pediatric chronic myeloid leukemia
Introduction
Introduction to pediatric chronic myeloid leukemia Chronic myelogen leukemia (CML) is the first known blood cell disease in leukemia, and its clinical manifestations and hematological examination have its own particularity. Chronic leukemia is less in childhood, accounting for 3% to 5% of childhood leukemia, mainly chronic myeloid leukemia. The disease is characterized by elevated white blood cells and splenomegaly, and is characterized by acute leukemia after sudden changes. CML has significant clinical and biological characteristics in adulthood compared with adult CML, so it can be divided into adult and juvenile types. The pathogenesis of CML is still unknown. It is generally considered that this disease is a pluripotent hematopoietic stem cell disease, and its occurrence is related to certain chemical substances and genetic factors. basic knowledge The proportion of illness: 0.0001%-0.0003% Susceptible people: children Mode of infection: non-infectious Complications: acute respiratory distress syndrome
Cause
Causes of childhood chronic myeloid leukemia
Cloning characteristics (25%):
CML is an acquired disease originating from bone marrow single-plant pluripotent stem cells. Because pluripotent stem cells have the potential to develop into multiple cell lines, CML has heterogeneity when it is rapidly changing, such as acute leaching, acute granulation, and acute variability. .
Cellular dynamics (30%):
The peripheral blood granulocytes in the chronic phase of CML are several times or even hundreds of times the number of normal granulocytes. These cells can be freely circulated in the bone marrow, peripheral blood and spleen. The half-life of CML cells is 5-10 times longer than that of normal human granulocytes. These cells are morphologically incompletely mature granulocytes, and the morphologically fully mature granulocyte half-life is also 2 to 4 times longer than normal. The proliferation rate of CML cells is slower than that of normal people, so prolonged cell life is the main reason for the marked increase of granulocytes in peripheral blood of CML, rather than its proliferation rate. The number of differentiated stem cells in the myeloid line of CML increased significantly in the chronic phase. Therefore, the number of granule-single cell colony forming units (GM-CFU) increased significantly in stem cell culture, which was 10-20 times higher than that of normal people.
Cell growth characteristics (20%):
CML proliferates from a single diseased cell until a large number of CML cells accumulate in the bone marrow, peripheral blood, and spleen, and various mechanisms are involved in this process.
The basis of disease transformation (10%):
When CML starts, more c-abl gene rearrangement occurs in hematopoietic stem cells, forming a pre-neoplastic blood cell clone. The cloning and cytogenetic changes in this transformation process form the Ph1 chromosome to fuse ber/abl, and the fusion gene down-regulates the case. Aminokinase activity, causing apoptosis disorder. Increased instability of genes in these cells and spontaneous errors in DNA replication allow diseased cells to progress in more abnormal directions until another new cytogenetic change occurs. With these changes, cell proliferation and differentiation lose normal relations, abnormal clones inhibit normal clonal growth, and abnormal immature clones are superior.
Prevention
Prevention of chronic myeloid leukemia in children
1. Avoid contact with harmful factors to avoid exposure to harmful chemicals, ionizing radiation and other factors causing leukemia. Those engaged in radiation work should use benzene as a chemical raw material to do personal protection and strengthen preventive measures. Avoid environmental pollution, especially indoor environmental pollution; infants and pregnant women are more sensitive to radiation and vulnerable, women should avoid exposure to excessive radiation during pregnancy, otherwise the incidence of leukemia in the fetus is higher.
2. Vigorously carry out prevention and treatment of various infectious diseases, especially viral infectious diseases. Do a good job of vaccination. Pay attention to the rational use of drugs, use cytotoxic drugs with caution, etc., must be guided by a doctor, do not use or abuse for a long time.
3. Do a good job in eugenics to prevent certain congenital diseases, such as 21-trisomy, Fanconi anemia, etc.
4. Strengthen physical exercise, pay attention to food hygiene, maintain a comfortable mood, work and rest, and enhance the body's resistance.
Complication
Pediatric chronic myeloid leukemia complications Complications, acute respiratory distress syndrome
Often complicated by repeated infections, followed by bleeding tendency, anemia and weight loss. Extramedullary infiltration, liver, spleen, lymph nodes, spleen enlargement can be giant spleen, abdominal pain, bone pain. During the acceleration period, there is often fever, weakness, progressive weight loss, and gradual bleeding and anemia. The drug that was originally effective became invalid. There are obvious laboratory inspection features. Acute prognosis is extremely poor and often dies within a few months.
Can be complicated by xanthoma and eczema-like dermatitis, but also complicated by multiple milk brown rash (common in neurofibroma).
