Myelodysplastic syndrome (MDS) refers to hematological neoplasms that occur when some of the blood-forming cells in the bone marrow fail to function properly. Bone marrow is found in the long bones. Several types of cells are present in the bone marrow: fat cells, blood-forming cells, and related tissues.
The inability of the cells of the bone marrow to produce healthy and mature blood cells results in myelodysplastic disorder.
Several causes may explain the occurrence of myelodysplastic syndrome. These are:
One reason for myelodysplastic syndrome is the dysfunction in blood cell production. In these patients, some bone marrow cells become abnormal and cannot produce new healthy blood cells.
The blood cells formed by these abnormal bone marrow cells have abnormal characteristics and die earlier than normal healthy cells. In addition, the body's immune system destroys some abnormal cells.
Although blood cells are produced by abnormal bone marrow cells, these are immature and unhealthy and do not perform the functions of healthy cells.
Over time, immature bone marrow cells accumulate in the blood and do not allow the healthy blood cells to perform their function. These immature bone marrow cells in the blood are known as blast cells. Thus, patients experience several symptoms that are attributed to the non-functioning of healthy blood cells.
The myelodysplasia disease can affect anyone. However, certain people are at increased risk of developing MDS cancer. These individuals include elderly people (>60 years of age), those with a history of treatment with chemotherapy and radiation therapy, those exposed to certain chemicals, e.g., benzene, male gender, people who smoke, those with a family history of myelodysplastic syndrome, and those having genetic syndromes, such as Diamond Blackfan anemia and Fanconi anemia.
Following are the different types of MDS:
In this type of MDS disease, only one cell type (white blood cells, platelets, or red blood cells) is low in number and has abnormal characteristics. Although dysplasia is reported in one cell type, the patients may have a reduced number of 1 to 2 cell types and have a normal number of other cell types. MDS with single lineage dysplasia is not a very common type. It has the potential to progress to acute myeloid leukemia. The prognosis for this type is good, as the patient may live long, even without treatment.
This type is characterized by the presence of dysplasia or abnormality in two or three types of blood cells. The patients experience low levels of ≥1 type of blood cell. The number of blasts in the bone marrow is normal, and there are usually no blasts in the blood.
Patients with this type of MDS have reduced numbers of one (MDS-RS-SLD) or more (MDS-RS-MLD) types of blood cells. This condition is characterized by the presence of rings of excess iron in the red blood cells in the bone marrow. For myelodysplastic syndrome diagnosis with ring sideroblasts, ≥15% of the red blood cells in the bone marrow should be ring sideroblasts.
This type of MDS is characterized by the absence of chromosome number 5 in the chromosomes of the bone marrow cells. The patients experience dysplasia in ≥1 cell type and have a low number of one or two blood cell types; one of them usually is the red blood cells. This type of MDS usually occurs in elderly women. The patients diagnosed with this MDS type have a good prognosis. The risk of progression of this MDS type to acute myeloid leukemia is very low.
This type of MDS is characterized by a relatively higher number of blasts in the blood or the bone marrow. The patients have low levels of ≥1 blood type and may or may not have severe bone marrow dysplasia. It is a relatively more common type of MDS and has a high risk of progressing to acute myeloid leukemia. The risk of acute myeloid leukemia increases as the number of blasts increases in the bone marrow or the blood.
It is not a common type of MDS. It is diagnosed when the blood and bone marrow analysis report does not meet the criteria of other types of MDS. In some cases, the blood cells have a normal appearance, but genetic analysis reveals chromosomal changes in the bone marrow cells, which is consistent with MDS.
Although there are no actual stages of myelodysplastic syndrome, unlike other types of cancers, certain scoring systems are used to classify the MDS into various risk categories. Some of the common scoring systems are:
1. Revised International Prognostic Scoring System (IPSS-R): Several factors are considered while categorizing the disease into a particular risk category. These factors include blast percentage in the bone marrow, chromosomal abnormalities (type and number) in the cells, platelet levels in the blood, red blood cell levels in the blood, and neutrophil levels in the blood.
