myelodysplastic syndrome in the elderly
Introduction
Introduction to myelodysplastic syndrome in the elderly Myelodysplastic syndrome (MDS) is a group of malignant clonal diseases originating from pluripotent hematopoietic stem cells. The main features are: 1 abnormal blood cell development, manifested as bone marrow ineffective and pathological hematopoiesis; 2 malignant clones retain a certain degree of differentiation potential, And the proliferation is relatively slow; the third part is eventually transformed into acute leukemia, mainly acute myeloid leukemia (AML). basic knowledge Sickness ratio: 0.05% Susceptible people: the elderly Mode of infection: non-infectious Complications: anemia, leukemia
Cause
The cause of myelodysplastic syndrome in the elderly
(1) Causes of the disease
The cause of MDS is not clear, but may be related to exposure to benzene, treatment with alkylating agents, ionizing radiation, etc., and some may be derived from aplastic anemia or paroxysmal nocturnal hemoglobinuria (PNH).
The pathogenesis of MDS has not yet formed a complete theory. 30% MDS has mutations in the ras gene. Mutations in the locus lead to activation of the ras gene, which causes malignant transformation of certain cells, produces abnormal proteins, and makes cells by interfering with cell differentiation. Metabolic abnormalities, some cases have C-fas gene mutations, C-fas gene products are M-CSF receptors, receptor defects can affect the proliferation of hematopoietic growth factors in bone marrow, promote the growth of abnormal clones, and eventually develop into MDS.
In recent years, MDS is associated with abnormal apoptosis of hematopoietic cells. Due to the overexpression of apoptotic genes or the reduction or lack of anti-apoptotic genes, hematopoietic stem cells are proliferating, premature differentiation, excessive apoptosis, and ineffective bone marrow formation. Hematopoietic.
The incidence of MDS is multi-stage, and the different manifestations of MDS in clinical findings may be related to different stages of development. In 1982, the FAB collaborative group divided MDS into 5 types:
1 refractory anemia (RA);
2 refractory anemia (RAS) with ringlet iron granules increased;
3 excessive refractory anemia of the original cells (RAEB);
4 primordial cells in transition, excessive refractory anemia (RAEB-T);
5 Chronic myelomonocytic leukemia (CMML), in fact, MDS may only have early, middle, and late points, but no type, each type has a close relationship with each other, some patients with MDS can experience typical The continuous transformation process of RA, RASRAEBRAEBTAML, CMML can be regarded as a special subtype with peripheral blood mononuclear cells. The classification of MDS may actually be different stages of the same disease.
(two) pathogenesis
Cytogenetic techniques have found that 50% of MDS patients have karyotypic abnormalities, and multiple cells have the same abnormal karyotype. Glucose-6-phosphate dehydrogenase (G6PD) isoenzyme studies have further found that MDS patients have only type A blood cells. G6PD isoenzymes, fibroblasts and epithelial cells contain both A and B types. Restriction fragment length polymorphism (RFIP) analysis also showed that MDS is clonal cell proliferation, and a large body of evidence indicates that MDS is a group of 1 An abnormal hematopoietic stem cell-derived clonal disease, even considered to be a malignant clonal disease.
It is believed that the pathogenesis of MDS is due to the above-mentioned possible causes of abnormal expression of oncogenes in pluripotent hematopoietic stem cells, resulting in abnormal synthesis of the corresponding proteins determined by them, which in turn affects the regulation of proliferation and maturation of the cells, showing tumor cloning. Sexual expansion causes damage to the bone marrow pluripotent stem cell pool, resulting in simultaneous hyperplasia and pathological hematopoiesis in the two or three cell lines of the bone marrow, and simultaneous reduction of two or three cell lines in the peripheral blood.
The main pathophysiological changes caused by the clonal expansion of this tumor are ineffective hematopoiesis, which is the main cause of cytopenia, that is, cells in the mature and defective DNA synthesis phase of primitive and relatively naive precursor cells in the bone marrow account for cell proliferation. The proportion of circulating cells is reduced, and the proliferation of hematopoietic progenitor cells and early precursor blood cells is usually still normal or even increased, so that the myeloproliferation is active, but it cannot accumulate a sufficient number of mature cells of each cell series, resulting in peripheral blood cells. The decrease in the number of clinical manifestations of anemia, infection and hemorrhage, in addition, the slight shortening of cell life of each line is also one of the causes of blood cell reduction. The characteristics of RAS patients are due to the primary damage of mitochondria, affecting the utilization of iron. And the production of hemoglobin leads to an increase in the number of blast cells in the bone marrow ring.
A considerable part of MDS will develop into leukemia. In vitro studies have found that the malignant cells of MDS can differentiate and mature, and the dividing cells and the evolved leukemia cells still have the original abnormal karyotype, indicating that even in the MDS, the cloning of leukemia has been established. And it grows faster than normal clones, and can mature. As time progresses, malignant clonal maturity disorders become more and more serious, and eventually become completely incapable of becoming acute leukemia. Some people think that general leukemia is different from MDS-transformed leukemia, general leukemia The target cells are mutated by "one hit" from normal cells and become the only surviving cells; the target cells of leukemia transformed by MDS are less damaged, so that morbid hematopoietic stem cells can survive and replace normal hematopoiesis. Stem cells, to evolve into leukemia, need to be mutated again.
