Acute promyelocytic leukemia in children

Summarize

1. General

● OVERVIEW: Childhood acute promyelocytic leukemia is a form of childhood acute myeloid leukemia with characteristic chromosome 15 and 17 translocations (notated as t(15;17)) and its formation of the PML-RARα fusion gene.

● Manifestations: The main manifestations of acute promyelocytic leukemia in children are no different from those of other types of leukemia, and can also include bleeding, fever, anemia, hepatosplenomegaly, and joint pain, with bleeding being more pronounced.

● Treatment: The mainstay of treatment for acute promyelocytic leukemia in children is all-trans retinoic acid and/or arsenic, and sometimes chemotherapeutic agents such as anthracyclines.

● Prognosis: Acute promyelocytic leukemia in children has a good prognosis, with a five-year survival rate of more than 90%.

2. Definition of disease

Childhood acute promyelocytic leukemia (APL) is a very specific form of childhood acute myeloid leukemia (AML), also known as childhood acute myeloid leukemia type M3. This leukemia has a characteristic chromosome 15 and 17 translocation (denoted as t(15;17)), and the PML-RARα fusion gene resulting from this chromosomal translocation can be detected.

Epidemiological

epidemiological

Acute promyelocytic leukemia in children accounts for 10% of childhood acute myeloid leukemia, and based on the incidence of childhood leukemia in China, it is estimated that there are about 300 new cases of acute promyelocytic leukemia per year in people under 18 years of age.

Etiolog & Risk factors

1. General

As with other types of childhood leukemia, childhood acute promyelocytic leukemia occurs primarily as a result of mutations that occur during the child's growth and development. In the vast majority of cases of childhood acute promyelocytic leukemia, the mutation is the occurrence of the PML-RARα fusion gene.

2. Underlying causes

Acute promyelocytic leukemia in children is caused by RARα fusion genes, the vast majority of which are PML-RARα fusion genes, and a very small number of which are caused by fusion genes such as PLZF-RARα, NPM-RARα, NuMA-RARα, STAT5B-RARα, and others. As a result of the altered genetic material, the development of promyelocytes in the bone marrow is abnormal; they do not undergo the normal maturation process and proliferate rapidly to form leukemia cells. These leukemia cells crowd out normal cells and can rapidly overflow into the blood stream and reach other parts of the body through the bloodstream, such as lymph nodes, spleen, liver, central nervous system (brain and spinal cord), or other organs, forming infiltrates that affect the normal function of other cells and lead to the various symptoms of leukemia.

Genetic variants in acute promyelocytic leukemia in children usually occur during the development of the child, are not hereditary, and are not usually passed on to offspring.

3. Predisposing factors

The predisposing factors for acute promyelocytic leukemia in children are unclear. It is generally accepted that high exposure to ionizing radiation (e.g., nuclear radiation, X-rays, etc.), certain carcinogens in the environment (e.g., benzene and its derivatives, formaldehyde, etc.), and other factors are associated with an elevated risk of childhood leukemia.

Classification & Stage

Disease grouping

According to the "Diagnostic and Treatment Guidelines for Acute Promyelocytic Leukemia in Children (2018 Edition)" developed by the National Health and Health Commission (NHHC), acute promyelocytic leukemia in children can be grouped according to risk 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 failure to achieve molecular biological remission before maintenance therapy in the low-risk group.

Clinical manifestations

1. General

Children with acute promyelocytic leukemia are more likely to have bleeding symptoms, and other major symptoms include fever, anemia, hepatosplenomegaly, and joint pain.

2. Typical symptoms

Bleeding: Children with acute promyelocytic leukemia often start with petechiae on the skin, nosebleeds, and in severe cases, disseminated intravascular coagulation (DIC), which can lead to fatal pulmonary or intracranial hemorrhage. This is mainly due to abnormalities in coagulation and platelets in children with acute promyelocytic leukemia.

● Fever: One of the causes of fever is mainly due to leukemia itself, which is usually a low to moderate fever of about 38°C, ineffective with antibiotics, and resolves more quickly after induction therapy. However, due to the abnormal leukocyte function of the child, the effective neutrophil value is reduced, leading to immunocompromise, and it is easy to combine with infections to cause fever. 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 any pathogen.

