Myelodysplastic syndrome

Introduction to myelodysplastic syndrome Myelodysplastic syndrome (MDS) is a group of heterogeneous clonal disorders originating from hematopoietic myeloid stem cells or pluripotent stem cells. The basic lesions are clonal hematopoietic stem and dysplasia, leading to dysplasia. The risk of ineffective hematopoiesis and malignant transformation is increased. The main features are ineffective hematopoiesis and high-risk evolution to acute myeloid leukemia. The clinical manifestations are abnormal changes in the quality and quantity of hematopoietic cells. The incidence of MDS is about 10/10 million to 12 The population of 100,000 people is more common in middle-aged and elderly people. The cases of 50 years old and above account for 50% to 70%, and the ratio of male to female is 2:1. basic knowledge Sickness ratio: 0.0001% Susceptible people: good for middle-aged and older people over 50 years old Mode of infection: non-infectious Complications: myelofibrosis chromosomal abnormalities systemic vasculitis osteoarthritis recurrent polychondritis dry syndrome rheumatic polymyalgia acute leukemia acute myeloid leukemia

Causes of myelodysplastic syndrome

Congenital factors (30%)

MDS is a clonal disease derived from the level of hematopoietic stem/progenitor cells. Its pathogenesis is similar to that of leukemia. At present, at least two lymphoblastic proliferative diseases, adult T-cell leukemia and cutaneous T-cell lymphoma, have been demonstrated. It is caused by retrovirus infection, and experiments have shown that the pathogenesis of MDS may be related to retrovirus action or (and) cell proto-oncogene mutation, tumor suppressor gene deletion or abnormal expression.

Physical and chemical factors (10%)

Patients often have obvious causes of morbidity, benzene aromatic hydrocarbon compounds, chemotherapeutic drugs, especially alkylating agents, radiation can induce cell gene mutations leading to MDS or other tumors. In addition, MDS occurs mostly in middle-aged and elderly, whether it can reduce cells by age. Internal repair gene mutation function may also be one of the pathogenic factors.

Myelodysplastic syndrome prevention

Although some cases of MDS are unclear, many cases are caused by biological, chemical or physical factors. Therefore, preventive measures should be taken. Medical personnel should recognize the harmfulness of drug abuse and use chemotherapy drugs. Caution; radiotherapy should also strictly control the indications; when dealing with hazardous substances such as benzene and polyvinyl chloride in industrial and agricultural production, labor protection should be done to prevent harmful substances from polluting the surrounding environment to reduce MDS. Onset.

(1) Life conditioning

Non-specific prevention has the effect of enhancing physical fitness, rational arrangement of eating and drinking, proper exercise such as Tai Chi exercise, walking, self-regulation of body imbalance, MDS is closely related to emotions, optimistic mood, and happy spirit to prevent disease Significant.

(two) diet conditioning

It is suitable for diet, can maintain health, prolong life, and can prevent disease. During the treatment of the disease or after treatment, dietary conditioning can avoid further development or recurrence of the disease, which is conducive to physical rehabilitation.

1. Pay attention to the reasonable nutrition of the diet, the intake of meat, eggs, fresh vegetables should be comprehensive, not partial eclipse.

2. Avoid chickens are yang, moving wind, MDS virtual and mixed, toxic poison inside the air, help the fire and wind products should be bogey, especially the yin deficiency fire, bleeding, phlegm and blood stasis, especially pay attention.

3. Cordyceps stewed duck, Cordyceps sinensis, duck 75 grams, 3 slices of ginger, rice wine station, water 200ml, seasoning with salt oil, simmer for 2 hours, soup and meat, treatment of MDS, lack of yin, fatigue, tongue Light red, fine pulse.

(3) Spiritual conditioning

Liver qi stagnation is closely related to the pathogenesis of MDS. Some data suggest that there are more serious mental stimuli for more than half a year before the onset of MDS. Therefore, it is also very important to promote vain, open chest and improve self-cultivation.

