Introduction:
Chronic myeloid leukemiaThe patient has a "Philadelphia chromosome" (Ph chromosome). There are chromosomes in each nucleated cell, and the Ph chromosome is caused by the cleavage of chromosome 22. There is a crossover between chromosome 9 and chromosome 22 in patients with chronic myeloid leukemia. The chromosome 9 is broken and associated with the "ABL" gene. The chromosome 22 fragment is associated with the "BCR" gene.
When a ninth chromosome is connected to the end of chromosome 22, a BCR-ABL oncogene is formed. The BCR-ABL oncogene controls the synthesis of a protein that causes chronic myelogenous leukemia.
Cause:
Patients with chronic myeloid leukemia have a "Philadelphia chromosome" (Ph chromosome). There are chromosomes in each nucleated cell, and the Ph chromosome is caused by the cleavage of chromosome 22. There is a crossover between chromosome 9 and chromosome 22 in patients with chronic myeloid leukemia. The chromosome 9 is broken and associated with the "ABL" gene. The chromosome 22 fragment is associated with the "BCR" gene.
When a ninth chromosome is connected to the end of chromosome 22, a BCR-ABL oncogene is formed. The BCR-ABL oncogene controls the synthesis of a protein that causes chronic myelogenous leukemia.
symptom:
Chronic leukemia is less in childhood, accounting for 3% to 5% of childhood leukemia, mainly chronic myelogenors leukemia (CML).
The clinical manifestations of CML in infancy are significantly different from those in adult CML, so pediatric CML is generally classified into juvenile and adult. There are also four types of infants, families, infants, and adults in the literature. Family and infants have similar performances, but they are often found in close relatives.
1. Juvenile chronic myogenous leukemia (JCML) This type occurs almost exclusively in children under 5 years of age, especially in infants under 2 years of age. Men have more morbidity than women. Can occur in familial neurofibromatosis, genitourinary malformation or mental retardation in children.
Onset can be urgent or slow, often with respiratory symptoms as the main complaint. More common facial rash or eczema-like rash, even purulent rash, skin coffee spots can also be seen, skin symptoms can occur several months before leukemia cell infiltration. The lymph nodes are swollen and even purulent. Progressive hepatosplenomegaly. It is not uncommon to send blood after thrombocytopenia.
JCML originates from pluripotent hematopoietic stem cells, which can cause erythroid hyperplasia, abnormal platelet count and quantity, and abnormal lymphocyte function. Different from adult type, its abnormal proliferation mainly occurs in the granule single system, and in vitro stem cell culture mainly forms CFU-GM. Most of the chromosome examinations are normal, and -7, +8 (8 trisomy) or +21 (21 trisomy) can be seen individually.
Peripheral blood leukocytes increased, thrombocytopenia 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.
Because JCML often has fever, hepatosplenomegaly, moderate anemia, and leukocytosis, it needs to be differentiated from leukemia-induced infection. It should also be differentiated from infectious mononucleosis.
2. The age of adult chronic myelogenous leukemia (ACML) is more than 5 years old, more common in 10 to 14 years old, rarely seen in children under 3 years old. There is little difference between men and women. Due to the malignant proliferation of pluripotent hematopoietic stem cells, granulocytes, erythroids, megakaryotes, and the like are involved, and the blast phase can be converted to lymphocytic leukemia. More than 85% of children have a Ph1 chromosome (ie t(9:22)). Those with negative Ph1 chromosomes can be divided into two subtypes: bcr recombination (phbcr+CML) and bcr-free recombination (PH-bcr-cml). The clinical symptoms of the former are similar to those of PH1 chromosome positive, and the clinical symptoms of the latter are not typical.
The onset is slow, and the symptoms are mild at the beginning, which is characterized by fatigue, weight loss, and bone and joint pain. Signs can be seen in the spleen, liver enlargement, mild lymph nodes, optic nerve head edema. There are very few bleeding symptoms.