● Anemia: manifests itself as pallor, weakness, shortness of breath after activity, drowsiness, etc. Nails and eyelid conjunctiva may also appear pale to varying degrees. When a child is weak due to anemia, it may manifest as a need to be held by an adult (especially in younger children). Joint pain may manifest as a reluctance to walk.

● Leukemic cell infiltration: usually presenting with enlarged lymph nodes in various areas and/or hepatosplenomegaly, often in conjunction with severe bleeding and disseminated intravascular coagulation, with a high risk of early death. If leukemia cells proliferate rapidly in the bone marrow for a short period of time or infiltrate the epiphyses of the bone, the child may present with symptoms such as bone or joint pain, or sternal tenderness. Leukemia cells may also invade the central nervous system, including the brain, and symptoms such as facial nerve paralysis may occur.

Clinical Department

1. General

The diagnosis of acute promyelocytic leukemia in children is confirmed with reference to clinical symptoms, signs, bone marrow cytology results, immunophenotyping, genetic features and molecular biology tests. This information is very important for the diagnosis of the disease. At the same time, doctors will also conduct other ancillary tests, such as ultrasound, chest X-ray, blood biochemistry, etc. 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 definitive diagnosis of acute promyelocytic leukemia in children is based on the results of cytomorphologic, immunologic, cytogenetic, and molecular biology testing of bone marrow samples. The cytomorphology of bone marrow samples in classical acute promyelocytic leukemia should have features typical of promyelocytic leukemia and detect the characteristic chromosomal translocation t(15;17)(q22;q21) or PML-RARα fusion gene.

2. Relevant inspections

1) Routine physical examination and history taking

Routine physical examination, including physical condition, manifestations of disease such as temperature, pale skin and mucous membranes, skin blebs and petechiae, lymph nodes and hepatosplenomegaly, and sternal tenderness. The doctor will also ask about previous disease history, family history and treatment.

2) Bone marrow examination

The doctor will perform a bone marrow aspiration, which involves puncturing the common bone marrow puncture sites (e.g., ilium, sternum) with a special hollow needle or syringe to extract a small amount of bone marrow, which is then sent to the laboratory for cytomorphologic, immunologic, cytogenetic, and molecular biologic tests in order to confirm the diagnosis.

3) Cerebrospinal fluid examination

Cerebrospinal fluid is a bodily fluid found in the body's central nervous system. The purpose of the cerebrospinal fluid test is to check whether the child has meningeal leukemia (also a type of central nervous system leukemia, in which leukemia cells infiltrate 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.

However, because of the obvious bleeding tendency of acute promyelocytic leukemia, lumbar puncture should not be performed in the early stage of treatment, and it is usually necessary to perform lumbar puncture and cerebrospinal fluid examination after the coagulation function has returned to normal.

4) Laboratory tests

The lab will perform a series of tests on blood, bone marrow samples, and cerebrospinal fluid lumbar puncture samples, for example:

● Bone marrow cytomorphometry: 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 for cases of classical acute promyelocytic leukemia with the characteristic chromosomal translocation t(15;17)(q22;q21) or the PML-RARα fusion gene. In general, detection of chromosomal translocations is usually performed by karyotyping. Detection of fusion genes can be performed by fluorescent in situ hybridization (FISH) technique or RT-PCR (reverse transcription-polymerase chain reaction) technique. If neither the chromosomal t(15;17) translocation nor the PML-RARα fusion gene is detected by any of these methods, supplemental RNA or DNA sequencing testing may be considered.

5) Blood tests

● Routine blood tests: platelet counts, counts of various types of white blood cells, hemoglobin levels, and red blood cell ratios. In addition to automated routine blood tests, blood smears are sometimes done for manual classification. In children with acute promyelocytic leukemia, hemoglobin and red blood cells are usually decreased to varying degrees, white blood cells are elevated in most cases and may be normal or decreased, and platelets are usually decreased; abnormal promyelocytes can be found in peripheral blood smears.

● Blood biochemistry tests: Routine biochemical markers in the blood are checked to determine if any are outside the normal range. Tests such as liver and kidney function, lactate dehydrogenase (LDH), cardiac enzymes, and electrolytes are usually checked.

