21st Century Adult Cancer Sourcebook: Myelodysplastic Syndromes (MDS), Refractory Anemia, Refractory Cytopenia - Clinical Data for Patients, Families, and Physicians
Edition 1.0 - October 2011
National Cancer Institute
Smashwords Edition
Copyright 2011 Progressive Management
Questions? Suggestions? Comments? Concerns? Please contact the publisher directly at
Remember, the book retailer can't answer your questions, but we can!
* * * * * * * * * * *
Smashwords Edition, License Notes
This ebook is licensed for your personal enjoyment only. This ebook may not be re-sold or given away to other people. If you would like to share this book with another person, please purchase an additional copy for each person you share it with. If you're reading this book and did not purchase it, or it was not purchased for your use only, then you should return to Smashwords.com and purchase your own copy. Thank you for respecting the hard work of this author.
* * * * * * * * * * *
Smashwords Edition, License Notes
This ebook is licensed for your personal enjoyment only. This ebook may not be re-sold or given away to other people. If you would like to share this book with another person, please purchase an additional copy for each person you share it with. If you're reading this book and did not purchase it, or it was not purchased for your use only, then you should return to Smashwords.com and purchase your own copy. Thank you for respecting the hard work of this author.
* * * * * * * * * * * *
IMPORTANT NOTE: Information in this e-book is not a substitute for professional medical advice. If you have or suspect that you have any illness, you must consult with a physician or professional healthcare provider! Call 911 and get to the nearest emergency room if you have serious or worsening symptoms.
This material represents a snapshot in time, with authoritative information formatted for ebook reading that was up-to-date at the moment of publication. For the latest cancer updates, please be sure to visit the NCI website:
From our Guide to Leading Medical Websites, here are three valuable sites with authoritative cancer information:
OncoLink * http://www.oncolink.upenn.edu/
eMedicine.com * http://www.emedicine.com/
American Cancer Society (ACS) * http://www.cancer.org/
* * * * * * * * * * * *
This is a privately authored news service and educational publication of Progressive Management. Our publications synthesize official government information with original material - they are not produced by the federal government. They are designed to provide a convenient user-friendly reference work to uniformly present authoritative knowledge that can be rapidly read, reviewed or searched. Vast archives of important data that might otherwise remain inaccessible are available for instant review no matter where you are. This e-book format makes a great reference work and educational tool. There is no other reference book that is as convenient, comprehensive, thoroughly researched, and portable - everything you need to know, from renowned experts you trust. For over a quarter of a century, our news, educational, technical, scientific, and medical publications have made unique and valuable references accessible to all people. Our e-books put knowledge at your fingertips, and an expert in your pocket!
PART ONE
Chapter 1A: Myelodysplastic Syndromes Patient Information
Chapter 2A: Myelodysplastic Syndromes Health Professional
Chapter 3A: Myelodysplastic Syndromes Clinical Trials
PART TWO
Chapter 1B: Levels of Evidence for Adult and Pediatric Cancer Treatment Studies (NCI)
Chapter 2B: Glossary of Clinical Trial Terms
Chapter 3B: Clinical Trials Background Information
Chapter 4B: Cancer Clinical Trials -The Basic Workbook
Chapter 5B: Cancer Clinical Trials - The In-Depth Program
Chapter 6B: Clinical Trials at NIH
Chapter 7B: How To Find A Cancer Treatment Trial: A Ten Step Guide
Chapter 8B: Taking Part in Cancer Treatment Research Studies
Chapter 9B: Cancer Clinical Trials
Chapter 10B: Access to Investigational Drugs
Chapter 12B: Taking Time: Support for People with Cancer
Chapter 13B: Facing Forward - Life After Cancer Treatment
Chapter 14B: Chemotherapy and You
* * * * * * * * * * * *
PART ONE
* * * * * * * * * * * *
Chapter 1A: Myelodysplastic Syndromes Patient Information
Myelodysplastic Syndromes Treatment
Patient Version
Last Modified: 09/27/2011
General Information About Myelodysplastic Syndromes
Key Points for This Section
* Myelodysplastic syndromes are a group of diseases in which the bone marrow does not make enough healthy blood cells.
* There are several types of myelodysplastic syndromes.
* Age and past treatment with chemotherapy or radiation therapy affect the risk of developing a myelodysplastic syndrome.
* Possible signs of myelodysplastic syndrome include feeling tired and shortness of breath.
* Tests that examine the blood and bone marrow are used to detect (find) and diagnose myelodysplastic syndromes.
* Myelodysplastic syndromes are diagnosed based on certain changes in the blood cells and bone marrow.
* Certain factors affect prognosis and treatment options.
Myelodysplastic syndromes are a group of diseases in which the bone marrow does not make enough healthy blood cells.
Myelodysplastic syndromes are diseases of the blood and bone marrow. Normally, the bone marrow makes blood stem cells (immature cells) that develop into mature blood cells over time. A blood stem cell may become a myeloid stem cell or a lymphoid stem cell. The lymphoid stem cell develops into a white blood cell. The myeloid stem cell develops into one of three types of mature blood cells:
* Red blood cells that carry oxygen and other materials to all tissues of the body.
* White blood cells that fight infection and disease.
* Platelets that help prevent bleeding by causing blood clots to form.
Blood cell development. A blood stem cell goes through several steps to become a red blood cell, platelet, or white blood cell.
In myelodysplastic syndromes, the blood stem cells do not mature into healthy red blood cells, white blood cells, or platelets. The immature blood cells, called blasts, do not function normally and either die in the bone marrow or soon after they enter the blood. This leaves less room for healthy white blood cells, red blood cells, and platelets to develop in the bone marrow. When there are fewer blood cells, infection, anemia, or easy bleeding may occur.
There are several types of myelodysplastic syndromes.
Myelodysplastic syndromes have too few of one or more types of healthy blood cells in the bone marrow or blood. Myelodysplastic syndromes include the following diseases:
* Refractory anemia.
* Refractory anemia with ringed sideroblasts.