Complications of myelodysplastic syndrome Complications Myelofibrosis Chromosomal abnormal systemic vasculitis Osteoarthritis Recurrent polychondritis Sjogren's syndrome Rheumatic polymyalgia Acute leukemia Acute myeloid leukemia

1. Nearly 50% of MDS patients with myelofibrosis have mild to moderate reticular fibers in the bone marrow. Among them, 10% to 15% of patients have obvious fibrosis, which is different from primary myelofibrosis. MDS combined with myelofibrosis in patients with peripheral blood often complete cytopenia, abnormal and broken red blood cells are rare; bone marrow often shows obvious three-line dysplasia, collagen fiber formation is very rare, and often no hepatosplenomegaly, MDS with myelofibrosis Found in various subtypes, some authors believe that it is one of the factors suggesting poor prognosis, and another rare condition called acute myelodysplasia with myelofibrosis (AMMF), acute onset, anemia , bleeding, infection and other symptoms and signs, no hepatosplenomegaly, complete blood loss in peripheral blood, mature red blood cell morphology changes, only a few broken red blood cells, even the original cells, immature granulocytes or nucleated red blood cells, The area of hematopoietic tissue in bone marrow tissue sections is increased, the development of three-line hematopoietic cells is abnormal, fibrosis is obvious, megakaryocytes are increased, and abnormal morphology is very prominent. The primordial cells are moderately increased, but do not form large pieces, clusters, and in a few cases, there are focal thick collagen fibers deposition and focal osteogenesis activity. The patient is in serious condition and often died of bone marrow failure within a few months. Converted to leukemia.

2. In patients with MDS with bone marrow hyperplasia about 10% to 15% lower, the bone marrow smear showed a marked decrease in nucleated cells, and the area of hematopoietic tissue in bone marrow tissue sections was reduced (the hematopoietic tissue area of patients under 60 years old was <30%, 60 years old). Some of the above patients <20%), some authors refer to this condition as hypoplastic MDS (hypoplastic or hypocellular MDS), and considered to be a special subtype of MDS, in fact, this situation is difficult to distinguish from aplastic anemia The following findings help to establish a diagnosis of MDS with low myeloproliferative:

1 dysplastic neutrophils or type I, type II blasts can be seen in the blood;

2 In the bone marrow smear, dysplastic granules can be seen, and erythroid cells can be found in type I and type II primordial cells, especially small megakaryocytes;

3 small megakaryocytes can be seen in the bone marrow sections, early granulocytes are relatively common or ALIP (), reticular fibers increase; 4 bone marrow cells have common clonal chromosomal abnormalities of MDS;

5 can prove monoclonal hematopoiesis, some authors believe that MDS with low myeloproliferative and severe aplastic anemia are the result of immune myelosuppression, but the degree is different, can use immunosuppressive therapy.

3. Concurrent immune diseases In recent years, reports on MDS complicated with immune diseases have been increasing. Immune diseases can occur before the diagnosis of MDS. After, or at the same time, Enright et al analyzed 221 patients with MDS and 30 patients with immune diseases. 13.6%, there are 10 cases of clinical non-immune diseases, but there are serological abnormalities of immune diseases. It has been reported that the immune diseases complicated by MDS are cutaneous or systemic vasculitis, rheumatoid osteoarthritis, inflammatory Enteropathy, recurrent polychondritis, acute febrile neutrophilic dermatitis (AFND, or Sweet's syndrome), necrotizing panniculitis, Hashimoto's thyroiditis, Sjogren's syndrome (Sjogren's syndrome), Rheumatoid polymyalgia, etc., immune diseases can be complicated by various subtypes of MDS, but more often in patients with clonality and complex chromosomal abnormalities, MDS complicated with certain immune diseases (such as Sweet's syndrome), the condition Often rapidly worsening or whitening in the short term, immunosuppressive therapy can control the condition and improve hematological abnormalities in some patients.

4. The most common complication is infection, fever is mainly pulmonary infection, anemia, severe cases can be complicated by anemia heart disease, bleeding mainly in the skin, mucosal and visceral bleeding, joint pain, etc., acute leukemia MDS RA, RAS type The incidence of acute myeloid leukemia was about 13%. The survival time of this group was 50 months. In the MDS, 35%-40% of the RAEB and CMML groups evolved into acute myeloid leukemia. The median survival time was only 14 to 16 months, RAEB-T evolution of acute leukemia, median survival of three months, about 20% of patients with MDS have bleeding, common in the skin, respiratory tract, digestive tract, etc., also have intracranial hemorrhage.

