Pediatric Myelodysplastic Syndrome
Introduction
Introduction to children with myelodysplastic syndrome Myelodysplastic syndrome (MDS), formerly known as leukemia, is a group of hematopoietic stem/progenitor cells that produce damage, lack of typical clinical manifestations, often anemia, sometimes infection or bleeding, and some cases have hepatosplenomegaly The blood shows a reduction in whole blood cells or a decrease in any one or two lines of cells. Myeloid hyperplasia is active, and the three or two blood cells have significant pathological hematopoiesis. The course of disease is slightly longer. If they do not die from infection or bleeding, they often become leukemia or bone marrow hematopoietic failure. basic knowledge Sickness ratio: 0.0001% Susceptible people: children Mode of infection: non-infectious Complications: ulcerative necrotic stomatitis
Cause
Causes of childhood myelodysplastic syndrome
(1) Causes of the disease
The cause is unknown, but a variety of factors such as patient sensitivity, age, gender, exposure to leukemia and infection before the onset may lead to MDS.
Primary: Children's MDS has little difference in clinical manifestations compared with adult MDS, but the chromosomal changes are mainly monomer 7, followed by the smaller proportion of trisomy 8 and chromosome 3.
Secondary MDS can be induced by exposure to malignant hematological diseases, immunosuppressive therapy, occupational or other causes of exposure to carcinogen-containing environments. Actual secondary MDS and secondary leukemia are different stages of a disease. Diseases caused by chemotherapy or (and) radiation therapy for MDS/AL include Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma, and ovary. Cancer, lung cancer, breast cancer, testicular cancer, digestive tract cancer, brain cancer, polycythemia vera, etc. About one-third of children with MDS are secondary to genetic abnormalities with MDS/AML predisposition. These children have early onset of MDS, mostly less than 2 years old.
(two) pathogenesis
The presence of proto-oncogene mutations in MDS, abnormal culture of bone marrow in vitro, and cytogenetic variation all suggest that the disease belongs to a clonal disorder. By measuring glucose-6-phosphate dehydrogenase (G-6-PD) isoenzymes in female patients with RAS, it was found that only red blood cells, granulocytes, platelets, macrophages, and B and T lymphocytes have type A isoenzymes. To confirm the clonality of the disease.
MDS eventually evolved into granulocyte leukemia, and a few evolved into lymphocytic leukemia. As for how MDS evolved into leukemia, scholars have discussed a lot. In general, it is believed that MDS may evolve into leukemia in many forms, which can be derived from the original pathological hematopoiesis. The cloning gradually cannot differentiate and mature, and the primordial cells gradually increase. Finally, the blood cells are mainly composed of primitive cells, and then become leukemia. At this time, the blood cells still retain the original abnormal karyotype, no new abnormal karyotype, and can also be ill-conditioned. Hematopoietic clones re-mutate and evolve into leukemia, a new abnormal karyotype.
In children with MDS, 40% to 45% of RAEB and RAEK-T are converted to leukemia, but the conversion of RA and RAS to leukemia is only seen in 5% to 15%. The Department of Internal Medicine, Düsseldorf Hospital, Germany, diagnosed MDS at 0.29% from 1975 to 1988. Odense in Denmark investigated the incidence of MDS in children, aged 0-14 years, with an annual incidence of 0.27/105. MDS accounted for 8.7% of malignant hematological diseases in the same period.
Prevention
Prevention of pediatric myelodysplastic syndrome
Avoid inoculation of various chemical substances, ionizing radiation, viruses and other harmful factors causing leukemia, avoid environmental pollution, especially indoor environmental pollution, use cytotoxic drugs with caution, phenylbutazone, chlorpromazine chloramphenicol and so on. Do a good job in eugenics to prevent certain congenital diseases, such as 21-trisomy, Fanconi anemia, etc.
If there is pale, bleeding, fatigue, fever, bone pain, should go to the hospital for treatment in time, blood tests should be carried out in accordance with the doctor's advice, if necessary, follow the doctor's advice to do bone marrow examination and bone marrow biopsy, in order to be able to diagnose and treat in time.
Mds is closely related to emotions. Emotional optimism and mental agility are very meaningful for disease prevention.
Complication
Pediatric myelodysplastic syndrome complications Complications ulcer necrotic stomatitis sepsis
Severe visceral hemorrhage such as urinary tract, digestive tract, respiratory tract and central nervous system bleeding, especially intracranial hemorrhage often endangers children's life; if repeated blood transfusion can cause hemosiderosis.
Often complicated by infection, mild can have persistent fever, weight loss, loss of appetite, repeated oral mucosal ulcers, necrotizing stomatitis and angina, can be complicated by sepsis, infection and more bleeding and death.
Liver, spleen, swollen lymph nodes, etc. Children with severe anemia and children with growth retardation.
