Childhood leukemia is a malignant proliferative disease of the hematopoietic system, a disease in which the differentiation of hematopoietic stem cells is blocked at some stage in the differentiation process and becomes malignantly proliferative, and the incidence of pediatric leukemia is 3/100,000-4/100,000 population.
In childhood acute leukemia, acute lymphoblastic leukemia (ALL) accounts for about 65%, and acute myeloid leukemia (AML) accounts for about 25-30%. In the past 30 years, with extensive and in-depth research on the disease in all aspects, human understanding of its nature and clinical treatment effects have developed greatly, and childhood ALL has become a curable malignancy.
I. Etiology and pathogenesis
The etiology of leukemia has not been elucidated, it is generally believed that the occurrence of human leukemia is related to physical, chemical and biological factors. Such as radiation, viruses, etc., cause damage to bone marrow cells, producing abnormal clones, cells can not differentiate and mature, but present uncontrolled and unlimited growth, factors that may cause childhood leukemia are the following.
1, viral infection, it has been confirmed that certain animals such as chickens, mice, cats and gibbons spontaneous leukemia tissue can be isolated from the leukemia virus, in human adults T-cell leukemia and human T-cell leukemia virus is related, but so far, no study can prove that which virus and childhood leukemia has a definite relationship.
2, environmental factors, it has been confirmed that ionizing radiation can cause leukemia, Japan, Hiroshima, Nagasaki has exploded atomic bombs, the incidence of leukemia in the two places are not subjected to radiation areas 30 times and 17 times, and pregnant women in the early stages of pregnancy, has received radiation radiation, the chance of children born with leukemia increased by 5 times, but after birth to receive radiological examination, there is no evidence that can cause childhood leukemia, but high doses of Radiation therapy can lead to the occurrence of tumors, and many chemicals that can cause bone marrow toxicity may lead to the occurrence of leukemia, such as anti-cancer drugs, and include stupid, pesticides, heavy metals, etc. Another cause that has been explored in recent years is the impact of electromagnetic fields, but some recent large studies have shown that electromagnetic fields do not cause childhood leukemia.
3, leukemia and the relationship between heredity, the survey found that some families occur in more than one leukemia, or several generations of multiple diseases, etc., indicating that the genetic factors of leukemia may lie in these families, but also can not ignore the role of environmental factors, because these families are basically the same environment in the next of kin, it is now generally believed that the occurrence of multiple leukemia in a family line, is due to the combined effect of internal and environmental factors. The study of leukemia in twin fetuses also concluded that twin fetuses are in the same environment, whether intrauterine or postnatal, and that environmental factors have some significance in the development of the disease, so that twin fetuses with leukemia cannot be considered genetic.
In recent years, it has been noted that the incidence of leukemia in certain congenital diseases, especially in people with immunodeficiency, is higher than in the general population. The above hereditary diseases have chromosomal abnormalities and also genetic mutations, and when some mutated leukocytes are produced and the patient’s immune system cannot remove them, these uncontrolled cells keep growing and thus develop into leukemia.
II. Classification of the disease
Acute leukemia is divided into two main categories, acute lymphoblastic leukemia and acute non-lymphoblastic leukemia, also known as acute myeloid leukemia, in childhood leukemia, acute lymphoblastic leukemia accounts for about 70-80%.
Clinical manifestations
The main clinical manifestations of various types of pediatric leukemia are basically similar, and the onset of the disease can be acute or slow.
Initial symptoms
There are a variety of manifestations, such as pallor, anemia, general malaise, fever, loss of appetite, some for unexplained fever, and some with bone and joint pain, some manifestations of local bleeding, nosebleeds, purple skin epilepsy or continuous bleeding after minor surgery, from the above symptoms, pallor and fever are most common.
1, anemia, progressive anemia is one of the prominent symptoms of pediatric acute leukemia, anemia is often manifested as mucous membranes, pale skin and weakness, and even shortness of breath after activity, dyspnea, anemia occurs, mainly due to normal bone marrow is infiltrated by leukemia cells, but the degree of bone marrow involvement and anemia is not completely consistent.
2, fever, fever is more common in pediatric acute leukemia, the fever pattern of children is inconsistent, can be manifested as low fever, irregular fever, persistent hyperthermia, the possible causes of fever are: infection due to bacteria, germs, mycobacteria or protozoa, leukemia cell breakdown metabolites and infiltration of leukemia cells in the hypothalamus.
Bleeding is seen in most pediatric acute leukemia children, with varying degrees of severity. Gastrointestinal bleeding, urinary tract bleeding is often seen in the late stages of the disease, intracranial bleeding is common in the terminal stage, and is one of the main causes of death.