* Refractory anemia with excess blasts.
* Refractory anemia with excess blasts in transformation.
* Refractory cytopenia with multilineage dysplasia.
* Myelodysplastic syndrome associated with an isolated del(5q) chromosome abnormality.
* Unclassifiable myelodysplastic syndrome.
Age and past treatment with chemotherapy or radiation therapy affect the risk of developing a myelodysplastic syndrome.
Anything that increases your risk of getting a disease is called a risk factor. Having a risk factor does not mean that you will get a disease; not having risk factors doesn’t mean that you will not get a disease. People who think they may be at risk should discuss this with their doctor. Risk factors for myelodysplastic syndromes include the following:
* Being male or white.
* Being older than 60 years.
* Past treatment with chemotherapy or radiation therapy.
* Being exposed to certain chemicals, including tobacco smoke, pesticides, and solvents such as benzene.
* Being exposed to heavy metals, such as mercury or lead.
Possible signs of myelodysplastic syndrome include feeling tired and shortness of breath.
Myelodysplastic syndromes often do not cause early symptoms and are sometimes found during a routine blood test. Other conditions may cause the same symptoms. A doctor should be consulted if any of the following problems occur:
* Shortness of breath.
* Weakness or feeling tired.
* Having skin that is paler than usual.
* Easy bruising or bleeding.
* Petechiae (flat, pinpoint spots under the skin caused by bleeding).
* Fever or frequent infections.
Tests that examine the blood and bone marrow are used to detect (find) and diagnose myelodysplastic syndromes.
The following tests and procedures may be used:
* Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken.
* Complete blood count (CBC) with differential: A procedure in which a sample of blood is drawn and checked for the following:
* The number of red blood cells and platelets.
* The number and type of white blood cells.
* The amount of hemoglobin (the protein that carries oxygen) in the red blood cells.
* The portion of the blood sample made up of red blood cells.
* Complete blood count (CBC). Blood is collected by inserting a needle into a vein and allowing the blood to flow into a tube. The blood sample is sent to the laboratory and the red blood cells, white blood cells, and platelets are counted. The CBC is used to test for, diagnose, and monitor many different conditions.
* Peripheral blood smear: A procedure in which a sample of blood is checked for changes in the number, type, shape, and size of blood cells and for too much iron in the red blood cells.
* Cytogenetic analysis: A test in which cells in a sample of blood or bone marrow are viewed under a microscope to look for certain changes in the chromosomes.
* Bone marrow aspiration and biopsy: The removal of bone marrow, blood, and a small piece of bone by inserting a hollow needle into the hipbone or breastbone. A pathologist views the bone marrow, blood, and bone under a microscope to look for abnormal cells.
* Bone marrow aspiration and biopsy. After a small area of skin is numbed, a Jamshidi needle (a long, hollow needle) is inserted into the patient’s hip bone. Samples of blood, bone, and bone marrow are removed for examination under a microscope.
Myelodysplastic syndromes are diagnosed based on certain changes in the blood cells and bone marrow.
* Refractory anemia: There are too few red blood cells in the blood and the patient has anemia. The number of white blood cells and platelets is normal.
* Refractory anemia with ringed sideroblasts: There are too few red blood cells in the blood and the patient has anemia. The red blood cells have too much iron. The number of white blood cells and platelets is normal.
* Refractory anemia with excess blasts: There are too few red blood cells in the blood and the patient has anemia. Five percent to 19% of the cells in the bone marrow are blasts and there are a normal number of blasts found in the blood. There also may be changes to the white blood cells and platelets. Refractory anemia with excess blasts may progress to acute myeloid leukemia.
* Refractory anemia with excess blasts in transformation: There are too few red blood cells, white blood cells, and platelets in the blood and the patient has anemia. Twenty percent to 30% of the cells in the bone marrow are blasts and more than 5% of the cells in the blood are blasts. Refractory anemia with excess blasts in transformation is sometimes called acute myeloid leukemia.
* Refractory cytopenia with multilineage dysplasia: There are too few of at least two types of blood cells. Less than 5% of the cells in the bone marrow are blasts and less than 1% of the cells in the blood are blasts. If red blood cells are affected, they may have extra iron. Refractory cytopenia may progress to acute leukemia.
* Myelodysplastic syndrome associated with an isolated del(5q) chromosome abnormality: There are too few red blood cells in the blood and the patient has anemia. Less than 5% of the cells in the bone marrow and blood are blasts. There is a specific change in the chromosome.
* Unclassifiable myelodysplastic syndrome: There are too few of one type of blood cell in the blood. The number of blasts in the bone marrow and blood is normal, and the disease is not one of the other myelodysplastic syndromes.
Certain factors affect prognosis and treatment options.
The prognosis depends on the following:
* Whether the myelodysplastic syndrome occurred after chemotherapy or radiation therapy for another disease.
* The number of blast cells in the bone marrow.
* Whether one or more types of blood cells are affected.
* Certain changes in the chromosomes.
Treatment options depend on the following:
* Whether the myelodysplastic syndrome occurred after chemotherapy or radiation therapy for another disease.
* Whether the myelodysplastic syndrome has progressed after being treated.
* The age and general health of the patient.
