What Is a Myeloproliferative Disorder?

MDS is a group of clonal hematopoietic stem cell diseases, characterized by reduced blood cells, one or more morbid hematopoietic hematopoietic cells, ineffective hematopoietic and high-risk transformation to leukemia. The international standard for prognostic scoring system (IPSS) recommended hemocytopenia is Hb <100g / L, absolute neutrophil (ANC) <1.8 × 10 ^ 9 / L, and platelet (PLT) <100 × 10 ^ 9 / L However, the actual diagnosis of MDS is not required to reach such a low level. Most cases of MDS are characterized by progressive bone marrow failure and will eventually develop into AML, but different subtypes have different whitening rates. Some patients have relatively inert biological characteristics, a long course of disease, and low whitening rates. .

He Guangsheng

(Deputy Chief Physician)

Department of Hematology, the First Affiliated Hospital of Soochow University

Myelodysplastic syndromes (MDS) are a group of heterogeneous myeloid clonal diseases that originate from hematopoietic stem cells. They are characterized by abnormal differentiation and development of myeloid cells, manifested as ineffective hematopoiesis, refractory blood cell reduction, and hematopoiesis. Functional failure, high-risk transition to acute myeloid leukemia (AML). MDS treatment mainly solves two major problems: bone marrow failure and complications, and AML conversion. As far as the patient population is concerned, the natural course and prognosis of MDS patients are very different, and treatment should be individualized.

Western Medicine Name: Myelodysplastic syndrome
English name: Myelodysplastic Syndromes, MDS

The main symptoms: Anemia, bleeding
Main cause: Unknown cause
Contagious: Non-contagious

Myelodysplastic Syndrome

After the definition of MDS is clear, the main difficulties in diagnosis and typing are those cases in which peripheral blood and bone marrow blasts do not increase, especially when pathological hematopoiesis is not significant; or with nutritional deficiencies, chemicals, poisoning, hematopoietic growth factors, inflammation and Identification of pathological hematopoiesis secondary to infection; hypoplasia of bone marrow or concomitant fibrosis, etc., fail to obtain sufficient cells to analyze possible disease processes. The diagnosis of hypoproliferative MDS and MDS with myelofibrosis is often difficult.

Causes of Myelodysplastic Syndrome

The cause of MDS is unknown.

Diagnosis of Myelodysplastic Syndrome

Myelodysplastic syndrome diagnosis process

Table 1 MDS diagnosis process

History	Corresponding symptoms of third-line blood cell reduction; history of chemotherapy / radiation, exposure to chemical poisons; family history of MDS / AML and other medical history
Checkup	Anemia, bleeding, signs of infection, swelling of some spleens
Peripheral blood count and smear	Reticulocyte count
Serum ferritin, VitB12, FA levels
Epo level	Try to check before transfusion
Bone marrow smear	Morphology, iron staining, PAS of nucleated red blood cells, POX examination of myeloid cells
Bone marrow biopsy	Histopathology and immunopathology
Bone marrow flow cytometry	MDS immunophenotype
Bone marrow cytogenetic analysis
DNA Testing	Suspected MDS / MPN for JAK2 mutation, PDGFR / gene rearrangement, etc.
Exclude reactive hematopoiesis	Alcoholism, HIV infection, juvenile poverty, PNH, LGL, hemolysis, autoimmune diseases, thyroid diseases, tumors, drugs, chemotherapy, growth factors, etc.

Note: VitB12: Vitamin B12, FA: Folic acid, Epo: Erythropoietin, PAS: Periodic acid stain, POX: Peroxidase, FISH: Fluorescence in situ hybridization, PDGFR: Platelet-derived growth factor receptor, HIV: Human immunodeficiency virus, PNH: paroxysmal nocturnal hemoglobinuria, LGL: large granular lymphocytic leukemia

Myelodysplastic syndromes diagnostic criteria

It is recommended to refer to the Vienna Standard (Table 2). MDS diagnosis needs to meet two necessary conditions and a certain criteria.