Scores are provided for each of the above factors, and the cumulative score defines the category of the diseases. Patients with low scores have a more favorable prognosis compared with patients with high scores. The categories include very low, low, intermediate, high, and very high risks. The categories are also helpful in planning the treatment.
2. WHO Prognostic Scoring System (WPSS): This is another scoring system used to categorize MDS based on risk. The factors considered while calculating the scores under this system are the type of MDS present according to the WHO classification, the requirement of blood transfusion, and the type of chromosomal abnormality (defined as poor, intermediate, and good).
The scores are indicated for each factor, and the cumulative score defines the disease category. The risk categories under the WPSS system are similar to those in the IPSS-R system.
The myelodysplastic syndrome symptoms depend upon the type of blood cells affected. Some of the myelodysplastic syndrome symptoms are:
Fatigue and weakness are among the most common myelodysplastic syndrome symptoms, especially in patients with low red blood cell levels. Low red blood cell levels below a specific limit characterize anemia. Studies have reported a strong negative association of fatigue and weakness with reduced quality of life.
Apart from low red blood cell levels, several factors contribute to chronic fatigue in patients with MDS. These factors include high oxidative stress, sleep disturbances, altered vascular function, and impaired physical conditioning.
Frequent infections are also one of the common myelodysplastic syndrome symptoms. The risk of infection or occurrence of frequent infections is because of the low levels of neutrophils. These are the types of white blood cells that assist the body in fighting against pathogens.
Apart from the low levels of neutrophils and functional neutrophil impairment, several other factors contribute to the development of frequent infections in patients with MDS. These include iron overload due to red blood cell transfusion (excess free iron alters the natural resistance to infection) and defects in the B-cells, T-cells, and NK cells. The majority of infections in patients with MDS are bacterial.
Easy bruising and bleeding are the common myelodysplastic syndrome symptoms. Platelets in the blood are responsible for preventing bleeding through blood clotting. Patients with MDS have low levels of platelets, which result in an increased risk of bleeding and bruising. The condition with low platelet levels is known as thrombocytopenia.
Approximately 35% to 40% of patients with MDS experience thrombocytopenia as one of the myelodysplastic syndrome symptoms. These patients complain of frequent minor mucocutaneous bleeding or easy bruising. Such patients may also present with petechiae or purpura. In severe cases, the patients may have an increased risk for hemorrhage or gastrointestinal bleeding.
It is also an MDS disease symptom. Shortness of breath, or dyspnea, is a sign of anemia in patients with MDS. Anemia also negatively affects lung function and respiratory muscle strength in patients with MDS.
Further, the elevated levels of pro-inflammatory cytokines in patients with MDS also affect lung function. Studies have demonstrated unfavorable effects on lung function tests because of the elevated levels of NF-kB and IL-8.
Pale or jaundiced skin is also a symptom of myelodysplastic syndrome (MDS). Patients with MDS, especially with sideroblastic anemia, are presented with pale skin and conjunctival pallor. These patients may also have bronze-colored skin because of iron overload. Pale or jaundiced skin is caused by the low levels of red blood cells in patients with MDS.
Certain factors have been found to increase the risk of MDS, and they are referred to as myelodysplastic syndrome risk factors. The possible MDS causes include:
The myelodysplastic syndrome causes may include genetic factors. Studies reported an association between genetic factors and the occurrence of MDS. MDS runs in families more often than others, partially because of the genetic mutation that runs in these families. In addition, myelodysplastic syndrome causes also include certain genetic syndromes. These syndromes include Fanconi anemia, Diamond Blackfan anemia, severe congenital neutropenia, Shwachman-Diamond syndrome, familial platelet disorder with a propensity to myeloid malignancy, and congenital dyskeratosis.
Some individuals develop MDS due to environmental or occupational exposure to certain chemicals. Studies have reported that exposure to benzene, exhaust gases, ammonia, solvents, pesticides, metals, and alcohol are the myelodysplastic syndrome causes. Certain lifestyle factors, including obesity and smoking, are also myelodysplastic syndrome causes. A study reported that meat consumption, alcohol intake, physical activity, and consumption of fruit and vegetables do not significantly influence the risk of MDS.
