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Myelodysplastic Syndrome

Myelodysplastic syndromes (MDS) are a group of diseases marked by abnormal production of blood cells by the bone marrow. Healthy bone marrow produces immature blood cells—called blasts—that then develop into red blood cells, white blood cells, and platelets. MDS disrupts this normal process so that the bone marrow is overactive, producing many immature cells. These blasts, however, do not fully develop into mature blood cells. As a result, patients with MDS have fewer mature blood cells, and the cells produced may be abnormal and not function properly.

Any or all blood cell types may be affected by MDS, which is different from leukemia in which only white blood cells are overproduced. The direct effects of MDS may include:

  • Anemia and fatigue if red blood cells counts are low
  • Increased risk of infection if white blood cell counts are low
  • Compromised ability to control bleeding if platelets counts are low

Failure of the bone marrow to produce normal cells is a gradual process. As such, MDS is primarily a disease of the aging and most patients are over 65 years of age. Some patients experience prolonged survival with MDS while approximately one-third will have their disease progress to acute myeloid leukemia (AML). AML that develops from MDS is a difficult disease to treat.

Treatments for MDS may consist of supportive care through administration of growth factors to stimulate immature cells to development into mature blood cells, chemotherapy, immunotherapy and newer precision caner medicines to destroy the abnormal cells and or replacement of the damaged bone marrow with healthy cells that develop into blood cells, a procedure called stem cell transplantation

About this MDS Treatment Information

The information contained on this site is a general overview of treatment for MDS. Treatment may consist of growth factors, chemotherapy with or without stem cell transplantation, targeted therapy, or a combination of these treatment techniques. In some cases, participation in a clinical trial utilizing new, innovative therapies may provide the most promising treatment.

Circumstances unique to each patient’s situation may influence how these general treatment principles are applied. This is intended to help educate patients about their treatment options and to facilitate a mutual or shared decision-making process with their treating physician.

Signs & Symptoms of Myelodysplastic Syndrome

Any or all blood cell types may be affected by MDS and the signs and symptoms that an individual may experience result from MDS direct effects on bone marrow blood cell production.

  • Decreased red blood cell production
    • Anemia
    • Fatigue or feeling tired
    • Shortness of breath
    • Pale skin
  • Decreased white blood cell production
    • Infections
  • Decreased platelet production
    • Easy bruising
    • Petechiae (flat, pinpoint spots under the skin caused by bleeding).
    • Inability to control bleeding

Risk factors

Anything that increases your chance of getting a disease is called a risk factor. Having a risk factor does not mean that you will get colon cancer and not having risk factors doesn’t mean that you will not get cancer, it simply means that you are at greater risk than normal to develop the cancer.

Risk factors for MDS include the following:

  • Past treatment with chemotherapy or radiation
  • Being exposed to certain chemicals, pesticides, fertilizers and solvents such as benzene.
  • Being exposed to heavy metals (mercury or lead)
  • Older age is also a risk factor for most cancers. The chance of getting cancer increases as you get older.

The cause of myelodysplastic syndromes in most patients is not known.

Normal Blood Cell Production

In order to better understand MDS and its treatment, a basic understanding of normal blood cell production is useful. Normal blood is made up of fluid called plasma and three main types of blood cells–white blood cells, red blood cells, and platelets. Each type of blood cell has a specific function:

  • White blood cells, also called leukocytes, help the body fight infections and other diseases.
  • Red blood cells, also called erythrocytes, make up half of the blood’s total volume and are filled with hemoglobin, which picks up oxygen from the lungs and carries it to the body’s organs.
  • Platelets, or thrombocytes, help form blood clots to control bleeding.

Blood cells are produced inside the bones in a spongy space called the bone marrow. The process of blood cell formation is called hematopoiesis. All blood cells develop from one common cell type, called a stem cell. Stem cells become mature blood cells by a process called differentiation. Immature blood cells are called blasts. Blasts grow or differentiate into mature red blood cells, white blood cells, and platelets. Once they are fully developed, these cells are released into the blood where they circulate throughout the body and perform their respective functions.

In healthy individuals, there are adequate stem cells to continuously produce new blood cells and mature blood cells are produced in a continuous and orderly fashion. MDS disrupts this normal process resulting in many blasts and few mature, healthy blood cells.

Diagnosis & Tests Used in Myelodysplastic Syndrome

In order to diagnose MDS and plan treatment, a physician must evaluate a patient’s bone marrow cells to determine the specific type of MDS. The cells are removed through a technique called a bone marrow aspiration and biopsy, which uses a large needle to withdraw cells directly from the bone marrow.

In addition to evaluating the appearance of the bone marrow, cells, and number of blasts in the biopsy specimen, additional special laboratory tests are conducted on the sample cells to determine whether there are abnormalities in the DNA of the blood cells. DNA contains the genetic code for the cell, which can be thought of as the instructions for what the cell looks like, what it does, and how it grows. Most forms of MDS and leukemias are characterized by specific abnormalities. Identifying these provides useful information about the prognosis, or duration of survival.

Additional tests that may be done on cells from the bone marrow aspiration and biopsy.

  • Fluorescence in situ hybridization (FISH) looks at the actual DNA or chromosomes. Pieces of DNA that contain a fluorescent dye are made in the laboratory and added to cells or tissues on a glass slide. When these pieces of DNA bind to specific genes or areas of chromosomes on the slide, they light up when viewed under a microscope with a special light.
  • Immunocytochemistry uses antibodies to check for certain antigens which can tell the difference between myelodysplastic syndromes, leukemia, and other health conditions.
  • Immunophenotyping is used to identify cells, based on the types of markers on the surface of the cell.
  • Flow cytometry measures the number of cells in a sample, the percentage of live cells in a sample, and certain characteristics of cells, such as size, shape, and the presence of tumor on the cell surface.

Types of Myelodysplastic Syndrome

There are several different types of MDS, which are classified by how the abnormal cells that were removed from the bone marrow appear under the microscope and how many blasts can be identified. MDS is classified into five different diseases characterized by ineffective blood cell production in the bone marrow and varying rates of progression to acute leukemia. Following is a description of the five classifications:

Refractory Anemia (RA): Patients have low blood counts, bone marrow blasts are less than 5%, and sideroblasts (iron containing cells) are less than 15%. The average survival is approximately 43 months but can be influenced by specific chromosomal abnormalities.

Refractory Anemia with Ringed Sideroblasts (RARS): Patients have low blood counts, bone marrow blasts are less than 5%, and sideroblasts are greater than 15%. The average survival is 55 months but can be influenced by specific chromosomal abnormalities.

Refractory Anemia with Excess Blasts (RAEB): Patients have low blood counts, 1-5% blasts in the blood, and bone marrow blasts between 5 and 20%. The average survival is 12 months but can be influenced by specific chromosomal abnormalities.

Refractory Anemia with Excess Blasts in Transition (RAEBt): Patients have low blood counts, over 5% blasts in the blood or cells in the blood containing an abnormality referred to as Auer rods, and bone marrow blasts between 20 and 30%. The average survival is 5 months but can be influenced by specific chromosomal abnormalities.

Chronic Myelomonocytic Leukemia (CMML): Blood cells called monocytes make up more than 1,000 ml in the blood and patients have less than 5% blasts. Bone marrow blasts are less than 20% and the average survival is 30 months but can be influenced by specific chromosomal abnormalities.

References


https://www.cancer.gov/types/myeloproliferative/patient/myelodysplastic-treatment-pdq

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Bren Doreck

Patient Story: Bren Doreck

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