Symptoms of myelodysplastic syndrome Common symptoms Hepatosplenomegaly, fatigue, nosebleed, pale, snot, joint swelling, pain, intracranial hemorrhage, leukocytosis, gingival bleeding, lymphadenopathy

1. Symptoms MDS has no specific clinical manifestations. MDS usually has a slow onset, and a few onsets are sharp. Generally, it is converted from leukemia to leukemia. It is more than 50% within one year and 90% of anemia patients, including pale. Weakness, palpitations after activity, shortness of breath, anemia in the elderly often causes the original chronic heart and lung disease to increase, and fever accounts for 50%, of which unexplained fever accounts for 10% to 15%, manifested as recurrent infections and fever, infection The site is mostly in the respiratory tract, around the anus and in the urinary system. Severe granulocyte deficiency can reduce the patient's resistance. The bleeding is 20%. It is common in the respiratory tract, digestive tract, and intracranial hemorrhage. The early bleeding symptoms are lighter and more For skin and mucous membrane bleeding, bleeding gums or snot, female patients may have menorrhagia, and the trend of late bleeding is worse. Cerebral hemorrhage is one of the main causes of death. Severe thrombocytopenia can cause skin ecchymosis, nosebleeds, bleeding gums. And internal organs bleeding, a small number of patients may have joint swelling and pain, fever, skin vasculitis and other symptoms, more with autoantibodies, similar to rheumatism.

2. Signs of MDS patients are atypical, often pale due to anemia, skin siltation caused by thrombocytopenia, ecchymosis, hepatosplenomegaly accounted for about 10%, very few patients may have lymphadenopathy and skin infiltration, Mostly patients with chronic myelomonocytic leukemia (CMMoL) type.

3. Special types of clinical manifestations

(1) 5q-syndrome: the patient's chromosome 5 long arm is missing without other chromosomal aberrations, mostly in elderly women, clinical manifestations of refractory giant cell anemia, except for occasional blood transfusion, the clinical condition is long-term stable, very Less conversion to acute leukemia, 50% of patients may have splenomegaly, platelets normal or occasionally increased, the most prominent manifestations in the bone marrow are low-lobed or non-lobulated megakaryocytes, often with moderate morbid hematopoiesis, but granulocyte hematopoiesis normal.

There are five important hematopoietic growth factor genes in the long arm of chromosome 5, namely IL-3, IL-4, IL-5, GM-CSF, G-CSF, and GM-CSF receptor gene, 5q-syndrome. How to influence the regulation of hematopoietic growth factors on hematopoiesis is not well understood.

(2) Monomer 7 syndrome: The cytoplasmic change of chromosome 7 occurs mostly in patients who have received chemotherapy before. Monomer 7 rarely appears alone, often with other chromosomal aberrations, and isolated monomer 7 chromosome aberrations. Common in children, can occur in FAB subtypes, most have hepatosplenomegaly, anemia and varying degrees of white blood cells and thrombocytopenia, 25% of patients with mononucleosis, neutrophil surface major glycoprotein reduction , granules, monocyte chemotactic function is weakened, often susceptible to infection, monomer 7 is a poor prognosis indicator, and some patients can develop acute leukemia.

(3) 11q-syndrome: the long arm of chromosome 11 is lost, mostly accompanied by other chromosomal aberrations, most of which are ring-shaped iron granulocytic refractory anemia (RAS) type, with ring-shaped iron granules and iron Increased storage, part of the refractory anemia with blast-producing (RAEB) type, clinically RAS type patients 20% have 11q-, the 11th chromosome long arm break point is reported differently, between q14 ~ q23, q14 break The significance of the point is unknown, but the ferritin H chain gene is known to be adjacent to q14 at q13, and the relationship between the two remains to be studied.

(4) 5q-syndrome: The long arm deletion of chromosome 5 (5q-) is one of the common cytogenetic abnormalities of MDS. It can be seen in various subtypes of MDS. There are two cases in 5q-: one is a single 5q- 5q- is the only karyotype abnormality; the other is complex 5q-, that is, in addition to 5q-, there are other chromosomal abnormalities at the same time. Because of the unique clinical manifestations and prognosis of single 5q-RA and RARS, The 5q-syndrome of MDS is specifically referred to in this case.

