Introduction
Myelodysplastic syndrome(myelodysplastic syndrome, MDS) is a group of heterogeneous clonal disorders originating from hematopoietic myeloid stem cells or pluripotent stem cells. The underlying lesions are clonal hematopoietic stem and dysplasia, leading to ineffective hematopoiesis and malignancy. The risk of conversion 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 12/100,000 people, mostly involving middle-aged and elderly people, 50% to 70% of cases over 50 years old, and the ratio of male to female is 2:1. MDS 30% to 60% is converted to leukemia. In addition to leukemia, most of the causes of death are due to infection, bleeding, and especially intracranial hemorrhage.
Cause
(1) Causes of the disease
The cause of MDS is still unclear. It is speculated that due to biological, chemical, or physical factors, genetic mutations cause chromosomal abnormalities to cause clonal proliferation of a malignant cell. It has been recognized that mutagens such as viruses, certain drugs (such as chemotherapeutics), radiation (radiotherapy), industrial reactants (such as benzene, polyethylene) and environmental pollution can cause carcinogenic effects. Mutagens can cause chromosome weight. Rows or gene rearrangements may also cause only changes in gene expression leading to MDS. However, it has been confirmed from cell culture, cytogenetics, molecular biology and clinical studies that MDS is a clonal disease derived from the level of hematopoietic stem/progenitor cells. The cause of the disease is similar to that of leukemia. At least two lymphoblastic proliferative diseases, adult T-cell leukemia and cutaneous T-cell lymphoma, have been shown to be caused by retroviral infection. Experiments have also 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. A common proto-oncogene involved in the pathogenesis of MDS patients is the N-ras gene. The Ras gene family is divided into three types: H, N, and K. The most common mutation in NDS is N-ras gene mutation, which occurs in exons 12, 13, and 61. The expression of N-ras gene encoded protein is abnormal after interference. The normal cell proliferation and differentiation signals lead to abnormal cell proliferation and differentiation. There are also reports of abnormal expression of p53 and Rb tumor suppressor genes in patients with MDS, but these genetic changes are more common in MDS than in advanced RAEB and RAEB-T patients, and less in early RA and RAS in MDS, suggesting that genetic mutations are difficult to explain. The cause of all MDS patients.
Patients with secondary MDS often have obvious pathogenesis. Benzene aromatic compounds, chemotherapeutic drugs, especially alkylating agents, and radiation can induce cell gene mutations leading to MDS or other tumors. In addition, MDS occurs mostly in middle-aged and elderly people. Whether age can reduce the function of intracellular repair gene mutation may also be one of the pathogenic factors.
(two) pathogenesis
MDS patients cause hematopoietic stem cell damage under the influence of pathogenic factors. The G6PD isoenzyme type, X chromosome with restriction length fragment polymorphism methylation, X chromosome inactivation analysis and other methods have determined that most MDS are lesions. Crohn's disease occurs at the level of hematopoietic stem cells, so not only the myeloid, erythroid, and megakaryocytic cells are involved, but also the lymphocyte lineage is affected, resulting in abnormal numbers and functions of T and B cells, and clinical manifestations of immunodeficiency or autoimmunity. disease. However, in some patients, the incidence can only be limited to the levels of granulocytes, red, megakaryocytes, and macrophage progenitor cells. Only granules, red, megakaryocytes, macrophages, etc. are involved and no lymphocytes are involved.
The onset of MDS has stage characteristics and may be related to changes in different proto-oncogenes and tumor suppressor genes. Proto-oncogene activation includes gene overexpression, expansion, rearrangement, translocation, point mutation, etc. The tumor suppressor gene changes include allelic loss, deletion, rearrangement, mutation, and decreased expression. Hematopoietic stem cells are regulated by different protooncogenes and tumor suppressor genes in different stages of proliferation and differentiation. This regulation is through their expression products such as growth factors, cell surface receptors, tyrosine kinases, ATP, cytosine threonine. / Serines, nuclear proteins, etc. are completed. These expression products are directly involved in various physiological steps of cell proliferation and differentiation according to strict procedures. For example, a physiological link may cause disorder of cell proliferation and differentiation due to abnormal regulation of protooncogene or tumor suppressor gene, leading to MDS or other diseases.
In the early stage of MDS, some hematopoietic stem cells with proto-oncogene or tumor suppressor gene changes have some abnormalities in their own proliferative differentiation function, but they can still be in a relatively stable stage for a long time. At this time, the patient's clinical condition is stable, only mild. Anemia, white blood cells, thrombocytopenia, but when this abnormal clone progresses further, another cloned stem cell with chromosomal aberrations derived from this clone is used as the main hematopoietic stem cell instead of hematopoiesis. Chromosomal aberrations make this stem cell have More obvious hyperplasia and differentiation, the blood cells in different stages of the various lines are often unable to differentiate and mature, the proportion of apoptosis in the middle is increased, and the blood cells of the peripheral blood 3 are further reduced. The feedback stimulates the bone marrow abnormal hematopoietic stem cells to strengthen the hyperplasia, and the bone marrow hyperplasia is accompanied by pathological conditions. Hematopoietic performance. Hyperproliferative abnormal clones Hematopoietic stem cells often have two evolutionary pathways: one is due to excessive proliferation and gradually evolves into hematopoietic decline, the bone marrow can be converted to hyperplasia, and the clinical manifestation is hematopoietic failure, which is the cause of death in more than half of patients with MDS. The other evolved into acute leukemia. Most of the acute leukemias converted from MDS to acute myeloid leukemia, only a small number of acute lymphoblastic leukemia, chemotherapy is poor, often difficult to relieve, even if the relief, the remission period is short.
symptom
1. Symptoms MDS has no specific clinical manifestations. MDS usually has a slow onset and a few onset are acute. It usually turns from leukemia to leukemia, which is about 50% or more within one year. Anemia patients account for 90%. Including pale, fatigue, palpitations after the event, shortness of breath, anemia in the elderly often makes the original chronic heart and lung disease worse. Fever accounts for 50%, of which unexplained fever accounts for 10% to 15%, manifested as recurrent infections and fever, with respiratory tracts, around the anus and urinary tract. Severe granulocytopenia can reduce the patient's resistance. Bleeding accounts for 20%, common in the respiratory tract, digestive tract, and also from intracranial hemorrhage. The early bleeding symptoms are mild, mostly skin and mucous membrane bleeding, gum bleeding or nasal discharge, and female patients may have menorrhagia. The trend of late bleeding is worse, and cerebral hemorrhage is one of the main causes of death. Severe thrombocytopenia can cause skin bruising, nosebleeds, bleeding gums, and visceral bleeding. A small number of patients may have joint swelling and pain, fever, skin vasculitis and other symptoms, mostly accompanied by autoantibodies, similar to rheumatism.
