myeloid leukemia have low neutrophils and may develop granulocyte deficiency in combination with infections, which are usually aggressive and rapidly progressive, and therefore require prompt initial empirical treatment, followed by targeted therapy once the pathogen has been identified.

In the event of granulocyte deficiency with fever, or significant mucosal inflammation, it may be necessary to temporarily discontinue chemotherapeutic agents until temperature is normalized, mucositis is restored, and infection is controlled.

2) Anemia

Children with acute myeloid leukemia are prone to anemia. It can usually be relieved by transfusion of red blood cells, and if the hematocrit reaches less than 60 g/L, a blood transfusion is necessary.

3) Pneumocystis carinii infection

Since children with acute myeloid leukemia are immunocompromised and at risk for Pneumocystis carinii infection, long-term administration of cotrimoxazole (SMZco) tablets is usually recommended to prevent Pneumocystis carinii infection until 3 months after completion of chemotherapy.

4. Recurrence

Acute myeloid leukemia in children has a certain relapse rate. Most relapses occur within 4 years of diagnosis. The vast majority of AML relapses are bone marrow relapses and central nervous system relapses are rare (3-6%).

Follow-up & Review

rechecking

The current review and follow-up program adopted by most hospitals in the country is:

● Within 1 year of stopping the drug: review every 3 months or so.

● Years 2 to 5 after stopping the drug: review every 6 months or so.

● After 5 years of discontinuation: annual review.

Usually, the review after the end of treatment includes a thorough general physical examination, laboratory tests, sometimes imaging and/or bone marrow aspiration, and possibly liver and kidney function tests. The exact tests to be performed will depend on the child's specific condition and will be based on the doctor's recommendation.

Routine

1. General

Complete the treatment as prescribed by the doctor, maintain good living habits and a clean living environment, and take care to prevent infection. Regular follow-ups should be conducted after the completion of treatment in order to monitor recurrence and long-term adverse effects. Meanwhile, in daily life, children should be provided with nutritionally balanced diets, encouraged to have moderate activities, and attention should be paid to the psychological health of the children.

2. Home care

Since children under treatment often have reduced immunity, care should be taken to prevent infection. Pay attention to washing hands frequently, keeping food and drinking water clean and hygienic, and good living hygiene habits. Keep the living environment neat and clean, open windows regularly to maintain air circulation. Do not put fresh flowers and potted flowers indoors for the time being. Garbage cans should be covered and garbage should not be stored for more than 2 hours. At the same time, the contact between the child and the infected patient should be reduced, and the infection of the accompanying staff should also be noted. If someone in the family has a cold, contact with the child should be avoided as much as possible; if contact with the child is necessary, hand washing (with soap or hand sanitizer), wearing a mask and other protective measures must be done. At the same time, parents should pay attention to daily observation of the child's condition and seek medical attention as soon as possible if there are signs of infection or fever.

3. Management of daily life

1) Diet

Both during and after treatment, it is recommended to provide children with a nutritious and balanced diet, guaranteeing the intake of high-quality proteins (e.g., meat, eggs, milk, poultry, fish and shrimp, soybeans and soybean products, etc.), as well as more grains and cereals, vegetables and fruits, and moderate consumption of dairy products and nuts to ensure the intake of other nutrients. At the same time should eat less refined rice and white flour, deep-processed snacks and processed meats, control oil and salt.

In addition, during the treatment period, the child's immunity will be reduced and expired, spoiled, unclean and potentially food-safe foods should be avoided. Specific dietary advice can be obtained from the dietitian at your hospital.

2) Movement

If the physical condition of the child allows, you can encourage and assist the child to do some activities. Moderate exercise is helpful in preventing muscle atrophy, increasing physical strength and endurance, and promoting appetite.

Appropriate regular exercise is recommended after the child has finished treatment. If available, consider 30-60 minutes of moderate-intensity exercise per day (e.g., brisk walking, bicycling, yoga, table tennis, etc.) or a moderate amount of high-intensity exercise per week (e.g., running, swimming, jumping rope, aerobics, basketball, etc.).

3) Lifestyle

The patient needs to be guaranteed a sleep schedule. Regular and quality sleep is helpful for recovery and immunity. A suitable sleep environment (usually dimly lit, quiet, and at the right temperature) may be helpful in improving the patient's quality of sleep.