A history of cancer treatments, including chemotherapy and radiation therapy, may also be one of the possible myelodysplastic syndrome causes. When MDS is caused by chemotherapy or radiation therapy, it is known as treatment-related MDS or secondary MDS.
The early symptoms of MDS are subtle and usually overlap with symptoms of other benign conditions. Thus, the patients should pay attention to the initial symptoms and consult the doctor to rule out the presence of MDS.
Some of the early symptoms of MDS are shortness of breath, fatigue, anemia, pale or jaundiced skin, frequent infections, easy bruising and bleeding, severe nosebleeds, dizziness, tiredness, bone pain, fever, loss of appetite, and weight loss.
There are several advantages of early symptom recognition and medical evaluation. These are:
1. More treatment options: Patients recognizing the disease early because of symptom recognition have more treatment options than those with advanced disease.
2. Early recovery: When MDS is diagnosed at an early stage, the drug used is of low potency, and a low dose may be required. Thus, the patients have fewer severe side effects and require less time for recovery.
3. Enhanced quality of life: Patients with early symptom recognition have enhanced quality of life because their symptoms are managed through appropriate treatment.
4. Low financial burden: Diseases recognized early can be managed through conventional treatment and usually do not require advanced treatment. There is also an early recovery. All these factors help reduce the financial burden on patients.
5. Increased survival: Early symptom recognition and myelodysplastic syndrome diagnosis have a more favorable prognosis than patients diagnosed at advanced stages.
Diagnosing myelodysplastic syndrome (MDS) begins with a physical exam to check for signs of bone marrow problems and low blood cell counts. A doctor will look for signs like pale skin, shortness of breath, a rapid heartbeat, mouth sores, infections, bruising, or tiny red spots on the skin.
While an enlarged spleen (splenomegaly) is rare in MDS, swollen lymph nodes (adenopathy) are even less common. Patients with MDS often feel tired, dizzy, or short of breath, mainly due to anemia (low red blood cells), which is the most common symptom.
Sometimes, patients may not show symptoms, and MDS is discovered accidentally during routine blood tests or checkups. It is also important for the doctor to know the patient's entire medical history, including any exposure to toxins, alcohol, medications, or past treatments that could be related to MDS. Infections or conditions like HIV can also be risk factors. This helps the doctor understand the possible causes and administer appropriate diagnostic tests.
Before confirming the myelodysplastic syndrome diagnosis, doctors conduct various tests while considering different MDS diagnosis criteria.
Diagnosing MDS typically starts with a complete blood count (CBC), which checks the levels of different blood cells. Most people with MDS will have low levels of red blood cells (anemia), white blood cells (neutropenia), or platelets (thrombocytopenia).
In advanced cases, there may be low levels of all three types of blood cells, known as pancytopenia. The red blood cells in MDS tend to be larger than usual, a condition called macrocytosis, and they may have abnormal shapes. The white blood cells can also show unusual characteristics, like abnormal nuclei or uneven granulation. Platelets may appear large or misshapen.
Doctors may also test for deficiencies in iron, vitamin B12, or folate to help rule out other conditions.
If blood tests suggest MDS, the next step is a bone marrow biopsy. This test involves examining the bone marrow, where blood cells are made. The bone marrow in MDS patients is often crowded with cells, but many of these cells are abnormal. In MDS, the bone marrow will show impaired development of blood cells, and there may be fewer than 20% blast cells (immature cells).
The test may also reveal abnormal red blood cells, called erythroid cells, and megakaryocytes, which produce platelets that can appear strange or malformed. Bone marrow fibrosis (scarring) is common in MDS and can affect the ability of the bone marrow to produce blood cells properly.
If MDS is suspected, blood smears are examined to look for abnormal cells. These smears might show unusual shapes in red blood cells, such as oval-shaped cells or cells with abnormal features like Howell-Jolly bodies.
White blood cells may show a condition called the pseudo-Pelger-Huet anomaly, where their nuclei look different from normal. The platelets are usually normal, but in some cases, they can look larger or have fewer granules.
Genetic tests are another important part of diagnosing MDS. These tests look for changes in the chromosomes or genes of blood cells. Abnormalities like missing or extra parts of chromosomes or mutations in specific genes can help confirm the diagnosis and guide treatment.