2. Signs of patients with signs of MDS are not typical. Often caused by anemia, pale, thrombocytopenia caused by skin spots, spots. Hepatosplenomegaly accounts for about 10%. Very few patients may have lymphadenopathy and skin infiltration, mostly in patients with chronic myelomonocytic leukemia (CMMoL).
3. Special types of clinical manifestations
(1) 5q-syndrome: The patient's chromosome 5 long arm is missing without other chromosomal aberrations. Occurred in older women, the clinical manifestations of refractory giant cell anemia, in addition to occasional blood transfusion, the clinical condition is long-term stable, rarely converted to acute leukemia. 50% of patients may have splenomegaly, normal or occasional increase in platelets. The most prominent manifestations in the bone marrow are low-lobed or non-lobulated megakaryocytes, often with moderately morbid hematopoiesis, but normal granulocyte hematopoiesis.
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. How 5q-syndrome affects 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. Isolated monomeric 7 chromosome aberrations are common in children and can occur in FAB typing subtypes, most have hepatosplenomegaly, anemia and varying degrees of leukopenia and thrombocytopenia, 25% of patients with mononucleosis, neutral The main glycoprotein on the surface of granulocytes is reduced, and the chemotactic function of granules and monocytes is weakened, which is often prone to infection. Monomer 7 is a poor prognostic indicator and some patients can develop acute leukemia.
(3) 11q-syndrome: The long arm of chromosome 11 is lost, mostly accompanied by other chromosome aberrations. Most of them are ring-shaped iron granulocytic refractory anemia (RAS) type, with ring-shaped iron granules increased and iron storage increased. Part of it is refractory anemia with blast-producing (RAEB) type. Clinically, 20% of patients with RAS have 11q-. The location of the long arm break point of chromosome 11 is different, between q14 and q23. The significance of the q14 breakpoint is unknown, but the ferritin H chain gene is known to be adjacent to q14 at q13. The connection 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, which can be found in various subtypes of MDS. 5q- has two cases: one is a single 5q-, that is, 5q- is the only karyotype abnormality; the other is complex 5q-, that is, in addition to 5q-, there are other chromosomal abnormalities. Because of the unique clinical manifestations and prognosis of a single 5q-RA and RARS, the 5q-syndrome of MDS is specifically referred to.
5q-syndrome mainly occurs in elderly women. The peripheral blood shows large cell anemia, the number of white blood cells is slightly reduced or normal, and the number of platelets is normal or increased. The most prominent change in the bone marrow is abnormal development of megakaryocytes, and the number of small megakaryocytes with reduced lobes is significantly increased. The manifestations of erythroid cell dysplasia may not be obvious at present, and there may be circular iron granule cells. The patient has a chronic clinical course, mainly refractory anemia, and bleeding and infection are rare. Generally, anti-anemia treatment is ineffective, but it can survive for a long time only by regular blood transfusion. 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 The iron is overloaded to form 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 reversible SA caused by alcoholism and certain drugs. The RARS of the MDS belongs to the acquired SA. One of the major subtypes of acquired SA is idiopathic acquired sideroblastic anemia (IASA). Kushner et al. analyzed the literature and his own IASA cases and found that: 1 the young red blood cells were negative for PAS staining; 2 the long course of disease, the median survival time was up to 10 years; 3 the survival curve of the patients was the same as the normal population, and not A mode of malignant disease; 4 whitening rate is very low (7.4%). Whether the RARS of MDS is equivalent to IASA, no specific description is given in FAB typing and WHO typing. However, the authors have suggested that there are two types of cases in RARS, one should be diagnosed as MDS, and the other should still be diagnosed as SA.
(6) 17p-syndrome: short arm loss of chromosome 17 (17p-) can occur in about 5% of patients with MDS. Most of them are due to the 17p unbalanced translocation, and can also be due to -17, iso (17q) or pure 17p-. 17p - often combined with other chromosomal abnormalities. The tumor suppressor gene p53 is located at 17p13. The 17p-, missing regions caused by the above various karyotypic abnormalities may not be identical, but all include the p53 gene region. And about 70% of patients with 17p-syndrome have p53 gene inactivation, indicating that another allele p53 gene has also been mutated.
The hematology of 17p-syndrome is characterized by abnormal granulocyte development, and peripheral blood neutrophils have pseudo-Pelger-Huet nuclear abnormalities and small vacuoles in 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 juvenile 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 is negative, may have splenomegaly. Later, the FAB team 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 has been reorganized into the new MDS/MPD category, which has solved this long-standing dispute. However, in some patients with MDS, the number of peripheral white blood cells was not significantly increased (<13×109/L), while monocytes were >1×109/L, and there was no hepatosplenomegaly in the clinic. The morphological manifestations of abnormal blood cell development in the bone marrow are very obvious. Fully compliant with MDS features. These patients do not have the characteristics of MPD, obviously should not be classified as MDM/MPD as CMML, but should still be diagnosed as MDS. As for whether it is necessary to have a single sub-type in the MDS, it is open to question.
(8) aCML: The disease is similar to Ph(+)CML, and the number of white blood cells in the peripheral blood is significantly increased, and there are >10% of immature granulocytes in each stage. However, unlike Ph(+)CML, there is no significant increase in basophils, and the morphological manifestations of abnormal blood cells in peripheral blood and bone marrow are very obvious, and often are three-line dysplasia. Both the Ph chromosome and the bcr-abl fusion gene were negative. Clinically, the drug for treating CML has a poor response, and the course of disease progresses rapidly. The median survival time is generally <2 years. In the past, this disease was diagnosed as Ph(+)CML as a variant of CML. After discussion by the WHO Classification Program Steering Committee and the Clinical Advisory Committee, the clinical course of the disease is not chronic. The name of the disease using aCML is easily misunderstood, thinking that it is a chronic disease associated with Ph(+)CML, but it has not been changed. A new disease name was agreed. Finally decided to follow the disease name of aCML and put it into the MDS/MPD category.
1. Diagnosis of refractory anemia that cannot be explained should take into account MDS. The morphological features of bone marrow like normal or hyperplastic hyperplasia with pathological hematopoiesis, the proportion of blast cells <30% can be diagnosed as MDS. For some cases of megaloblasts, serum folate and vitamin B12 levels should be examined. Clonal karyotypic abnormalities can further support the diagnosis. Then, carefully examine the blood and bone marrow to make a subtype diagnosis of MDS.