Symptom
Symptoms of children with myelodysplastic syndrome Common symptoms Whole blood cell reduction Lymph node swelling Granulocyte reduction Hepatosplenomegaly
Children's MDS can be found in any age range from infant to adolescence. According to Beijing Children's Hospital, the minimum is 5 months and the maximum is 13 years old. The incidence of boys is slightly more than that of girls. The symptoms are mainly anemia, hemorrhage, fever, infection and liver and spleen. Swelling, the majority of patients have anemia, but to a lesser extent, mainly due to the ineffective formation of red blood cells, the incidence of bleeding is 23% to 95%, mostly lighter skin, mucosal bleeding, the disease progresses to the late stage There may be severe bleeding, and even cerebral hemorrhage and death. The incidence of fever and infection varies from 50% to 60%, and increases with the progression of the disease. The cause of infection is neutropenia and Functional changes and decreased immunity of the body, 10% to 76% of liver, spleen, lymph nodes, but rare in RA subtype, liver is more common than the spleen, there are fewer lymph nodes, in short, MDS The clinical manifestations vary widely. Generally, the symptoms of RA and RAS are mild, and gradually increase with the progression of the disease.
1. Any blood in the peripheral blood or any secondary or whole blood cells, even leukocytosis, visible nucleated red blood cells or giant red blood cells or other pathological hematopoiesis.
2. Bone marrow like bone marrow has three or two lines or blood cells of any line are pathological hematopoiesis.
3. Except for other diseases with pathological hematopoietic manifestations.
4. Classification according to specific classification criteria.
Examine
Examination of children with myelodysplastic syndrome
Blood test
Blood: more than 90% have anemia, 50% of whole blood cells decrease. Hemoglobin F can be increased. Platelets are slightly reduced, occasionally elevated. Most patients with white blood cells <5×109/L, and half of the patients have absolute neutrophil counts <2×10 9 /L. Leukopenia has a higher proportion of lymphocytes.
Blood smear: red blood cells are large cells or positive cells, red blood cells are too large, MCV is often >95/fl. The cells vary in size, occasionally with giant red blood cells (diameter > 2 times normal red blood cells). Visible red blood cells, dot-colored cells, HJ bodies and nucleated red blood cells, often Pelger-Hut leukocyte abnormalities and ring-shaped nucleated cells, specific or reduced cytoplasmic specific particles. Immature granulocytes and degranulation can be seen. Platelet size is uneven on blood smears, occasionally huge platelets, and some patients have loose platelets that cannot aggregate into clusters. Individual patients have lymphoid small megakaryocytes or single-nuclear small megakaryocytes.
2. Bone marrow examination
Bone marrow: active bone marrow hyperplasia, red blood cell line giant young and obvious, showing "old pulp young nuclear", multi-nuclear, nuclear fragmentation and nuclear form strange, dual-nucleus especially odd-numbered nuclear red blood cells and giant red blood cells are characteristic. Granule maturity is stagnant, nucleoplasmic development is imbalanced and binuclear cells are common. The RA and RAS red systems are hyperproliferative, the granule system is relatively reduced, the granule/red is reduced or inverted, but the neutrino is increased. At RAEB-T, the granulosa system may increase and the red system may decrease. The nucleated cells in each stage can be seen as binuclear, and the binuclear cell bodies are about twice as large as normal, which is characteristic of MDS diagnosis. Increased monocytes. The number of megakaryocytes is mostly increased or normal, and about one-fourth of patients have reduced megakaryocytes. The morphologically distinct lymphoid megakaryocytes, single-nuclear small megakaryocytes, multi-nuclear megakaryocytes, large single-nuclear megakaryocytes, binuclear megakaryocytes or multi-lobed megakaryocytes can be seen. Among them, lymphoid small megakaryocytes are the most characteristic.
Bone marrow biopsy: The abnormal location of the granulocyte premature cells (AL-IP) can be seen. More common in primordial refractory anemia (RAEB), transformed primordial refractory anemia (RAEB-T) and chronic myelomonocytic leukemia (CMML). ALIP positive patients have a short survival period. The ALIP phenomenon is sometimes seen in bone marrow smears.
Bone marrow histochemical staining: neutrophil peroxidation plum, alkaline phosphate plum decreased, monocyte non-specific lipume, acid phosphate plum decreased, iron red blood cells increased.
3. Chromosome examination
50% of patients have chromosomal abnormalities, such as -7, +8 and 5q-, etc., and those with abnormal karyotype are more likely to be transformed into leukemia. The chromosomal changes in children are mainly monomer 7, followed by the changes in the smaller proportion of trisomy 8 and chromosome 3.
4. Progenitor cell culture
The bone marrow progenitor cells were cultured in vitro, and some were similar to the growth of leukemia cells. The colony formation of CFU-GM, CFU-MK and CFU-E was low or absent. Small plexus type, no growth type and obvious increase in clumping ratio were pre-leukemia growth type, indicating poor prognosis.