Certain chromosomal changes, like deletions on chromosomes 5 or 7, are linked to a better or worse myelodysplastic syndrome prognosis. Gene mutations (like those in the TP53 or TET2 genes) are also often found in MDS and can affect how blood cells develop. These tests help doctors understand the severity of the condition and how best to treat it.
Blood transfusions are crucial in treating myelodysplastic syndrome (MDS) to manage symptoms of anemia and thrombocytopenia. Red blood cell (RBC) transfusions help alleviate fatigue and shortness of breath caused by low red blood cell counts, while platelet transfusions prevent bleeding. The timing of transfusions is usually based on symptoms and falling blood counts, as optimal timing data is limited. Patients may require regular transfusions, sometimes as frequently as weekly. While transfusions improve symptoms, they only provide temporary relief. Long-term iron buildup from repeated transfusions may require treatment with iron chelation therapy. Transfusion therapy aims to improve quality of life and manage bleeding.
These are used to treat anemia in low-risk myelodysplastic syndrome (MDS) patients by increasing red blood cell production. ESAs, such as epoetin alfa, may be combined with granulocyte colony-stimulating factor (G-CSF) to enhance effectiveness. This MDS medication can help reduce the need for blood transfusions, improving patients' quality of life. Early use of ESAs after diagnosis, especially within six months, increases the chances of a positive response. Response rates vary, and patients who have yet to be transfused typically respond better. While ESAs as MDS therapy options do not affect disease progression, they offer survival benefits for low-risk MDS patients, especially responders.
In myelodysplastic syndrome (MDS), infections, particularly fungal, pose significant risks due to neutropenia and other immune defects. Prophylactic antibiotics and antifungal agents may be considered for high-risk patients with severe neutropenia. However, the benefits of routine antibacterial or antifungal prophylaxis in MDS are uncertain. While antibiotics can reduce febrile episodes, their use may lead to bacterial resistance. Fungal prophylaxis is generally not recommended, except in patients with intensive chemotherapy for acute myeloid leukemia (AML). The role of prophylaxis must be carefully evaluated to balance infection prevention and the risk of drug resistance. Regular monitoring and immediate treatment of infections are imperative when patients are on such myelodysplastic syndrome medications.
Chemotherapy for myelodysplastic syndrome (MDS) uses drugs to target abnormal cells in the bone marrow, allowing healthy cells to grow back. Hypomethylating agents like azacitidine and decitabine help control gene activity, improve blood counts, and reduce leukemia risk. This MDS treatment can be administered orally or intravenously. Standard chemo drugs, such as cytarabine, may be used for higher-risk MDS, especially if it progresses to acute myeloid leukemia (AML). Chemo for MDS can help manage myelodysplastic syndrome symptoms, reduce blood transfusions, and improve quality of life, but it may cause side effects like fatigue, fever, and blood count drops.
Immunosuppressive therapy (IST) is used for lower-risk myelodysplastic syndromes (MDS), especially in immune-mediated bone marrow failure cases. While IST can help reduce the need for blood transfusions, its effectiveness varies, and predicting who will benefit is challenging. Factors like age, transfusion history, and genetic markers like HLA-DR15 influence response. Despite its potential, IST is not commonly used in clinical practice due to operational challenges and severe side effects. However, this MDS treatment can be a valuable option for certain patients.
Hematopoietic stem cell transplantation (HSCT) is the only potential cure for myelodysplastic syndrome (MDS). Studies reported that it improves survival and quality of life. It involves using high-dose chemotherapy or radiation to destroy the patient's abnormal bone marrow, followed by the infusion of stem cells from a matched donor. Allogeneic HSCT is most common for MDS, though its risks, such as infections, graft-versus-host disease, and relapse, make it more suitable for younger, healthier patients. Recent advancements in reduced-intensity transplants have made this myelodysplastic syndrome medical procedure more accessible to older patients, though side effects remain a concern.