Table 2 Diagnostic criteria for MDS

condition
I. Necessary conditions	1 Continuous (6 months) one or more blood cell reductions: red blood cells (Hb <110g / L); neutrophils (ANC <1.5 × 10 ^ 9 / L); platelets (BPC <100 × 10 ^ 9 / L) 2 Exclude other hematopoietic and non-hematopoietic disorders that can cause blood cell loss and pathological hematopoietic
Determine the standard	1 Morbid hematopoietic: at least 10% of any of the red blood cell lines, neutrophils, and megakaryocytes of the bone marrow smear; 2 Proportion of nucleated red blood cells in annular iron granules 15% 3 Primitive cells: 5-19% in bone marrow smears 4 Chromosomal abnormalities (refer to Table 6)
Third, auxiliary standards	(Used to meet the necessary standards, fail to meet the established standards, clinical manifestations of typical MDS) 1 Flow cytometry revealed abnormal bone marrow cell phenotype, suggesting the existence of a monoclonal cell population in the red blood cell line and / or myeloid line 2 There are clear molecular signs of the monoclonal cell population: HUMARA (human androgen receptor) analysis, gene chip pattern or point mutation (such as RAS mutation) 3 Significant and long-lasting reduction of CFU colony (± cluster) formation of progenitor cells in bone marrow or / and circulation

When patients do not meet certain criteria, such as: atypical chromosomal abnormalities, morbid hematopoietic <10%, 4% of primordial cells, etc., and clinical manifestations are highly suspected of MDS, such as transfusion-dependent large cell anemia, MDS auxiliary diagnostic criteria Test (see Table 2), the responders were basically clonal myeloid diseases with bone marrow failure, and these patients were diagnosed as highly suspected MDS. If auxiliary tests are not possible or the results are negative, the patient is followed up, or temporarily classified as idiopathic cytopenia of undetermined significance (ICUS), and checked regularly to confirm the diagnosis.

Morphological abnormalities of MDS

Protocell standards: Type is blast cells without azophil granules, and type is blast cells containing azophil granules without the presence of paranuclear Golgi. Those with Golgi near the nucleus were promyelocytic.

A pathological biopsy is a necessary complement to a bone marrow smear (Table 4). It is required that the length of bone marrow tissue taken from the posterior iliac crest should not be less than 1.5 cm. All patients with suspected MDS should be tested for immunohistochemical (IHC) (Table 5).

Cytogenetic testing

All patients with suspected MDS should be tested for chromosome karyotype, and 20 to 25 bone marrow cells should be tested for metaphase division (Table 6). For those suspected of MDS, when the chromosome test fails, the FISH test is performed, including at least 5q31, CEP7, 7q31, CEP8, 20q, CEPY, and p53.

For those suspected of MDS disease progression, karyotype should be detected during follow-up, usually once every 6 to 12 months.

Gene expression profiling and point mutation detection

In MDS, detection of gene expression profiling (GEP) based on CD34 + cells or CD133 + cells can find specific, prognostic, and genetic markers that have some correlation with FAB, WHO, or IPSS subtypes . But between high-risk MDS and secondary AML, low-risk MDS and normal people, these GEP abnormalities overlap.

For patients with suspected mastocytosis or thrombocytosis, detection of the D816V mutation of the KIT gene or the V617F mutation of the JAK2 gene can help the differential diagnosis.

Application of flow cytometry in MDS

No specific antigenic marker or marker combination has been found in patients with MDS, but flow cytometry is of significance in the differential diagnosis of reactive bone marrow changes and patients with clonal myeloid tumors, as shown in Table 7.

Differential diagnosis of myelodysplastic syndrome

The main problem in diagnosing MDS is to determine whether abnormal bone marrow hyperplasia is caused by clonal disease or other factors. Morbid hematopoiesis is not in itself definite evidence of clonal diseases.