5q-syndrome mainly occurs in elderly women, peripheral blood is characterized by large cell anemia, white blood cell count is slightly reduced or normal, platelet count is normal or increased, and the most prominent change in bone marrow is megakaryocyte dysplasia, small megakaryocyte with reduced lobulation The number of cells is obviously increased, and the abnormal development of erythroid cells may not be obvious. There may be ring-shaped iron granule cells. The patient has a chronic clinical process, mainly refractory anemia. Hemorrhage and infection are rare. Generally, anti-anemia treatment is ineffective, but only relying on it. Regular blood transfusion can survive for a long time, the median survival time can reach 81 months, and the whitening rate is extremely low.

(5) iron granulocyte anemia (SA): SA is a group of heterogeneous diseases, the common feature is the heterogeneous heme biosynthesis disorder in young red blood cells due to different reasons, resulting in mitochondria Excessive iron loading, forming iron particles arranged around the nucleus, ie, circular iron granule cells, SA can be divided into three categories: 1 hereditary and congenital SA; 2 acquired SA; 3 by alcoholism and certain drugs The reversible SA, the RARS of MDS belongs to acquired SA, and one of the major subtypes of acquired SA is idiopathic acquired sideroblastic anemia (IASA). Kushner et al. have documented their own IASA cases. The analysis showed that: 1 the young red blood cells were negative for PAS staining; 2 the disease duration was long, and the median survival time was as long as 10 years; 3 the survival curve of the patients was the same as that of the normal population, but not the malignant disease pattern; 4 the whitening rate was very low. (7.4%), whether the RARS of MDS is equivalent to IASA, no specific description in FAB classification and WHO classification, but the author has proposed two types of RARS, one should be diagnosed as MDS, and the other should still be diagnosed as MDS. Should be diagnosed as SA, the identification points of these two categories are shown in Table 1. Shown.

(6) 17p-syndrome: short arm loss of chromosome 17 (17p-) can occur in about 5% of patients with MDS, mostly due to 17p non-equilibrium translocation, but also due to -17, iso (17q) or simple 17p-, 17p- often combined with other chromosomal abnormalities, the tumor suppressor gene p53 is located at 17p13, the 17p- caused by the above various karyotypic abnormalities, the missing regions may not be identical, but all include the p53 gene region, and about 70% In patients with 17p-syndrome, p53 gene is inactivated, indicating that another allelic p53 gene has also been mutated.

The hematology of 17p-syndrome is characterized by dysplasia of granulocyte cells, pseudo-Pelger-Huet nuclear abnormalities in the peripheral blood neutrophils and small vacuoles in the cytoplasm. This change can also be seen in immature granulocytes in the bone marrow. Patients have poor clinical response to treatment and poor prognosis.

(7) CMML: In the early 1970s, Hurdle et al. and Meischer first reported CMML, which is considered to be a chronic myeloproliferative disease (MPD) characterized by normal or increased peripheral blood leukocyte counts. Or young red blood cells, monocytes > 0.8 × 109 / L, bone marrow nucleated cells, may have abnormal developmental morphological manifestations, mainly granulocyte proliferation, mononuclear cells also increased, Ph chromosome negative, may have splenomegaly Later, the FAB collaboration group included MDS as a subtype because of its morphological manifestations of blood cell dysplasia. However, this classification has been questioned because of the obvious MPD characteristics of this disease. Now, in the WHO classification scheme, CMML will be used. The newly added MDS/MPD category has solved this long-standing controversy, but there are some patients with MDS who have no significant increase in peripheral white blood cell count (<13×109/L), but mononuclear The cells are >1×109/L, and there is no hepatosplenomegaly in the clinic. The morphology of blood cell dysplasia in the bone marrow is very obvious, which is completely consistent with the characteristics of MDS. These patients do not have the characteristics of MPD, and obviously should not be classified as CMML. In MDS/MPD, it should still be diagnosed as MDS, Whether it is necessary to separate the MDS subtypes, it is open to question.

