pediatric acute lymphoblastic leukemia
Introduction
Introduction to acute lymphoblastic leukemia in children Acute lymphocytic leukemia (pediatricacutelymphoblasticleukemia) is the most common neoplastic disease in children. It refers to a malignant disease caused by clonal abnormal proliferation of precursor B, T or mature B lymphocytes. Leukemia cells originate from the bone marrow. The normal hematopoietic components in the bone marrow are usually replaced by leukemia cells and disseminated by blood, involving extramedullary tissues and organs (such as liver, spleen, lymph nodes, etc.), causing corresponding clinical manifestations. In the past 40 years, especially since the 1980s, great achievements have been made in the basic and clinical research of children's ALL. Children's ALL has become a malignant tumor that can be cured, and it is the most effective and curetable malignant tumor disease. First, it brings confidence and reasonable clinical research mode to the treatment of malignant tumors in other children. At present, the complete remission (CR) rate of pediatric ALL can reach over 95%, and the rate of continuous complete remission (CCR) for more than 5 years can reach 65%-80%. basic knowledge Probability ratio: The disease occurs in children with a 0.001% probability. Susceptible people: children Mode of infection: non-infectious Complications: anemia, sepsis
Cause
The cause of acute lymphoblastic leukemia in children
Environmental factors (30%):
Contact with ionizing radiation is conducive to the occurrence of leukemia. After the atomic bomb explosion in Japan during World War II, the increase in the incidence of local leukemia confirms this. Exposure to therapeutic radiation also increases the incidence of leukemia, long-term exposure to toxic chemicals such as benzene and acute Non-lymphocytic leukemia is associated with other diseases that may be associated with the onset of ALL include herbicides, insecticides, pregnant women, alcohol, contraceptives, tobacco and chemical solvents, but the exact relationship between these factors and the onset of ALL is not yet certain.
Infection factor (20%):
Smith and other studies have found that intrauterine fetal infection in pregnant women can increase the risk of ALL in children under 5 years of age. The mechanism of infection leading to increased risk of ALL may be due to increased dysfunction of the genome caused by infection. Data suggest that Epstein-Barr virus infection may be associated with L3 type ALL. There are also cases of ALL related to HIV infection. Hepatitis A virus infection is associated with high incidence of childhood ALL. Improving public health can reduce maternal infection and neonatal infection, and it will not be neglected to reduce the risk of ALL. The role of breastfeeding can reduce the incidence of infectious diseases in infants, and the correlation between feeding methods and childhood acute leukemia (AL) is different. The current view is that breastfeeding can reduce the risk of childhood leukemia, and other infection-related Factors include immunization, history of animal exposure, history of drug use (eg chloramphenicol), seasonal changes, etc., and their exact relevance to childhood leukemia remains inconclusive.
Congenital gene (genetic) factors (30%):
Early literature reports that the identical twins of 2 months and 14 years of age at the time of diagnosis were confirmed by molecular biological methods. The same fetus from the same cell in the uterus was identical, and the occurrence of identical twins in the same cell was identical or identical. Because the disease has no clinical and biological differences in twins, it has been hypothesized that some of the only child's leukemia may originate in the fetus, and further speculate that additional factors or postnatal environmental factors lead to leukemia at any time after birth. To validate this hypothesis, the researchers used a neonatal blood mark to detect existing clones or patient-specific polyclonal-associated fusion gene sequences (TEL-AML1) and found t(12;21) and TEL non-translocation alleles. The correlation between the deletions is most common in B-lineage ALL. These studies suggest that childhood acute lymphoblastic leukemia is of intrauterine origin. The incidence of leukemia in children with leukemia (including ALL) is 2 to 4 times higher than that of the general population. After leukemia occurs in one of the twins, the chance of another leukemia is as high as 25%; the younger the age of onset, the higher the chance of another onset; When the age of onset is >7 years old, the chance of another onset is significantly reduced, indicating that the occurrence of leukemia can be involved in congenital genetic factors, but the exact genetic factors are not yet clear.
2. Classification: According to morphology, immunology and genetic typing (ie MIC typing), can be divided into several subtypes, treatment and prognosis are closely related to typing.
(1) Morphological classification: At present, the international FAB classification, that is, according to the size of the cells, the proportion of nucleoplasm, the size and number of nucleoli, and the degree of cytoplasmophilia, the acute lymphoblast is divided into three types of L1 to L3 (Table 1). Pediatric ALL is most common in L1 type, accounting for about 70%, L2 is about 25%, and L3 is only 0% to 4%.