In conclusion, the pathogenesis of MDS may activate certain oncogenes of normal stem cells for certain pathogenic factors, so that a malignant cell (mostly myeloid stem cells or pluripotent stem cells) clonal hyperplasia becomes MDS, and some In this case, the malignant clone is gradually unable to mature and develops to be completely immature, and it becomes leukemia. This leukemia is different from general leukemia.
Prevention
Prevention of myelodysplastic syndrome in the elderly
There is currently no effective underlying treatment for this disease. Therefore, treatment should be treated according to the condition of the individual. Because most of them are old, the general constitution is poor and can not tolerate strong chemotherapy. Therefore, the advantages and disadvantages should be weighed in treatment.
Complication
Complications of myelodysplastic syndrome in the elderly Complications anemia leukemia
Anemia, infection, bleeding, and ultimately into leukemia.
Symptom
Symptoms of myelodysplastic syndrome in the elderly Common symptoms Lack of lymph nodes, splenomegaly, thrombocytopenia, dizziness, hemolytic anemia, sternal tenderness
About 50% of patients are asymptomatic at the time of initial diagnosis; about 30% of patients with MDS complain of fatigue and dizziness due to anemia; some patients have repeated infections and bleeding due to granulocyte or thrombocytopenia and functional defects.
Liver and splenomegaly are more common, mostly mild swelling, some patients have swollen lymph nodes, and a few have sternal tenderness.
Examine
Examination of myelodysplastic syndrome in the elderly
Blood picture
(1) More than 90% of cases Hb<100g/L, anemia is positive cells, positive pigmentation, but a small number of RAS patients are small cell, reticulocytes are normal or reduced, red blood cell morphology is abnormal; sometimes there are nucleated red blood cells.
(2) Half of the cases have leukopenia and neutropenia, and there are morphological abnormalities, and immature granulocytes can appear.
(3) Some patients have thrombocytopenia and may have abnormal morphology and function, showing huge platelets.
(4) About 50% of patients showed a complete reduction in blood cells.
2. Bone marrow
(1) Myeloproliferation is active or extremely active, and bone marrow hyperplasia is reduced in a few cases.
(2) Red blood cells are ill-formed, showing nucleus aberration of young red blood cells, giant and young changes, mature red blood cells of different sizes, abnormal red blood cells, visible spotting and polytropic red blood cells, Hao-week body is easy to see.
(3) Abnormal granulocytes showed immature cell growth and megaloblastic changes, nucleoplasmic development imbalance and Pelger-Huët malformation.
(4) The number of megakaryocytes is normal or increased or decreased, but the morphology is abnormal. The mature megakaryocytes are excessively lobulated or large mononuclear, sometimes see small megakaryocytes, and small megakaryocytes >10% are helpful for diagnosis. Great platelets.
3. Cell chemistry
Granulocyte alkaline phosphatase (NAP) activity decreased significantly, POX activity decreased, erythrocyte glycogen staining was often positive, bone marrow iron and iron granulocytes increased, and ring-shaped iron granules often appeared.
4. Cytogenetics
40% to 70% of patients with primary MDS have chromosomal abnormalities, and the common change is the deletion or increase of chromosomes, such as 5q-, 7q-, +8.
5. Bone marrow cell culture
The colony was reduced, abortion or no growth, the plexus increased, and the proportion of clusters increased.
6. Immunological examination
Peripheral blood may have T helper cells (Tb) decreased, T suppressor cells (Ts) normal or slightly elevated, Th/Ts ratio decreased, NK cells decreased and dysfunction, and approximately 1/3 of patients have elevated polyclonal immunoglobulin .
Bone marrow biopsy: visible erythroid precursor cell maturation disorder, naive precursor cell abnormal localization (ALIP), ie, more than 3 to 5 original and promyelocytes are clustered in the inter-trabecular region and trabecular area, ALIP positive The possibility of MDS being converted to leukemia is high.
Diagnosis
Diagnosis and diagnosis of myelodysplastic syndrome in the elderly
The early diagnosis of MDS is difficult, mainly based on the peripheral blood cell reduction and active bone marrow hyperplasia, accompanied by the pathological hematopoiesis of the three lines of cells, but the pathological hematopoiesis is not unique to MDS, and other kinds of blood diseases can also occur such abnormalities, so Diagnosis of MDS should be cautious, and must exclude other diseases with pathological hematopoies such as chronic granules, myelofibrosis, etc., and should also rule out erythroid hyperplasia such as hemolytic anemia, megaloblastic anemia.
The serum vitamin B12 or folic acid is reduced in patients with megaloblastic anemia. After treatment, the megaloblastic changes quickly disappear. The bone marrow biopsy has no ALIP, which helps to identify. MDS should also be differentiated from atypical aplastic anemia. The latter can sometimes show focal bone marrow. Hyperplasia, but generally no pathological hematopoiesis, multi-site puncture often suggests low bone marrow hyperplasia, bone marrow biopsy without ALIP phenomenon and megakaryocyte morphology, abnormal development.