4, bone and joint lesions bone, bone and joint pain and bone marrow lesions are more common in childhood leukemia, bone marrow symptoms often appear in the early stages of the disease, clinical manifestations similar to rheumatoid arthritis, mostly involving major joints, such as lower limb joints and the spine, some children appear lower sternal pressure pain, pain often without redness, swelling, heat symptoms, the length of pain varies, can vary from a few hours to a few days, when the pain is severe, even When the pain is severe, even strong analgesics and sedatives are needed to relieve the symptoms. The cause of bone and joint pain in pediatric acute leukemia is due to the proliferation of a large number of leukemia cells, which increases the tension in the bone marrow cavity, and the leukemia cells infiltrate the bone and penetrate under the periosteum, causing the periosteum to separate. After the infiltration of leukemia cells, the bone is destroyed and pathological fractures occur, etc. On skeletal X-ray, osteoporosis, osteolysis, thinning and destruction of bone cortex, periosteal augmentation and pathological fracture can be seen.
5, lymph node hepatosplenomegaly, lymph node enlargement is more common in the neck, followed by occipital and behind the ear, and general lymph node enlargement is also more common. In children with leukemia hepatosplenomegaly is also a common symptom, especially in acute gonorrhea, hepatosplenomegaly is generally soft in texture, and no pressure pain.
6, skin and mucous membrane damage, leukemia skin changes commonly subcutaneous nodules, oral mucosal ulcers, swollen gums, and sponge-like hyperplasia.
Other systemic involvement
In childhood leukemia, due to the infiltration of leukemia cells into tissues and bleeding, the clinical symptoms of various systemic involvement can be manifested.
1. Central nervous system.
In recent years, with the progress of leukemia treatment, the survival period of leukemia patients is prolonged, and many chemotherapeutic drugs cannot pass the brain barrier, so the leukemia cells remaining in the central system are able to multiply, and central nervous system leukemia occurs. The cerebrospinal fluid pressure and protein are increased, and the white blood cell count is increased, mainly by leukemic cells.
2. Testicular infiltration. In addition to the central reaching system is commonly involved, the testes are also one of the organs often infiltrated, clinical conscious symptoms less unilateral or bilateral testicular enlargement as the main symptom, a few patients have a feeling of swelling and pain, slightly hard local.
3. Kidney is also one of the most frequently involved organs. Clinical changes in urine, hematuria, proteinuria, etc. are often seen.
4. Pulmonary infiltration, clinical symptoms of pulmonary infection are mostly seen.
IV. Diagnosis and differential diagnosis diagnosis
The diagnosis of acute leukemia in children is mainly based on clinical manifestations and laboratory tests, especially based on blood and bone marrow images, and bone marrow primitive cells need to be greater than 30% to confirm the diagnosis of leukemia. In addition, cytomorphological and histochemical examinations are required, and cytoimmunophenotypic, cytogenetic and molecular biological examinations are also very important to confirm the diagnosis.
(i) Blood picture In typical cases, the blood picture shows anemia, thrombocytopenia, and qualitative and quantitative changes in the white blood cells.
1, red blood cells and hemoglobin, nearly 1/3 of children with the disease, hemoglobin is reduced.
2. Platelets, 50-60% of the children have a reduced platelet count, which is more pronounced in advanced stages of the disease.
Nearly 50% of the children have elevated total white blood cells, while 20-30% have normal white blood cells, and about 20% have lower than normal blood cells.
(ii) Bone marrow picture
In children with leukemia, bone marrow aspiration is necessary to confirm the diagnosis, and bone marrow aspiration can confirm the diagnosis.
Differential diagnosis
Acute leukemia needs to be differentiated from certain diseases
1, bone and joint pain, may be misdiagnosed as rheumatoid arthritis and other autoimmune diseases, but generally speaking, rheumatoid arthritis anemia, liver and spleen lymph node enlargement is not very obvious, sometimes bone marrow aspiration is required to identify.
2.Primary thrombocytopenic purple epilepsy.
Clinical bleeding is dominant, skin purple epilepsy, petechiae, sometimes accompanied by gastrointestinal tract, urinary tract bleeding, but the blood picture is often white blood cells, red blood cells normal liver, spleen is not large.
3, infectious diseases, such as infectious mononucleosis and other viral infections, fever, superficial lymph node enlargement, abnormal lymphocytes in the blood picture, but generally speaking, no progressive anemia, thrombocytopenia, positive serum heterophilic agglutination test, the course of the disease is benign self-limiting, some cytomegalovirus infection, toxoplasmosis, etc. can also have fever, lymph node, liver, spleen enlargement, abnormal blood picture, but However, according to the clinical manifestation and evolution, blood and bone marrow examination, it is not difficult to distinguish.
4.Bone marrow metastasis of other tumors with symptoms similar to leukemia, such as neuroblastoma and lymphoma, but can be differentiated by electron microscopy and other pathological examinations.
