adult chronic myeloid leukemia
Introduction
Introduction to adult chronic myeloid leukemia The disease was characterized by splenomegaly, anemia and neutropenia in 1845. CML is recognized by clinicians. CML accounts for 15% to 20% of all leukemias. It can be expressed in two types of CML in children: adult CML (ACML) And JMML, JMML is limited to children and has unique clinical, laboratory and cytogenetic characteristics. The age of onset of adult-type chronic myeloid leukemia is more than 5 years old, more common in 10 to 14 years old, and rarely seen in children under 3 years old. There is little difference between men and women. The incidence of ACML under the age of 20 is less than 1/100,000, 20 to 50 years old is 1/100,000 to 2/100,000, and slowly rises after 50 years of age. The median age at diagnosis is 67 years, and the ratio of male to female is 1.8: 1. basic knowledge Sickness ratio: 0.0001% Susceptible people: no specific people Mode of infection: non-infectious Complications: optic disc edema
Cause
Causes of adult chronic myeloid leukemia
Ionizing radiation (30%):
The etiology of most patients is unknown. Ionizing radiation is the only clear risk factor for ACML. It is reported that among the Japanese nuclear explosion survivors, the incidence of ACML has increased sevenfold, and the incidence of young people is the highest among this group, especially 5 Children under the age of one.
Genetic (30%):
Chronic leukemia is less in childhood, accounting for 3% to 5% of childhood leukemia, mainly chronic myeloid leukemia. The clinical manifestations of chronic myeloid leukemia in children are significantly different from those in adult chronic myeloid leukemia, so it is generally chronic in children. The granulocytic leukemia is divided into juvenile and adult types. In the past, there are also infants, families, infants, and adults. Among them, the family and infants have similar performances, but they are often seen in close relatives. In 1974, Smith et al. classified children with chronic myeloid leukemia into three types: 1 adult; 2 familial; 3 juvenile.
Cell apoptosis is suppressed (30%):
CML is a malignant tumor involving the hematopoietic stem cell line. It is currently believed that CML is mainly caused by inhibition of cell apoptosis.
Pathogenesis
CML has a characteristic Philadelphia chromosome (ph) t (9; 22) (q34.1; q11.21) to fuse the proto-oncogene c-abl on chromosome 9 with the bcr gene on chromosome 22. The bcr-abl chimeric gene is a gene marker for malignant clones. This marker is present in the granulocyte, erythroid, megakaryocyte and lymphoid lines of CML patients, indicating that the lesion occurs at the level of hematopoietic stem cells, and the chimeric gene is transcribed -8.5 Kb mRNA, encoding the fusion protein-P210 bcr/abl, which plays an important role in the pathogenesis of CML by inhibiting the apoptosis delay of leukemia cells. Because it is a malignant proliferation of pluripotent hematopoietic stem cells, the granules are red. Departments, megakaryotes and other multi-line involvement, blast phase can be converted to lymphocytic leukemia.
About 85% of children with CML have Ph1 chromosome, t(9;22), and those with negative Ph1 chromosome can be divided into bcr recombination (Ph-bcr CML) and bcr-free recombination (Ph). -ber-CML) two subtypes, the former clinical symptoms are similar to those of Ph1 chromosome positive, the latter clinical symptoms are not typical.
Prevention
Adult chronic myeloid leukemia prevention
1. Avoid contact with harmful factors. Pregnant women and children should avoid exposure to harmful chemicals, ionizing radiation and other factors that cause leukemia. When exposed to poisons or radioactive materials, various protective measures should be strengthened; avoid environmental pollution, especially indoor environmental pollution; Pay attention to the rational use of drugs, use cytotoxic drugs with caution.
2. Vigorously carry out prevention and treatment of various infectious diseases, especially viral infectious diseases, and do a good job of vaccination.
Complication
Adult chronic myeloid leukemia complications Complications optic disc edema
Visible spleen, liver, swollen lymph nodes, optic disc edema, pulmonary dysfunction, spleen infarction, hemorrhage, extramedullary infiltration.
Symptom
Adult symptoms of chronic myeloid leukemia Common symptoms Lymph node enlargement Joint pain Liver enlargement Penis abnormal osteolytic damage Skin infiltration fatigue High fever bone pain Low fever
1, symptoms
Most patients are in the chronic phase at the time of diagnosis, and the onset is slow. The symptoms and signs are mild at the beginning. Common symptoms include: general malaise, fatigue, weight loss, fever, bone and joint pain, a few patients are asymptomatic, only in routine blood tests. When the number of white blood cells is increased, the disease is diagnosed, severe bone and joint pain, bleeding, unexplained hyperthermia or extramedullary infiltration are more common in the blast phase.
2, signs
(1) Hepatic spleen lymph node enlargement: visible spleen, enlarged liver, mild lymph nodes, full upper abdomen or lumps in the left upper abdomen, about 90% of patients with splenomegaly, varying degrees, under the ribs The spleen is often hard and has a notch. The severe pain in the spleen area or the rubbing sound in the spleen area is a sign of spleen infarction. 50% of patients have mild to moderate hepatic enlargement, and lymph node enlargement is rare.
(2) CNS involvement: retinopathy, optic disc edema, etc.
(3) Skin: A small number of patients have skin infiltration and skin nodules.
(4) Others: pulmonary dysfunction and arthritis, abnormal penile erection can also occur, about 14% of patients are prone to ulcer disease, mostly caused by increased basophils, white blood cell retention due to excessive primordial count The disease is common in children with ACML, but the symptoms are mild.
Examine
Examination of adult chronic myeloid leukemia
1, around the blood
Mainly for leukocytosis, 80% is above 100 × 109 / L, hemoglobin is about 80g / L, thrombocytosis, classification can be seen increased granules, including acidophilia, basophils, granulocyte increase is not obvious, in the middle , young and mature granulocytes.