Glossary Terms
abnormal (ab-NOR-mul)
* Not normal. An abnormal lesion or growth may be cancer, premalignant (likely to become cancer), or benign (not cancer).
acute leukemia (uh-KYOOT loo-KEE-mee-uh)
* A rapidly progressing cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of white blood cells to be produced and enter the blood stream.
acute myeloid leukemia (uh-KYOOT MY-eh-loyd loo-KEE-mee-uh)
* An aggressive (fast-growing) disease in which too many myeloblasts (immature white blood cells that are not lymphoblasts) are found in the bone marrow and blood. Also called acute myeloblastic leukemia, acute myelogenous leukemia, acute nonlymphocytic leukemia, AML, and ANLL.
anemia (uh-NEE-mee-uh)
* A condition in which the number of red blood cells is below normal.
benzene (BEN-zeen)
* A chemical that is used widely by the chemical industry, and is also found in tobacco smoke, vehicle emissions, and gasoline fumes. Exposure to benzene may increase the risk of developing leukemia.
blast (blast)
* An immature blood cell.
blood (blud)
* A tissue with red blood cells, white blood cells, platelets, and other substances suspended in fluid called plasma. Blood takes oxygen and nutrients to the tissues, and carries away wastes.
blood clot (blud klot)
* A mass of blood that forms when blood platelets, proteins, and cells stick together. When a blood clot is attached to the wall of a blood vessel, it is called a thrombus. When it moves through the bloodstream and blocks the flow of blood in another part of the body, it is called an embolus.
bone marrow (bone MAYR-oh)
* The soft, sponge-like tissue in the center of most bones. It produces white blood cells, red blood cells, and platelets.
bone marrow aspiration (bone MAYR-oh AS-pih-RAY-shun)
* A procedure in which a small sample of bone marrow is removed, usually from the hip bone, breastbone, or thigh bone. A small area of skin and the surface of the bone underneath are numbed with an anesthetic. Then, a special wide needle is pushed into the bone. A sample of liquid bone marrow is removed with a syringe attached to the needle. The bone marrow is sent to a laboratory to be looked at under a microscope. This procedure may be done at the same time as a bone marrow biopsy.
bone marrow biopsy (bone MAYR-oh BY-op-see)
* A procedure in which a small sample of bone with bone marrow inside it is removed, usually from the hip bone. A small area of skin and the surface of the bone underneath are numbed with an anesthetic. Then, a special, wide needle is pushed into the bone and rotated to remove a sample of bone with the bone marrow inside it. The sample is sent to a laboratory to be looked at under a microscope. This procedure may be done at the same time as a bone marrow aspiration.
cell (sel)
* The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.
chemotherapy (KEE-moh-THAYR-uh-pee)
* Treatment with drugs that kill cancer cells.
chromosome (KROH-muh-some)
* Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes.
complete blood count (kum-PLEET blud kownt)
* A test to check the number of red blood cells, white blood cells, and platelets in a sample of blood. Also called blood cell count and CBC.
cytogenetics (SY-toh-jeh-NEH-tix)
* The study of chromosomes and chromosomal abnormalities.
cytopenia (SY-toh-PEE-nee-uh)
* A condition in which there is a lower-than-normal number of blood cells.
dysplasia (dis-PLAY-zhuh)
* Cells that look abnormal under a microscope but are not cancer.
hemoglobin (HEE-moh-GLOH-bin)
* The substance inside red blood cells that binds to oxygen in the lungs and carries it to the tissues.
infection (in-FEK-shun)
* Invasion and multiplication of germs in the body. Infections can occur in any part of the body and can spread throughout the body. The germs may be bacteria, viruses, yeast, or fungi. They can cause a fever and other problems, depending on where the infection occurs. When the body’s natural defense system is strong, it can often fight the germs and prevent infection. Some cancer treatments can weaken the natural defense system.
lymphoid (LIM-foyd)
* Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop.
myelodysplastic syndromes (MY-eh-loh-dis-PLAS-tik SIN-dromz)
* A group of diseases in which the bone marrow does not make enough healthy blood cells. Also called preleukemia and smoldering leukemia.
myeloid (MY-eh-loyd)
* Having to do with or resembling the bone marrow. May also refer to certain types of hematopoietic (blood-forming) cells found in the bone marrow. Sometimes used as a synonym for myelogenous; for example, acute myeloid leukemia and acute myelogenous leukemia are the same disease.
oxygen (OK-sih-jen)
* A colorless, odorless gas. It is needed for animal and plant life. Oxygen that is breathed in enters the blood from the lungs and travels to the tissues.
pathologist (puh-THAH-loh-jist)
* A doctor who identifies diseases by studying cells and tissues under a microscope.
peripheral blood smear (peh-RIH-feh-rul blud smeer)
* A procedure in which a sample of blood is viewed under a microscope to count different circulating blood cells (red blood cells, white blood cells, platelets, etc.) and see whether the cells look normal.
pesticide (PES-tih-side)
* Any substance that is used to kill insects and other pests.
petechiae (peh-TEE-kee-ee)
* Pinpoint, unraised, round red spots under the skin caused by bleeding.
physical examination (FIH-zih-kul eg-ZA-mih-NAY-shun)
* An exam of the body to check for general signs of disease.
platelet (PLATE-let)
* A tiny piece of a cell found in the blood that breaks off from a large cell found in the bone marrow. Platelets help wounds heal and prevent bleeding by forming blood clots. Also called thrombocyte.
prognosis (prog-NO-sis)
* The likely outcome or course of a disease; the chance of recovery or recurrence.
progression (pruh-GREH-shun)
* In medicine, the course of a disease, such as cancer, as it becomes worse or spreads in the body.
protein (PROH-teen)
* A molecule made up of amino acids that are needed for the body to function properly. Proteins are the basis of body structures such as skin and hair and of substances such as enzymes, cytokines, and antibodies.
radiation therapy (RAY-dee-AY-shun THAYR-uh-pee)
* The use of high-energy radiation from x-rays, gamma rays, neutrons, protons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body near cancer cells (internal radiation therapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that travels in the blood to tissues throughout the body. Also called irradiation and radiotherapy.
red blood cell (red blud sel)
* A cell that carries oxygen to all parts of the body. Also called erythrocyte and RBC.
refractory (reh-FRAK-tor-ee)
* In medicine, describes a disease or condition that does not respond to treatment.
risk factor (... FAK-ter)
* Something that increases the chance of developing a disease. Some examples of risk factors for cancer are age, a family history of certain cancers, use of tobacco products, being exposed to radiation or certain chemicals, infection with certain viruses or bacteria, and certain genetic changes.
solvent (SOL-vent)
* A liquid that is able to dissolve a solid.
stem cell (stem sel)
* A cell from which other types of cells develop. For example, blood cells develop from blood-forming stem cells.
