pediatric adult chronic myeloid leukemia
Introduction
Introduction to adult-type chronic myeloid leukemia in children In 1845, CML characterized by splenomegaly, anemia and neutropenia was recognized by clinicians. Until the discovery of Ph chromosome in 1960, the understanding of CML was further improved. In 1951, Dameshek first proposed chronic myelogenous leukemia (CML), polycythemia vera, essential thrombocythemia and agnogenic myeloid metaplasia (AMM) are associated with myeloproliferative syndrome, although each Diseases have unique clinical, laboratory, and biological characteristics, but the common feature is the polyclonal proliferation of whole myeloid cells, suggesting that the disease occurs in pluripotent hematopoietic stem cells. CML accounts for 15% to 20% of all leukemias and can be expressed in two types in children's CML: adult CML (ACML) and JMML. JMML is restricted to children and has unique clinical, laboratory and cytogenetic characteristics. basic knowledge The proportion of illness: 0.003%--0.005% Susceptible people: children Mode of infection: non-infectious Complications: optic disc edema
Cause
Causes of childhood adult chronic myeloid leukemia
(1) Causes of the disease
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 In children under the age of CML, CML is a malignant tumor involving hematopoietic stem cell line. It is believed that CML is mainly caused by inhibition of cell apoptosis. Chronic leukemia is less in childhood, accounting for 3% to 5% of childhood leukemia. For chronic myeloid leukemia, the clinical manifestations of chronic myeloid leukemia in children are significantly different from those in adult chronic myeloid leukemia. Therefore, chronic myeloid leukemia in children is generally divided into juvenile and adult types. Type, family, infant type, adult type IV, of which family type and infant type have similar performance, but often occur in close relatives. In 1974 Smith et al. classified children with chronic myeloid leukemia into three types: 1 adult Type; 2 family type; 3 juvenile type.
(two) 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. Department, megakaryocytic and other multi-line involvement, blast crisis can be converted to lymphocytic leukemia, about 85% of children with CML have Ph1 chromosome, ie t (9; 22), for Ph1 chromosome negative, using molecular biology techniques It can be divided into two subtypes: bcr recombination (Ph-bcr CML) and no bcr recombination (Ph-ber-CML). The former clinical symptoms are similar to those of Ph1 chromosome positive, and the latter clinical symptoms are not typical.
Prevention
Adult 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; Rational use of drugs, caution with cytotoxic drugs.
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
Pediatric 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
Infant adult type chronic myeloid leukemia symptoms Common symptoms Liver enlargement Lymph node enlargement Leukocytosis Low heat Eosinophils Increase bone pain Joint pain Edema Edema Skin infiltration
Symptom
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.
Examine
Examination of childhood adult chronic myeloid leukemia
Blood around
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 cultured colonies and clusters of bone marrow increased. Conventional chest radiography, B-ultrasound, electrocardiogram examination, and other selection according to clinical needs.
Diagnosis
Diagnosis and diagnosis of adult chronic myeloid leukemia in children
diagnosis
Leukocyte retention caused by excessive blast cells is common in children with ACML, but the symptoms are mild. 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%, granulocytes.
(2) Ph1 chromosome positive and/or bcr-abl fusion gene negative: 3 items in the following (1) to (4) plus item (5) can be diagnosed, 1 splenomegaly. 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) leukemia reaction, JMML or other: type of myelodysplastic syndrome (MDS), other types of myeloproliferative disorders.
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) Chronic stage staging criteria are: 1 asymptomatic or low fever, fatigue, excessive sweating, weight loss and other symptoms, 2 increased white blood cell count, mainly neutral, young and rodent granulocytes, primordial cells (I II Type) nucleated red blood cells, 3 hyperplasia is extremely active, mainly granulocyte hyperplasia, middle and late granulocyte nuclear granulocytes increase, primordial cells (I II type).
(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 the accelerated period. A few patients develop acute leukemia in a short period of time and often die within a few weeks. About 2/3 of the patients developed an accelerated phase 2 to 3 years after diagnosis. The main manifestations of this period were progressive anemia and bone pain and joint pain due to osteolytic lesions. The following two items have been considered for this period: 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) blast 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 have undergone rapid changes in just a few months after diagnosis. Occasional cases have changed rapidly after more than 10 years. 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
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 ALL ACML acute lymphocyte differentiation is differentiated from Ph ALL. The size of the fusion protein is different. ACML is usually 210KD, and Ph ALL is 185KD. The breakpoint of fusion transcription is detected by reverse transcription PCR. Helping to identify, the response to treatment is also different, ALL patients after chemotherapy, complete remission of Ph chromosome disappeared, karyotype returned to normal.