2, blood test
Leukocyte alkaline phosphatase decreased, HbF did not increase, serum immunoglobulin did not increase, serum and urine lysozyme did not increase, but vitamin B12 and vitamin B12 carrier protein increased.
3, bone marrow examination
Active hyperplasia, mainly granulocyte hyperplasia, granulocytes <10%, mostly medium, late granulocytes and rod-shaped nucleated cells, granule: red is 10 ~ 50:1, some patients can see bone marrow fibrosis, bone marrow megakaryocytes The number of cells increased significantly, mainly in mature megakaryocytes, and the number of cultured colonies and clumps increased.
4, other
Regular chest X-ray, B-ultrasound, ECG, and other options based on clinical needs.
Diagnosis
Diagnosis and diagnosis of adult chronic myeloid leukemia
Diagnostic criteria
The diagnostic criteria commonly used in China are summarized as follows:
1. Domestic diagnostic criteria
(1) Ph1 chromosome positive and/or bcr-abl fusion gene positive: and any of the following can be diagnosed.
1 Peripheral blood: white blood cells are elevated, mainly neutrophils, immature granulocytes >10%, and granulocytes <10%.
2 Bone marrow: The granulocyte is highly proliferated, with neutral young, young, granulocytes and granulocytes, and the original cells (type I II) <10%.
(2) Ph1 chromosome positive and/or bcr-abl fusion gene negative: 3 items plus 5 items in the following 1 to 4 can be diagnosed.
1 spleen.
2 Peripheral blood: white blood cell count continued to increase >30 × 109 / L, mainly neutrophils, immature granulocytes > 10%, basophils increased, blast cells (I II type) <10%.
3 bone marrow: hyperplasia is extremely active, with neutral mesangial cells, late myelocytes, granulocytial growth, primordial cells (I II type) <10%.
4 Neutrophil phosphatase (NAP): reduced score.
5 can exclude leukemia-like reactions, JMML or other types: myelodysplastic syndrome (MDS), other types of myeloproliferative diseases.
2, staging
Clinically, according to the development process of the disease, it can be divided into a chronic phase, an accelerated phase and a blast phase.
(1) The chronic phase staging criteria are:
1 asymptomatic or have low fever, fatigue, sweating, weight loss and other symptoms.
2 white blood cell count increased, mainly in neutral, young and rod-shaped granulocytes, blast cells (I II type) <5% to 10%, eosinophils and basophils, there may be a small number of nucleated red blood cells .
3 hyperplasia was marked to be extremely active, mainly granulocyte hyperplasia, medium and late granulocyte nuclear granulocytes increased, primordial cells (I II type) <10%.
4 has the Ph1 chromosome.
5CFU-GM culture showed a significant increase in colonies or clusters compared with normal.
(2) Acceleration period: The difference between juvenile type and adult type is shown in Table 1.
About 10% of the children in the first year after diagnosis are in an accelerated phase. A small number of patients develop acute leukemia in a short period of time, often dying within a few weeks. About 2/3 of the patients develop an accelerated phase within 2 to 3 years after diagnosis. The main manifestations of this period are progressive anemia and bone pain and joint pain due to osteolytic damage. Those who have the following two considerations have entered this issue:
1 Unexplained fever, anemia, increased bleeding and/or bone pain.
2 spleen progressive enlargement.
3 non-drug-induced platelet progressive reduction or increase.
4 primordial cells (I plus type II) in the blood and/or bone marrow > 10%.
5 peripheral blood basophils >20%.
6 There is significant collagen fibrosis in the bone marrow.
7 There are other chromosomal abnormalities other than the Ph1 chromosome.
8 is ineffective against traditional anti-slow granule drugs.
9CFU-GM has defects in proliferation and differentiation, clustering increases, and the ratio of clusters and colonies increases.
(3) catastrophic period: 75% to 85% of children continue for 1 to 5 years (average 3, 5 to 4, 5 years) into the blast phase, a few cases in a few months after the diagnosis is a sudden change, occasional cases more than 10 years After a sudden change, one of the following can be diagnosed for this period:
1 primordial cells in the peripheral blood or bone marrow (I plus type II) or the original leaching plus young drench, or the original single plus young single > 20%.
2 In the peripheral blood, the primary particles plus promyelocytes are >30%.
3 granules in the bone marrow plus promyelocytes 50%.
4 There is extramedullary primordial cell infiltration. In this period, the clinical symptoms and signs are worse than the accelerated phase. CFU-GM culture grows in small clusters or does not grow. In acute change, the acute marrow changes into the main, including acute granules and urgency. Occasionally, acute red blood changes and acute megakaryocyte changes, etc., acute lymphocytosis accounted for about 20%.
Differential diagnosis
1, leukemia-like reaction
Leukemia-like reactions can be secondary to severe infections, congenital heart disease and metastatic cancer. These diseases are elevated by white blood cells, but generally do not exceed 50 × 109 / L. There are poisonous particles in neutrophils, and basophils are absent. Primitive and immature cells are rare, neutrophil alkaline phosphatase activity is enhanced, cytogenetic examination is normal, no Ph chromosome, molecular biology examination BCR/ABL (-), white blood cell count can be restored after primary disease control normal.
2, Ph's ALL
Acute lymphocyte changes in ACML are distinguished from those of Ph. The size of the fusion proteins is different. ACML is usually 210KD, and Ph ALL is 185KD. Detection of the breakpoint of fusion transcription by reverse transcription PCR also helps to identify. The response to treatment was also different. After chemotherapy, the Ph chromosome disappeared and the karyotype returned to normal.