(2) Immunological typing: The maturation of leukemia occurs that leukemia is the result of a certain clone of hematopoietic cells being arrested at a certain stage of differentiation and abnormal proliferation, so leukemia cells have corresponding stages of normal cell differentiation. Immunolabeling, internationally named "McAb" by "cluster of differentiation". Currently, ALL is mainly divided into T cell line and B cell line. Child ALL is B cell line. Mainly, accounting for about 80%, B cell line ALL can be divided into several sub-categories, there is no unified standard at present, each family is different, some are divided into 4 types (Table 2), and some are divided into 6 types, T Cytological ALL is generally divided into 3 types (Table 3). Because leukemia cells have "heterogeneity" and "non-synchronization", the expression of immunophenotype is very different. A few patients can express two or two simultaneously or sequentially. The characteristics of the above series, called mixed lineage leukemia (MAL) or hybrid leukemia (HAL), may originate from pluripotent stem cells, generally divided into 3 types: 1 double phenotype : refers to the same white Hematological cells simultaneously express lymphoid and myeloid characteristics, 2 double-type (double-clonal): refers to the simultaneous existence of two independent cell populations with lymphoid and myeloid characteristics, 3 conversion type: refers to leukemia cells from a series Another series of conversions.
(3) Cytogenetic typing: Due to the development of cytogenetics, especially the high-resolution banding technology and the application of molecular probes, the typing of leukemia has been further advanced. It is found that more than 90% of ALLs are clonal. Chromosomal abnormalities, chromosomal abnormalities include quantitative abnormalities and structural abnormalities. Most of the ALL are 46 chromosomes, of which pseudo-diploid is dominant, followed by hyperdiploid, and 1 number is abnormal: A. Hyperdiploid: about ALL 1/4 of the previous B-ALL is more common, although diploid can affect any chromosome, but 4,6,10,14,17,18,20,21 and X chromosomes are the most common, B. false double Body: 46 chromosomes with structural abnormalities, often expressed as chromosomal translocation, more common in L2 type, C. subdiploid: less common, accounting for 3% to 8%, mostly in 45 cases, Generally, chromosome 20 is missing, 2 structural abnormalities: in children ALL, nearly 40 non-random chromosomal structural abnormalities have been found, of which about 50% are chromosomal translocations, and most of them have their gene mapping. For childhood leukemia, comparison Important and common are: At(1;19)(q23;p13): more common Child pre-BALL, the 19p13 E2A gene is a housekeeping gene belonging to the HOX gene family, and the pre-BALL of the E2A/PBXI fusion gene has poor prognosis and therapeutic effect, Bt(12;21)(p13;q22): This is a relatively common chromosomal translocation that has been discovered in recent years. The TEL gene located at 12p13 has a helix-turn-helix structure, which also encodes a transcription factor. The prognosis of ALL with this translocation is better. Unclear, Ct(8;21)(q22;q22) translocation: mainly found in AML-M2, the ETO gene located in 8q22 contains two zinc finger structures, possibly encoding a transcription factor, but currently considered AML1/ETO fusion gene The formation is not a key factor in the pathogenesis of leukemia, there must be other genetic changes to cause disease, Dt (9; 22) (q34; q11): seen in 95% of CML and 3% to 5% of children ALL, this is the most classic The leukemia chromosomal translocation results in the production of a BCR/ABL (break-point cluster region gene, abelson oncogene) fusion gene, which is considered to be the root cause of malignant transformation. In addition, the BCR/ABL fusion gene is also considered to be a detection. An important marker of minimal residual disease (MRD), Et(15;17)(q24;q 21): Found in AML-M3, the PML/RAR fusion gene is formed. AML-M3 with this translocation is sensitive to all-trans retinoic acid treatment. At the same time, PML/RAR is also considered to be an important marker for detecting MRD. F.inv(16)(p13;q22): found in AML-M4Eo, the result of chromosomal inversion results in a CBF/MYHl1 (smooth muscle myosin heavy chain gene) fusion gene, G. Chromosome aberration involving the MLL gene: MLL gene Located at 11q23, also known as the ALL1, HRX, Hrtx1 gene, has many properties of transcription factors and DNA methyltransferases, and its chromosomal aberrations include t(1;11), t(4;11),t(6; 11), t (9; 11), t (10; 11), t (11; 17), t (x; 11), etc., more common in infant leukemia, including ALL, AML and MDS, etc., so called mixed Lineage leukemia gene, children with poor prognosis, because of the numerous chromosomal translocations involved in leukemia, how to quickly and easily detect these distortions has become a clinical problem to be solved, Beijing Children's Hospital has established and began to use multiplex PCR method A new diagnosis of chromosomal translocation in children with leukemia. This method uses 8 parallel PCR reactions and simultaneously detects 29 Leukemia-related chromosome structural aberrations/translocations (including 87 mRNA splice variants), the currently detected aberrations are t(1;19), t(7;10), t(8;21),t( 8; 22), t (12; 21), t (15; 17), TAL1D, dup (11q23) and other 8 chromosome aberrations (13 splice variants).