symptom (SIMP-tum)
* An indication that a person has a condition or disease. Some examples of symptoms are headache, fever, fatigue, nausea, vomiting, and pain.
tissue (TIH-shoo)
* A group or layer of cells that work together to perform a specific function.
tobacco (tuh-BA-koh)
* A plant with leaves that have high levels of the addictive chemical nicotine. The leaves may be smoked (in cigarettes, cigars, and pipes), applied to the gums (as dipping and chewing tobacco), or inhaled (as snuff). Tobacco leaves also contain many cancer-causing chemicals, and tobacco use and exposure to secondhand tobacco smoke have been linked to many types of cancer and other diseases. The scientific name is Nicotiana tabacum.
transformation (TRANZ-for-MAY-shun)
* In medicine, the change that a normal cell undergoes as it becomes malignant.
white blood cell (hwite blud sel)
* A type of immune cell. Most white blood cells are made in the bone marrow and are found in the blood and lymph tissue. White blood cells help the body fight infections and other diseases. Granulocytes, monocytes, and lymphocytes are white blood cells. Also called leukocyte and WBC.
Table of Links
1 http://www.cancer.gov/cancertopics/pdq/treatment/mds-mpd/Patient
2 http://www.cancer.gov/cancertopics/pdq/treatment/myeloproliferative/Patient
3 http://www.cancer.gov/cancertopics/pdq/treatment/adultAML/Patient
Stages of Myelodysplastic Syndromes
There is no staging system for myelodysplastic syndromes. Treatment is based on whether the disease developed after the patient was exposed to factors that cause myelodysplastic syndrome or whether the disease was previously treated. Myelodysplastic syndromes are grouped for treatment as follows:
De novo myelodysplastic syndromes
De novo myelodysplastic syndromes develop without any known cause.
Secondary myelodysplastic syndromes
Secondary myelodysplastic syndromes develop after the patient was treated with chemotherapy or radiation therapy for other diseases or after being exposed to radiation or certain chemicals that are linked to the development of myelodysplastic syndromes. Secondary myelodysplastic syndromes may be harder to treat than de novo myelodysplastic syndromes.
Previously treated myelodysplastic syndromes
The myelodysplastic syndrome has been treated but has not gotten better.
Glossary Terms
chemotherapy (KEE-moh-THAYR-uh-pee)
* Treatment with drugs that kill cancer cells.
de novo (deh NOH-voh)
* In cancer, the first occurrence of cancer in the body.
myelodysplastic syndromes (MY-eh-loh-dis-PLAS-tik SIN-dromz)
* A group of diseases in which the bone marrow does not make enough healthy blood cells. Also called preleukemia and smoldering leukemia.
radiation (RAY-dee-AY-shun)
* Energy released in the form of particle or electromagnetic waves. Common sources of radiation include radon gas, cosmic rays from outer space, medical x-rays, and energy given off by a radioisotope (unstable form of a chemical element that releases radiation as it breaks down and becomes more stable).
radiation therapy (RAY-dee-AY-shun THAYR-uh-pee)
* The use of high-energy radiation from x-rays, gamma rays, neutrons, protons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body near cancer cells (internal radiation therapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that travels in the blood to tissues throughout the body. Also called irradiation and radiotherapy.
staging (STAY-jing)
* Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. It is important to know the stage of the disease in order to plan the best treatment.
Treatment Option Overview
Key Points for This Section
* There are different types of treatment for patients with myelodysplastic syndromes.
* Treatment for myelodysplastic syndromes aims to relieve symptoms, slow progression, and improve quality of life.
* Three types of standard treatment are used:
* Chemotherapy
* Supportive care
* Chemotherapy with stem cell transplant
* New types of treatment are being tested in clinical trials.
* Patients may want to think about taking part in a clinical trial.
* Patients can enter clinical trials before, during, or after starting their treatment.
* Follow-up tests may be needed.
There are different types of treatment for patients with myelodysplastic syndromes.
Different types of treatments are available for patients with myelodysplastic syndromes. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with a myelodysplastic syndrome. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.
Treatment for myelodysplastic syndromes aims to relieve symptoms, slow progression, and improve quality of life.
Treatment options for patients with myelodysplastic syndromes range from supportive care that helps relieve symptoms to aggressive treatment that may slow or prevent progression of the disease.
Problems caused by low blood cell counts, such as fatigue and infections, may be treated with transfusions of blood products or the use of growth factors.
Chemotherapy may be used to delay progression of the disease. Other drug therapy may be used to lessen the need for transfusions. Certain patients may benefit from aggressive treatment with chemotherapy followed by stem cell transplant using stem cells from a donor.
Three types of standard treatment are used:
Chemotherapy
In myelodysplastic syndromes, chemotherapy is a treatment that uses drugs to stop the growth of immature blood cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). The way the chemotherapy is given depends on the disease being treated.
Supportive care
Supportive care is given to lessen the problems caused by the disease or its treatment. Supportive care may include the following:
* Transfusion therapy
* Transfusion therapy (blood transfusion) is a method of giving red blood cells, white blood cells, or platelets to replace blood cells destroyed by disease or treatment. Patients who receive frequent red blood cell transfusions may have their tissues and organs damaged from the buildup of extra iron. Iron chelation therapy is a treatment that uses drugs that attach to the extra iron. The drug and the iron are removed from the body in the urine.
* Platelet transfusions are usually given when the patient is bleeding or is having a procedure that may cause bleeding.
* Growth factor therapy
* Erythropoietin may be given to increase the number of red blood cells and lessen the effects of anemia. Sometimes granulocyte colony-stimulating factor (G-CSF) is given with erythropoietin to help the treatment work better.
* Drug therapy
* Deferoxamine may be used to treat the build-up of too much iron in the blood of patients receiving blood transfusions. It is sometimes given with vitamin C.
* Lenalidomide may be used to lessen the need for transfusions in patients who have myelodysplastic syndrome caused by a specific chromosome change.