(1) Nutritional factors, poisoning or other reasons can cause changes in pathological hematopoiesis, including the lack of Vit B12 and FA, the lack of essential elements in the human body, and exposure to heavy metals, especially arsenic and other commonly used drugs and biological agents.

(2) Congenital hematological diseases, such as congenital anemia of abnormal red blood cells (CDA), can cause erythropoiesis. Parvovirus B19 infection can cause a decrease in naive red blood cells, accompanied by giant giant juvenile red blood cells. The immunosuppressant mycophenolate can also cause a decrease in naive red blood cells.

(3) Drug factors. Compound Xinnuoming can lead to reduced neutrophil nuclear defoliation, which is easily confused with pathological hematopoiesis in MDS. Chemotherapy can cause significant hematopoietic hematopoiesis. G-CSF can cause morphological changes in neutrophils, such as a significant increase in cytoplasmic granules and a decrease in nuclear lobes; primitive cells can be seen in peripheral blood, but rarely exceed 10%. The proportion of primitive cells in bone marrow is generally normal, but also Can be raised.

It is important to know the clinical history, including the history of exposure to drugs and chemicals, and to identify non-clonal diseases when identifying myelodysplastic disorders, especially those with low blasts. If the diagnosis is difficult, bone marrow and cytogenetics can be performed after a few months.

(4) other blood diseases

Differentiation of aplastic anemia from MDS. The reticulocytes of RA can be normal or elevated, nucleated red blood cells can be seen in peripheral blood, pathological hematopoiesis of bone marrow is obvious, the proportion of early cells is not low or increased, chromosomal abnormalities, and aplastic anemia generally do not have the above abnormalities.

PNH can also lead to pancytopenia and morbid hematopoietic, but PNH test can detect the reduction of CD55 +, CD59 + cells, Flaer can detect the loss of GPI anchorin of granulocytes and monocytes, a positive Ham test and changes in intravascular hemolysis.

Whole blood cell reduction caused by autoantibodies, and pathological hematopoiesis can also be seen. Positive Coombs test and flow cytometry can detect autoantibodies related to hematopoietic cells, and the use of glucocorticoids and immunosuppressants often appears better in the short term reaction.

(5) Thyroid disease can also occur with whole blood cell reduction and morbid hematopoietic, but abnormal thyroid function tests.

(6) Solid tumors may also exhibit pancytopenia and pathological hematopoiesis, which can be ruled out by relevant tests. ^[1-2]

Classification of myelodysplastic syndromes

In 1982, the FAB collaboration group proposed a morphology-based FAB standard (Table 8), which is mainly based on the pathological hematopoietic of peripheral blood and bone marrow cells in patients with MDS, especially the proportion of primitive cells, the number of annular iron granulocytes, Auer bodies and peripheral blood. The number of monocytes is divided into 5 types: refractory anemia (RA), RA with ringed sideroblasts (RAS), refractory anemia with increased primordial cells (RA with excess blasts (RAEB)), refractory anemia with RAEB in transformation (RAEB-t), chronic myelomonocytic leukemia (CMML).

In 1997, the WHO began to revise the typing scheme of the FAB and published it in 2001. The WHO classification has been widely accepted and confirmed by multiple independent research groups. The latest WHO classification in 2008 includes the following changes (Table 9), (1) clear guidance on specimen collection, analysis of primordial cells and primordial cell lines, and analysis of genetic changes, (2) diagnosis of MDS / MPN and Differentiation, (3) will have the main specific changes of MDS, such as blood cell reduction, but there is no clear morphological evidence in the bone marrow, called pending MDS, (4) the addition of refractory hemocytopenia with single-line morbid hematopoietic Subtype, (5) RCMD-ring-like ring-shaped iron granulocytes (RCMD-RS) with multi-line pathological hematopoiesis.