(4) MIC classification: In April 1985, a MIC collaboration group was formed in Belgium, combining morphological, immunological and cytogenetics to develop MIC classification (Tables 4, 5), (5) Clinical classification. Clinically, ALL is divided into two categories: standard risk (SR) and high risk (HR). In June 1998, Shandong Rongcheng Chinese Medical Association Pediatric Hematology Group "Children's Emergency Leukocyte Treatment Recommendation" classification The following are the following: 1 Risk factors associated with the prognosis of pediatric ALL: A. <12 months of infant leukemia, B. Central nervous system leukemia (CNSL) and/or testicular leukemia (TL) have been diagnosed, C. chromosome The karyotype is t(4;11) or t(9;22) anomaly, D. is less diploid than 45 chromosomes, E. Peripheral blood leukocyte count at diagnosis >50×109/L, F. prednisone Induction test 60mg / (m2 · d) × 7 days, on the 8th day, peripheral blood leukemia cells 1 × 109 / L (1000 / l), determined to be adverse effects of prednisone, G. standard risk ALL induction chemotherapy 6 Those who do not have complete remission (CR) in the week, 2 according to the above risk factors, the clinical classification is divided into 2 types: A. High-risk ALL (HR-ALL): those who have any one or more of the above risk factors, B. Standard risk ALL (SR-ALL): Those who do not have any of the above risk factors, with or without t(12;21) karyotype and high diploid B-line ALL of 50 chromosomes.
(II) Pathogenesis There are many researches on the pathogenesis of leukemia, including studies on molecular genetic changes, prognostic factors, molecular epidemiology and pharmacogenetics. It is speculated that there are two possibilities, namely, acquired genetic damage can activate cells. The initial oncogene or inactivated tumor suppressor gene (anti-cancer gene), both of which can lead to loss of tumor monitoring ability, resulting in uncontrolled proliferation of leukemia cells, these genetic changes can be point mutation, gene amplification, gene deletion Or chromosomal translocations, chromosomal translocations can be seen in many leukemias, translocations can hide a gene into a new position, making a new initial oncogene a promoter or an enhancer on other unique genes, eg at t (8;14) In this chromosomal translocation, the enhancer of the immunoglobulin heavy chain gene is a juxtaposed component close to the MYC gene, resulting in Burkitts lymphoma, which can also occur within two genes, resulting in gene rearrangement. And chimeric proteins, such as t(9;22) translocation found on ALL and CML, mixed linge leukemia (MLL) gene rearrangement and 11q23 abnormality Occur in lymphoid and myeloid leukemia, Ph chromosome can be detected as early myeloid cells or erythroid in Ph chromosome-positive ALL, suggesting ALL patients, in addition to involving the lymphatic system multilineage hematopoietic stem cells.
Prevention
Prevention of acute lymphoblastic leukemia in children
1. Avoid contact with harmful factors: avoid contact with harmful chemicals, ionizing radiation and other factors causing leukemia. When contacting poisons or radioactive materials, strengthen various protective measures; avoid environmental pollution, especially indoor environmental pollution; pay attention to rational use of drugs, caution Use cytotoxic drugs, etc.
2. Vigorously carry out prevention and treatment of various infectious diseases, especially viral infectious diseases, and do a good job of vaccination.
3. Do a good job in eugenics, prevent certain congenital diseases, such as 21-three-body, Fanconi anemia, etc., strengthen physical exercise, pay attention to food hygiene, maintain a comfortable mood, work and rest, and enhance the body's resistance.