HCG Cancer Centre offers advanced facilities to diagnose and treat different types of cancer, including MDS. The diagnosis of MDS requires state-of-the-art facilities to analyze the bone marrow samples obtained through biopsy. Cytogenetic analysis also plays a role in diagnosing MDS, and the HCG Cancer Centre has the required facility to perform this analysis. The oncologists at the hospital are experienced and trained at various international institutions of repute.
We do not know the exact cause of MDS. However, some factors have been found to increase its risk. The following are the common myelodyshkcplastic syndrome risk factors:
Age is a myelodysplastic syndrome risk factor. Elderly patients are at higher risk for developing MDS. The disease is less common in people below the age of 50 years. Most patients with myelodysplastic syndrome diagnosis are over the age of 60 years.
Gender is also a myelodysplastic syndrome risk factor. Males are relatively at greater risk for developing MDS compared with females. Although the exact reason for this is not known, it has been proposed that the higher risk in men may be due to increased exposure to environmental or occupational pollutants or due to higher smoking habits.
Patients with a history of undergoing radiation therapy and chemotherapy are at increased risk for myelodysplastic syndrome. The risk further increases when chemoradiation therapy is administered in the patients. The myelodysplastic syndrome caused by the treatment of cancer is known as treatment-associated MDS.
The risk also depends on the type of drugs used, the dose and frequency of the chemotherapy drugs, and radiation therapy. Patients undergoing stem cell transplantation are also at increased risk for developing MDS because of the involvement of intensive chemotherapy during the procedure.
Certain genetic syndromes increase the risk of myelodysplastic syndrome. These syndromes include Fanconi anemia, Diamond Blackfan anemia, severe congenital neutropenia, Shwachman-Diamond syndrome, familial platelet disorder with a propensity to myeloid malignancy, and congenital dyskeratosis.
Certain blood conditions, such as clonal hematopoiesis of indeterminate significance, idiopathic cytopenia of unknown significance, and clonal cytopenia of unknown significance, also increase the risk of MDS.
Studies reported an increased risk of myelodysplastic syndrome in people who smoke compared to people who do not smoke or stopped smoking. It may be because of the cancerous substances present in the tobacco. Once these substances are absorbed in the blood, they may travel to the bone marrow and cause abnormalities in the bone marrow cells.
There is also an association between the MDS risk and familial MDS, as the disease runs in certain families because of the inheritance of mutated genes.
Environmental and occupational exposure to certain chemicals, including benzene, exhaust gases, ammonia, solvents, pesticides, and metals, are myelodysplastic syndrome risk factors.
Exposure to high-energy radiations, such as those from a nuclear reactor accident, also increases the MDS risk.
Although there is no method for complete myelodysplasia prevention, specific measures lower the risk of MDS. These measures include:
Avoiding smoking is an important measure that helps in myelodysplasia prevention. People who do not smoke or have stopped smoking have a lower risk of developing MDS.
People should avoid or limit their exposure to toxic substances for myelodysplasia prevention. People at risk for occupational exposure to these chemicals should take preventive measures, such as wearing face shields, to avoid exposure. Doctors should prefer to use drugs that have the potential to cause side effects during cancer treatment. The type of drug dose and frequency of radiation therapy should balance the therapeutic effect and the side effects.
Early detection of the MDS and appropriate management help slow the progression of the disease. Individuals may also undergo preventative measures, which include monitoring their exposure to toxic substances.
Individuals, especially those at increased risk of developing MDS, should undergo routine health screenings. Patients at higher risk should have routine complete blood counts, learn about different myelodysplastic syndrome symptoms, and pay attention to them when observed.
Genetic counseling is important for myelodysplasia prevention. Certain individuals are at a higher risk for developing MDS because of genetic factors, such as individuals with a family history of MDS and patients with certain genetic conditions. Such individuals should undergo genetic counseling and genetic testing to identify their risk for developing the disease.
MDS is characterized by the inability of the cells of the bone marrow to produce mature, healthy blood cells. Based on the number of types of blood cells affected, the disease is classified into single lineage and multi-lineage. Although it may occur in any individual, elderly people, people who smoke, have a history of chemotherapy or radiation therapy, have a family history of MDS, and have exposure to toxic chemicals are at increased risk for developing MDS.