2. Diagnostic criteria
(1) Diagnostic criteria for classification of collaborative groups (FAB classification) in France, the United States, and the United Kingdom:
1 refractory anemia (RA): blood: anemia, occasional neutropenia, thrombocytopenia without anemia, reticulocyte reduction. The morphology of erythrocytes and granulocytes may be abnormal, and the original cells have no or <1%; bone marrow: hyperplasia is active or significantly active. Erythroid hyperplasia and pathological hematopoiesis. It is rare to see pathological hematopoiesis in granulocytes and megakaryotes. Primitive 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%. Myeloid hyperplasia was markedly active, and both granulocyte and erythroid hyperplasia. The three lines have pathological hematopoiesis. The original cell type I II is 5% to 20%. 4 Chronic myelomonocytic leukemia (CMMoL): The granulocytes and pathological hematopoiesis in bone marrow and peripheral blood are the same as RAEB, the original monocytes are <5%, and the mature monocytes in the blood are mainly >1× 109/L.
5 RAEB (RAEB-T) in transition: 20% to 30% of the original cells in the bone marrow, the same as RAEB.
Primitive cells include type I and type II granulocytes. Type I: Different sizes, no cytoplasmic granules, loose nuclear chromatin, obvious nucleoli, large nuclear/mass ratio. Type II: There is a little azurophilic granule in the cytoplasm, the ratio of nuclear/mass is small, the nucleus is in the middle, 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 peripheral blood has a line, second line or whole blood cell reduction, and even leukocytosis, visible nuclear red or giant red blood cells and other pathological hematopoietic manifestations.
3 Except for other diseases that cause pathological hematopoies, such as erythroleukemia, myelofibrosis,Chronic myeloid leukemia, primary thrombocytopenic purpura, megaloblastic anemia, aplastic anemia. After diagnosis of MDS, RA, RAS, RAEB, and RAEB-T were further divided according to the percentage of bone marrow and peripheral blood granules + promyelocytes. CMMoL in the FAB subtype is already leukemia and is no longer classified as MDS. From the clinical application of Peking Union Medical College Hospital in recent years, the diagnosis of MDS is still based on the application of FAB classification. The domestic standard replaces the original granules and promyelocytes with the original cells type 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 type III is the same as FAB diagnostic criteria, delete RAEB-T and CMMoL type II in FABA. In addition, the following types have been added.
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-line reduction of MDS, etc. can not be included. Therefore, the following points should be noted in the application of FAB standard fashion. 1 pathological hematopoiesis is not simply cell morphology, but also includes cell proportions.
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 significantly different from senile leukemia in clinical, cell biological characteristics and treatment response, and the two cannot be equal. Multiple refractory cells with pathological hematopoiesis have reduced cells, cannot classify MDS, lack biological, genetic, and clinical basis, and cannot be used as independent types.
(4) IPSS classification criteria: comprehensive cytogenetics, blood, bone marrow blastoma counts 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, there will be new classification standards for comprehensive molecular biology and genetics and clinical multi-angle systems in the future.
diagnosis
The disease should be associated with acute myeloid leukemia,Myelofibrosis,Aplastic anemiaIdentification of diseases such as hemolytic anemia, megaloblastic anemia, and non-hematopoietic tumors.
The typical feature of MDS is that the peripheral blood three-line blood cells are reduced, the bone marrow hyperplasia is active, and there are 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. However, about 10% of patients with MDS can present with low bone marrow hyperplasia at the time of treatment. About 1/4 of the patients have no obvious pathological hematopoietic manifestations. At this time, they need to have megaloblastic anemia, aplastic anemia, hemolytic anemia and other myeloproliferative disorders. Identification. There are three types of differential diagnosis methods applied clinically:
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. For example, serum folic acid and Vit B12 are normal, and the hemolysis test is negative, accompanied by one or more of the following indicators: chromosomal aberrations, reduced hematopoietic progenitor colony formation, increased clusters/colony, and normal bone marrow radionuclide imaging in the peripheral and central hematopoietic tissues. Or decreased, but with multiple focal hematopoietic foci, the proportion of CD34 in bone marrow mononuclear cells increased significantly, N-ras gene mutation, increased axl gene expression, increased erb-A, erb-B expression, etc. all support the diagnosis of MDS.
2. Continuous observation of clinical conditions to change nutritional megaloblastic anemia,Paroxysmal nocturnal hemoglobinuria(PNH) may have pathological hematopoiesis but may disappear after treatment. FAB subtypes can be transformed into each other during the course of MDS. In most cases, RA or RAS-RAEB→RAEB-T→ sequence is transformed, but F can be converted from RAEB to RA or RAS due to treatment or other unknown factors, and RAEB-T is converted to RAEB or RA. The degree of myeloproliferation can also be changed from hyperplasia to hyperplasia, from hyperplasia to hyperplasia. Pathological hematopoiesis in the bone marrow can also be from nothing to nothing. Clinically, by continuously observing the patient's condition, after the exclusion of other diseases, the characteristics of typical MDS appear at a certain stage can be diagnosed.
3. Experimental treatment After a month of regular supplementation of folic acid, Vit B12 and no significant anemia in patients can basically exclude megaloblastic anemia. Treatment with androgen + immunosuppressive agents for more than half a year does not support the diagnosis of aplastic anemia. The use 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 rule out the disease that is clinically confusingly confused with MDS, thereby contributing to the diagnosis of MDS. However, a small number of cases are difficult to identify and require long-term clinical follow-up.
complication
1. Combined with myelofibrosis Nearly 50% of patients with MDS have mild to moderate reticular fibers in the bone marrow, of which 10% to 15% have significant fibrosis. Different from primary myelofibrosis, MDS 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 can be seen in various subtypes, which is considered by the author to be one of the factors suggesting poor prognosis. Another rare condition is called acute myelodysplasia with acute myel fibrosis (acutemyelodysplasia with myelofibrosis, AMMF). The patient has acute onset, symptoms and signs such as anemia, hemorrhage, infection, and no hepatosplenomegaly. The whole blood cells in the peripheral blood are reduced, and the morphology of mature red blood cells is lightly changed. Only a few broken red blood cells can be seen, and primitive cells, immature granulocytes or nucleated red blood cells can be seen. The area of hematopoietic tissue in bone marrow tissue sections increased, and the three lines of hematopoietic cells developed abnormally and became fibrotic. The number of megakaryocytes is increased and the abnormal morphology is very prominent. The primordial cells are moderately increased, but large fragments and clusters are not formed. In a few cases, there is an increase in focal crude collagen fiber deposition and focal osteogenesis. The patient is in serious condition and often dies of bone marrow failure or conversion to leukemia within a few months.