Complication
Complications of acute lymphoblastic leukemia in children Complications anemia sepsis
1. Anemia and hemorrhage: anemia is progressively aggravated, palpitations, tinnitus, hemolysis and varying degrees of bleeding may occur, subcutaneous hematoma may occur, retinal hemorrhage may occur, causing vision loss, digestive tract and urinary tract bleeding, intracranial hemorrhage, intracranial Increased pressure, manifested as headache, vomiting, convulsions and coma, etc., digestive tract and intracranial hemorrhage can cause death.
2. Infection: often complicated by infection, easy to spread to sepsis; common infection sites are respiratory system, skin bloated, intestinal inflammation, perianal inflammation, etc., can occur thrush, perianal fungal disease, fungal enteritis and deep fungus Infection, etc.
3. Leukemia cell infiltration: can be complicated by bone marrow failure and systemic organ infiltration, liver and spleen, lymphadenopathy; superior vena cava syndrome; joint swelling and pain, hindering action; central nervous system infiltration can be complicated by central nervous system leukemia It can be manifested as increased intracranial pressure, headache, vomiting, blurred vision caused by optic disc edema, can also cause cranial nerve damage such as facial paralysis, and even epileptic seizures, disturbance of consciousness, etc.; Testicular leukemia; obvious enlargement of the kidney; symptoms of visceral dysfunction caused by skin, gastrointestinal tract, lung, pleura and heart infiltration.
Symptom
Symptoms of acute lymphoblastic leukemia in children Common symptoms Fever relaxation, heat, low heat, blood loss, appetite, withdrawal, blood, tendency to convulsion, shortness of breath, nosebleed, bleeding
The clinical manifestations of various types of acute leukemia in children are similar. The main clinical manifestations are attributed to anemia, hemorrhage, fever and leukemia cells to the organs of the whole body, tissue infiltration caused by symptoms, except for the onset of T-ALL, the general onset is relatively slow. It usually manifests as progressive paleness, fatigue, loss of appetite, night sweats, weakness, low fever and bleeding tendency. It also has symptoms of upper respiratory tract infection, or rash, and then symptoms such as weakness, from onset to diagnosis. For several months, it can also suddenly start, with irregular fever, rapid progressive pale, obvious bleeding symptoms and bone and joint pain embolism as the first performance, the diagnosis can be diagnosed from days to weeks, but most patients are Diagnosis is confirmed within 2 to 6 weeks after onset.
1. Anemia: often appear early, varying in severity, manifested as progressive pale, with obvious skin and mucous membrane mucosa, may appear after exercise, shortness of breath, palpitations, facial edema, weakness and other symptoms, T-ALL due to acute disease Anemia is not serious at the time of diagnosis, and the degree of anemia and bleeding is often disproportionate.
2. Bleeding: Most children have different degrees of skin and mucous membrane bleeding, manifested as skin purpura, black and ecchymosis, and even subcutaneous hematoma, gingival bleeding, nose bleeding, oral mucosal oozing, severe cases may appear Retinal hemorrhage in the fundus, leading to vision loss, increased intracranial pressure, digestive tract and urinary tract bleeding, clinical manifestations of blood in the stool, hematemesis and hematuria, intracranial hemorrhage manifested as headache, vomiting, convulsions and coma, etc., the cause of bleeding in addition to the quality of platelets In addition to the abnormal amount, the infiltration of leukemia cells to the blood vessel wall may increase the permeability, and the T-ALL may occasionally develop DIC, which may be caused by the release of thrombin, kinase and the like from the original T-ALL cells.
3. Fever and infection: More than half of the children have fever, and the heat type is uncertain. The main cause of fever is secondary infection. Most children have different degrees of fever when they are onset, which may be low fever, irregular fever, continuous high fever or relaxation. Heat, temporary hot retreat often sweating, the cause of fever includes neoplastic fever and infectious fever, the former is not effective with antibiotics, and with indomethacin (indomethacin) 0.5mg / kg body weight, oral every 8 hours, Heat can be repelled to identify neoplastic fever and infectious fever. Common infections include respiratory system, sepsis, gums, mouth ulcers, skin swelling, intestinal inflammation, and perianal inflammation. Common pathogens are also common. For Escherichia coli, Pseudomonas aeruginosa, Gram-negative bacilli such as Escherichia coli, Gram-positive cocci such as Staphylococcus aureus and Staphylococcus epidermidis, and other Streptococcus faecalis, Klebsiella, and bacillus Nitrate-negative bacilli, Serratia marcescens, Fusaric acid bacterium and other pathogenic bacteria and anaerobic bacteria, in addition to giant cell inclusion body virus (CMV), herpes virus, Epstein-Barr virus infection, fungi Transfection more common, thrush caused by Candida albicans, fungal perianal disease, fungal disease and deep fungal infections, the aforementioned various infections can occur alone or in mixed infection, or the clinical irregularly remittent usually febrile.