5.Aplastic anemia
Clinical manifestations and blood changes sometimes resemble leukemia, but enlarged lymph nodes, hepatomegaly and splenomegaly are rarely seen, and bone marrow examination can confirm the diagnosis.
V. MTCM typing
In recent years, MICM typing of pediatric leukemia, i.e., bone marrow cell morphology, immunology, cytogenetics, and from molecular biology, MICM typing can reflect the biological and clinical characteristics of leukemia cells more comprehensively, thus making a more accurate assessment of the disease and prognosis and facilitating the treatment of the disease.
(I) Morphologic typing
1.Pediatric acute lymphoblastic leukemia, FAB typing, divides this type of leukemia into L1, L2, L3
2, pediatric acute non-lymphoblastic leukemia FAB typing as M1 , M2 , M3 , M4 , M5 , M6 , M7.
(II) Immunologic typing
Immunological typing has become one of the basic tools for the study of leukemia, complementing morphological and cytochemical examinations. Although no specific antigens for leukemic cells have been identified clinically, immunological typing can help to identify the acute lymphocyte type (T cells or B cells) and its stage of differentiation, and for morphologically undifferentiated leukemia can help to identify the cell type, diagnose mixed or biphenotypic leukemia, identify acute leukemia from other hematopoietic and nonhematopoietic malignancies.
1. In childhood acute lymphoblastic leukemia, highly sensitive markers are CD19 of the B lineage and CD7 of the T lineage, and highly specific ones are CD19 of the B lineage and CD3 of the T lineage. The application of these cellular immunological markers can make immunological typing diagnosis for 95% of pediatric acute leukemia.
2. Immunophenotyping of acute non-lymphoblastic leukemia (ANLL).
At present, the accuracy of immunophenotyping for ANLL diagnosis can reach more than 90%, and the main immunophenotypes are CD13, CD33, CD15 and CD14.
Among them, CD13 and CD33 have a broader response spectrum.
3. Cytogenetic and molecular genetic typing
80% of acute childhood leukemia have clonal chromosomal abnormalities, of which about 60% are specific chromosomal rearrangements, and the karyotype of leukemia cells is extremely important for diagnosis and prognosis.
Karyotyping has important clinical implications
1, Clonal chromosomal abnormalities contribute to the diagnosis of acute leukemia.
2, Specific chromosomal rearrangements are used for the typing of leukemia.
3, Chromosomal abnormalities can be used as an indicator of remission or relapse of the disease.
4, Independent prognostic indicator.
5, Sex chromosome markers or autosomal polymorphic markers can be used as the basis for AL relapse.
There are three main techniques for molecular genetic typing of leukemia blotting technique, polymerase chain reaction and fluorescence in situ hybridization. The diagnostic purposes of molecular tests for acute leukemia are.
1, molecular diagnosis can identify the characteristics of cell lines when genetic changes in the differentiation process are not phenotypically obvious.
2, Detection of non-random chromosomal aberrations associated with leukemia.
3.Detect the presence of cell clones.
VI. Treatment
Treatment of acute lymphoblastic leukemia in children.
Childhood acute lymphoblastic leukemia can be classified as standard-risk, intermediate-risk and high-risk according to clinical manifestations, cellular morphological features, immunological and cytogenetic manifestations.
Modern treatment of childhood acute lymphoblastic leukemia has made great progress, and according to the experience of treatment in several centers, the chance of long-term survival of childhood ALL has reached 80% or even cured by active treatment. To achieve this ideal goal, it is necessary to use the corresponding strong and weak chemotherapy regimens according to the different risk levels of childhood ALL and follow the principle of early and continuous intense chemotherapy.
Measures for long-term disease-free survival of childhood ALL, as seen in current studies in multiple treatment leukemia centers around the world, chemotherapy is the preferred and primary effective treatment. Chemotherapy for childhood ALL includes.
1.Induction of remission therapy ;
2.Consolidation therapy ;
3, Treatment of extramedullary leukemia;
4.Early intensive treatment ;
5.Maintenance therapy.
Treatment of acute non-lymphoblastic leukemia in children.
In the past 20 years or so, there has been an in-depth understanding of the cell morphology, immunophenotype, cytogenetics and even molecular biology of childhood acute non-lymphoblastic leukemia, and treatment strategies and methods have been improved and innovated. -60%. However, the efficacy of pediatric acute NHL is far less than that of pediatric acute NHL. In the last 20 years or so, the treatment of pediatric acute gonorrhea has improved the remission rate and the long-term disease-free survival rate has improved significantly, however, the main and achievable method for pediatric acute gonorrhea is still chemotherapy. Chemotherapy in children with acute NHL is divided into two phases: remission induction therapy; and maintenance therapy after remission.