Table 3 Morphological changes of morbid hematopoietic (WHO, 2008)

Red line	Grain line	Meganucleus
Nuclei Nuclear sprouting Nuclear bridge Nuclear fragmentation Nuclear polylobal Giant
	Reduced nuclear defoliation	Small megakaryocyte
	(False Pelger-Huët; pelgeriod)	Nucleus lobulation
	Increased irregular nuclear defoliation	Multinucleated (normal megakaryocytes are mononucleated)


Cytoplasm Annular iron granulocytes Vacuole PAS staining
	Cell body is small or abnormally enlarged
	Reduced or no particles
	Fake Chediak-Higashi particles Auer body

Table 4 Significance of MDS pathological biopsy

significance

Differentiation from AML [when bone marrow smear is diluted by blood (CD34-IHC)]

Differentiation from hypoproliferative AML (CD34-IHC)

Differentiation from aplastic anemia

CD34 + Progenitor Cell Multifocal Aggregation (CD34-IHC)

Abnormal distribution / location of CD34 + progenitor cells (ALIP) (CD34-IHC)

Abnormal morphology and aggregation of megakaryocytes (IHC: CD31, CD42, or CD61)

Definite myelofibrosis (Gömöri's silver stain)

Clear Increased Angiogenesis (CD34-IHC)

Defining a second (associated) myeloid tumor

Diagnosing hypoproliferative MDS

Diagnosis of MDS-U and systemic mastocytosis with MDS (SM-MDS)

FISH for cytogenetic testing [when routine karyotype fails]

Table 5 Recommended histochemical antibodies for MDS pathological biopsy

Sign	Cell type
Lowest combination
CD34	Primitive cells, progenitor cells, endothelial cells
CD31, CD42, or CD61	Megakaryocyte
Tryptase *	Mast cells, basophils, myeloid progenitor cells
Additional combination
CD3	T cells
CD15	Monocytes, granulocytes
CD20	B cells
CD25	T and B cell subsets, atypical mast cells
CD38	Plasma cell
CD68, CD68R	Monocytes, macrophages, myeloid cells
Lysozyme #	Monocytes, macrophages
CD117 *	Progenitor cells, mast cells
2D7, BB1	Basophils

* Very few patients with MDS have CD34-negative blasts but CD117-positive. The primitive cell tryptase response was weak or negative.

# Monocytes / macrophages are used to identify immature monocytes and blasts (CMML vs. AML).

Table 6 Chromosomal abnormalities and their proportions in MDS (WHO, 2008)

abnormal	MDS	t-MDS
Non-equilibrium
+ 8 *	10%
-7 / 7q-	10%	50%
-5 / 5q-	10%	40%
20q- *	5-8%
-Y *	5%
i (17q) / t (17p)	3-5%
-13 / 13q-	3%
11q-	3%
12p- / t (12p)	3%
9q-	1-2%
idic (X) (q13)	1-2%
Balance
t (11; 16) (q23; p13.3)		3%
t (3; 21) (q26.2; q22.1)		2%
t (1; 3) (p36.3; q21.2)	1%
t (2; 11) (p21; q23)	1%
inv (3) (q21; q26.2)	1%
t (6; 9) (p23; q34)	1%

* The morphology is not up to standard, and the cytogenetic abnormality alone cannot be used as the definitive evidence for the diagnosis of MDS. If it is accompanied by continuous hemocytopenia, the proposed diagnosis of MDS can be considered.