May be associated with other extramedullary infiltrates, resulting in vascular obstruction and corresponding clinical conditions, such as central nervous system symptoms, respiratory distress syndrome, visual impairment. A leukemia crisis can occur.
Symptom
Symptoms of chronic myeloid leukemia in children Common symptoms Fatigue bleeding tends to change fundus and exudation of hepatosplenomegaly, abdominal discomfort, abdominal distension, leukocytosis, unexplained fever
(A) early symptoms: fatigue, fatigue, anorexia, excessive sweating and weight loss. Some patients have upper abdominal discomfort due to splenomegaly compression and bloating after eating.
(2) Hepatosplenomegaly: About 90% of patients have splenomegaly at the time of treatment, and the degree of swelling is often significant. It can be several centimeters below the left costal margin to the flat umbilicus. There is no tenderness in the quality, and a small number of patients may have spleen infarction. Significant abdominal pain and local tenderness and friction sounds. Spleen rupture is rare. The liver is also often swollen, but to a lesser extent. Lymph node enlargement is rare, but it can be used as the first manifestation of early catastrophe.
(C) fever, anemia and bleeding: due to high metabolism can occur low heat weight loss and sweating. Very few infections occur early in the disease. Significant anemia and hemorrhage occur only during the devastating period of the disease.
(D) fundus changes: When the white blood cells are significantly increased, the veins are dilated and filled with distortion. In the course of the disease, there may be retinal and optic nerve head edema, fundus hemorrhage with exudate and nodules.
(5) Others: The sternal tenderness is more common, mostly in the sternum body. Female amenorrhea is more common, and late platelet hypoxia may have vaginal bleeding. An infiltrating mass of the skin, called granulocytic sarcoma. When white blood cells exceed 100,000/mm3, white blood cell stasis can occur, and there is a high viscosity syndrome, which is manifested as tinnitus, dizziness, and even central nervous system hemorrhage or respiratory distress syndrome. Hyperhomocytosis can also occur with a significant increase in basophils.
Examine
Examination of chronic myeloid leukemia in children
Peripheral blood
(1) Chronic phase: mild anemia, the number of granulocytes is significantly increased with left shift, the count is (8.0 ~ 80) × 109 / L, the average is 25 × 109 / L, more than 50 × 109 / L cases more than adults See, smear classification of all stages of cells are visible, but less than fully mature granulocytes less than 15%, the absolute value of eosinophils and basophils increased, and eosinophilic double-stained cells can be seen. The number of platelets is often increased, approaching 500 x 109/L.
(2) Acceleration period: The number of granulocytes decreased, but the proportion of primitive and naive cells increased significantly. The number of platelets decreased. In this period, 50% of patients develop acute leukemia, and another 45% gradually develop into myelodysplastic syndrome-like state.
(3) The blast phase: platelets and hemoglobin decreased further, and the proportion of the original plus naive cells was further increased similar to acute leukemia.
(4) juvenile type: more severe anemia, increased reticulocytes, white blood cell count (15 ~ 100) × 109 / L, thrombocytopenia, white blood cell classification of neutral young, lobular granulocytes, basophilic No increase in granulocytes.
2. The bone marrow characteristics
(1) Chronic phase: The bone marrow is highly proliferated, mainly granulosa, see cells at various stages, mainly middle and late myelocytes and rod-shaped nucleated cells, the proportion of original plus naive cells is less than 5%. Easy to see basophilic and eosinophils. Myelofibrosis is not obvious. Occasionally, lipid-deposited tissue cells resembling high snow cells and navy cells. Histochemical staining showed a marked decrease in leukocyte alkaline phosphatase (AKP) activity.
(2) Acceleration period and blast phase: The ratio of the original plus naive cells in the bone marrow is more than 30%, which is the main basis for rapid changes. The proportion of the original plus naive cells in the accelerated phase is 5% to 30%. 60% to 70% of patients have acute changes to the myeloid system, but peroxidase (POX) is usually negative. Using monoclonal antibody as a surface antigen test, we can find that a small number of megakaryocytes, erythroid and mononuclear cells are also contained in the naive cells. . 30% of patients have a rapid change to the lymphatic system, most of which are pre-B cell type, and very few are T cell type. A small number of cases have a double clone or a polyclonal phenotype, such as a granule-leaf double phenotype (or double clone).
(3) Juvenile type: There is no special morphological abnormality in the bone marrow, and the neutrophilic granulocytes are significantly proliferated, and the erythroid and megakaryocytic systems are reduced.