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). The above patients <20%). Some authors refer to this condition as hypoplastic MDS (hypoplastic or hypocellular MDS) and consider it to be a special subtype of MDS. In fact, this situation is difficult to distinguish from aplastic anemia. The following findings have helped to establish a diagnosis of MDS with low myeloproliferation: 1 dysplastic neutrophils or type I and type II blasts can be seen in the blood; 2 dysplastic granules can be seen in the bone marrow smear , erythroid cells, can see type I, type II blasts, especially small megakaryocytes; 3 small megakaryocytes can be seen in bone marrow sections, early granulocytes are relatively common or ALIP (), reticular fibers increase; 4 Bone marrow cells have common clonal chromosomal abnormalities in MDS; 5 can prove monoclonal hematopoiesis. Some authors believe that MDS with both myeloproliferative and severe aplastic anemia are the result of immune myelosuppression, but to varying degrees. Immunosuppressive therapy can be used.
3. Concurrent immunological diseases In recent years, reports on MDS complicated with immune diseases have been increasing. Immune diseases can occur before, after, or at the same time as the diagnosis of MDS. Enright et al analyzed 221 patients with MDS and 30 patients with immune diseases, accounting for 13.6%. There are also 10 cases of clinical non-immune diseases, but there are serological abnormalities of immune diseases. Immune diseases that have been reported to occur in MDS include cutaneous or systemic vasculitis, rheumatoid osteoarthritis, inflammatory bowel disease, recurrent polychondritis, acute febrile neutrophilic dermatitis (AFND, or Sweet's Syndrome), necrotizing panniculitis, Hashimoto's thyroiditis, Sjogren's syndrome (Sjogren's syndrome), rheumatic polymyalgia, and so on. Immune diseases can be complicated by various subtypes of MDS, but more often in patients with clonal and complex chromosomal abnormalities. When MDS is complicated by certain immune diseases (such as Sweet's syndrome), the condition often deteriorates rapidly or turns white in a short period of time. Immunosuppressive therapy can control the condition and improve hematological abnormalities in some patients.
4. The most common complication is infection, fever is mainly lung infection, anemia, severe cases can be complicated by anemia. Bleeding is mainly found in skin, mucous membranes and internal organs bleeding, joint pain and so on. In acute leukemia MRS, the incidence of RA, RAS type evolved into acute myeloid leukemia was about 13%, and the survival time of this group was 50 months. In MDS, 35%-40% of RAEB and CMML group evolved into acute marrow. In cell leukemia, the median survival time is only 14 to 16 months. RAEB-T evolves into acute leukemia with a median survival of three months. About 20% of patients with MDS have bleeding manifestations, which are common in the skin, respiratory tract, digestive tract, etc., and also have intracranial hemorrhage.
treatment
(a) treatment
Since the etiology and pathogenesis have not yet been fully elucidated, there is no uniform specific treatment plan for MDS so far. However, the understanding of the principles of MDS treatment has gradually become more consistent.
Although MDS is essentially a group of malignant clonal disorders, the risk of conversion to leukemia is high, but the natural clinical course and outcome of patients vary greatly, and the number of patients who actually switch to AML does not exceed 30% of the total. Most patients do not have leukemia conversion in their lifetime, but have been in a state of refractory blood cell reduction. The real threat to the lives and lives of these patients is the deterioration in quality of life and complications caused by blood cell reduction, such as infection, bleeding, and anemia of the heart. In addition, early low-risk MDS diagnosed according to current diagnostic criteria and testing methods cannot be 100% certain of its malignant nature. Therefore, the treatment of MDS must be individually determined. For patients with a clear characterization of leukemia, such as RAEB-II, RAEBT, the same treatment options as AML can be considered, with the goal of killing malignant clones and restoring normal hematopoiesis. For most patients with stable disease, mainly refractory cytopenia, and essentially no malignant characterization, such as RA, RARS, and some RAEB-I, the goal should be to increase blood cell count and maintain a better quality of life. It is not advisable for such patients to use prematurely intense chemotherapy with great risk.
Experience has shown that the assessment of IPSS risk, patient age and blood cell biological characteristics including karyotype have important guiding significance for MDS treatment decision-making.
Various treatments that have been used for MDS are now described below.
Supportive treatment
People with severe anemia regularly use concentrated red blood cells to maintain a good quality of life. Platelets <20 × 109 ~ 30 × 109 / L and bleeding tendency can be used to concentrate platelets. Infected patients are indicated to use anti-infective treatment, and if necessary, intravenous gamma globulin infusion. Those who have excessive iron load due to repeated blood transfusions can be treated with iron drive, and so on. Support for low-risk MDS should be used as a basic treatment.
2. Promote blood cell formation and differentiation and maturation, reduce ineffective hematopoiesis. Drugs belonging to this category are mainly suitable for patients with low-risk MDS, but the efficacy is not satisfactory.
(1) androgen: stannazole (Collytron) 2mg, 3 times / d; danazol 200mg, 3 times / d;Testosterone undecanoate(Anxiong) 80mg, 3 times / d, about 30% of patients treated may have different degrees of hemoglobin increase.
(2) Cytokines: There are several recombinant hematopoietic factors that have been used to treat MDS. However, the number of treatments in each report is small, and the dose, course of treatment, and efficacy are quite different, and it is not possible to draw a more mature conclusion.
1 Erythropoietin (EPO): The dose used is 50-300 U/(kg·d), which most authors think is >200 U/(kg·d). It can be administered 2 to 7 times a week for 6 to 12 weeks until half a year. About 20% of patients can detach or reduce blood transfusions, or have elevated red blood cells and hemoglobin. The number of white blood cells and platelets remained essentially unchanged. No obvious side effects were observed. Bone marrow cells cultured in vitro with erythroid colony growth and EPO can stimulate colony increase, plasma endogenous EPO <200U / L, the effect is better.