The surrounding blood picture is mainly leukocytosis, 80% 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.
diagnosis:
1. Spleen caused by other causes: schistosomiasis, chronic malaria, kala-azar, liver cirrhosis, hypersplenism, etc. have splenomegaly. However, each disease has its own clinical features of primary disease, and there is no change in CML in blood and bone marrow. Ph chromosome is negative.
2. Leukemia-like reactions: often secondary to serious infections, malignant tumors and other diseases, and have the clinical manifestations of the corresponding primary disease. The number of white blood cells can reach 50×l09/L. There are often poisonous particles and vacuoles in the cytoplasm of granulocytes. Eosinophils and basophils do not increase. The NAP reaction is strongly positive. Ph chromosome is negative. Platelets and hemoglobin are mostly normal. After the primary disease control, the leukemia-like reaction disappeared.
3.Myelofibrosis: Primary medullary fibrosis splenomegaly, leukocytosis in the blood, and the appearance of granulocytes, easily confused with CML. However, the number of peripheral blood leukocytes in primary myelofibrosis is generally less than that of CML, and it does not exceed 30 × l09 / L, and the fluctuation is not large. NAP positive. In addition, the young red blood cells continue to appear in the peripheral blood, and the red blood cell morphology is abnormal, especially the teardrop-shaped red blood cells are easy to see. Ph chromosome is negative. Multiple parts of bone marrow puncture dry pumping. Bone marrow biopsy reticular fiber staining positive.
complication:
When the white blood cell count is >100×109/L, there may be leukocyte stasis syndrome, dyspnea, purpura, organ infarction, fundus vein dilatation, optic nerve head edema, fundus hemorrhage, nerve changes and even central nervous system hemorrhage. Giant spleen can be associated with spleen infarction.
treatment:
1. Principle of treatment: For the treatment of chronic granules, it is not necessary to be rushed. Patients with a white blood cell count below 100×109/L do not need immediate treatment, because the circulation is mainly mature granulocytes, which is smaller than the original cells and has better volume. Deformability, active treatment should be taken when the white blood cell count is above 200×109/L. Currently, cytotoxic drugs are used as chemotherapy. For those symptoms caused by extreme hyperplasia of white blood cells, such as abnormal penile erection, respiratory distress, blurred vision, psychopathy, etc., should be treated with myelosuppressive agents on the basis of acute leukocyte removal.
2. Chemotherapy: Effective drugs are BUS (Maliland), HU (Hydroxyurea), CTX, CLB, 6-MP (6-巯基嘌呤), MMC (Mitomycin). Among them, BUS is the preferred drug, followed by HU. BUS is currently the most effective drug, with a response rate of over 95%. It is convenient to take this medicine. The usage is 2 mg 3 times a day, and it is used until the white blood cells fall below 14×109/L for discontinuation or intermittent administration. The general rule is that the symptoms are improved after 1 to 2 weeks of treatment, and obviously improved after 4 to 6 weeks. When the white blood cells are reduced to 10×109/L, the amount is reduced to 1-2 mg/d, which is maintained for 2 to 3 months. After stopping the drug, if the white blood cell fluctuation is between 10 and 50×109/L, it can be considered to maintain the small dose for more than one year. Leukocytes should be reduced to 5-10 x 109/L platelets below 100×109/L, or there should be a tendency to slow granules to stop. The toxic side effects of Malilan are mainly myelosuppression, especially thrombocytopenia. Individual patients may have a complete reduction in blood cells and a slower recovery, although the dose is small. Long-term use of this drug can cause pulmonary fibrosis and skin pigmentation. Similar to the symptoms of chronic adrenal insufficiency, lack of semen or menopause.
The starting dose of HU was 3 g per day, orally. After use, the number of white blood cells drops rapidly. When it is reduced to about 20 x 109 / L, the dose is reduced to half; when it is reduced to 10 × 109 / L, the dose is further reduced. The maintenance dose is about 0.5 to 1.0 g per day. Generally, the drug is not completely stopped, and the white blood cell count rises rapidly after stopping the drug. The advantage of this medicine is that it is fast; if the white blood cells drop too much, it can rise quickly after stopping the drug; The disadvantage is that regular blood tests are needed to guide treatment. In addition, slow granules can also be treated in combination with α-IFN (α-interferon).