Examine
Examination of acute lymphoblastic leukemia in children
1. Peripheral blood: The change of white blood cells is characteristic of this disease. The total number of white blood cells can be higher than 100×109/L, about 30% is below 5×109/L, the number of white blood cells can be very low in low proliferative ALL, and the peripheral blood is similar. Aplastic anemia, the three lines are reduced, there are no naive cells, high proliferative can be as high as hundreds of thousands, more children can be seen in the peripheral blood of immature cells, the proportion of immature lymphocytes in the classification The diagnosis is different in the morning and evening and the classification. Most of them are more than 20%, and there are more than 90%. A few patients do not have immature lymphocytes in the early stage. The leukemia is classified into lymphocytes, and the peripheral blood is erythroid and myeloid. And megakaryotypes often have abnormal changes of 2 lines, most of the children have anemia, anemia is generally positive cells positive pigmentation, but in severe cases, its MCV may increase, may be due to bone marrow erythropoiesis, reticulocytes are normal or Low, the degree of anemia is different, the incidence is severe, the degree of anemia is light, the platelets are mostly reduced, about 25% are in the normal range, and a small number of children can be ignored and delayed due to the insignificant or abnormal normal peripheral blood. Broken, abnormal peripheral blood can not serve as basis for the diagnosis of leukemia, when the clinical suspicion of leukemia, the need for timely for bone marrow aspiration smears to confirm the diagnosis.
2. Bone marrow (cell morphology) : Bone marrow examination is an important basis for establishing diagnosis and evaluation of efficacy. Most leukemia bone marrow smears are active with nucleated cells, which are active or extremely active, 5% to 10%. Acute leukemia with low bone marrow hyperplasia, called hypoproliferative leukemia, the main basis for the diagnosis of ALL is the sum of the original and naive lymphocytes in the bone marrow nucleated cells 30%, more than 50%, or even more than 90%, some bone marrow Almost all of them are occupied by leukemia cells. At this time, normal erythroid, megakaryocyte cell lines and granules are often inhibited or even disappeared. In addition to the obvious proliferation of leukemia cells, sometimes different degrees of bone marrow fibrous tissue proliferation may be accompanied. Bone marrow fluid is more difficult, called "dry pumping" phenomenon. The typical histochemical staining of ALL bone marrow smear is positive or strong positive for glycogen, negative for peroxidase and negative for non-specific esterase, according to France, USA And British (FAB) morphological classification, ALL is divided into L1, L2, L3 type, 90% of children's ALL morphological classification is L1, cell morphology is small; L3 type tumor cell morphology Similar Burkitt lymphoma cells; L2 uneven cell size, interposed between L1 and L3, not only rely on differential morphology of bone marrow cells and non-Hodgkin's lymphoma ALL bone marrow infiltration.
3. Immunophenotyping : According to the reaction of monoclonal antibody (McAb) on leukemia cell surface differentiation antigen and cytoplasmic immunoglobulin chain, ALL can be divided into two series of T and B.
(1) T-type lymphocyte type (T-ALL): about 10% to 15% of children's ALL, often express T lymphocyte differentiation antigen markers, such as CD1, CD2, CD3, CD4, CD5, CD7, CD8 and TdT, etc. Clinically, it may be accompanied by a widening of the mediastinum and a high white blood cell count in the peripheral blood.
(2) B-type lymphocyte type (B-ALL): about 80% to 90% of children's ALL, can be roughly divided into immature type (in order of developmental maturation, including B lymphocyte progenitor cell, early pre-B lymphocyte sex) And pre-B lymphocyte type) and relatively mature type, cytoplasmic immunoglobulin (CyIg) from scratch, followed by the appearance of cell membrane surface immunoglobulin (SmIg) reflects the development of B cells in the mature direction, SmIg positive Often indicated as relatively mature, other commonly used differentiation antigens of B-series lymphocytes are labeled with TdT, HLA-DR, CD19, CD22, CD10, CD20 and CD24, in which CD20 and CD10 appear later, and the pre-B lymphocyte type appears. Mature B lymphocytic leukemia often expresses smIg as well as B-cell non-Hodgkin's lymphoma cells.