2 filgrastim (Granulocyte colony stimulating factor): The dosage is a large dose (50-500 μg/m2) and a small dose (0.1-10 μg/m2), 1 to 2 times a day for 4 to 8 weeks or longer. The number of white blood cells and the absolute number of neutrophils increased in 80% to 90% of cases. A small number of patients also have elevated red blood cells and/or platelets. Leukocytes often fall back to pre-treatment levels within 1 month after withdrawal. Continued medication can maintain efficacy. Side effects include nausea, anorexia, bone pain, and hyperuricemia. The original karyotypic abnormality of the filgrastim treatment is unchanged, and the hematopoiesis remains monoclonal. An international multi-unit clinical trial to study the long-term use of filgrastim in high-risk MDS patients (RAEB/RAEBT) concluded that there was no significant difference in whitening rate and survival time compared with controls.
3 Morastatin (granular single cell colony stimulating factor): The dose is from 5 to 10 μg / (m 2 · d) to 750 μg / (m 2 · d) for 7 to 14 days. 50% to 80% of patients have elevated white blood cells and neutrophils in a dose-dependent manner. In a few cases, there may be a decrease in blood transfusion requirements or an increase in platelets. However, the primordial cells in the bone marrow are often increased by more than 10% to 15%. Toxic side effects include fever, flu-like symptoms, excessive white blood cell growth, bone pain, and lethargy.
4 Interleukin-3 (IL-3): A dose of 30 to 100 μg / (m 2 · d) is used for 4 to 28 days or longer. 30% to 60% of patients with elevated neutrophils, 10% to 30% of patients with elevated platelets, no effect on anemia. Toxic side effects include fever, bone pain, and headache.
(3) Inducing differentiation agent:
One-dimensional class A drugs: A.13-cis-retinoic acid (13-CRA) has been reported to treat MDS. The dose is 20-120 mg/(m2·d), or 2-4 mg/(kg·d), for 6-8 weeks until several months. 10% to 30% of patients have varying degrees of efficacy. However, randomized controlled trials showed that the efficacy was not significantly better than the supportive or placebo group, and there were even signs of increased whitening. B. There are few reports of retinoic acid (all-trans retinoic acid) in the treatment of MDS. Shanghai Ruijin Hospital treated 50 cases, the dose was 30 ~ 90mg / d, the course of treatment 1 ~ 9 months. The curative effect was 43%, of which 16% was effective. However, Aul et al treated 15 cases of MDS with the same dose, and no significant effect was obtained. In general, the effect of retinoids on the treatment of MDS is not ideal, and the toxic side effects such as dry mucosa, skin cleft palate, bone and joint pain, and liver damage are common. Only a small number of patients can choose to try.
2 Vitamin D: Trihydroxyl D3 (1-OHD3) and 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], which have been tested for the treatment of MDS, are essentially ineffective.
(4) Others: In recent years, authors have tried azacitidine (azacytidine), decitabine (5-az-2-deoxycytidine), amifostine, pentoxifylline pentoxifilline ) and other treatment of MDS, and reported a certain effect. All belong to the stage of exploration and trial, and more clinical verification is still needed.
3. Immunosuppressive therapy Because there is evidence that some patients with MDS have abnormal immune function, in recent years, the authors have tried immunosuppressive agents to treat MDS and achieved certain effects:
(1) Corticosteroids: Motoji and other trials used high-dose methylprednisolone (1000mg/d×3 days) to treat 5 cases of RA and 6 cases of RAEB. Two cases of RA had obvious curative effect, while RAEB was ineffective.
(2) Cyclosporine (cyclosporine A): Jonasova was treated with cyclosporine in 16 patients with RA and 1 patient with RAEB for 5 to 31 months. All 12 patients who were originally dependent on blood transfusion were excised from blood transfusion, and both white blood cells and platelets were significantly elevated. The general course of treatment begins to take effect in about 3 months.
(3) Antithymocyte globulin (ATG): Molldrem et al. used ATG [40mg/(kg·d) × 4 days] to treat 25 patients with RA and RAEB who were dependent on blood transfusion, 11 patients were detached from blood transfusion after treatment, and 8 patients had obvious Progress in hematology. The median duration of effect was 10 (3 to 38) months; follow-up to 38 months after treatment. 84% of patients are still alive.
(4)Thalidomide(Reaction stop): Raza et al treated thalidomide in 83 patients with MDS. The starting dose was 100 mg/d and gradually increased to 400 mg/d. Twenty-six patients were discontinued due to intolerance within 12 weeks, and 21 of the 57 patients who were consistent with medication were effective, with a median time of 10 weeks.
Some authors have analyzed factors associated with the efficacy of immunosuppressive therapy, such as younger age, shorter time to blood transfusion, and HLA-DRB1 ( ).
4. Low-dose single-agent chemotherapy is mainly used in elderly patients with high-risk MDS, with the most use of low-dose cytarabine and more mature experience. The dose is 10 ~ 20mg / (m2 · d), divided into 2 subcutaneous injections or continuous intravenous infusion, the course of treatment is 7 to 21 days, usually 20 days. The effective rate is about 40%, but the effective and complete remission is only 20%, the duration is short, and most of them do not exceed half a year. The side effects are mainly myelosuppression, and the treatment-related mortality rate is 10% to 25%. However, there is currently no positive evidence that this treatment can prolong survival or reduce whitening rate than supportive care alone. Initial reports have suggested that this treatment is achieved by inducing differentiation of diseased cells in vivo. However, more observations later showed that the therapeutic mechanism is still through the cytotoxic effect of cytarabine.
In addition to cytarabine, some authors have tried other small doses of single-agent chemotherapy for MDS. Such as arubicin (Aclaramycin) [3 ~ 14mg / (m2 · d), continued 2h intravenous infusion, 7 to 10 days for a course of treatment], scorpion scorpion (VPl6, 50mg / d, continued 2h intravenous infusion, 2 to 7 days per week, at least 4 weeks), cephalosporin (Halamine) 0.5 ~ 1.0mg / d, intravenous drip, once a day or every other day, 10 ~ 15 times for a course of treatment), idarubicin (4-demethoxydaunorubicin) [25 ~ 50mg / (m2 · d), 14 to 21 days for a course of treatment], melphalan (2mg / d, Even served 2 to 4 months) and so on. These treatment methods have all reported a certain effect. Because of the lack of such reports and treatments, it is not possible to make a definitive assessment.