Table 7 MDS phenotypic abnormalities detected by flow cytometry

CD34 + myeloid progenitor cells

Absolute and relative increase in CD34 + cell population

CD11b and / or CD15

CD13, CD33 or HLA-DR expression is missing

Lymphatic antigen expression: CD5, CD7, CD19 or CD56

CD45 expression decreased

CD34 density increases or decreases abnormally

CD38 expression decreased

CD34 + B progenitor cells (CD34 + / CD10 +)

CD34 + / CD10 + cells absolute and relative decline in CD34 + cell population

Mature myeloid cells (neutrophils)

Granule-free neutrophils (decreased neutrophil scattering angle)

Abnormal expression relationship between myeloid antigens

Mature out of sync

CD34

Lymphatic antigen

CD45 expression decreased

Monocyte

Abnormal expression patterns of HLA-DR, CD11b, CD13, CD14, and CD33 antigens

CD13, CD14, CD64 or CD33 expression is missing

CD34

Lymphatic antigen expression (excluding CD4)

Erythroid precursor cells

CD45 expression is abnormal

CD34

CD71, CD117, CD235a expression abnormal

Table 8 FAB typing of MDS

FAB type	Peripheral blood	marrow
RA	Primitive cells <1%	Primitive cells <5%
RAS	Primitive cells <1%	Primal cells <5%, ring iron granulocytes> 15% of nucleated red blood cells
RAEB	Primitive cells <5%	5% ~ 20% of original cells
RAEB-t	Primitive cells 5%	Primitive cells> 20% and <30%; or Auer bodies appear in promyelocytic cells
CMML	Primitive cells <5%, Monocyte absolute value> 1 × 10 ^ 9 / L	5% ~ 20% of original cells

Table 9 MDS revised WHO classification in 2008

Typing

Peripheral blood

marrow

Refractory Hemocytopenia with Monoline Morbid Hematopoietic (RCUD)

Refractory Anemia (RA)

Refractory neutropenia (RN)

Refractory Thrombocytopenia (RT)

One or two lines of blood cells decrease

No or rare primitive cells (<1%)

First-line morbid hematopoietic: 10% or more of morbid hematopoetic cells

Primitive cells <5%

Ring iron granulocytes <15%

Refractory anemia with annular iron granulocytes (RARS)

anemia

No primitive cells

Ring iron granulocytes 15%

Erythropoietic hematopoiesis only

Primitive cells <5%

Refractory Hemocytopenia with Multiline Morbid Hematopoietic (RCMD)

Reduced blood cells

No or rare primitive cells (<1%)

Auer body

Monocytes <1 × 10 ^ 9 / L

2 lines of morbid hematopoietic cells 10%

Primitive cells <5%

Auer body

± Circular iron granulocytes 15%

Refractory anemia with blasts-1

(RAEB-1)

Reduced blood cells

Primitive cells <5%

Auer body

Monocytes <1 × 10 ^ 9 / L

One or more morbid hematopoiesis

5-9% of original cells

Auer body

Refractory anemia with blasts-2

(RAEB-2)

Reduced blood cells

5-19% of primitive cells

With or without Auer bodies

Monocytes <1 × 10 ^ 9 / L

One or more morbid hematopoiesis

10-19% of primitive cells

With or without Auer bodies

MDS-Uncategorized (MDS-U)

Reduced blood cells

Primitive cells 1%

One or more lines of diseased cells <10% with cytogenetic abnormalities

Primitive cells <5%

MDS with simple 5q-

anemia

Normal or elevated platelets

No or rare primitive cells (<1%)

Normal or increased megakaryocytes with reduced defoliation

Primitive cells <5%

Cytogenetic abnormalities are only seen in 5q-

Auer body

Occurrence of hematocrit in two lines is rare. Whole blood cell reduction should be diagnosed as MDS-U.

If the blasts in the bone marrow are <5% and 2-4% in the peripheral blood, RAEB-1 is diagnosed. If the peripheral blood blasts of RCUD and RCMD patients are 1%, MDS-U should be diagnosed.