4. Cytogenetic examination : (1) abnormal chromosome number: when the number of chromosomes is <46, it is called low diploid, when the chromosome is <40, the prognosis is poor, and when the chromosome is >46, it is called superdiploid. >50 super-diploids have a good prognosis, (2) abnormal chromosome structure: common relative mature B-cell type ALL chromosomal abnormalities have t(8;14), t(2;8),t(8;22 ), similar to B-cell non-Hodgkin's lymphoma, the common chromosomal structural abnormalities of B-line immature ALL are t(11;v), t(9;22), t(1;19),t(4) ;11), t(12;21), etc., common T-ALL chromosome structural abnormalities are t(11;14), t(8;14), t(10;14),t(1;14)t( 4;11) Etc., modern leukemia diagnosis should include Morphology (M), Immunology (I) and Cytogenetics (C), ie MIC comprehensive diagnosis, ALL should also make a clinically dangerous diagnosis, Guide the choice of clinical treatment options.
5. Cerebrospinal fluid examination : ALL should be routinely used for cerebrospinal fluid examination, including routine cell counting and classification of cerebrospinal fluid, biochemical, centrifugal sputum to find tumor cells, and the National Cancer Institute (NCI) children's ALL central nervous system leukemia (CNSL) diagnostic criteria see Table 6. 6. Clinical risk scores Pediatric ALL has risk factors that significantly affect prognosis, including:
(1) Peripheral blood white blood cell count at diagnosis 50 × 109 / L.
(2) Age 1 or > 12 years old.
(3) There is CNSL at the time of diagnosis.
(4) The karyotype is abnormal in t(9;22) or t(4;11).
(5) prednisone induction test 60mg / (m2 · d) × 7 days, on the 8th day, peripheral blood leukemia cells 1 × 109 / L (1000 / l), or 15 to 19 days of treatment of bone marrow naive lymphocyte proportions still More than 25%, those with the above risk factors 1 are high-risk ALL (HR-ALL), suggesting a poor prognosis, requiring a stronger treatment plan; no one of them is a standard-risk ALL (SR-ALL), Prompt prognosis is good, under reasonable treatment, long-term disease-free survival rate can reach 70% to 85%.
6. Other examinations : prolonged bleeding time may be caused by abnormal platelet mass and quantity. Leukemia can cause prothrombin and fibrinogen to decrease, resulting in prolonged prothrombin time and bleeding, liver function test SAST, mild or Moderately elevated, due to massive destruction of myeloid leukemia cells, resulting in increased LDH.
7. X-ray film
(1) chest X-ray plain film examination: 5% to 15% of children with mediastinal widening and mass, thymus infiltration or mediastinal lymphadenopathy.
(2) Bone X-ray film: About 50% of long bone fragments can be seen in a wide range of bone sparse, and the horizontal or transverse band with reduced density can be seen on the proximal side of the iliac crest, which is the leukemia line. Sometimes there may be worm-like lesions, visible bone. Changes in quality defects and periosteal hyperplasia.
8. Abdominal B-mode ultrasound or CT: Some cases have different degrees of kidney, liver invasive lesions and abdominal lymphadenopathy, bone scan has abnormal concentration of bone infiltration.
Diagnosis
Diagnosis and diagnosis of acute lymphoblastic leukemia in children
Diagnostic criteria
1. Infectious fever: The diagnosis of this disease should be considered for patients with unexplained anemia, hemorrhage, fever, fever that cannot be completely explained by infection, and symptoms of multiple organ infiltration.
2. Anemia, liver, spleen, and swollen lymph nodes: An anemia, liver, spleen, and swollen lymph nodes that are not consistent with the degree of bleeding are found in the physical examination, especially those with parotid gland, testicular and soft tissue infiltrates, and Patients with obvious bone and joint pain should consider the diagnosis of this disease.
3. Laboratory examination: Peripheral blood found 2 series of abnormalities or seeing immature cells should consider the possibility of this disease, further bone marrow smear examination, bone marrow examination is very important for diagnosis, but should pay attention to the distribution of leukemia cells in the body Inhomogeneity, if necessary, multiple sites can be diagnosed.