5. Intensive combination chemotherapy with MDS strongly combined with chemotherapy indications should be determined based on the patient's age, physical status (PS) and IPSS risk. Most of today's authors tend to be ≤60-65 years old. The time after diagnosis is not long, PS is good, and patients with IPSS-risk-II and high-risk MDS can choose strong combination chemotherapy. Due to the relevance of MDS to AML, chemotherapy regimens for the treatment of AML are generally employed. There were 58 pairs of high-risk MDS patients who underwent combined chemotherapy or supportive therapy. The median survival time was 18 months: August, and the 5-year survival rate was 18%: 7%. It can be seen that combined chemotherapy has a positive short-term and long-term effect on high-risk MDS. However, in general, compared with AML, MDS combined with chemotherapy has a lower CR rate, shorter CR duration, and higher recurrence rate; and because of the poor hematopoietic reserve capacity of patients with MDS, the ability to withstand strong chemotherapy is very high. Low, prone to severe and persistent inhibition of bone marrow hematopoiesis after chemotherapy, leading to treatment-related death.
Reports on the efficacy of MDS intense chemotherapy vary widely from one another, with CR rates as low as 15% and as high as 65%, with individual reported CR rates as high as 80%. This may be primarily related to differences in case selection. The treatment-related mortality rate was 15% to 35%, and the median survival rate was 10 to 18 months. Age <50 years old, karyotype is normal, RAEBT subtype, blast cells in the bone marrow increase rapidly in a short period of time, Auer body (positive), etc., the effect is better. However, some authors believe that the efficacy of MDS combined with chemotherapy is not worse than AML. For example, Bemstein and other retrospective analysis of 915 AML patients who received combination chemotherapy between 1984 and 1992, 38 cases were diagnosed as MDS according to FAB criteria. The efficacy and outcome of the 38 patients and the remaining 877 patients with AML were compared: the complete response rate was 83%: 77%, the treatment-related mortality was 8%: 12%, and the median complete response duration was 11.9 months: 15.4 months. The survival time was 14 months: 16.5 months. There is no significant difference between the two.
In recent years, the trial of VP16/fludarabine/cytarabine or VPl6/topotecan (topological peptide)/cytarabine combination therapy has achieved a higher CR rate in high-risk MDS (> 60%), worth further trial and verification.
6. Hematopoietic stem cell transplantation
(1) Allogeneic hematopoietic stem cell transplantation (Allo-HSCT): Allo-HSCT is currently the only means to cure MDS. Similar to the case of intense chemotherapy, the results reported by the authors vary widely and are mainly related to case selection. The following series of reports can reflect an overview of the results of this treatment in recent years. The International Bone Marrow Transplant Registry (IBMTR) registered 449 MDS patients who received HLA-matched donor Allo-BMT from 1989 to 1994. Disease-free survival (DES) 4 years after transplantation: RA/RARS 49%, RAEB 31%, CMML 28%, RAEBT 25%; Transplant-related mortality (TRM) 48%. The BMT Center in Seattle, USA, implemented 251 Allo-BMT patients with MDS from 1981 to 1996. 6 years DFS 40%, of which DFS is 60% of those aged <20 years old, and DFS is only 20% of >50 years old. Recurrence rate (Rip) was 18% and non-recurrent mortality was 42%. The European BMT (EBMT) group implemented 1378 cases of Allo-BMT in patients with MDS in 1997. 3 years DFS 36%, RIp 36%. Of these, 885 were recipients of HLA-contracted cell bone marrow; RA/RARS DFS was 55%, Rip was 13%, and high-risk MDS was 28% and 43%, respectively. Factors affecting Allo-BMT outcome in patients with MDS include age of the patient, time to diagnosis of BMT, percentage of blasts in the bone marrow before BMT, karyotype abnormalities indicating poor prognosis before BMT, FAB subtype, IPSS risk, kinship or non- Relative donors and so on.
Current biased opinion on Allo-HSCT in patients with MDS: age <50 years old, patients with high-risk and intermediate-risk IPS of HLA-matched donors, I, II patients should strive to implement Allo-HSCT as soon as possible; and IPSS with the same conditions Patients, due to their relatively benign natural course, should carefully weigh the pros and cons and strictly control the indications for treatment.
(2) Autologous hematopoietic stem cell transplantation (Auto-HSCT): It has been demonstrated that in patients with MDS after complete chemotherapy (CR) with strong chemotherapy, polyclonal progenitor cells may be harvested in the peripheral blood. This finding provides a theoretical basis for the implementation of Auto-HSCT in patients with MDS. But so far, there have been few reports in this area. De Witte et al. reported in 1997 the results of Auto-HSCT in 79 patients with high-risk MDS and post-MD AML (SAML) in the EBMT group: 19 patients with MDS had a 2-year total survival rate of 46%, RIp 58%, and TRM 5%. The same author recently reported that 35 patients with MDS and SAML underwent Auto-HSCT after the first CR, 17 from the bone marrow, 13 from the peripheral blood, and 5 from both. RESULTS: Three patients had TRM, 19 had recurrence, and 13 had persistent CR survival. It can be seen that the Auto-HSCT has a very low TRM compared to Allo-HSCT, but the RIp is significantly increased. At present, the opinion of Auto-HSCT in patients with MDS is: Auto-HSCT can be selected as an intensive treatment after intensive chemotherapy remission without suitable donor or high-risk MDS patients who are not suitable for Allo-HSCT.
Treatment-related MDS (t-MDS), also known as secondary MDS (sMDS), is a long-term secondary disease after treatment with cytotoxic drugs (especially alkylating agents) and/or radiation therapy. One, mainly in patients with malignant disease who have achieved long-term survival after successful chemotherapy and/or radiation therapy, and a small number of non-malignant diseases that have received such treatment (egRheumatoid Arthritis, systemic lupus erythematosus, etc.) patients also occasionally occur. Most of the t-MDS will continue to evolve into t-AML after the occurrence of t-MDS. A small number of patients with a history of treatment can directly develop t-AML without undergoing a significant t-MDS stage. Due to the close relationship between t-MDS and development, some authors often combine the two reports.
Regarding the incidence of t-MDS/t-AML, an overview can be seen from the comprehensive analysis of 417 cases in the literature by Dianchi Zhibang. There were 180 males and 237 females in 417 cases. The average age is 59 (1 to 86) years old. In the original disease, blood diseases accounted for 48%, solid tumors accounted for 48%, and benign diseases accounted for 1%. Hodgkin's disease (HD) is the most common in blood diseases (43%), followed by non-Hodgkin's lymphoma(NHL, 26%), multiple myeloma (MM, 15%),Polycythemia vera(PV, 11%), other blood diseases (5%). Breast cancer in solid tumors (24%) andOvarian cancer(23%) was the most, followed by lung cancer (10%), stomach and colorectal cancer (10%). Other tumors (33%). Among the treatments received, chemotherapy alone accounted for 31.0%. Radiotherapy alone accounted for 17.7%, and combined radiochemotherapy accounted for 33.1%. The average incubation period from the first chemotherapy and/or radiation to the diagnosis of t-MDS/t-AML was 57 (7-331) months. Of the 417 cases, 115 were t-MDS. The ratio of each subtype was RA 30%, RAPS 14%, RAEB 27%, RAEBT 16%, and CMML 13%.