Methods, oral HU2.0 ~ 6.0g / d, while subcutaneous injection. α-IFV 3 million u, iv, 3 times a week, application 8 to 32 weeks. When the white blood cells are reduced to 10 × 109 / L, the HU reduction continues for 1 to 2 weeks, depending on the situation or with a small dose. The HU maintenance amount is 0.5 to 1.0/d, and those who have the condition can continue to use it. α-IFN 3 million u, iv, once a week. The blood routine was checked twice a week during the medication, and the bone marrow was examined every 4 weeks.
3. Radiation therapy: deep x-ray, with deep x-rays to the whole body and local liver and spleen areas and infiltrated parts. The spleen area irradiation dose is 50 cGy, and thereafter 100 to 200 cGy per day or every other day. When the white blood cells fell to 20 × 109 / L, they stopped. Radiotherapy can be used for poor or recurrent chemotherapy. It is reported that its efficacy is not lower than BUS. Radionuclide 32P treatment is only used for poor efficacy of BUS and spleen radiotherapy. The dose of 32P is determined according to the degree of leukocytosis. If the total number of white blood cells is >50×109/L, the starting dose of 32P is 1 to 2.5 mCi, and intravenous injection. After 2 weeks, 1 to 1.5 mCi was used, and the same dose was given once every 2 weeks, and was stopped when the white blood cells fell to 20×109/L. During the remission period, observe once every 1 to 3 months. When the white blood cells are >25×l09/L, you can give 1 to 1.5 mCi.
4. Splenectomy: The spleen may be the first site of chronic granule dysfunction. Resection of the spleen may delay jerk and prolong survival. Surgical indications for resection of the spleen: 1 confirmed as slow-particle; 2 good response to chemotherapy; 365 years of age and no major surgery contraindications. Slow granule catastrophe is a contraindication to surgery.
5. Bone marrow transplantation: Patients aged 45 to 50 years in the chronic phase are transplanted with the same allogeneic bone marrow of the brothers and sisters HLA. Successful transplants generally achieve long-term survival or cure.
6. Other treatments: If the number of white blood cells before chemotherapy is above 500×109/L, you can use a blood cell separator for leukapheresis to rapidly reduce the number of white blood cells and avoid the risk of cerebrovascular accident caused by excessive white blood cells that may block microvessels. At the beginning of chemotherapy, especially when treated with Hu, it is advisable to add 0.1 g of allopurinol 3 times a day to prevent uric acid nephropathy caused by excessive destruction of cells.
7. Treatment of chronic granule blast: The treatment of chronic granule dysfunction is more difficult than the treatment of acute leukemia, and the complete remission is only 10.7%. The current treatment plan for chronic granule blast is as follows: Ara-c (cyclosacidine) 100 mg/m2·d Days 1 to 14; ADM (doxorubicin) 30 mg/m2·d, days 1 to 3; VCR 2 mg, day 1; the above drugs were sequentially intravenously infused. PDN 40mg/m2·d, divided orally, day ～7.
prevention:
[Prognosis prevention]
The prognosis of chronic granules is poor, the median survival is mostly 3 years, and <20% patients have a survival of more than 5 years. Since the development of allogeneic bone marrow transplantation, the prognosis of chronic granules has been significantly improved. Bone marrow transplantation HLA match, the International Bone Marrow Transplant Registry in 1990 reported that the 5-year disease-free survival rate was 45 ± 4% in the chronic phase, 32 ± 6% in the accelerated phase, and 9 ± 6% in the blast phase, indicating the allogeneic bone marrow transplantation. The only effective way to treat chronic particles, but early diagnosis, timely transplantation is the key.
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