Differential diagnosis
Clinical diagnosis of ITP, aplastic anemia, neutropenia, infectious mononucleosis, various arthritis, leukemia-like reactions should be thought of this disease, when it is not certain that leukemia is excluded, it should be timely bone marrow puncture The tablet is further clarified and should be identified with the following diseases:
1. Leukemia-like reactions: peripheral blood leukopenia, significantly increased and/or emergence of immature white blood cells called leukemia-like reactions, usually infection, poisoning, tumor, blood loss, hemolysis, drugs, etc., granule, monocytic leukemia There are significant white blood cells in the reaction, and there are immature white blood cells in the peripheral blood. However, the former neutrophil alkaline phosphatase score is significantly increased, lymphocyte peripheral blood leukocytes can be slightly increased, but naive lymphocytes appear, generally speaking After removing the cause of the leukemia reaction, the leukemia reaction can be restored to normal. Moreover, the red blood cells and platelets in the peripheral blood of the leukemia-like reaction are not affected, and the bone marrow has no leukemia-like changes, and the clinically rare cases of leukemia-like reactions are difficult to distinguish from leukemia. Close observation, supplemented by immune, genetic and other methods carefully.
2. Aplastic anemia: bleeding, anemia, fever and whole blood reduction of this disease is similar to leukopenia ALL, easy to be confused with hypoproliferative leukemia, but the liver, spleen, lymph nodes are not swollen, bone marrow hyperplasia is low and no Primitive, the proportion of naive cells increased.
3. Malignant histiocytosis: This disease is a malignant proliferative disease of the mononuclear-macrophage system. It can be clinically characterized by fever, anemia, hemorrhage, liver, spleen and lymphadenopathy, as well as extensive invasive lesions throughout the body. Identification with leukemia, peripheral blood is similar to leukemia, Hb and BPc decrease, more than half of white blood cells are reduced, and immature red blood cells and immature granulocytes can be found, but if malignant tissue cells are found, the disease is highly suggestive, and bone marrow hyperplasia is active or decreased. , reticular cells increase, how many tissue cells can be seen, according to the morphology can be divided into general abnormal tissue cells, mononuclear tissue cells, lymphoid tissue cells, multinuclear giant tissue cells and phagocytic tissue cells, if you see a lot Phagocytic tissue cells and general abnormal tissue cells support the diagnosis of this disease, malignant histiocytosis lacks specific diagnostic means, bone marrow support and clinical non-conformity can not be diagnosed, and vice versa Diagnosis, so the disease relies on comprehensive analysis and diagnosis, sometimes biopsy such as bone marrow and lymph nodes can Children with blood cancer diseases for certain evidence.
4. Infectious mononucleosis: The disease is caused by EB (Epstein-Barr) virus infection, clinical fever, rash, angina, liver, spleen, lymph node enlargement; blood leukocyte increase with lymphocyte elevation Mainly, and the variant lymphocytes often reach more than 10%, the clinical manifestations and bloody signs are easily confused with acute white, but the disease recovers quickly, the bone marrow appears as no proto-lymphocytes, and EBV-specific antibodies such as EBV-VCA-IgM are detected. Can be diagnosed.
5. Rheumatism and rheumatoid arthritis: fever, joint pain, anemia, increased white blood cells and the like are similar to ALL, but the liver, spleen and lymph nodes are not swollen. It is not difficult to distinguish bone marrow examination.
6. Myelodysplastic syndrome (MDS): is a group of hematopoietic and dysfunctional diseases caused by hematopoietic stem cell damage. The disease is mainly characterized by anemia, which may be accompanied by varying degrees of bleeding. Hepatic spleen lymph node enlargement, a few cases also have bone pain, MDS should not only be differentiated from acute leukemia, and 20% to 30% of cases eventually turn into acute leukemia, the bone marrow of this disease is three or two or any Department of pathological hematopoiesis, red ratio such as too high (>60%) or too low (<5%), red blood cells of the ring iron, nuclear lobulation, fragmentation or multinuclear red blood cells, megakaryocytes may appear small lymphoid Giant nucleus, single nucleus small megakaryocyte, multi-nuclear megakaryocyte, etc., granulocyte-mononuclear system can see the increase of primary or young mononuclear cells and morphological changes, but the proportion of primordial cells (or original single singly) is less than 30%, so it can not Diagnosed as acute leukemia, it has been proposed in foreign countries that the diagnosis of ANLL can be clinically considered according to Figure 1, including differential diagnosis with MDS.