The risk factors for the onset of t-MDS/t-AML are: 1 age at the time of treatment. The incidence of t-MDS/t-AML in patients with HD at 7 years after treatment was 20.7% in the age group >40 years old and 6.6% in the <40-year-old group. 2 treatment methods. The incidence of t-MDS/t-AML was 7 to 10 years after HD treatment, 6.2% in combination with radiotherapy and chemotherapy, and the incidence of MDS/t-AML in the chemotherapy group alone was 6.4% in the 6-course group and 11.3% in the 7- to 12-course group. >12 courses group 37.5%. 2.5%, single radiotherapy group 0. 3 treatment intensity. HD patients received chemotherapy with MOPP regimen, and the original disease type was 4 years after chemotherapy. The incidence of t-MDS/t-AML in the first 10 years after treatment, HD 5.4%, NHL 6% to 8%, PV 9%, and MM can be as high as 20% to 25%. In the case of solid tumors, both breast cancer and testicular cancer are <2%, ovarian cancer is 10%, and lung cancer can be as high as 25%.
The hematologic performance of t-MDS differs from that of primary MDS: 1 About 25% of patients may have basophilia in blood and/or bone marrow smears. 2 About 25% of patients in the bone marrow tissue section showed a decrease in nucleated cell proliferation. 325% to 50% of patients have increased medullary reticular fibers. 4 The morphological changes of blood cell dysplasia are very significant. The incidence of chromosomal abnormalities in hematopoietic cells of t-MDS is extremely high, reaching 80% to 98%. Most are complex karyotype abnormalities, and a few can be single karyotype abnormalities. Single karyotype abnormalities are mainly -5,5q-, -7 and 7q-, sometimes 12p- or t(1;7). Complex karyotypic abnormalities also often affect chromosomes 5 and 7. In addition, there are more chromosomes 3 and 17 that are involved. Overall, single or complex karyotype abnormalities of -5/5q- and -7/7q- accounted for 70% to 95% of t-MDS/t-AML karyotype abnormalities.
In the third MIC collaborative study group (1987), when discussing t-MDS, it was considered that, unlike primary MDS, t-MDS was not easy to make accurate typing and prognosis estimation according to FAB morphological classification criteria. This is because the percentage of blast cells in the bone marrow of t-MDS is generally low (<5%) in the initial stage, while the morphological changes of dysplasia are common in the case of the three-line hematopoietic cells, so it is not possible to see which line. Mainly affected. Such cases correspond to the RA/RARS subtype according to the FAB diagnostic criteria, but are actually different from the RA/RARS of the primary MDS. The severity of dysplasia of the three bone cells in the former is more prominent. Such seemingly low-risk MDS cases of t-MDS often experience a rapidly evolving clinical process similar to high-risk, MDS.
The prognosis of t-MDS is worse than that of primary MDS. Once it happens, it tends to evolve progressively toward AML. The turning rate is as high as 60% to 80%. Many patients die of infection and bleeding before the AML diagnostic criteria (≥30% of the original cells in the bone marrow). t-MDS responds poorly to various existing treatments, either before or after whitening. The median survival time was 3 to 9 (0.5 to 43) months.
In children with MDS, children with MDS are less common than adults. Hasle et al reported that in the Fyn and Jutland regions of Denmark from 1980 to 1990, the annual incidence of MDS in children <15 years old was 3.4/1 million. The annual incidence of infants and young children is significantly higher than that of older children. In the above report, the annual incidence of MDS in infants aged 0-2 years was 11.3/1 million, compared with 2.2/1 million for children aged 3-14. The MDS in infants and young children is mainly CMML subtype, and the minimum age of onset of MDS in children is 1 day after birth. Male children are more common in female children. There are no statistics on the incidence of MDS in children in China.
Children's MDS, especially infant MDS, is very different from adults. First, CMML is the most common in FAB subtypes, accounting for almost 50%, followed by RAEB and RAEBT, and RA accounts for about 10%, while RARS is rare. Secondly, children with MDS can be combined with other congenital anomalies, such as Down syndrome, Fanconi anemia, type I neurofibromatosis, mental dysplasia, and hypoplasia. Furthermore, individual children can spontaneously relieve.
Recent studies have found that most children with MDS, especially in older children, have substantially the same hematological characteristics as adult MDS. However, some children with CMML and a few other subtypes are actually juvenile chronic myelomonocytic leukemia (JMML) or -7 syndrome. Therefore, some authors believe that FAB MDS typing recommendations are not fully applicable to children. It is recommended that children with MDS should increase JMML and infantile monosome 7 syndrome (IMo7S) in addition to the five subtypes of FAB. type. However, recent studies have tended to be that IMO7S is not an independent disease, but a variant of JMML.
JMML occurs mostly in infants and children under 4 years of age, with enlarged spleen and enlarged liver and lymph nodes. More than 50% of children have skin damage. The blood picture shows anemia, white blood cells increase (generally <100×109/L), mononuclear cells increase, and there may be immature granulocytes and nucleated red blood cells. The degree of proliferation of bone marrow nucleated cells increased, the percentage of granulocytes increased, the percentage of erythroids and megakaryocytes decreased, and monocytes increased. Erythrocyte HbF levels are increased (often >10%). 30% to 40% of children have karyotypic abnormalities, mainly -7, and Ph chromosome is negative. Peripheral blood N-ALP activity can be reduced, normal or even increased. Peripheral blood CFU-GM can be self-generated and highly sensitive to exogenous GM to CSF, both of which are of great value in the diagnosis of JMML. The clinical process of JMML is in progressive development. The median survival time after diagnosis was <10 months, and most of the children died within 2 years.
The authors also suggested that the FAB collaboration group should use more than 30% of the original cells in the bone marrow as the dividing line between AML and MDS, and not fully applicable to children. Chan et al (1997) analyzed 49 cases of primordial cells in the bone marrow <30%, and considered that 8 of them were AML with a low blast count (AML-LBC) instead of MDS. AML-LBC differs from MDS in that it has: 1 chromosomal abnormalities specific to primary AML, such as t(8;21), t(15;17), Inv(16),t(9;11),t( 1l; 17) and so on. 2 can occur in granuloma. 3 No morphological changes or changes in blood cell dysplasia. 4 The response to AML treatment was good (CR rate 88%, while the MDS CR rate was only 30%), and the survival period was long (4% survival rate was 50%, while MDS was only 23%).