* Antithymocyte globulin (ATG) may also be used to lessen the need for transfusions in patients with a certain form of myelodysplastic syndrome.
* Antibiotics may be given to fight infections.
Chemotherapy with stem cell transplant
Stem cell transplant is a method of giving chemotherapy and replacing blood-forming cells destroyed by the treatment. Stem cells (immature blood cells) are removed from the blood or bone marrow of a donor and are frozen for storage. After the chemotherapy is completed, the stored stem cells are thawed and given back to the patient through an infusion. These reinfused stem cells grow into (and restore) the body's blood cells.
Stem cell transplant (Step 1). Blood is taken from a vein in the arm of the donor. The patient or another person may be the donor. The blood flows through a machine that removes the stem cells. Then the blood is returned to the donor through a vein in the other arm.
Stem cell transplant (Step 2). The patient receives chemotherapy to kill blood-forming cells. The patient may receive radiation therapy (not shown).
Stem cell transplant (Step 3). The patient receives stem cells through a catheter placed into a blood vessel in the chest.
New types of treatment are being tested in clinical trials.
Information about clinical trials is available from the NCI Web site 2.
Patients may want to think about taking part in a clinical trial.
For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the medical research process. Clinical trials are done to find out if new treatments are safe and effective or better than the standard treatment.
Many of today's standard treatments for disease are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.
Patients who take part in clinical trials also help improve the way diseases will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.
Patients can enter clinical trials before, during, or after starting their treatment.
Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose disease has not gotten better. There are also clinical trials that test new ways to stop a disease from recurring (coming back) or reduce the side effects of treatment.
Clinical trials are taking place in many parts of the country. See the Treatment Options section that follows for links to current treatment clinical trials. These have been retrieved from NCI's clinical trials database.
Follow-up tests may be needed.
Some of the tests that were done to diagnose the disease may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests.
Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the disease has recurred (come back). These tests are sometimes called follow-up tests or check-ups.
Glossary Terms
abdomen (AB-doh-men)
* The area of the body that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs.
aggressive (uh-GREH-siv)
* In medicine, describes a tumor or disease that forms, grows, or spreads quickly. It may also describe treatment that is more severe or intense than usual.
anemia (uh-NEE-mee-uh)
* A condition in which the number of red blood cells is below normal.
antibiotic (AN-tee-by-AH-tik)
* A drug used to treat infections caused by bacteria and other microorganisms.
antithymocyte globulin (AN-tee-THY-moh-site GLAH-byoo-lin)
* Serum from blood that contains antibodies that bind to human T cells. Antithymocyte globulin is given to a patient before a stem cell transplant to kill T cells and lower the risk of graft-versus-host disease (GVHD). It is also used to treat GVHD and after a kidney transplant to help keep the body from rejecting the kidney. Also called antilymphocyte globulin.
blood (blud)
* A tissue with red blood cells, white blood cells, platelets, and other substances suspended in fluid called plasma. Blood takes oxygen and nutrients to the tissues, and carries away wastes.
blood cell count (blud sel kownt)
* A test to check the number of red blood cells, white blood cells, and platelets in a sample of blood. Also called CBC and complete blood count.
blood transfusion (blud tranz-FYOO-zhun)
* A procedure in which a person is given an infusion of whole blood or parts of blood. The blood may be donated by another person, or it may have been taken from the patient earlier and stored until needed. Also called transfusion.
bone marrow (bone MAYR-oh)
* The soft, sponge-like tissue in the center of most bones. It produces white blood cells, red blood cells, and platelets.
cavity (KA-vih-tee)
* A hollow area or hole. It may describe a body cavity (such as the space within the abdomen) or a hole in a tooth caused by decay.
cell (sel)
* The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.
cerebrospinal fluid (seh-REE-broh-SPY-nul FLOO-id)
* The fluid that flows in and around the hollow spaces of the brain and spinal cord, and between two of the meninges (the thin layers of tissue that cover and protect the brain and spinal cord). Cerebrospinal fluid is made by tissue called the choroid plexus in the ventricles (hollow spaces) in the brain. Also called CSF.
chemotherapy (KEE-moh-THAYR-uh-pee)
* Treatment with drugs that kill cancer cells.
chromosome (KROH-muh-some)
* Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes.
clinical trial (KLIH-nih-kul TRY-ul)
* A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called clinical study.
deferoxamine (DEH-feh-ROK-suh-meen)
* An iron-chelating agent that removes iron from tumors by inhibiting DNA synthesis and causing cancer cell death. It is used in conjunction with other anticancer agents in pediatric neuroblastoma therapy.
diagnosis (DY-ug-NOH-sis)
* The process of identifying a disease, such as cancer, from its signs and symptoms.
drug (drug)
* Any substance, other than food, that is used to prevent, diagnose, treat or relieve symptoms of a disease or abnormal condition. Also refers to a substance that alters mood or body function, or that can be habit-forming or addictive, especially a narcotic.
erythropoietin (eh-RITH-roh-POY-eh-tin)
* A substance that is naturally produced by the kidneys, and that stimulates the bone marrow to make red blood cells. When erythropoietin is made in the laboratory, it is called epoetin alfa or epoetin beta.
fatigue (fuh-TEEG)
* A condition marked by extreme tiredness and inability to function due lack of energy. Fatigue may be acute or chronic.
granulocyte colony-stimulating factor (GRAN-yoo-loh-SITE KAH-luh-nee-STIM-yoo-LAY-ting FAK-ter)
* A colony-stimulating factor that stimulates the production of neutrophils (a type of white blood cell). It is a cytokine that is a type of hematopoietic (blood-forming) agent. Also called filgrastim and G-CSF.
growth factor (grothe FAK-ter)
* A substance made by the body that functions to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy.
infection (in-FEK-shun)
* Invasion and multiplication of germs in the body. Infections can occur in any part of the body and can spread throughout the body. The germs may be bacteria, viruses, yeast, or fungi. They can cause a fever and other problems, depending on where the infection occurs. When the body’s natural defense system is strong, it can often fight the germs and prevent infection. Some cancer treatments can weaken the natural defense system.