3. Cytogenetics
Most patients were positive for Ph1 chromosome and the bcr/abl fusion gene (P210) was detected. There are often new chromosomal changes in the blast phase, such as Ph1 replication, 8-trisomy, 19-trisomy, 17q isoforms, and so on.
4. Other
Ph chromosome is negative, fetal hemoglobin is increased (40% to 60%, a few <9%), and hemoglobin A2 is decreased. Regular chest X-ray examination, B-ultrasound examination, CT and other examinations if necessary.
5. X-ray film
Chest radiographs can be found with mediastinal widening and hilar lymph node enlargement. Bone radiographs may have worm-like lesions or osteoblasts of the epiphysis.
6. Abdominal B-mode ultrasound or CT
Some cases may have different degrees of invasive lesions of the kidney and liver and abdominal lymphadenopathy. There is an abnormal concentration of bone scans when there is bone infiltration.
Diagnosis
Diagnosis and diagnosis of chronic myeloid leukemia in children
diagnosis
CML can be diagnosed according to clinical features plus laboratory examination of leukocytosis and reduction of white blood cell alkaline phosphatase.
About 15% of adults have Ph1 chromosomes, and the surrounding blood is mainly leukocytosis, 80% of which is above 100×109/L. Hemoglobin is around 80g/L. Thrombosis. The classification showed an increase in granules, including acidophilia and basophilia. The granulocyte proliferation was not obvious, mainly middle, young and mature granulocytes. Leukocyte alkaline phosphatase is reduced. HbF does not increase. Serum immunoglobulin does not increase. Myeloid hyperplasia is active, mainly granulocyte hyperplasia, granulocytes <10%, mostly middle and late myelocytes and rod-shaped nucleated cells. Grain: Red is 10 to 50:1. Some patients have bone marrow fibrosis. Marrow megakaryocytes are significantly increased, mainly mature megakaryocytes. Serum and urinary lysozyme did not increase, but VitB12 and VitB12 carrier protein increased. Bone marrow culture colonies and clusters increased.
Juvenile type chromosome examinations were mostly normal, peripheral blood leukocytes increased, platelet reduction and moderate anemia. The white blood cells are moderately increased, mostly below 100×109/L. Immature granulocytes and nucleated red blood cells can appear in the surrounding blood and have mononuclear cells. Leukocyte alkaline phosphatase decreased, even normal. Increased lysozyme in serum and urine. HbF increased. Bone marrow: red is 3 to 5:1. Granulocyte and mononuclear hyperplasia are prosperous, and erythroid hyperplasia is abnormal. The original granulocytes are below 20%. Megakaryocytes are reduced. In vitro bone marrow cell culture is dominated by monocytes.
Differential diagnosis
1. Myelofibrosis: There are many nucleated red blood cells, teardrop-shaped red blood cells and debris in the peripheral blood of this disease. Bone marrow puncture is often "dry pumping", bone marrow hyperplasia is low, biopsy for fibrous tissue hyperplasia can be distinguished from slow granules.
2. Leukemia-like reactions: often have primary disease. The number of peripheral white blood cells can be significantly increased, and more than 5% of naive cells can be seen, which is easily confused with slow particles. However, the leukemia-like reaction has a significant increase in alkaline phosphatase scores and no chromosomal abnormalities.
3. Osteoopesis: Adult chronic granules should be differentiated from osteopetrosis, also known as marble disease, characterized by systemic osteosclerosis, progressive anemia, hepatosplenomegaly, and easy fracture. . Family history can often be found. X-ray examination found that the general dense atherosclerosis of the whole body is the basis for diagnosis.
4. Primary thrombocytosis: Clinically, hemorrhage is predominant, white blood cells <50×109/L, platelets are significantly increased, and abnormal platelets are seen. The bone marrow megakaryocytic proliferation is dominant, and the ph1 chromosome is negative.
5. Polycythemia: The patient's skin and mucous membranes are dark red, purple lips, red blood cells are increased, neutrophil alkaline phosphatase is enhanced, ph1 chromosomes are generally negative, and granules have no nucleus pulp development imbalance.
6. Chronic lymphocytic leukemia: more common in the elderly, splenomegaly is not as good as slow granules, white blood cells are usually at 100 × 109 / L, blood and bone marrow are classified into mature lymphocytes, occasionally with primary lymphocytes and young lymphocytes.
7. Infectious mononucleosis: its clinical features are fever, pharyngitis, swollen lymph nodes, increased white blood cell counts in peripheral blood, and thrombocytopenia. The proportion of lymphocytes increased, and the atypical lymphocytes exceeded 10%; the heterophilic agglutination test was positive, and anti-EBV antibodies appeared in the body after infection.