Studies have shown that children with leukemia have a higher risk of cardiovascular disease, metabolic disease, and secondary cancer in the long term than the general population. A healthy lifestyle, such as a balanced diet and moderate exercise, is the most important and effective means of preventing these diseases. Children are also advised to pay attention to weight control, as being overweight may increase the risk of developing cancer (e.g., breast, pancreatic, rectal, endometrial, etc.) later in life.

4) Emotional psychology

The process of treating acute myeloid leukemia can be very challenging for the child and requires attention to the child's mental health. The physical changes and pain caused by the disease and treatment, the lack of external peer contact due to isolation during treatment, falling behind in school, and the fear of not being accepted by peers can all affect the child's mental health. Parents need to guide their children to face the disease with a positive attitude, accept their physical changes, and encourage them to maintain external contacts, play with classmates and friends, and return to school and reintegrate into the society as early as possible under the premise of ensuring hygiene during the treatment process. If the child has a psychological disorder, a psychologist can be called in to intervene.

4. Daily condition monitoring

It is necessary to pay attention to the side effects caused by radiotherapy (e.g., hair loss, fatigue, vomiting, etc.), recurrence of tumor metastasis, and abnormal growth and development. Consult your doctor when fever, worsening symptoms, new symptoms, and treatment-induced side effects occur.

5. Special Considerations

1) Precautions to be taken when platelets are too low

If the child's platelets are too low (usually less than 20x109 /L), care needs to be taken to avoid bleeding, to stay away from sharp, prickly toys and objects, and to avoid all impact sports (such as bouncing, soccer, basketball, etc.). When eating, avoid bones and other foods that tend to poke the mouth, and use a soft-bristled brush when brushing teeth. At the same time, for younger children, should try to avoid violent crying to avoid intracranial hemorrhage. In addition, take care to keep the child's bowels clear, and do not self-administer anal suppositories or measure anal temperature to avoid rectal bleeding. Do not give your child medications that tend to cause bleeding, such as aspirin or ibuprofen, unless your doctor recommends it. Some over-the-counter cold medicines may have ingredients such as ibuprofen that require special attention.

2) Keeping case records

Patients with childhood acute myeloid leukemia are at risk for long-term side effects and secondary tumors, which may occur many years after the end of the child's treatment, and which are related to the regimen and dosage of the leukemia treatment. Therefore, it is important to keep a record of all the child's visits and treatments for future reviews and referrals.

6. Prevention

Since the exact cause of the vast majority of AML in children is not known, there is no corresponding prevention method. However, certain environmental factors and genetic disorders are known to be associated with an increased risk of AML in children (see "Predisposing Factors"). Therefore, parents can take care to avoid relevant environmental factors. If the child has a related genetic disorder, screening for childhood leukemia is recommended. In addition, parents can pay attention to the early symptoms of AML in children, and seek early medical attention once it is detected, so as to achieve early detection and early treatment, and to strive for the best therapeutic effect.

Cutting-edge Therapeutic & Clinical Research

not have

References

1. Wang N, Feng YJ, Wang BH, Fang LW, Cong SH, Li YC, Yin P, Zhou MK, Wang LH. Analysis of the burden of disease of leukemia in the Chinese population in 1990 and 2013. Chinese Journal of Epidemiology. 2016. 37(6): 783-787.

2. Hematology Group of the Pediatrics Branch of the Chinese Medical Association, Editorial Board of the Chinese Journal of Pediatrics. Recommendations for the Diagnosis and Treatment of Acute Myeloid Leukemia in Children. Chinese Journal of Pediatrics. 2006. 44(11): 877-878.

3. Liu Lanbo, Tang Jingyan. Progress related to the treatment of childhood acute myeloid leukemia. Journal of Clinical Pediatrics. 2012. 33(5): 487-491.

4. Childhood Acute Myeloid Leukemia/Other Myeloid Malignancies Treatment (PDQ®) (Health Professional Version)

5. Childhood Acute Myeloid Leukemia/Other Myeloid Malignancies Treatment (PDQ®) (Patient Version)

6. National Health and Health Commission of the People's Republic of China. Diagnostic and treatment norms for acute promyelocytic leukemia in children (2018 version).

http://www.nhc.gov.cn/ewebeditor/uploadfile/2018/10/20181016180416637.doc

7. Chinese Medical Association. Clinical pathway for acute promyelocytic leukemia in children (2017 edition).

https://www.cma.org.cn/attachment/201765/1496631243573.rar

8. arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016. 127(20): 2391-2405.