infusion (in-FYOO-zhun)
* A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion.
injection (in-JEK-shun)
* Use of a syringe and needle to push fluids or drugs into the body; often called a "shot."
iron (I-urn)
* An important mineral the body needs to make hemoglobin, a substance in the blood that carries oxygen from the lungs to tissues throughout the body. Iron is also an important part of many other proteins and enzymes needed by the body for normal growth and development. It is found in red meat, fish, poultry, lentils, beans, and foods with iron added, such as cereal.
lenalidomide (leh-nah-LIH-doh-mide)
* A drug that is similar to thalidomide, and is used to treat multiple myeloma and certain types of anemia. It is also being studied in the treatment of other types of cancer. Lenalidomide belongs to the family of drugs called angiogenesis inhibitors. Also called CC-5013 and Revlimid.
myelodysplastic syndromes (MY-eh-loh-dis-PLAS-tik SIN-dromz)
* A group of diseases in which the bone marrow does not make enough healthy blood cells. Also called preleukemia and smoldering leukemia.
organ (OR-gun)
* A part of the body that performs a specific function. For example, the heart is an organ.
platelet (PLATE-let)
* A tiny piece of a cell found in the blood that breaks off from a large cell found in the bone marrow. Platelets help wounds heal and prevent bleeding by forming blood clots. Also called thrombocyte.
prevention (pree-VEN-shun)
* In medicine, action taken to decrease the chance of getting a disease or condition. For example, cancer prevention includes avoiding risk factors (such as smoking, obesity, lack of exercise, and radiation exposure) and increasing protective factors (such as getting regular physical activity, staying at a healthy weight, and having a healthy diet).
progression (pruh-GREH-shun)
* In medicine, the course of a disease, such as cancer, as it becomes worse or spreads in the body.
recur
* To come back or to return.
red blood cell (red blud sel)
* A cell that carries oxygen to all parts of the body. Also called erythrocyte and RBC.
regional chemotherapy (REE-juh-nul KEE-moh-THAYR-uh-pee)
* Treatment with anticancer drugs directed to a specific area of the body.
side effect (side eh-FEKT)
* A problem that occurs when treatment affects healthy tissues or organs. Some common side effects of cancer treatment are fatigue, pain, nausea, vomiting, decreased blood cell counts, hair loss, and mouth sores.
standard therapy (... THAYR-uh-pee)
* Treatment that experts agree is appropriate, accepted, and widely used. Also called best practice, standard medical care, and standard of care.
stem cell (stem sel)
* A cell from which other types of cells develop. For example, blood cells develop from blood-forming stem cells.
stem cell transplant (stem sel tranz-plant)
* A method of replacing immature blood-forming cells in the bone marrow that have been destroyed by drugs, radiation, or disease. Stem cells are injected into the patient and make healthy blood cells. A stem cell transplant may be autologous (using a patient’s own stem cells that were saved before treatment), allogeneic (using stem cells donated by someone who is not an identical twin), or syngeneic (using stem cells donated by an identical twin).
supportive care (suh-POR-tiv kayr)
* Care given to improve the quality of life of patients who have a serious or life-threatening disease. The goal of supportive care is to prevent or treat as early as possible the symptoms of a disease, side effects caused by treatment of a disease, and psychological, social, and spiritual problems related to a disease or its treatment. Also called comfort care, palliative care, and symptom management.
symptom (SIMP-tum)
* An indication that a person has a condition or disease. Some examples of symptoms are headache, fever, fatigue, nausea, vomiting, and pain.
systemic chemotherapy (sis-TEH-mik KEE-moh-THAYR-uh-pee)
* Treatment with anticancer drugs that travel through the blood to cells all over the body.
therapy (THAYR-uh-pee)
* Treatment.
tissue (TIH-shoo)
* A group or layer of cells that work together to perform a specific function.
transfusion (tranz-FYOO-zhun)
* A procedure in which a person is given an infusion of whole blood or parts of blood. The blood may be donated by another person, or it may have been taken from the patient earlier and stored until needed. Also called blood transfusion.
urine (YOOR-in)
* Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra.
vein (vayn)
* A blood vessel that carries blood to the heart from tissues and organs in the body.
vitamin C (VY-tuh-min…)
* A nutrient that the body needs in small amounts to function and stay healthy. Vitamin C helps fight infections, heal wounds, and keep tissues healthy. It is an antioxidant that helps prevent cell damage caused by free radicals (highly reactive chemicals). Vitamin C is found in all fruits and vegetables, especially citrus fruits, strawberries, cantaloupe, green peppers, tomatoes, broccoli, leafy greens, and potatoes. It is water-soluble (can dissolve in water) and must be taken in every day. Vitamin C is being studied in the prevention and treatment of some types of cancer. Also called ascorbic acid.
white blood cell (hwite blud sel)
* A type of immune cell. Most white blood cells are made in the bone marrow and are found in the blood and lymph tissue. White blood cells help the body fight infections and other diseases. Granulocytes, monocytes, and lymphocytes are white blood cells. Also called leukocyte and WBC.
Table of Links
1 http://www.cancer.gov/cancertopics/pdq/treatment/myelodysplastic/Patient/Table1
2 http://cancer.gov/clinicaltrials
Treatment Options for Myelodysplastic Syndromes
De Novo and Secondary Myelodysplastic Syndromes
Treatment of de novo and secondary myelodysplastic syndromes may include the following:
* Supportive care with transfusion therapy.
* High-dose chemotherapy with stem cell transplant using stem cells from a donor.
* Supportive care with growth factor therapy.
* Chemotherapy with azacitidine, decitabine, or other anticancer drugs.
* Supportive care with drug therapy.
* A clinical trial of a new anticancer drug.
* A clinical trial of low- dose chemotherapy with stem cell transplant using stem cells from a donor.
* A clinical trial of a combination of treatments.