In addition, a pre-leukemia (Pre-ALL) of acute lymphoblastic leukemia can also be seen in children. There are such pre-ALLs accounting for about 2% of children's ALL. It is characterized by the age of the child is generally <6 years old, more women than men, with a short-term bone marrow nucleated cell proliferation low onset. Peripheral blood shows a decrease in whole blood cells, but thrombocytopenia is often relatively light, and there are no immature cells in the blood. Bone marrow smears are similar to aplastic anemia, with individual primordial cells visible. Hematopoietic cells in bone marrow tissue sections are reduced, sometimes normal, megakaryocytes are relatively common, and reticular fibers are increased. This state lasts for 6 to 30 days and is completely normal without any treatment or support and corticosteroid treatment. After 3 weeks to 9 months, it suddenly changes to ALL, which is often the pre-B cell ALL of CALLA( ). The response to the ALL treatment regimen was good and the CR rate was essentially the same as the primary ALL. Therefore, in the diagnosis of aplastic anemia in children, the possibility of Pri-ALL should be considered.
The UK MDS guidelines development team proposed treatment options for symptomatic anemia and stem cell transplantation in patients with MDS for clinical practice (Figures 1, 2, 3).
7. The efficacy criteria are shown in Table 5.
(two) prognosis
The course of MDS has roughly the following three main evolution patterns:
In the first mode, the patient's condition is stable, and the primordial cells in the bone marrow do not increase or increase slightly, but do not exceed 5%. Leukemia has never changed in the follow-up, and it can survive for years or even more than 10 years with general supportive care.
In the second mode, the patient's initial condition is stable. Similar to the first one, the primordial cells in the bone marrow do not increase or slightly increase, but generally <10%. After a period of time, the original cells in the bone marrow suddenly increased rapidly and turned into AML.
In the third mode, the primordial cells in the patient's bone marrow gradually increase progressively, and the clinical condition progresses until it is converted into AML.
Abnormal changes in the biological characteristics of bone marrow cells in patients with MDS often suggest the possibility of leukemia transformation, such as the appearance of new chromosomal abnormalities or oncogene abnormalities, prolonged cell cycle, and leukemia-like growth patterns in vitro.
Almost all changes in MDS to leukemia are converted to acute myeloid leukemia (AML). There are many subtypes of M1, M2, M4 and M6. It has also been reported that individual cases are converted to acute lymphoblastic leukemia or myeloid leukemia.
The survival time and whitening of 1914 MDS in the comprehensive literature of Sanz et al. can reflect the outcome of MDS in general (Table 6): RARS has the best prognosis in each subtype, followed by RA, CMML and RAEB. RAEBT has the worst prognosis. This proves that each subtype of MDS can reflect the prognosis itself. MDS has been classified into low risk (RA/RARS) and high risk (RAEB/RAEBT).
The analysis of the prognostic significance of many parameters of MDS showed that the most important prognostic factor was the percentage of blast cells in the bone marrow. The higher the percentage, the worse the prognosis. Chromosomal abnormalities (especially -7/7q-, 8 or complex karyotypic abnormalities) are also of great importance. Other factors with independent poor prognostic significance include: significant reduction of peripheral blood cells, especially thrombocytopenia and whole blood cell reduction, advanced age (>60 years), ALIP ( ), megakaryocyte abnormalities (especially lymphocyte-like small megakaryocytes) , accompanied by myelofibrosis, SCD (-) and so on.
Some authors selected several parameters with strong prognosis and easy to obtain, and designed the integral system of MDS prognosis. And through a retrospective analysis of the larger case series, it is proved that the prognosis of the high score group is worse than the low score group. It is believed that the application of these integral systems to calculate the scores of patients during the visit will be helpful in estimating the prognosis and determining the treatment guidelines. Table 7 shows an example of the MDS prognostic score system.
The 1997 International MDS Risk Analysis Symposium synthesized some large series of MDS prognostic data. After analyzing each important prognostic factor, it was determined that the percentage of bone marrow blasts, bone marrow hematopoietic karyotype and peripheral blood cell reduction series had the most prognostic significance. . Based on this, an MDS International Prognostic Scoring System (IPSS) is proposed to classify MDS into low-risk, intermediate-risk I, intermediate-risk II and high-risk four-risk groups (Table 8), indicating the survival of patients and The leukemia transition has a positive significance (Table 9). After the IPSS was put forward, it was quickly verified and recognized by some authors. It has been replaced by other prognostic score systems and is widely accepted. Many authors have seen it as a clinical MDS typing program that suggests prognosis and guiding treatment.
About half of the causes of death in patients with MDS are due to aggravation of hematopoiesis in the bone marrow, and hemorrhage and infection caused by progressive reduction of blood cells in the peripheral blood. 30 to 40% is due to a leukemia transition. 10% to 20% are due to other diseases not directly related to MDS.
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 dangers of drug abuse. Care should be taken when using chemotherapy drugs. Radiotherapy should also strictly control indications; exposure to chemicals and other harmful substances (such as benzene, poly in industrial and agricultural production) When vinyl chloride is used, labor protection should be done to prevent harmful substances from polluting the surrounding environment to reduce the incidence of MDS.
(1) Life conditioning
Non-specific prevention has the effect of enhancing physical fitness. Reasonable arrangement of eating and drinking, proper exercise such as Tai Chi exercise and walking can self-regulate the imbalance of the body. MDS is closely related to emotions. Emotional optimism and good spirits are very meaningful for disease prevention.
(two) diet conditioning
Eat well, can maintain health, prolong life, and prevent disease. In the course of 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 that are yang, moving wind. MDS is a mixture of sinister and sinister, and the sinister poison is in the air, and the products that help the fire and the wind should be bogey, especially those with yin deficiency, bleeding, and dampness.
3. Cordyceps stewed duck, Cordyceps sinensis, duck 75 grams, 3 slices of ginger, rice wine station, water 200ml, seasoned with salt oil, simmer for 2 hours, drink soup and eat meat. Treatment of MDS, lack of qi and yin, Shenpi fatigue, pale tongue, fine pulse.
(3) Spiritual conditioning
Liver qi stagnation is closely related to the pathogenesis of MDS. There are data suggesting 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 advocate the vain, the open mind, and the improvement of self-cultivation.
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