VII. Prevention
The incidence of leukemia is about 4 per 100,000, plus various other types of blood patients have a rising trend in recent years, how to prevent the occurrence of leukemia is a cause for concern.
Modern medical research confirms that bad mood is one of the causes of morbidity. From the perspective of Chinese medicine, emotional instability and irritability can cause immune disorders in the human organism, qi stagnation can lead to blood stagnation, qi stagnation and blood stagnation form a lower detoxification function in the body, which then affects the bone marrow and hematopoietic disorders, forming a blood system disease.
Prevention of leukemia can be divided into two aspects: internal and external causes
Internal factors refer to autoimmunity, the enhancement of human immunity, one relies on strengthening physical fitness, that is, through daily exercise, activities, so that physical fitness, physical health and vigor, enhance the ability to resist disease, the second relies on optimism, a positive attitude to life, gas produces a hundred diseases, that is, bad mood is the root cause of disease, since this is the case, we must learn in daily life, calm mood, exclude worries, avoid excessive emotional changes to the body harm.
The external causes of blood disease formation, modern medicine believes that there are environmental pollution, nuclear radiation, improper medication, unknown viruses, etc. Leukemia virus may exist in a variety of normal animals and can be passed on from generation to generation, it has the potential to cause disease, once encountered with external triggering factors can develop. Understanding the internal and external factors of blood disease formation, people have found a way to prevent blood disease, external factors to try to avoid, away from pollution sources, not arbitrary use of drugs, internal factors to regulate their emotions, have a good attitude, positive attitude to life. Now children leukemia, 2 years old – 4 years old children mostly, of which urban children account for about 1/3, resulting in the increase of urban leukemia children do not exclude the causes of pollution caused by home renovation, because the common adhesives used in renovation, paint, floor tiles, plywood, etc. will release formaldehyde, lead, stupid and other harmful substances, causing damage to the human body, the weaker resistance will cause leukemia, according to the survey, the renovation of heat caused by Environmental pollution may be one of the reasons for the increase in children with leukemia. Therefore, it is recommended that the best way to decorate homes to meet the environmental requirements of the system of materials, before moving in, it is best to open the windows to ventilate more than January, ask the professional indoor environmental testing department to test, qualified before living. Second, pay attention to dietary hygiene, because containing fertilizers, pesticides, vegetables, fruits and other food, easy to cause harm to the human body, and thus the onset of disease, so vegetables, fruits to wash before using raw, fertilizers, pesticides and other residues to a minimum. Do not abuse drugs, the use of chloramphenicol, cytotoxic anti-cancer drugs, immunosuppressive drugs to be careful, must have a doctor’s guidance, but also do not use long-term, in addition try not to use hair dye, which causes leukemia is 3-4 times the risk of ordinary people. It is now believed that the effects of light on the human body, some even suggest that the increased incidence of childhood leukemia may be related to exposure to light at night, in addition, care should be taken to stay away from high voltage lines, substations and microwave ovens being used.
Another key to preventing leukemia is to understand some of the early symptoms of leukemia for early detection and timely treatment.
1, unexplained fever, anemia, bleeding, swollen liver and spleen lymph nodes, muscle and joint pain or sternal pressure pain, swollen gum erosion for a long time, purple skin epilepsy, etc.
2. Various kinds of blood cytopenias with unknown causes, long-standing ineffective treatment, and unexplained leukocyte hyperplasia.
3. Severe anemia in children, treated with corticosteroids with significant effect.
4. Leukocytosis, especially with the appearance of immature cells.
Any of the above symptoms, go to the hospital early.
VIII. Care
1. Diet
Parents of patients often ask: Do you want to avoid eating after having leukemia, modern medicine believes that children should not avoid eating, after leukemia patients have the disease, due to the disease itself or the digestive side effects of chemotherapy, appetite is generally poor, often eating very little, the body constantly consumes protein, if not timely replenishment, often affect the growth and development of children, affecting the patient’s internal balance, this should encourage Patients should be encouraged to eat more high-protein, high-calorie, easily digested and absorbed animal protein, more fruits and vegetables, beans and soy products, more varieties, full range, but to limit the intake of fat.
2.Prevent infection
Children with leukemia should pay attention to rest and prevention of infection.
1.Protective isolation, avoid going to crowded public places, visitors, staff should wash their hands carefully before contacting the affected child, living environment to clean to avoid cross-infection, regular disinfection;
2, pay attention to personal hygiene, keep the mouth clean, daily warm water or salt water sitz bath, carefully observe the early symptoms of infection, early treatment;
3, increase nutrition, pay attention to dietary hygiene, give high protein, high vitamin, high calorie diet, fruits should be washed, peeled ;
4, warm help and care for the child, sincere life, build confidence to overcome the disease.