* A clinical trial of growth factor therapy.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with de novo myelodysplastic syndromes 1 and secondary myelodysplastic syndromes 2. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site 3.
Previously Treated Myelodysplastic Syndromes
Treatment of previously treated myelodysplastic syndromes may include the following:
* High-dose chemotherapy with stem cell transplant using stem cells from a donor.
* Chemotherapy with azacitidine or decitabine.
* Supportive care with transfusion therapy, growth factor therapy, and/or drug therapy.
* A clinical trial of low- dose chemotherapy with stem cell transplant using stem cells from a donor.
* A clinical trial of new drug therapy.
* A clinical trial of a combination of treatments.
* A clinical trial of growth factor therapy.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with previously treated myelodysplastic syndromes 4. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site 3.
Glossary Terms
azacitidine (ay-zuh-SY-tih-deen)
* A drug that is used to treat myelodysplastic syndromes and is being studied in the treatment of other types of cancer. It belongs to the family of drugs called antimetabolites. Also called Mylosar and Vidaza.
chemotherapy (KEE-moh-THAYR-uh-pee)
* Treatment with drugs that kill cancer cells.
clinical trial (KLIH-nih-kul TRY-ul)
* A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called clinical study.
de novo (deh NOH-voh)
* In cancer, the first occurrence of cancer in the body.
decitabine (deh-SIH-tuh-been)
* A drug that is used to treat myelodysplastic syndromes and is being studied in the treatment of other types of cancer. It is a type of antimetabolite. Also called Dacogen.
dose (dose)
* The amount of medicine taken, or radiation given, at one time.
drug (drug)
* Any substance, other than food, that is used to prevent, diagnose, treat or relieve symptoms of a disease or abnormal condition. Also refers to a substance that alters mood or body function, or that can be habit-forming or addictive, especially a narcotic.
growth factor (grothe FAK-ter)
* A substance made by the body that functions to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy.
high-dose chemotherapy (hy-dose kee-moh-THAYR-uh-pee)
* An intensive drug treatment to kill cancer cells, but that also destroys the bone marrow and can cause other severe side effects. High-dose chemotherapy is usually followed by bone marrow or stem cell transplantation to rebuild the bone marrow.
myelodysplastic syndromes (MY-eh-loh-dis-PLAS-tik SIN-dromz)
* A group of diseases in which the bone marrow does not make enough healthy blood cells. Also called preleukemia and smoldering leukemia.
stem cell (stem sel)
* A cell from which other types of cells develop. For example, blood cells develop from blood-forming stem cells.
stem cell transplant (stem sel tranz-plant)
* A method of replacing immature blood-forming cells in the bone marrow that have been destroyed by drugs, radiation, or disease. Stem cells are injected into the patient and make healthy blood cells. A stem cell transplant may be autologous (using a patient’s own stem cells that were saved before treatment), allogeneic (using stem cells donated by someone who is not an identical twin), or syngeneic (using stem cells donated by an identical twin).
supportive care (suh-POR-tiv kayr)
* Care given to improve the quality of life of patients who have a serious or life-threatening disease. The goal of supportive care is to prevent or treat as early as possible the symptoms of a disease, side effects caused by treatment of a disease, and psychological, social, and spiritual problems related to a disease or its treatment. Also called comfort care, palliative care, and symptom management.
therapy (THAYR-uh-pee)
* Treatment.
transfusion (tranz-FYOO-zhun)
* A procedure in which a person is given an infusion of whole blood or parts of blood. The blood may be donated by another person, or it may have been taken from the patient earlier and stored until needed. Also called blood transfusion.
Table of Links
1 http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?Diagnosis=40812&tt=1&format=1&cn=1
2 http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?Diagnosis=41145&tt=1&format=1&cn=1
3 http://www.cancer.gov/clinicaltrials
4 http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?Diagnosis=41144&tt=1&format=1&cn=1
* * * * * * * * * * * *
Chapter 2A: Myelodysplastic Syndromes Health Professional
Myelodysplastic Syndromes Treatment
myelodysplastic syndromes (MY-eh-loh-dis-PLAS-tik SIN-dromz)
A group of diseases in which the bone marrow does not make enough healthy blood cells. Also called preleukemia and smoldering leukemia.
General Information About Myelodysplastic Syndromes
The myelodysplastic syndromes (MDS) are a group of disorders characterized by one or more peripheral blood cytopenias secondary to bone marrow dysfunction. The MDS are diagnosed in slightly more than 10,000 people in the United States yearly for an annual age-adjusted incidence of 3.4/100,000 people.[1] The MDS are more common in men and whites. The syndromes may arise de novo, or secondarily after treatment with chemotherapy and/or radiation therapy for other diseases. Secondary myelodysplasia usually has a poorer prognosis than does de novo myelodysplasia. Prognosis is directly related to the number of bone marrow blast cells and to the amount of peripheral blood cytopenias. The MDS transform to acute myeloid leukemia (AML) in about 30% of patients after various intervals from diagnosis and at variable rates.
The acute leukemic transformation is much less responsive to chemotherapy than is de novo AML. Prognosis is also related to the type of myelodysplastic syndrome. Supportive care has been the mainstay of treatment. Judicious use of platelet and blood transfusions and iron chelation may prevent or delay alloimmunization and iron overload and favorably affect prognosis.
The MDS are characterized by abnormal bone marrow and blood cell morphology. Megaloblastic erythroid hyperplasia with macrocytic anemia, which is associated with normal vitamin B12 and folate levels, is frequently observed. Circulating granulocytes are frequently severely reduced, often hypogranular or hypergranular, and may display the acquired pseudo-Pelger-Huet abnormality. Early, abnormal myeloid progenitors are identified in the marrow in varying percentages, depending on the type of myelodysplastic syndrome. Abnormally small megakaryocytes (micromegakaryocytes) may be seen in the marrow and hypogranular or giant platelets may appear in the blood.