(8) aCML: The disease is similar to Ph(+)CML, and the number of white blood cells in peripheral blood is significantly increased. There are >10% of immature granulocytes in each stage, but unlike Ph(+)CML, basophils are absent. Significantly increased, the morphological manifestations of abnormal blood cells in peripheral blood and bone marrow are very obvious, and often three-line dysplasia, Ph chromosome and bcr-abl fusion gene are negative, clinically, the drug response to treatment of CML is poor, the course of disease is better Fast, median survival time is generally <2 years. In the past, the disease was diagnosed as Ph(+)CML. As a variant of CML, the WHO classification protocol development steering committee and the clinical advisory committee discussed that the clinical course of the disease is not chronic. The use of aCML's disease name is easily misunderstood, thinking that it is a chronic disease associated with Ph(+)CML, but failed to agree on a new disease name, and finally decided to follow the name of aCML and classify it into MDS/ Among the MPD categories.

Examination of myelodysplastic syndrome

1. Peripheral blood: Whole blood cell reduction is the most common and basic manifestation of MDS patients. A small number of patients may show anemia and leukopenia or thrombocytopenia in the early stage of the disease. Very few patients may have no anemia and only white blood cells and/or thrombocytopenia. However, as the disease progresses, most of them develop into a complete blood cell reduction. All kinds of cells in MDS patients may have abnormal morphological changes, and a few primitive cells, immature granulocytes or nucleated red blood cells may appear in peripheral blood.

2. Bone marrow: The degree of nucleated cell proliferation is increased or normal, the percentage of blast cells is normal or increased, the percentage of erythroid cells is significantly increased, the number of megakaryocytes is normal or increased, the percentage of lymphocytes is reduced, and the percentage of red, granulocyte and megakaryocyte cells is at least one. There are clear morphological changes in these dysplasias, often involving at least the second line.

(1) abnormal erythrocytosis (dyserythropoiesis): increased red blood cells in peripheral blood, uneven red blood cell size, visible red blood cells (> 2 red blood cells), shaped red blood cells, colored red blood cells, nucleated red blood cells, young bone marrow Red blood cells are megaloblastic, polynuclear cells are multinucleated, nucleus is irregular, nuclear lobes, nuclear buds, nuclear fragmentation, internuclear bridges, cytoplasmic neurites, Howell-Jolly bodies, and ring-shaped iron granules can appear. Mature red blood cell morphology changes with peripheral blood.

(2) abnormal granulocyte production (dysgranulopoiesis): neutrophil granules in peripheral blood are reduced or absent, cytoplasm is persistently basophilic, pseudo-Pelger-Het-like nucleus abnormal, and atypical granulocytes appear in bone marrow (type I, Type II), the granulocyte development of the granulocytes is not parallel, the azurophilic granules are coarse, the regression is delayed, the neutral granules are reduced or absent, the immature granulocytes are giant, the circular nucleus cells are seen, and the mature granulocyte morphology changes with the peripheral blood. The morphological characteristics of the atypical granulocytes are as follows: the morphological characteristics of type I are basically the same as those of normal granulocytes, but the size can be quite different, the karyotype can be slightly irregular, the nucleolus is obvious, there is no granule in the cytoplasm, and the form of type II The characteristics are the same as type I, but there are a few (<20) azurophilic particles in the cytoplasm.

(3) abnormal megakaryocyte formation (dysmegalokaryocytopoiesis): large platelets can be seen in peripheral blood, small megakaryocytes appear in bone marrow (cell area <800m2), including lymphocyte-like small megakaryocytes, small round nuclei (1 to 3 nuclei) Small megakaryocytes, or large megakaryocytes with multiple small nuclei, the common megakaryocytes also have obvious changes in nuclear lobes and cytoplasmic granules. The morphological features of lymphocyte-like small megakaryocytes are as follows: size and appearance and mature lymphoid The cells are similar, the nucleoplasmic ratio is large, the cytoplasm is very small, the nucleus is round or slightly concave, the nuclear chromatin is dense, the structure is unclear, there is no nucleoli, the cytoplasm is strongly alkalophilic, and there are irregular hairy tear edges around or Bubbling.

