myelodysplastic syndrome (medicine)



Overview of Myelodysplastic Syndrome

Myelodysplastic syndromes are clonal disorders originating from bone marrow hematopoietic stem cells that can present with anemia such as fatigue and pallor, and low-grade fever, etc. They are mainly treated with general therapy, chemotherapy, and allogeneic bone marrow transplantation, etc. Revised MDS International Prognostic Score belongs to the medium-low risk category, and the prognosis is better after active treatment.

What is myelodysplastic syndrome?

Definition

Myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid clonal disorders originating from hematopoietic stem cells. Abnormal clonal cells, with impaired differentiation and maturation in the bone marrow, appear as pathological, ineffective hematopoiesis.

Classification/typing

Classification according to the cause of pathogenesis

Primary: Myelodysplastic syndromes without a clear pathogenetic cause.

Secondary: Myelodysplastic syndromes with a clear cause.

Clinical Classification

1）、IPSS Scoring System

IPSS is a commonly used risk stratification system for patients with myelodysplastic syndromes, in which hematopoiesis is mainly defined as absolute neutrophil count <1.8×109/L, hemoglobin <100 g/L, and platelet count <100×109/L. The IPSS score is the result of the sum of each score.

The summed result of each point is the IPSS risk classification result: low risk (0 points), intermediate risk-1 (0.5-1 points), intermediate risk-2 (1.5-2 points), and high risk (greater than or equal to 2.5 points)

1

1.5

2

Bone marrow primitive cells (%) <55~10-11~2021~30

Bone marrow primitive cells (%)

<5

5~10

-Bone Marrow Primitive Cells (%)

11~20

21~30

Chromosome karyotype good to poor

Chromosome karyotype

good

Medium

Poor

Hematocrit series 0~12~3

Hematocrit series

0~1

2~3

2）、WPSS points typing

The WPSS is based on the WHO typing standard. The WPSS is suitable for prognostic judgment of MDS patients at any point in the course of the disease, and is also suitable for prognostic judgment of patients with secondary myelodysplastic syndromes.

The WPSS scoring system categorizes patients with myelodysplastic syndromes into very low-risk (0 points), low-risk (1 point), intermediate-risk (2 points), high-risk (3-4 points), and very high-risk (5-6 points) groups.

Morbidity

High prevalence: Patients are mostly found in middle-aged and elderly people over fifty years old.

Questions you may be concerned about

How long does a person with myelodysplastic syndrome usually live?

Survival of patients with myelodysplastic syndromes varies widely depending on the risk stratification of the condition.

The median survival for very low-risk patients is about 141 months; for low-risk patients, it is about 66 months; for intermediate-risk patients, it is about 48 months; for high-risk patients, it is about 26 months; and for very high-risk patients, it is about 9 months.

Median survival refers to the median survival of all patients in the group.

What is the cure rate for myelodysplastic syndromes?

Disease-free survival of more than 5 years is often referred to as clinical cure.

Because myelodysplastic syndromes are a heterogeneous group of diseases, their treatment and prognosis can vary depending on the level of risk. The cure rate for very low-risk patients exceeds 80%; for low-risk patients, the cure rate is between 60% and 80%; for intermediate-risk patients, the cure rate is between 40% and 50%; for high-risk patients, the cure rate is around 30%; and for very high-risk patients, the cure rate is less than 15%.

It is recommended to actively treat the disease under the guidance of a physician in order to improve the cure rate and prolong the survival period.

Can Chinese medicine cure myelodysplastic syndromes?

Chinese medicine can be used to treat myelodysplastic syndromes according to clinical symptoms, but whether it can cure the disease depends on the individual’s condition.

In the treatment of this disease, most of the medicines are given to replenish blood, benefit qi, nourish yin and activate blood, or given orally with proprietary Chinese medicines to replenish qi and nourish blood, and to promote the recovery of positive qi. At the same time, the combination of traditional Chinese medicines and chemotherapeutic drugs can shorten the period of myelosuppression of the patient and improve the quality of life of the patient, which has certain clinical advantages.

Causes

Causes

The cause of primary myelodysplastic syndrome is still unclear.

Secondary myelodysplastic syndromes may be related to exposure to radiation (radiations), chemicals (e.g. benzene, alkylating agents, etc.), or the use of drugs (topoisomerase II inhibitor type chemotherapeutic drugs), and so on.

Symptoms

Main Symptoms

Anemia

Mild anemia has no obvious symptoms.