● Coagulation function tests: including prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (FIB), D-dimer (DD), fibrin degradation product (FDP). Since coagulation abnormalities are usually present in children with acute promyelocytic leukemia, coagulation should be examined promptly if acute promyelocytic leukemia is suspected or diagnosed in order to prevent and treat severe bleeding early.

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).

Clinical Management

1. General

The primary treatment for acute promyelocytic leukemia in children is a combination of all-trans retinoic acid and arsenic. If the patient already has significant clotting abnormalities, all-trans retinoic acid therapy should be started as soon as the diagnosis of acute promyelocytic leukemia is confirmed, even if all laboratory tests have not been completed. The cure rate can be more than 90% if the risk of bleeding from vital organs caused by coagulation abnormalities early in treatment is overcome. The efficacy of all-trans retinoic acid as well as arsenic in PML-RARa fusion gene-positive acute promyelocytic leukemia is definitive, and the combination has a synergistic effect, with positive implications for leukemic cell clearance.

PML-RARα fusion gene-negative acute promyelocytic leukemia (often positive for other RARα fusion genes) may not respond as well to all-trans retinoic acid and arsenicals as PML-RARa fusion gene-positive acute promyelocytic leukemia. In particular, PLZF-RARα fusion gene-positive acute promyelocytic leukemia tends to respond poorly to all-trans retinoic acid and arsenicals.

2. Chemotherapy

1) Chemotherapy regimen

The chemotherapy regimen for acute promyelocytic leukemia in children can be divided into induction, consolidation, intensification, and maintenance phases, which are adjusted according to different levels of risk.

Medication in the low-risk group is primarily oral all-trans retinoic acid (ATRA) + arsenic (either intravenous arsenic trioxide (ATO) or oral compounded yellow dock tablets (RIF)). All-trans retinoic acid needs to be administered immediately upon morphological confirmation of acute promyelocytic leukemia in the bone marrow. Arsenic needs to be administered at the time of molecular biology confirmation of a positive PML-RARa fusion gene, which is recommended within one week.

Medication in the high-risk group consisted primarily of oral all-trans retinoic acid + arsenic (IV arsenic trioxide or oral cotrimoxazole tablets) + IV anthracyclines (desmethoxyzoxazolidine (IDA) or zoerythromycin (DNR)). The timing of administration of all-trans retinoic acid and arsenic was consistent with the low-risk group.

If the initial or post-induction white blood cell count is greater than 10 x 109/L, choose one of the following drugs: hydroxyurea, cytarabine, or hypertriglycerides. Anthracyclines are added to this in the high-risk group.

Intrathecal chemotherapy is required for acute promyelocytic leukemia in children to prevent or treat CNS leukemia. However, because acute promyelocytic leukemia in children can cause disseminated intravascular coagulation (DIC), which is very dangerous, it is important to wait until DIC is controlled before administering intrathecal chemotherapy injections during induction therapy.

2) Complications and adverse reactions

i) Disseminated intravascular coagulation

Disseminated intravascular coagulation (DIC) is a complication of abnormal coagulation that is more common in children with acute promyelocytic leukemia and can progress very rapidly. The main symptoms include bleeding, bruising, hypotension, dyspnea, and confusion, which can lead to severe bleeding and life-threatening multi-organ failure.

ii) differentiation syndrome

Differentiation syndrome is a common complication that occurs after the use of all-trans retinoids or arsenicals, usually occurring 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.

iii) Pseudotumor cerebri (idiopathic elevated intracranial pressure)

All-trans retinoic acid may cause pseudotumor cerebri, also known as idiopathic increased intracranial pressure, with the main symptoms being headache, optic papilla edema, adductor nerve palsy, and visual problems. Pseudotumor cerebri occurs mostly within 35 days of starting all-trans retinoic acid.

If a child is suspected of having a pseudotumor cerebri, all-trans retinoic acid should be suspended and normal dosage should be resumed gradually after the symptoms have subsided.

iv) Cardiotoxicity

Anthracyclines and arsenic can cause 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 dexpropylenimine (Zinecard) may be selected for treatment according to the condition. If available, cardiology consultation can be invited to assist in the treatment.

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.

v) 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.