3. Karyotype analysis

1 karyotype abnormalities: karyotype abnormalities of bone marrow cells in patients with MDS have been reported, among which -5, -7, 8, 5q-, 7q-, 11q-, 12q-, 20q- are more common.

2 sister chromatid differentiation (SCD) delay: using Brdu SCD assay, bone marrow cells cultured in vitro for 56h did not appear SCD phenomenon as SCD-, which is a reflection of cell cycle prolongation, after repeated confirmation by many authors, MDS The presence or absence of chromosomal abnormalities and the type of abnormality in patients is of great importance for diagnostic typing, assessment of prognosis and treatment decisions. Therefore, cytogenetic examination must be listed as one of the MDS routine testing items. In addition, according to our experience, MDS Patient SCD- has a positive value for predicting conversion to leukemia.

4. Bone marrow cells cultured in most MDS patients BFU-E, CFU-E, CFU-MK, CFU-GEMM colonies were significantly reduced or no growth, CFU-GM growth in the following cases:

1 set of drop yield is normal;

2 colonies reduced or no growth;

3 colonies decreased and clusters increased significantly;

4 The colony yield is normal or even increased, accompanied by cell differentiation and maturation in colonies, and becomes a primitive cell colony. Some authors believe that the first two growth patterns suggest non-leukemia growth; the latter two modes suggest leukemia growth, often indicating conversion to leukemia The growth of CFU-GM of RARS, which is mainly red-affected, can be normal.

5. Biochemical examination MDS patients may have serum iron, transferrin and ferritin levels increased, serum lactate dehydrogenase activity increased, serum uric acid levels increased, serum immunoglobulin abnormalities, red blood cell hemoglobin F content increased, etc., these are non-special Heterosexual changes have no important value for diagnosis, but have reference value for assessing patients' condition.

6. Bone marrow biopsy: The original cells are abnormally distributed, and there are aggregated distribution of primordial cells and promyelocytes between the trabecular bone.

7. Bone histochemical staining: erythrocyte glycogen staining was diffusely positive; pathological megakaryocyte glycogen staining was blocky positive.

8. Cytogenetic examination: Ph1 chromosome is negative; other chromosomal abnormalities can be seen.

9. Other authors have suggested some specific subtypes of MDS, such as MDS with eosinophilia (MDS-Eo), abnormal chromatin clumping in leukocyte syndrome (ACCLS), etc. Most of the reports are reported in individual cases. Whether they can form a special subtype remains to be seen.

Pathological examination

1 The area of hematopoietic tissue is increased (>50%) or normal (30% to 50%),

2 Hematopoietic cell localization disorder: erythroid cells and megakaryocytes are not distributed around the central sinus, but distributed in the area of the trabecular bone or trabecular surface; granulocytes are not distributed on the surface of the trabecular bone and distributed in the central area between the trabeculae And have the phenomenon of clustering together,

3 (granulation) abnormal localization of immature precursors (ALIP) phenomenon: protoplasts and promyelocytes form clusters (3 to 5 cells) or clusters in the central region between trabeculae (>5 cells), at least 3 clusters and/or clusters can be seen on each bone marrow slice as ALIP( ),

4 matrix changes: sinus wall degeneration, rupture, interstitial edema, enhanced bone remodeling activities, increased reticular fibers.

According to the condition, clinical manifestations, symptoms, signs, choose to do B-ultrasound, X-ray, electrocardiogram and other tests.

Diagnosis and diagnosis of myelodysplastic syndrome

diagnosis

1. Diagnosis of refractory anemia that cannot be explained should take into account MDS, morphological characteristics of normal or hyperplastic hyperplasia with pathological hematopoiesis. The proportion of blast cells <30% can be diagnosed as MDS, and some are present in juvenile In cases of red blood cells, serum folate and vitamin B12 levels should be examined. Clonal karyotypic abnormalities can further support the diagnosis. Then, blood and bone marrow images are carefully examined to make a subtype diagnosis of MDS.