1 multi-directional progenitor cells (CFU-MIX): more often showed poor growth, suggesting that MDS lesions start from pluripotent stem cells.
2 capsules - single progenitor cells (CFU-GM): Most of them were colonies, clusters increased, and clusters and colonies increased.
3 erythroid progenitor cells (CFU-E and BFU-E): It is believed that both CFU-E and BFU-E are reduced, and BFU-E is not increased after T cells are removed in culture: indicating a decrease in MDS erythroid progenitor cells Not due to the inhibition of T cells.
4 megakaryocyte progenitor cells (CFU-MK): its growth has a certain relationship with FAB typing. The CFU-MK of RA and RAS grew well, about half of the colonies were normal, and most colonies of RAEB, RAEBT and CMML decreased or did not grow.
5. Other
The use of CD41 monoclonal antibody for immunoenzymatic labeling of bone marrow smear or bone marrow sections can increase the detection rate of pathological megakaryocytes. Regular X-ray and B-ultrasound examinations, if necessary, do CT examinations.
Diagnosis
Diagnosis and diagnosis of children with myelodysplastic syndrome
diagnosis
Diagnosis is based on clinical performance and examination.
Differential diagnosis
Aplastic anemia: It is a kind of incompleteness of bone marrow hematopoietic function caused by various reasons. It is more common in children. The main symptoms are anemia, hemorrhage and repeated infection. A group of comprehensive symptoms of complete hematocytopenia and no enlargement of the liver, spleen and lymph nodes. The RA of MDS is characterized by chronic progressive anemia, which can be delayed for several years without any obvious liver and splenomegaly. The blood picture can be reduced by whole blood cells. In some cases, the bone marrow hyperplasia is also reduced. These are very similar to aplastic anemia, especially chronic aplastic anemia, and karyotyping helps to distinguish between the two.
Megaloblastic anemia
A biochemical disorder in the synthesis of DNA (DNA) and a disease caused by a slowing of DNA replication. Affects bone marrow hematopoietic cells - red blood cell line, granulocyte cell line and megakaryocyte cell line to form anemia, and even complete blood cell reduction. The characteristics of bone marrow hematopoietic cells are that the development and maturation of the nucleus and cytoplasm are not synchronized. The former is slower than the latter, and the result is a cell with abnormal morphology, quality and quantity, and function, that is, a giant young change of cells. MDS bone marrow red system sometimes has giant morphological changes, so it is easy to be confused with megaloblastic anemia. However, in the MDS, blood folic acid and vitamin B12 increase, while megaloblastic anemia is reduced in folic acid or vitamin B12. MDS treatment with folic acid or vitamin B12 is ineffective, while megaloblastic anemia is effective.
Hemolytic anemia
It is a kind of anemia that occurs when the red blood cell destruction is accelerated by various causes, and the bone marrow hematopoietic function is insufficient. The life span of normal red blood cells is 110 to 120 days. Under normal circumstances, about 1% of aging red blood cells are swallowed and destroyed in the spleen every day, replaced by new red blood cells, so as to maintain a constant number of red blood cells to play a normal physiological function. The MDS red bone marrow red system is increased, sometimes the pathological hematopoiesis is very significant, and the reticulocytes in the blood are slightly increased, which is very similar to hemolytic anemia. MDS can have abnormalities in karyotype, but hemolytic anemia is rare. In addition, hemolytic anemia may have a corresponding cause, such as Coombs test positive, Ham test positive, etc., and most negative in MDS. After treatment, the reticulocytes of the MDS rise first, then the hemoglobin rises, while the hemolytic anemia decreases after the treatment, and then the hemoglobin rises.
Idiopathic thrombocytopenic purpura (ITP)
Children and young people are more common because of a large decrease in platelets, which causes skin, mucous membranes, hemorrhage, snot, bleeding gums and menorrhagia. The ratio of male to female is 1:2. The megakaryocytes of the MDS bone marrow are increased (small megakaryocytes), and the ITP megakaryocytes are also increased. Therefore, sometimes the two are mixed, but whether it is effective for prednisone according to clinical treatment, whether the bone marrow image has significant pathological hematopoiesis, and whether the chromosomes are abnormal or not. Distinguish the two diseases.
Myeloproliferative diseases and non-hematopoietic malignancies
Such as chronic myeloid leukemia, polycythemia vera, essential thrombocythemia and myelofibrosis, bone marrow has pathological hematopoiesis, except in the diagnosis of MDS. Some patients have malignant tumors of non-hematopoietic tissue. Anemia occurs before the tumor is not revealed. Some pathological hematopoiesis can also be manifested in the bone marrow, but it is not as significant as the pathological hematopoiesis of MDS.