When elevated direct bilirubin occurs during chemotherapy, if it is due to differentiation syndrome, it should be treated as differentiation syndrome; if it is due to leukemic infiltration, chemotherapy should be given as usual; if it is not due to leukemic infiltration and not due to differentiation syndrome, chemotherapy dosage should be adjusted according to the condition. Before the start of the chemotherapy course, chemotherapy can be delayed for 1 week if the direct bilirubin is too high; if the bilirubin is still high after 1 week, adjust the dose and start chemotherapy.

There are some "liver-protecting drugs" on the market, but their role is not clear. Internationally, major clinical programs do not routinely use "liver-protecting drugs" as prophylaxis, and there are no reports of "liver-protecting drugs" increasing the safety of chemotherapy. There are no reports that "hepatoprotective 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 prophylactic application of hepatoprotective drugs is not recommended.

vi) Nephrotoxicity

In children with renal dysfunction, this can lead to delayed excretion of cytarabine, which can exacerbate its toxic side effects. Therefore, if the child's serum creatinine level is higher than 176 mol/L or twice the normal value, the child should be hydrated by the oral or intravenous route.

If a child presents with abnormal renal function, the cause of the differentiation syndrome needs to be ruled out first; if it is indeed due to the differentiation syndrome, the child should be treated as if he/she had the differentiation syndrome and be put on dialysis. If there is a progressive increase in serum creatinine over a short period of time, or if the increase in serum creatinine is accompanied by a rise in blood potassium, all-trans retinoic acid or/and arsenicals need to be suspended or dialysis should be administered. Because arsenic is excreted primarily by the kidneys and slowly, with less than 10% excreted per day, it is not necessary to adjust the arsenic dosage based on renal function for induction of remission therapy, but subsequent therapy should be based on renal function to shorten the course of arsenic without lowering the daily dose.

vii) Neurotoxicity

The chemotherapeutic drug cytarabine may sometimes produce neurotoxicity. When symptoms of cytarabine-related neurotoxicity are so pronounced that they interfere with the normal life of the child, the treatment regimen needs to be adjusted to avoid the use of cytarabine.

viii) Acute Respiratory Distress Syndrome (ARDS)

Cytarabine is toxic to the lungs and may cause acute respiratory distress syndrome (ARDS); differentiation syndrome sometimes complicates ARDS. Acute respiratory distress syndrome is characterized by, for example, dyspnea, hypoxemia (SpO2 < 92%), and chest X-rays suggesting infiltration of both lungs. Children with such symptoms need to first be excluded from lung infection and other chemotherapy drug cardiotoxicity by chest CT and cardiac ultrasound. If the acute respiratory distress syndrome is determined to be due to cytarabine, it can be treated with glucocorticoids, with methylprednisolone recommended; if it is due to differentiation syndrome, it should be treated as such. A pediatric pulmonologist can be invited to consult if available.

ix) Hematological toxicity

Certain chemotherapeutic agents can affect the blood picture. Prior to chemotherapy with anthracyclines, the blood picture should be as close as possible to the following criteria: white blood cell count (WBC) ≥ 2.0 x 109 /L, absolute neutrophil count (ANC) ≥ 0.8 x 109 /L, and platelets (PLT) ≥ 80 x 109 /L. However, there is no need to delay or discontinue medication based on the blood count prior to treatment with all-trans vincristine and arsenicals.

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.

If the child develops anemia, it can usually be relieved by a transfusion of red blood cells, which should generally be administered for a hematocrit of 60 g/L.

x) Neutrophil deficiency with fever

Children with acute promyelocytic leukemia may develop granulocyte-deficient coinfections due to the disease itself or treatment, which are usually aggressive and rapidly progressive, and therefore require prompt initial empiric anti-infective therapy, followed by targeted therapy once the pathogen is identified.

3. Hematopoietic stem cell transplantation

1) Hematopoietic stem cell transplantation

Allogeneic hematopoietic stem cell transplantation may be considered for children with acute promyelocytic leukemia who are not responding well to chemotherapy or who repeatedly turn positive for molecular markers (fusion genes) after discontinuing therapy.

2) Graft-versus-host disease

Children who have undergone allogeneic hematopoietic stem cell transplantation may develop graft versus host disease (GVHD) due to differences in the genes of the donor and the child. Symptoms of graft versus host disease focus on the skin, liver, and digestive tract and include erythema, rash, blisters, painful skin on the palms of the hands and feet, dry cracked or flaking skin, darkening of the skin, thickening or even hardening of the skin with desquamation, a rash (which has a mossy appearance), jaundice (yellowing of the skin and/or the whites of the eyes), nausea, vomiting, abdominal pain, diarrhea, and more.