2. Diagnostic criteria

(1) Diagnostic criteria for classification of classification groups (FAB classification) of France, the United States, and the United Kingdom:

1 refractory anemia (RA): blood: anemia, occasional neutropenia, thrombocytopenia without anemia, reticulocyte reduction, red blood cells and granulocyte morphology may be abnormal, primitive cells no or <1%; bone marrow: Proliferation is active or significantly active, erythroid hyperplasia and pathological hematopoiesis, rarely seen granulocyte and megakaryocytic hematopoiesis, primordial cells <5%.

2 ring-shaped iron granulocyte refractory anemia (RAS): iron staining showed that the ring-shaped iron granules in the bone marrow accounted for more than 15% of all nucleated cells, and the same as RA.

3 refractory anemia with blasts (RAEB): blood: secondary or whole blood cell reduction, more common granulocyte hematopoiesis, blast cells <5%, markedly active bone marrow hyperplasia, granulocyte and erythroid proliferation, three The system has pathological hematopoiesis, and the original cells type I II is 5% to 20%. 4 Chronic myelomonocytic leukemia (CMMoL): The granulocytes in the bone marrow and peripheral blood and the pathological hematopoiesis are the same as RAEB, the original mononuclear The cells were <5%, and the blood was mainly mature monocytes and the number was >1×109/L.

5 RAEB (RAEB-T) in transition: 20% to 30% of the original cells in the bone marrow, the same as RAEB.

The original cells include type I and type II granulocytes, type I: different sizes, no cytoplasmic granules, loose nuclear chromatin, distinct nucleoli, large nuclear/mass ratio, type II: a small amount of azurophilic granules in the cytoplasm The nuclear/mass ratio is small, the nuclear center is the same, and the other is the same type I.

(2) Domestic diagnostic criteria:

1 There are at least two lines of pathological hematopoietic manifestations in the bone marrow.

2 There is a line in the peripheral blood, the second line or whole blood cells are reduced, and even leukocytosis can be seen. There are nuclear red or giant red blood cells and other pathological hematopoietic manifestations.

3 Except for other diseases that cause pathological hematopoiesis such as erythroleukemia, myelofibrosis, chronic myeloid leukemia, idiopathic thrombocytopenic purpura, megaloblastic anemia, aplastic anemia, diagnosis of MDS followed by bone marrow and peripheral blood The percentage of granule + promyelocytes is further divided into RA, RAS, RAEB, RAEB-T, and FAB subtypes. CMMoL is already leukemia and is no longer classified as MDS. From the clinical application of Peking Union Medical College Hospital in recent years, MDS diagnosis still uses FAB. The classification is suitable. The domestic standard replaces the original granules and promyelocytes with the original cells I and II, which makes the proportion of RAEB and RAEB-T in the diagnosis increase.

(3) WHO diagnostic criteria: WHO has developed diagnostic criteria for MDS based on the assistance of some pathologists:

1 refractory anemia (RA).

2 ring iron granulocyte refractory anemia (RAS).

3 refractory anemia with blasts (RAEB); this three types are the same as FAB diagnostic criteria, delete the RAEB-T and CMMoL ditypes in FABA, in addition to the following types.

4 refractory cells with multi-lineage hematopoietic dysfunction, that is, those with hematopoietic dysfunction with two or more pathological hematopoiesis without anemia.

55q-syndrome.

6 can not be classified, refers to MDS that cannot be included in the above types.

3. Evaluation of diagnostic criteria

(1) FAB diagnostic criteria: morphological diagnosis is easy to grasp and popularization is closely related to prognosis and treatment. The disadvantage is that some clinical special types, such as low-proliferation MDS, single-dip reduction MDS, etc., are not included, so the application FAB standard fashion should pay attention to the following points: 1 Pathological hematopoiesis is not simple cell morphology, but also includes cell proportion.

2 The proportion of peripheral blood granules in FAB classification is not as important as the ratio of bone marrow granules. It is necessary to diagnose MDS at least 2 times, and the results of bone marrow puncture in different parts are comprehensively judged.

3 It is not enough to be RAEB-T simply because there are Auer bodies in a few original grains.

4 For a small number of relatively rare MDS should pay attention to their respective characteristics, and should continue to observe the patient changes and then make a diagnosis.