If the patient’s anemia is severe, there may be dizziness, fatigue, general malaise, palpitations or shortness of breath after activity, and in severe cases, coma may occur.

Fever

10%~15% of patients have unexplained low-grade fever.

If the patient is infected, high fever may occur.

Bleeding

Petechiae and ecchymosis appear on the skin.

Gums bleed.

Hematomas occur after minor body injuries, such as bumps.

Other manifestations

Joint pain manifests in a few patients.

Complications

Febrile neutrophilic dermatitis.

Also known as Sweet’s syndrome, it presents as a sudden onset of painful red nodules or plaques on the extremities and face, often with fever.

Necrotizing pyoderma

Necrosis and ulcers on the surface of the skin, some with boil-like nodules, pustules or hemorrhagic macules.

Acute myeloid leukemia

Some myelodysplastic syndromes may progress to acute myeloid leukemia. In addition to anemia and fever, patients may develop blindness, convulsions, and in severe cases, death.

Consultation

Department of Medicine

Hematology

If symptoms such as dizziness, blurred vision, pallor, bone pain, recurrent infections, fatigue, lack of appetite, lumbago, increased nocturia, etc. occur, it is recommended to consult a doctor promptly.

Preparation for medical treatment

Preparation for medical consultation: registration, preparation of documents, frequently asked questions

Tips for seeking medical treatment

Do not use your own medication before going to the doctor.

Preparation List

Symptom list

Pay particular attention to the time of onset of symptoms, special manifestations, etc.

Are there any symptoms such as shortness of breath, fatigue, pale lips and mouth, pale eyelids?

When did the bone pain start? Where is the specific site?

Is there any relationship between the onset of pain and body position or labor?

Under what circumstances did the pain appear to worsen or ease?

Has there been any fever recently?

Are there any symptoms such as increased nocturia or constipation?

Medical History Checklist

Has there been any recent viral infection, such as a cold?

What is the occupational environment? Has there been exposure to ionizing radiation, chemical toxins, etc.?

Are there any autoimmune diseases?

Is there a family history of hematologic neoplasms?

Checklist

Test results in the past 6 months, which can be brought along to the doctor’s office

Routine blood tests and blood biochemistry

X-ray, CT, Magnetic Resonance Imaging (MRI)

Medication list

Medication used in the last 3 months, if available, bring the box or package with you to the doctor’s office

Bisphosphonates: clodronate, pamidronate disodium, zoledronic acid

Glucocorticoids: dexamethasone, prednisone, etc.

Others: iron, folic acid, vitamin B12

Diagnosis

Diagnosis is based on

Medical History

The patient may have had recent exposure to radiation, benzene or received alkylating agents, etc., and a history of treatment with topoisomerase II inhibitor chemotherapeutic agents.

Clinical manifestations

Symptoms

Low-grade fever, dizziness, fatigue, general malaise, palpitations or shortness of breath after activity may be present.

Physical signs

Skin petechiae, ecchymosis, bleeding gums, etc.

Sternal pressure pain.

Liver and spleen enlargement.

Laboratory Tests

Blood count

Routine blood counts show a decrease in whole blood cells.

Cytomorphologic examination

Patients undergo bone marrow aspiration to obtain bone marrow blood, and cytomorphologic examination of the smear is an important diagnostic modality for myelodysplastic syndromes.

Morphologic abnormalities in peripheral blood and bone marrow smears of patients with myelodysplastic syndromes are categorized into two groups: increased percentage of primitive cells and abnormal cell development.

Cytogenetic testing

Bone marrow aspiration, where bone marrow cells are obtained and chromosomal karyotyping is performed, is diagnostically valuable as it can detect non-randomized chromosomal abnormalities in patients with myelodysplastic syndromes.

Flow cytometry

To determine the proportion of abnormal cell morphology, mainly used for differential diagnosis and judging prognosis.

Molecular genetics testing

It can detect the presence of gene mutation in patients and help to determine the typing of myelodysplastic syndromes.

Immunology

Immunological examination of patients with myelodysplastic syndromes reveals abnormalities of immune cells, which can be manifested as hypergammaglobulinemia, lymphocytopenia, and some patients may be positive for antinuclear antibody and rheumatoid factor.

Diagnostic criteria

The diagnosis of myelodysplastic syndromes (MDS) requires the fulfillment of two necessary conditions and one major criterion.

Requirements (both must be met)

Persistent mono- or multilineage hematopenia for 4 months (diagnosis can be made without waiting if primitive cytosis or MDS-related cytogenetic abnormalities are detected).

