Myelodysplastic syndromes (MDS) are a group of “clonal disorders of hematopoietic stem cells” that are characterized by abnormalities in the bone marrow and hematopoietic function of the patient, resulting in reduced and/or abnormal functioning of peripheral blood cells (including white blood cells, red blood cells and/or platelets), i.e., ineffective Hematopoiesis. Clinical manifestations are: ① anemia (easy fatigue, pallor, weakness, panic, aggravated after physical activity, etc.); ② infection (due to leukocyte nuclear neutrophil reduction, such as respiratory and intestinal infections, etc.); ③ bleeding (due to thrombocytopenia, such as skin petechiae, petechiae, purpura, injection site petechiae, hematuria, black stool, and even intracranial bleeding, etc.). Zhang Min, Department of Hematology, Wuhan Union Medical College Hospital
The international IPSS score based on the proportion of primitive cells in the bone marrow, karyotype, and hematocrit in MDS patients divides MDS into four types: low-risk, intermediate-risk type 1, intermediate-risk type 2, and high-risk type (Table 1). The higher the risk level, the greater the chance of conversion to acute leukemia (commonly known as “white out”) and the shorter the survival period (Figure 1). Treatment goals and therapies vary for patients at different risk levels (Figure 2).
For low- and intermediate-risk type 1 patients, the main goal is to reduce transfusion dependence and improve the patient’s quality of life. Blood transfusion, supportive therapy with hematopoietic stimulating factors, immunosuppressants, immunomodulators and demethylation therapy (decitabine) are generally used. Among them, supportive therapies such as blood transfusion and stimulating factors cannot fundamentally solve the patient’s current situation and are prone to transfusion dependence and ineffectiveness. Demethylation therapy can promote the differentiation of stem cells into normal cells, thus correcting the ineffective hematopoiesis of MDS bone marrow and improving clinical hematology by up to 60% or more.
For patients with intermediate-risk2 and high-risk MDS, since the chance of “turning white” is higher, the aim of treatment is to change the natural course of the disease, delay the time of “turning white” and improve the survival rate. The current treatments are as follows: (1) allogeneic HSCT; (2) demethylation therapy (Dacor); and (3) conventional chemotherapy. Allogeneic HSCT is mostly used for patients younger than 55 years old with HLA compatible donors, while MDS mostly occurs in older patients who lose the opportunity of allogeneic HSCT. In addition, older patients with MDS have poorer general body status and pathological hematopoiesis in the bone marrow, which makes them less tolerant to conventional chemotherapy and less effective in chemotherapy. Therefore, demethylation therapy has become a better alternative to allogeneic hematopoietic stem cell transplantation.
According to clinical data from the prestigious Anderson Hematology Oncology Research Center in the United States, the overall efficiency of decitabine can be as high as 81%, and the complete remission rate can reach 39%. Data from the Anderson Center also show that decitabine has the advantage of longer survival (22 months vs. 12 months) and lower treatment-related mortality (7% vs. 23% at three months) compared to chemotherapy.
Appendix.
Table I: WHO 2008 MDS typing
Disease type
Peripheral blood
Bone marrow
Refractory thrombocytopenia with unilineage developmental abnormalities (RCUD)
Refractory anemia (RA)
Refractory neutropenia (RN)
Refractory thrombocytopenia (RT)
Unilineage cytopenia or bilineage cytopenia1
Absence of primitive cells or rare (<1%)2
Monophyletic developmental abnormalities: ≥10% of cells in one myeloid lineage with abnormal development
Primitive cells <5%
Ringed iron granulocytes <15%
Refractory anemia with annular
iron-granulocytes (RARS)
Anemia
No primitive cells
Ringed iron granulocytes ≥15%
Abnormal red lineage development only
Primocytes <5%
Refractory hematocrit with
multilineage developmental abnormalities (RCMD)
Hematocrit
No primitive cells or rare (<1%)2
No Auer vesicles
Monocytes
Cells ≥l 0% (neutrophils and/or red lineage)
progenitor cells and/or megakaryocytes)
Bone marrow primitive cells <5%
No Auer vesicles
Ringed iron granulocytes ±15%
Refractory anemia with primitive cells
Excess-I (RAEB-I)
Hematocrit
Primocytes <5%
No Auer vesicles
Monocytes
Primitive cells 5% to 9%
No Auer vesicles
Refractory anemia with primitive cells
Excess-II (RAEB-II)
Hemocytopenia
Primitive cells 5% to 19%
With or without Auer vesicles3
Monocytes < l×l09/L
1 or multiple lineage developmental abnormalities
Primitive cells 10% to 19%
With or without Auer vesicles 3
MDS unclassifiable (MDS-U)
Hemocytopenia
Primitive cells ≤1%2
Less than 10% of cells in lineage 1 or more myeloid lineages with abnormal development but with abnormal cytology that is presumptive evidence for MDS diagnosis
Primitive cells <5%
MDS with simple del(5q)
Anemia
Normal or elevated platelet count
Absence or rarity of primitive cells (<1%)
Normal or increased megakaryocyte count with
reduced nuclear fractionation
Primitive cells <5%
Simple del(5q)
No Auer vesicles
Figure 1 Survival and risk of AML transformation for MDS according to IPSS risk stratification
Figure 2 MDS stratification treatment strategy