(2) Domestic diagnostic criteria: The original granules + early granules are used as the criteria for judging the deficiencies, and the promyel granules are not related to the prognosis, so that the patient's condition is not overestimated.

(3) WHO standard: WH0 standard classifies RAEB-T into leukemia, but it is clinically different from senile leukemia in terms of cell biology and treatment response. The two are not equivalent. The refractory multi-line cells with pathological hematopoiesis Reduced, can not classify MDS two types, lack of biology, genetics and clinical basis, can not be used as a stand-alone type.

(4) IPSS classification criteria: comprehensive cytogenetics, blood, bone marrow myeloblasts to determine the clinical course and prognosis of patients, more comprehensively reflect the clinical course of MDS, and the most closely related to prognosis, is currently the most classified standard Good, but limited to the use of chromosome technology in many units, and the need for more skilled laboratory personnel to master chromosome technology, its application is limited.

Under the current conditions, it is still easy to grasp and popularize with FAB classification. It is recommended that the grassroots adopt this classification method to facilitate data exchange and comparison. Of course, with the further deepening of the understanding of MDS, comprehensive molecular biology and inheritance will appear in the future. Learning, a new classification standard for clinical multi-angle systems.

Differential diagnosis

The disease should be differentiated from acute myeloid leukemia, myelofibrosis, aplastic anemia, hemolytic anemia, megaloblastic anemia, and non-hematopoietic tumors.

The typical characteristics of MDS are peripheral blood three-cell blood cell reduction, active bone marrow hyperplasia, and more than one line of pathological hematopoietic manifestations in the bone marrow. It is easy to make a diagnosis when it has the above three characteristics, but about 10% of patients with MDS can present with low myeloproliferation. About 1/4 of patients have no obvious pathological hematopoietic manifestations. At this time, they need to be differentiated from megaloblastic anemia, aplastic anemia, hemolytic anemia and other myeloproliferative disorders. The clinically applied differential diagnosis methods are as follows:

1. Comprehensive judgment and differential diagnosis indicators include serum folic acid, Vit B12; Coombs, Ham, syrup, snake venom hemolysis test, detection of CD55 and CD59 negative cells, and other tests for hemolytic anemia; bone marrow radionuclide imaging; cellular immunophenotype ; chromosome; N-ras gene mutation; axl gene expression; hematopoietic progenitor cell culture, such as serum folic acid, Vit B12 normal, hemolysis test negative, accompanied by one or more of the following indicators: chromosomal aberrations, hematopoietic progenitor colony formation Decreased, clustering/colony increased, bone marrow radionuclide imaging peripheral or central hematopoietic tissue normal or decreased but with multiple focal hematopoietic foci, bone marrow mononuclear cells CD34 proportion increased significantly, N-ras gene mutation, axl gene expression Increased, increased erb-A, erb-B expression, etc. support the diagnosis of MDS.

2. Continuous observation of clinical conditions to change the nutritional megaloblastic anemia, paroxysmal nocturnal hemoglobinuria (PNH) may have pathological hematopoiesis but disappear after treatment, FAB subtypes can be transformed into each other during the course of MDS, most cases According to RA or RAS-RAEBRAEB-T sequential transformation, but due to treatment or other unknown factors F can be converted from RAEB to RA or RAS, from RAEB-T to RAEB or RA, the degree of myeloproliferation can also be Proliferative activity is converted to hyperplasia, from hyperplasia to hyperplasia, pathological hematopoiesis in the bone marrow can also be from nothing, from to no, clinically through continuous observation of patients with disease changes, after excluding other diseases, at a certain stage The characteristics of a typical MDS can be diagnosed.

3. The experimental treatment of folic acid supplemented by regular dose for 1 month, Vit B12 and patients without significant anemia can basically eliminate megaloblastic anemia, the application of androgen + immunosuppressive therapy for more than half a year without improvement, most do not support aplastic Diagnosis of anemia, the application of adrenocortical hormone and immunosuppressive agents may be effective in supporting hemolytic anemia or primary thrombocytopenic purpura. The use of the above test treatment combined with other characteristics of the disease can exclude clinically confusing diseases that are easily confused with MDS. It is helpful for the diagnosis of MDS, but a few cases are difficult to identify and require long-term clinical follow-up.

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