Myelodysplastic Syndrome

What is myelodysplastic syndrome (MDS)

Myelodysplastic syndrome (MDS) refers to a group of disorders in which abnormal blood component cells develop in the spinal cord. Different types of cells might be affected, although the most common finding is decreasing numbers of red blood cells (anemia). 

It happens mostly on people above 50 years old, specially on ones above 65. Men are more prone to this illness than women. 

Subtypes of myelodysplastic syndrome 

WHO (World Health Organization) divides myelodysplastic syndrome in seven categories:

• Refractory Cytopenia with Unilineage Dysplasia (RCUD) – patients exhibit low scores on a specific blood component cell type, but all other types have normal scores. Between 5% and 10% of all myelodysplastic syndrome display RCUD. This myelodysplastic syndrome rarely evolves into acute myelogenous leukemia;
• Refractory Anemia with Ringed Sideroblasts (RARS) – similar to refractory anemia, except 15% or more red blood cells in the blood or the spinal cord have iron deposits around the nucleus. Rarely evolves into leukemia;
• Refractory Cytopenia with Multiple Dysplasia (RCMD) – scores of at least two blood component cells (red blood cells, white blood cells or platelets) are below average. Ringed sideroblasts may or may not be present. Blast numbers in the spinal cord are below 5%. Corresponds to roughly 40% of myelodysplastic syndrome patients. May evolve into leukemia in roughly 10% of cases. 
• Refractory Anemia with Excess Blasts-1 (RAEB-1) – one or more cell types score low in blood and present abnormalities in the spinal cord. Number of blasts in the spinal cord is higher, but still below 10%. Risk of RAEB-1 evolving into acute myelogenous leukemia is roughly 25%;
• Refractory Anemia with Excess Blasts-2 (RAEB-2) – similar to RAEB-1, except the spinal cord contains blasts between 10% and 20%. Risk of RAEB-2 evolving into acute myelogenous leukemia can reach 50%;
• Myelodysplastic Syndrome, Unclassified (MDS-U) – this type of myelodysplastic syndrome is uncommon. To be considered a MDS-U, it’s necessary that all blood and spinal cord findings aren’t framed on any other myelodysplastic syndrome type;
• Myelodysplastic Syndrome Associated with Isolated Long Arm Deletion of Chromosome 5 – on this type, spinal cord chromosomes display lack of part of chromosome 5. Red blood cells score low, but white blood cells score normal. Often, platelets score higher. For unknown reasons, patients with this type of myelodysplastic syndrome have an extremely good prognosis and rarely develop leukemia. 

Myelodysplastic syndrome symptoms and signals

Symptoms depend on which type of cell is being affected and can evolve very slowly. In general, they include:

• Fatigue, weakness and other anemia-related symptoms;
• Fever due to infections (if there’s a low white blood cells score)
• Abnormal hemorrhages; 
• Bruises (if there’s a low platelet score);
• Bone pain;
• Appetite loss. 

Since these symptoms might also be caused by illnesses other than MDS, it’s fundamental to seek medical assistance to correctly diagnose the symptoms’ origin. 

Myelodysplastic syndrome diagnosis

Some people present signals or symptoms that suggest myelodysplastic syndrome (MDS), and then tests are requested for further investigation. In some cases, even without any symptoms, suspicion might arise from routine blood work. 

In both possibilities, the doctor must request further testing to analyze blood component cells and bone marrow to conclude the diagnosis. Understand which procedures might be executed:

• Complete blood count – measures red blood cells, white blood cells and platelet levels. MDS patients usually score low on red blood cells (anemia). They might also have low white blood cells and platelet scores. Some MDS types also present myeloblasts (“blasts”) in blood, which are precocious blood cells normally present only in bone marrow. Blood abnormalities might point towards MDS, but a doctor can’t achieve an exact diagnosis without a bone marrow cells sample. 
• Other blood tests – further exams may be requested to identify other possible causes for blood count alterations. As an example, low iron levels, B12 vitamin or folic acid may also cause anemia. If one of those is abnormal, an MDS diagnosis is way less likely. 
• Bone marrow tests – samples are usually harvested from the back of the pelvic (hip) bone. These tests are at first used for diagnosis and classification, and might be repeated to monitor whether MDS is responding to treatment or evolving into acute leukemia. For the procedure, the skin over the hip bone surface is anesthetized, a thin hollow needle is inserted in the bone and a syringe is used to draw a small quantity of liquid bone marrow. Bone marrow biopsy is also performed through harvesting a small bone and marrow sample with a bigger needle. Size, shape and other cell characteristics will be evaluated. For an MDS diagnosis, a patient must score less than 20% blasts in their bone marrow and blood. Patients with more than 20% blasts in bone marrow and blood diagnosed with acute myeloid leukemia (ALM);
• Flow cytometry and immunohistochemistry – cell samples are treated with antibodies. These tests can tell apart different types of MDS or leukemia from other illnesses. 

Cytogenetic assessment is extremely important for MDS diagnosis, since it analyzes chromosomes in the cells. Each cell must contain 46 chromosomes (23 pairs), and abnormal chromosomes are common in MDS. Certain chromosome alterations in cells can help predict the syndrome’s probable course. As an example: deletion of part of chromosome 5, or del (5q), usually predicts a better result (as long as there’s no other alterations). Alterations in 3 or more chromosomes or chromosome 7 deletion tend to have worse prognosis. Chromosome tests are: 

• Karyotype with bands – cells are examined under microscope to check if its chromosomes have any abnormalities. Results usually take between 2 to 3 weeks, since cells must grow on lab dishes before their chromosomes can be visualized;
• Fluorescent in situ hybridization (FISH) – examines cell DNA closer, using fluorescent dyes that bond exclusively to specific genes or chromosome alterations. FISH doesn’t require cells undergoing active division, therefore, it can provide results in a few days;
• Molecular evaluation – polymerase chain reaction (PCR) – very sensitive DNA test that can find some chromosome alterations that are too small for microscopic viewing, even if there’s few abnormal cells in a sample.

Treatment

Support therapies help treat myelodysplastic syndromes (MDS) symptoms or complications. They can be used on their own or with other MDS treatments. As an example: for many MDS patients, one of the main treatment goals is to prevent issues caused by low blood cell scores. 

Other alternatives are:

Treatment of low red blood cell count (anemia) – low red blood cell counts (anemia) can cause fatigue and other symptoms. MDS and anemia patients can benefit from injections of erythropoietin growth factor, which helps the bone marrow in producing more red blood cells. Another option can be red blood cells transfusion;

Treatment for iron buildup in blood transfusion – blood transfusions might create an iron buildup in the body. As time passes, iron might build up in the liver, in the heart and other internal organs, affecting their functions. Drugs called chelating agents, that bond to iron so the body can get rid of it, can be used in patients that develop iron buildup on red blood cells transfusions (unless they have altered kidney functions).

Treatment for low platelet counts – MDS patients with low platelet counts can easily have bleeding or bruising issues. Options to treat lack of platelets may include platelet transfusions or growth factor therapy;

Treatment for low white blood cell counts – patients with low white blood cell counts are more prone to infections. Their doctors must be informed immediately of any infection signs such as fever, pneumonia symptoms (coughing, shortness of breath), or UTIs (burning sensation when urinating).

Prevention 

Currently, there’s no widely recommended tests for myelodysplastic syndromes (MDS) triage, because their causes are completely unknown. It’s not possible to avoid the syndrome, only keeping healthcare and exams in check so, if need be, diagnosis happens at the very beginning.