Exclusion of other hematopoietic and non-hematopoietic disorders that can lead to hematopenia and developmental abnormalities.

Relevant (major) criteria (at least one fulfilled)

Developmental abnormalities: ≥10% of cells with developmental abnormalities in the erythroid lineage, granulocyte lineage, and megakaryocyte lineage on bone marrow smear.

Cyclic iron granulocytic erythrocytes: ≥15% of erythrocytes with nucleated nuclei or ≥5% with concurrent SF3B1 mutation.

Primitive cells: bone marrow smear with 5% to 19% primitive cells (or peripheral blood smear with 2% to 19%).

Chromosomal abnormalities of diagnostic significance for MDS detected by routine karyotyping or FISH.

Auxiliary Criteria

Ancillary Criteria The diagnosis of suspected MDS was made in patients who met the necessary criteria, did not meet the major criteria, and had common clinical manifestations such as transfusion-dependent macrocytic anemia, if ≥2 of the ancillary criteria were met.

Morphologic or immunohistochemical findings on bone marrow biopsy sections supported the diagnosis of MDS.

Flow cytometry of bone marrow cells reveals multiple MDS-associated phenotypic abnormalities and suggests the presence of monoclonal cell populations in the red and myeloid lineages.

Gene sequencing detects MDS-related mutations and suggests the presence of a clonal population of myeloid cells.

Differential Diagnosis

Myelodysplastic syndromes need to be differentiated from other causes of anemia, such as megaloblastic anemia due to folate and vitamin B12 deficiency, and anemia due to infections and tumors.

These disorders are often difficult to distinguish from other causes of anemia and require cytology by bone marrow aspiration.

Treatment

Treatment goal: improve hematopoietic function, improve quality of life, delay disease progression, prolong survival.

Treatment principle: supportive therapy, promoting hematopoiesis, demethylation drugs and biological response modifiers.

General treatment

Component blood transfusion

Patients presenting with clear symptoms of anemia require blood transfusion.

Platelet transfusion is required when there is active bleeding or platelet reduction.

Hematopoietic growth factors

Patients with neutrophil deficiency and recurrent infections are treated with hematopoietic growth factor.

Deferritization

For patients who have regular blood transfusions, serum ferritin levels need to be monitored regularly to prevent iron deposition caused by excessive iron levels in the body, which may result in heart and liver damage.

Patients with iron deposition need to be treated with iron removal therapy, commonly used drugs include deferoxamine and deferasirox.

Immunomodulators

Immunomodulators can effectively improve the hematopoietic function of patients and reduce or get rid of blood transfusion dependence.

Commonly used immunomodulatory drugs include thalidomide and lenalidomide.

Adverse effects: mainly include dizziness, thirst, drowsiness, nausea, vomiting, constipation, sensory disturbances and so on.

Immunosuppressive therapy

Appropriate population: patients with a prognostic grouping of lower risk, a bone marrow primitive cell percentage of <5% or hypoproliferative myelopoiesis, a normal karyotype or simple +8, the presence of transfusion dependence, HLA-DR15 positivity, or the presence of a PNH clone.

Immunosuppressive therapy (IST) includes anti-thymocyte globulin (ATG) and cyclosporine A.

Demethylating agents

Individuals: patients in the high-risk group.

Commonly used demethylating agents include 5-azacitidine (AZA) and 5-aza-2-deoxycytidine (decitabine).

Chemotherapy

Individuals: Higher Vi patients in the higher risk group, especially those with increased proportions of primitive cells.

Treatment regimen: low-dose cytarabine in combination with aracetamycin or hypertriglyceride or desmethylxorubicin, which may be combined with demethylating agents as appropriate.

Allogeneic hematopoietic stem cell transplantation

Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) is currently the only cure for myelodysplastic syndromes.

Suitable people

Patients <65 years of age in the higher risk group for MDS.

Patients <65 years of age in the lower risk group with severe hemopenia, failure of other treatments, or poor prognostic genetic abnormalities (e.g., -7, 3q26 rearrangements, TP53 mutations, complex karyotypes, monosomal karyotypes).

Precautions

Radiotherapy, chemotherapy and immunosuppressive therapy are required prior to HSCT, and patients may experience adverse reactions such as nausea, vomiting, diarrhea, and oral mucosal ulcers.

Strict isolation in a sterile compartment after transplantation is required as prescribed by the physician.

Other treatments

Androgens

Androgens are commonly used as adjuvant therapy in the treatment of MDS, as they promote red line hematopoiesis in some MDS patients with anemia.