Usually, children need to take anti-rejection drugs to control graft-versus-host disease. Commonly used drugs include glucocorticoids, cyclosporine, sirolimus, mertiomaxolide, azathioprine, and tacrolimus. Since mild cases of graft-versus-host disease have some anti-leukemic effect and can help prevent leukemia relapse, the graft-versus-host disease is usually kept under control with medications in an appropriate range. The exact course of treatment is determined on a case-by-case basis, depending on the type of disease, the type of transplant, donor selection, and post-transplant complications.

Prognosis

1. General

The prognosis for childhood acute promyelocytic leukemia is good, with the vast majority of studies showing a five-year overall survival rate of 90% or more. In particular, children with a positive PML-RARα fusion usually have a better prognosis than children with other fusion types.

2. Recurrence

In general, after treatment of acute promyelocytic leukemia in children is completed, if relapse does not occur within 5 years, the rate of relapse after that is very low.

Follow-up & Review

rechecking

For two years after stopping the drug, it is recommended to review every six months. After the third year of discontinuation, it can be reviewed annually.

Usually, the review after the end of treatment includes a thorough general physical examination, laboratory tests, bone marrow aspiration and lumbar puncture (cerebrospinal fluid test), and sometimes imaging tests and/or liver and kidney functions. The exact tests to be performed will depend on the child's specific condition and will be based on the doctor's recommendations. If symptoms of recurrence occur, repeat the examination at any time.

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. After finishing the treatment, regular follow-up should be conducted to monitor the recurrence and long-term 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

Whether during or 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, quinoa, etc.), as well as more grains and cereals and fruits and vegetables, and moderate consumption of dairy products and nuts, in order to ensure the intake of other nutrients. At the same time should eat less refined rice and white flour, deep-processed snacks and processed meat, 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 promyelocytic leukemia is 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 in case of low platelets

During chemotherapy, 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 impact sports (such as bouncing, soccer, basketball, etc.). When eating, be careful to avoid bones and other foods that tend to poke the mouth, and use a soft-bristled brush when brushing teeth.

Meanwhile, for younger children, if platelets are too low during chemotherapy, it is recommended to try to avoid children crying violently, so as not to cause serious bleeding. In addition, attention should be paid to keep the child's bowels clear, and it is recommended not to use anal suppositories or measure anal temperature on your own to avoid causing 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) Pneumocystis carinii infection

Because children with acute promyelocytic leukemia are immunocompromised and at risk for infection with Pneumocystis carinii (once known as Pneumocystis carinii), long-term administration of cotrimoxazole (SMZco) is usually recommended to prevent Pneumocystis carinii infections up to 3 months after completion of chemotherapy.

3) Keeping medical records

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

4) Secondary tumor risk

The chemotherapeutic agents themselves may increase the risk of secondary tumors, which is usually distant, even years after treatment has ended. Therefore, children with acute promyelocytic leukemia should be followed up with review. Care should be taken to screen for cancer after a certain age.

6. Prevention

There is no definitive prevention of acute promyelocytic leukemia in children. Parents can avoid environmental factors that are associated with the risk of leukemia. At the same time, they can pay attention to the early symptoms of childhood acute promyelocytic leukemia, and seek early medical attention once it is detected, so that early detection and early treatment can achieve the best therapeutic effect.

Cutting-edge Therapeutic & Clinical Research

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

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

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

5. chinese medical association. Clinical pathway for acute promyelocytic leukemia in children (2017 edition).

6. 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.

7. Kutny MA, Alonzo TA, Gerbing RB, et al.: Arsenic Trioxide Consolidation Allows Anthracycline Dose Reduction for Pediatric Patients With Acute Promyelocytic Leukemia: Report From the Children's Oncology Group Phase III Historically Controlled Trial AAML0631. j Clin Oncol 35 (26): 3021-3029,. 2017.

8.Testi AM, Pession A, Diverio D, et al.: Risk-adapted treatment of acute promyelocytic leukemia: results from the International Consortium for Childhood APL. Blood 132 (4): 405-412, 2018.