With Auer bodies, blasts <5% in peripheral blood and <10% in bone marrow, should be diagnosed as RAEB-2

Myelodysplastic Syndrome Treatment

MDS treatment mainly solves two major problems: bone marrow failure and complications, and AML conversion. As far as the patient population is concerned, the natural course and prognosis of MDS patients are very different, and treatment should be individualized. According to the prognostic score of patients with MDS, combined with the age, physical condition, and compliance of patients, a comprehensive assessment was made to select a treatment plan. Low-risk group MDS treatment includes component blood transfusion, hematopoietic factor treatment, immunomodulatory agents, and epigenetic drug treatment. Chemotherapy and hematopoietic stem cell transplantation are generally not recommended for patients in the low-risk group, but young patients in the low-risk group can tolerate high-intensity therapy and are expected to produce better results / risk ratios and progression-free survival and overall survival.

MDS in the high-risk group has a poor prognosis and is easily converted to AML, requiring high-intensity treatment, including chemotherapy and hematopoietic stem cell transplantation. High-intensity therapy has higher treatment-related complications and mortality, and is not suitable for all patients.

Myelodysplastic Syndrome Supportive Treatment

These include blood transfusions, erythropoietin (Epo), granulocyte colony-stimulating factor (G-CSF), or granulocyte-macrophage colony-stimulating factor (GM-CSF). It is used by most senior MDS and low-risk MDS. The main goals of supportive care are to improve symptoms of MDS, prevent infection and bleeding, and improve quality of life.

1 blood transfusion

In addition to anemia caused by the disease of MDS itself, many other factors can aggravate anemia, such as malnutrition, bleeding, hemolysis, and infection. These factors should be addressed in improving anemia.

Red blood cells are usually transfused when Hb is <60g / L, or when there are obvious symptoms of anemia. In the elderly, the compensatory response ability is limited, and the oxygen demand is increased. The infusion can be relaxed without Hb <60g / L.

2 iron removal treatment

Patients undergoing blood transfusion treatment, especially in patients with red blood cell transfusion-dependent MDS, may experience reduced overall survival if iron overload is not treated or not treated properly.

Serum ferritin (SF) measurement and assessment of iron overload can indirectly reflect the body's iron load, but SF levels fluctuate greatly and are susceptible to infection, inflammation, tumors, liver disease and alcohol abuse. For red blood cell transfusion-dependent patients, SF should be monitored 3 to 4 times per year. Patients receiving iron removal should be monitored for iron load in accordance with the guidelines for the use of the selected drug, and regularly evaluate the function of the affected organs.

Iron chelation therapy (ICT) can reduce SF levels, iron content in the liver and heart, and the effectiveness of treatment is related to the drug use time, dose, patient tolerance and simultaneous blood transfusion. Desulfurization can be discontinued when the SF drops below 500 g / L and the patient no longer needs blood transfusion, and can also be discontinued if desulfurization is no longer the patient's greatest benefit point. Commonly used drugs are: deferoxamine, deferiprone, and delarox.

3 platelet transfusion

It is recommended that the infusion point for patients with risk factors for platelet depletion (infection, bleeding, use of antibiotics or anti-human thymocyte immunoglobulin, etc.) is 20 × 10 ^ 9 / L, and that for stable patients is 10 × 10 ^ 9 / L.

4 neutrophil therapy

For patients with neutrophil deficiency, G-CSF / GM-CSF can be given so that the neutrophils are> 1 × 10 ^ 9 / L. Routine use of antibiotics to prevent infection is not recommended for MDS.

5Erythropoiesis treatment

Epo is the main initial treatment for low-risk MDS and transfusion-dependent patients. Adding G-CSF can increase the erythroid response for 6 weeks. For non-responders, Epo can be added and treatment is continued for 6 weeks. For those who respond to the treatment, once the maximum effect is achieved, gradually reduce the application of G-CSF and Epo until the original effect is maintained with the smallest dose.

IST Myelodysplastic Syndrome Immunosuppressive Therapy (IST)

ATG alone or in combination with cyclosporine for IST selection may be effective in low-risk / intermediate-risk-1 patients 60 years of age with no clonal evidence, or hypoplasia of bone marrow, HLA-DR15, or with small PNH clones. IST is not recommended for blasts> 5%, with chromosome-7 or complex karyotype.

