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 those they do have 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 may survive 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.
The possible treatments for MDS, which may be used alone or in combination, include the following:
- Supportive care through administration of growth factors to stimulate immature cells to development into mature blood cells
- Destruction of abnormal cells through administration of chemotherapy, at either low, conventional, or high doses, depending on the condition of the patient and the aggressiveness of their disease
- Replacement of damaged bone marrow with healthy cells that develop into blood cells, a procedure called stem cell transplantation
Targeted therapy that may include the new drug Revlimid® (lenalidomide), which is thought to work by regulating the immune system
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. Multi-modality treatment, which utilizes two or more treatment techniques, is increasingly recognized as an important approach for improving a patient’s chance of cure or prolonging survival.
In some cases, participation in a clinical trial utilizing new, innovative therapies may provide the most promising treatment. Information about treatments for MDS that are being evaluated in clinical trials is discussed under Strategies to Improve Treatment.
Circumstances unique to each patient’s situation may influence how these general treatment principles are applied. The potential benefits of multi-modality care, participation in a clinical trial, or standard treatment must be carefully balanced with the potential risks. The information on this website is intended to help educate patients about their treatment options and to facilitate a mutual or shared decision-making process with their treating cancer physician.
MDS Treatment Sections:
Background: 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.
In order to diagnose MDS and plan treatment, a physician must evaluate the patient’s bone marrow cells to determine the specific type of MDS. The cells are removed through a technique called a bone marrow biopsy, which uses a large needle to withdraw cells directly from the bone marrow.
A special laboratory test is conducted on the sample cells, called a cytogenetic analysis. The purpose of this test is 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 patient’s prognosis, or duration of survival.
Types of MDS
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. At the time of bone marrow evaluation, cells are also removed for cytogenetic analysis. 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.
Planning Treatment for MDS
Since a stem cell transplant utilizing cells from a donor—called an allogeneic stem cell transplant—holds the most hope for cure, a major decision faced by patients with MDS is not whether to undergo transplantation, but when. Patients with MDS that is likely to progress to leukemia early—which results in shorter survival—may be willing to accept higher risks of treatment and proceed quickly to a stem cell transplant. Patients with MDS that progresses more slowly are likely to live longer and may wish to pursue a more conservative treatment approach, opting to use supportive care and wait a longer period before undergoing a stem cell transplant.
However, patients who choose conservative treatment approaches should always be prepared to receive more aggressive treatment in case their disease progresses more rapidly than anticipated. To prepare for a possible stem cell transplant, patients should consider arranging for a stem cell donor and/or having their own stem cells collected and stored shortly after diagnosis. This is important because as MDS progresses and treatment is initiated, it becomes increasingly difficult to collect stem cells.
In order to better plan treatment, doctors try to identify how quickly patients are likely to progress to acute myeloid leukemia (AML). A score is assigned that reflects this tendency to progress, and is based on a system called the International Prognostic Scoring System (IPSS). A higher score is associated with a type of MDS that is likely to progress to leukemia more quickly. The IPSS score takes into account three important factors in MDS:
- The percent of bone marrow blasts—more blasts contributes to a higher score
- Genetic abnormalities—more abnormalities contribute to a higher score
- Severity of low white blood cell counts—lower counts of white blood cells, platelets, and red blood cells contribute to a higher score
Relationship between a patient’s risk of progressing to leukemia and timing of stem cell transplant: Research shows that knowing a patient’s risk of progressing to leukemia is important for determining optimal timing of stem cell transplantation. Based on information about 1,000 patients who had been diagnosed with MDS, researchers from several U.S. cancer centers have determined that patients with a low or low-intermediate risk of progression to leukemia have better outcomes if their transplant was not performed at the time of diagnosis, but was delayed. Patients with a high or high-intermediate risk experienced optimal survival if they underwent an allogeneic transplant at the time of diagnosis, without delay. Furthermore, the patients with lower risk achieved optimal outcomes if their transplant was administered prior to progression of their disease to acute myeloid leukemia compared to after progression. 
Overview of Treatment of MDS
The objective of treatment is to control the growth of the abnormal cells so that more normal cells can grow and improve blood cell production. Some treatments are designed to manage the complications associated with ineffective blood cell production, while others extend survival or even cure the disease.
Treatment of MDS is individualized and depends on two main factors:
- The severity of low blood counts
- The risk of progression to acute myeloid leukemia
Other factors that influence treatment decisions include patient’s age, other medical conditions, and the severity of the myelodysplastic syndrome.
The potential treatment options for MDS include the following:
Currently, only stem cell transplant utilizing cells from a donor—called an allogeneic transplant—can consistently cure patients with MDS. Other therapies are directed at prolonging survival and decreasing the symptoms from these diseases.
 Cutler C, Lee S, Greenberg P, et al. A decision analysis of allogeneic bone marrow transplantation for the myelodysplastic syndromes: delayed transplantation for low-risk myelodysplasia is associated with improved outcome. Blood. 2004;104:579-585.