(MDS-EB) Guideline

(2022 Edition)

Myelodysplastic syndromes (MDS) are a group of heterogeneous myeloid clonal disorders of hematopoietic stem cell origin characterized by abnormal development of myeloid cells. MDS is a group of heterogeneous myeloid clonal disorders of hematopoietic stem cell origin characterized by abnormal myeloid cell development, manifested by ineffective hematopoiesis, refractory hematocrit, and a high risk of transformation to acute myelogenous leukemia (AML).

The diagnostic and staging criteria for MDS have been refined over the past 40 years since they were first established by the FAB Collaborative Group in 1982. The subtype MDS with excess blasts (MDS-EB) is defined as a subtype of MDS with 5~19 , with a further increased risk of transition to AML than other subtypes.

The global incidence of MDS is approximately (2-12)/100,000, and the incidence in China is

(0.23 to 1.51)/100,000. The incidence of MDS increases with age, with 80 Age of onset is >60 years. MDS is more common in men than in women, with a prevalence of 33.9 per 100,000 men and 18 per 100,000 women in the German population aged ≥70 years, and a ratio of 1.8:1 in men to women in the Swedish population.

The clinical manifestations of MDS-EB are nonspecific, with a predominance of allogeneic cytopenias, often

Significant anemia, hemorrhage, and infections may be associated with splenomegaly, often progressing to acute leukemia within a short period of time, with a conversion rate of up to 40, and some patients do not progress to acute leukemia but often die from infection and bleeding.

The diagnosis of MDS relies on a combination of laboratory testing techniques, of which bone marrow aspiration smear cytomorphology and cytogenetic testing techniques are central to the diagnosis of MDS.

• Bone marrow aspiration smear: Morphologic abnormalities in peripheral blood and bone marrow smears of MDS patients are divided into 2 categories: increased percentage of primitive cells and abnormal cell development. Primitive cells can be divided into 2 types: type 1 (EB-1) are primitive cells without asplenophilic granules; type 2 (EB-1) are primitive cells with asplenophilic granules but without paranuclear halo area, and those with paranuclear halo area are judged as early juvenile granulocytes. In a typical patient with MDS, abnormal developmental cells account for ≥10 of the cells of the appropriate lineage. All patients with proposed MDS should have a bone marrow iron stain to count ringed iron-granulated juvenile erythrocytes, defined as those with more than 5 blue granules in the cytoplasm of the juvenile erythrocytes and more than 1/3 of the circumference around the nucleus.
  
• Bone marrow biopsy pathology: All patients with suspected MDS should undergo a bone marrow biopsy, usually at the posterior superior iliac spine, of at least 1.5 cm in length. Bone marrow biopsy cytology helps to exclude other factors or diseases that may contribute to hematocrit and provides important information on the degree of marrow cell proliferation, megakaryocyte count, primitive cell population, degree of myelofibrosis, and tumor marrow metastasis. Patients with suspected MDS should undergo Gomori silver staining and in situ immunohistochemistry, and commonly used markers include CD34, MPO, GPA, CD61, CD42, CD68, CD20
  

and CD3.

FISH should be performed in suspected MDS patients with dry bone marrow aspirations, no mid-stage divisions, or <20 analyzable mid-stage divisions. CEP7, 7q31, CEP8, 20q, CEPY, and TP53.

Common risk stratification systems for patients with MDS include the International Prognostic Scoring System

(international prognostic score system, IPSS), WHO

the WHO adapted prognostic scoring system (WPSS) and the revised international prognostic scoring system (IPSS-R). In addition, the MD Anderson Cancer Center (MDACC) stratification system introduced parameters such as age and physical status in addition to the usual primary parameters.

1. IPSS: The grading of IPSS risk was developed in 1997 and was determined based on 3 factors: the proportion of bone marrow primitive cells, the degree of hematocrit, and the cytogenetic characteristics of the bone marrow. Bone marrow progenitor cells 5 to 10 (EB-1) score of 0.5.

Bone marrow primitive cells 11～20(EB-2) Points 1.5. 2. WPSS: developed in 2007, erythrocyte infusion-dependent and iron overload not only leads to

Organ damage can also directly impair hematopoietic function, which may affect the natural course of MDS patients. As a time-continuous evaluation system, prognosis can be assessed at any point in the patient’s disease course. Bone marrow primitive cells 5 to 10 (EB-1) score of 2.

Bone marrow primitive cells 11~20(EB-2) Score 3.

3. IPSS-R: The IPSS-R scoring system is considered the gold standard for prognostic assessment of MDS and is the latest version of the IPSS prognostic scoring system revised by the International Task Force on MDS Prognosis in 2012, and its validity for assessing prognosis is It is significantly better than IPSS and WPSS.2 Points 1, bone marrow primitive cells 5 ~10 (EB1) score 2, bone marrow primitive cells >10 (EB-2) score 3 points. However, IPSS-R also has its limitations. Whether its prognostic assessment

applicable to patients treated with chemotherapy or targeted agents remains unknown; furthermore, other factors with independent prognostic significance are not included, such as infusion dependence of red blood cells, genetic mutations, and especially genetic mutations may contribute to a more precise prognostic assessment.

The treatment of MDS should be based on the prognostic grouping of patients with MDS, as well as a comprehensive analysis of the patient’s age, physical status, co-morbidities, and adherence to treatment, etc. MDS can be divided into 2 groups according to the prognostic score system. The lower risk group [IPSS low risk group, intermediate risk-1 group, IPSS-R very low risk group, low risk group, and intermediate risk group (≤

AZA) and 5-aza-2′-deoxycytidine (decitabine). In the higher-risk group of MDS patients, demethylating drugs reduced the risk of progression to AML and improved survival compared with the supportive care group.

The combination of BCL-2 inhibitors [(Venetoclax (VEN)], immune checkpoint inhibitors (programmed death protein-1 inhibitors, etc.), oral histone deacetylase inhibitors, and CD47 monoclonal antibodies for demethylation in the treatment of high-risk MDS has yielded initial promising results. The future has the potential to improve the overall prognosis of patients with MDS-EB.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently the only cure for MDS. The indications for allo-HSCT are: (i) patients <65 years of age in the higher risk group for MDS; (ii) patients <65 years of age with severe hematocrit, who have failed other treatments, or who have poor prognostic genetic abnormalities

(e.g., -7, 3q26 rearrangements, TP53 mutations, complex karyotypes, haplotypes) in the lower-risk group. Patients with MDS-EB to undergo allo-HSCT may be treated with chemotherapy or demethylating agents or a combination of both to bridge allo-HSCT while awaiting transplantation, but transplantation should not be delayed.

Based on the internationally standardized efficacy criteria proposed by the International Working Group (IWG) on MDS in 2000 and revised in 2006, the response to treatment for MDS includes the following four categories.

(i) Modification of the natural course of the disease.

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• Complete remission: bone marrow: primitive cells ≤5 and all cell lines are maturing positively
  

normal. Peripheral blood: primitive cells were 0, hemoglobin ≥110 g/L, neutrophils ≥1.0×109/L, platelets ≥100×109/L.

Elevated ≥15 g/L; decreased red blood cell transfusion, at least 4 U per 8-week infusion compared to pretreatment; only pretreatment hemoglobin ≤90 g/L and requiring red blood cell transfusion were included in the red blood cell transfusion efficacy assessment.

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