Recent prospective randomized controlled studies have found that IST is comparable to optimal supportive care survival. For MDS, treatment that inhibits T-cell function requires caution.

Immunomodulatory treatment of myelodysplastic syndrome

Immunomodulatory drugs (IMiDs)

After thalidomide treatment, hematological improvement is mainly red, with long-lasting effects, but neutrophil and platelet improvement are rare. The relationship between dose and response rate has not been confirmed, and long-term application is poorly tolerated.

Lenalidomide works well for those with chromosomal 5q-abnormalities, but the standard dose (lenalidomide 10mg / d for 21 days) has a high rate of bone marrow suppression; for patients with complex chromosomal abnormalities and p53 gene mutations, use Lenalidomide causes disease progression and promotes whitening. It is recommended that 5q-patients use Epo first, and then switch to nalidamine if it is ineffective. Detection of chromosome and p53 mutations before and during lenalidomide use.

Epigenetic Modification of Myelodysplastic Syndrome

5-Azacitidine (AZA) and 5-Aza-2-deoxycytidine (Decitabine, decitabine) can reduce the overall methylation of DNA in the cell and cause changes in gene expression. Both drugs have demethylation at low doses and cytotoxicity at high doses. The specific dosage regimen of azacitidine and decitabine in the treatment of MDS is still being optimized. Patients with high-risk MDS are suitable subjects for demethylation drugs; for patients with low-risk patients with severe blood cell reduction and / or blood transfusion dependence, they are also suitable subjects for demethylation drugs. Increasing the course of treatment can improve the effectiveness of AZA or decitabine treatment.

1 Azacitidine (AZA)

High-risk patients with MDS were treated with AZA 75mg / m2 subcutaneously or intravenously for a total of 7 days, with a course of 28 days as the current recommended regimen.

AZA can significantly improve the quality of life of patients, reduce the need for blood transfusion, and significantly delay the time to conversion or death of AML patients at high risk. Even if the patient does not reach CR, AZA can improve survival.

On the premise of tolerance to toxicity and peripheral blood signs suggesting no progression of the disease, those who did not improve after 6 courses of AZA treatment were switched to other drugs.

2 Decitabine

The recommended regimen of decitabine is 20 mg / m2 intravenous infusion per day for 5 days, 1 course of 4 weeks.

Most patients started to respond at the end of the second course, and reached the best results at the same time. Usually a sufficient amount of 3 to 4 cycles of decitabine treatment is considered ineffective before discontinuing treatment.

Cytotoxic chemotherapy with myelodysplastic syndrome

The prognosis of MDS in the high-risk group, especially the blast cell subtype is relatively poor, and treatment similar to AML should be started. The complete remission rate is 40-60%, but the remission time is short. The elderly are often intolerable. The 5-year overall survival rate of young (<65 years) and normal karyotype patients after chemotherapy was about 27%.

The pre-excitation protocol is based on a small dose of Ara-c (10mg / m2, q12hs × 14d) with G-CSF and combined with aclamycin (ACR) or homoharringtonine (HHT) or noroxydron Mycin (Ida). Pre-excitation programs are commonly used in China. Because MDS is more common in the elderly, the body condition is poor or often accompanied by factors such as chronic lung disease, cardiovascular disease and diabetes that are not suitable for strong chemotherapy. Therefore, low-dose chemotherapy prolongs the survival of these patients. Improving quality of life provides a treatment option. The CR rate for treating MDS is about 40% -60%, and the effective rate is 60% -70%. Age has no significant effect on efficacy, but patients aged 60 years have less tolerance to chemotherapy.

Myelodysplastic Syndrome Hematopoietic Stem Cell Transplantation

Allo-HSCT may cure MDS, but transplant-related complications also increase with age. The indications are as follows:

1 RAEB, RAEB-t, CMML, and MDS transformed AML patients in the FAB classification have short survival and are indications for Allo-HSCT.

2 Intermediate-2 and high-risk MDS in the IPSS system are indications for performing Allo-HSCT. Patients with high-risk karyotypes in IPSS have a poor prognosis, and Allo-HSCT should be performed.

3 Allo-HSCT should be performed before organ function impairment in low-risk patients with severe blood transfusion dependence and clear evidence of cloning.

4 MDS patients have a strong willingness to transplant.

Efficacy and Follow-up of Myelodysplastic Syndrome

The International Working Group (IWG) of the MDS proposed an international unified efficacy standard in 2000 and further revised it in 2006 to make the results of different clinical treatment schemes comparable. The main purpose of MDS treatment is to change the natural course and improve the quality of life (Table 10) to evaluate the efficacy.

Table 10 IWG efficacy standards

category	Efficacy Standards (Effectiveness must be maintained for 4 weeks)
complete relief	Bone marrow: blasts 5% and all cell lines are mature and normal Persistent pathological hematopoiesis should be noted Peripheral blood: Hemoglobin: 110g / L Neutrophils: 1.0 × 10 ^ 9 / L Platelets: 100 × 10 ^ 9 / L 0% original cells
Partial remission	Absolute peripheral blood must last at least 2 months All other conditions reached the standard of complete remission (when there were abnormalities before treatment), but the bone marrow blasts were only reduced by 50% compared with before treatment, but still> 5% Regardless of bone marrow cell proliferation and morphology
Complete bone marrow remission	Bone marrow: blasts 5% and 50% less than before treatment Peripheral blood: If hematological improvement (HI) is achieved, this should also be noted
Stable disease	Failure to meet the minimum criteria for partial response but no evidence of disease progression for at least 8 weeks
Hematological improvement (the efficacy must be maintained for 8 weeks)
Erythroid reaction (<110g / L before treatment)	Hemoglobin rise 15g / L The red blood cell infusion was reduced, and the infusion volume was reduced by at least 4 units every 8 weeks compared with before treatment. Only patients with hemoglobin 90g / L before treatment and who need red blood cell transfusion were included in the evaluation of the efficacy of red blood cell transfusion.
Platelet response (<100 × 10 / L before treatment)	Pre-treatment platelet count> 20 × 10 ^ 9 / L, the net increase is 30 × 10 ^ 9 / L; Or increase from <20 × 10 ^ 9 / L to> 20 × 10 ^ 9 / L and increase at least 100%
Neutrophil response (<1.0 × 10 / L before treatment)	Increase by more than 100% and absolute value increase> 0.5 × 10 ^ 9 / L
Treatment failure	Death or disease progression during treatment, manifested by increased blood cell loss, increased bone marrow blasts, or development of a more progressive FAB subtype than before
Relapse after complete remission or partial remission	At least one of the following: Bone marrow blasts rise to pre-treatment levels The number of granulocytes or platelets is reduced by 50% or more than when the optimal effect is achieved Hemoglobin drops 15g / L or depends on blood transfusion
Progression or relapse after hematological improvement	There are at least one of the following: The number of granulocytes or platelets is reduced by 50% or more than the optimal effect Hemoglobin drops 15g / L Blood transfusion dependent
Cytogenetic response	complete relief: Chromosomal abnormalities disappear and no new abnormalities Partial relief: Reduction of chromosomal abnormal cells by 50%
Disease progression	Those with less than 5% original cells: 50% increase in original cells to 5% 5% -10% of original cells: increase of original cells 50% to 10% 10% -20% of original cells: original cells increased by 50% to 20% 20% -30% of original cells: increase of original cells 50% to 30% Any of the following: Granulocyte or platelet count decreased by 50% compared to the best response / effect Hemoglobin drops 20g / L Blood transfusion dependent
survive	End time: Overall survival: death for any reason Event-free survival: treatment failure or death for any reason Progression-free survival: progression or death from MDS Disease-free survival: until relapse Special cause of death: MDS-related deaths