The MDS occur predominantly in older patients (usually >60 years), though patients as young as 2 years have been reported.[2] Anemia, bleeding, easy bruising, and fatigue are common initial findings. (Refer to the PDQ summary on Fatigue for more information.) Splenomegaly or hepatosplenomegaly may occasionally be present in association with an overlapping myeloproliferative disorder. Approximately 50% of the patients have a detectable cytogenetic abnormality, most commonly a deletion of all or part of chromosome 5 or 7, or trisomy 8.[3] Although the bone marrow is usually hypercellular at diagnosis, 15% to 20% of patients present with a hypoplastic bone marrow.[4] Hypoplastic myelodysplastic patients tend to have profound cytopenias and may respond more frequently to immunosuppressive therapy.
A variety of risk classification systems have been developed to predict the overall survival of patients with MDS and the evolution from MDS to AML. These classification systems include the French-American-British classification,^ the Bournemouth score,[6] the Sanz score,[7] the Lille score,[8] and the World Health Organization classification.^ Clinical variables in these systems have included bone marrow and blood myeloblast percentage, specific cytopenias, age, lactate dehydrogenase level, and bone marrow cytogenetic pattern.
An International MDS Risk Analysis Workshop was convened, and the clinical data from 816 patients with primary MDS from seven previously reported studies, which used independent risk-based prognostic systems, were combined and collated.[1 0] The combined data were analyzed centrally, and a global analysis was performed, which formed the basis of a new prognostic system called the International Prognostic Scoring System for MDS.Q0] In multivariate analyses, significant predictors for both survival and AML evolution included bone marrow blast percentage, number of peripheral blood cytopenias, and cytogenetic subgroup. The data are used to assign MDS patients a score, which stratifies patients into one of the following four risk groups:
• Low risk.
• Intermediate-1.
• Intermediate-2.
• High risk.
The time for the development of AML in the risk groups was 9.4 years, 3.3 years, 1.1 years, and 0.2 years, respectively. Median survival for the groups was 5.7 years, 3.5 years, 1.2 years, and 0.4 years, respectively. The system has been incorporated into clinical trial design for MDS.
References
1. Ma X, Does M, Raza A, et al.: Myelodysplastic syndromes: incidence and survival in the United States. Cancer 109 (8): 1536-42, 2007.
2. Tuncer MA, Pagliuca A, Hicsonmez G, et al.: Primary myelodysplastic syndrome in children: the clinical experience in 33 cases. Br J Haematol 82 (2): 347-53, 1992.
3. Gyger M, Infante-Rivard C, D'Angelo G, et al.: Prognostic value of clonal chromosomal abnormalities in patients with primary myelodysplastic syndromes. Am J Hematol 28 (1): 13-20,1988.
4. Nand S, Godwin JE: Hypoplastic myelodysplastic syndrome. Cancer 62 (5): 958-64, 1988.
5. Bennett JM, Catovsky D, Daniel MT, et al.: Proposals for the classification of the myelodysplastic syndromes. Br J Haematol 51 (2): 189-99, 1982.
6. Mufti GJ, Stevens JR, Oscier DG, et al.: Myelodysplastic syndromes: a scoring system with prognostic significance. Br J Haematol 59 (3): 425-33, 1985.
7. Sanz GF, Sanz MA, Vallespf T, et al.: Two regression models and a scoring system for predicting survival and planning treatment in myelodysplastic syndromes: a multivariate analysis of prognostic factors in 370 patients. Blood 74 (1): 395-408, 1989.
8. Aul C, Gattermann N, Heyll A, et al.: Primary myelodysplastic syndromes: analysis of prognostic factors in 235 patients and proposals for an improved scoring system. Leukemia 6 (1): 52-9, 1992.
9. Brunning RD, Bennett JM, Flandrin G, et al.: Myelodysplastic syndromes. In: Jaffe ES, Harris NL, Stein H, et al., eds.: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press, 2001. World Health Organization Classification of Tumours, 3, pp 61-73.
10. Greenberg P, Cox C, LeBeau MM, et al.: International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 89 (6): 2079-88, 1997.
Classification of Myelodysplastic Syndromes
The myelodysplastic syndromes (MDS) are classified according to features of cellular morphology, etiology, and clinical presentation. The morphological classification of the MDS is largely based on the percent of myeloblasts in the bone marrow and blood, the type and degree of myeloid dysplasia, and the presence of ringed sideroblasts.Q] The clinical classification of the MDS depends upon whether there is an identifiable etiology and whether the MDS has been treated previously.
Cellular Classification
Work on the French-American-British (FAB) classification scheme for the MDS began in the late 1970s under the direction of the French-American-British Cooperative Group (see table below). The version published in 1982 was the first diagnostic classification scheme to clearly and reproducibly distinguish MDS from acute myelogenous leukemia (AML).[1J According to the FAB scheme, the percentage of bone marrow blasts required for the diagnosis of MDS ranges from less than 5% to as much as 29%. The FAB scheme is still frequently used by clinicians to categorize the MDS.
Several weaknesses were identified in the FAB classification of MDS. The inclusion of chronic myelomonocytic leukemia (CMML) was problematic; CMML is a disease that combines features of both MDS and chronic myeloproliferative disorders.[2] In addition, the FAB classification did not take cytogenetic findings into account. For example, the cytogenetically defined MDS subtype del(5q) represents a distinct clinical entity.[3]
In 1997, under the auspices of the World Health Organization (WHO), a working group of pathologists and clinicians from around the world agreed to a new cellular classification scheme for hematopoietic and lymphoid malignancies.[4] Significant changes to the FAB classification of these malignancies were made. For the classification of MDS, the new WHO classification lowered the threshold to 20% for the number of myeloblasts required to make the diagnosis of AML.[5] This arbitrary threshold value for blast percentage eliminated the cellular type, refractory anemia with excess blasts in transformation (RAEB-t), found in the FAB classification scheme. In the WHO cellular classification scheme, RAEB-t is no longer considered a distinct clinicopathologic entity; instead, RAEB-t is included within the broader category, AML with multilineage dysplasia, and identified as AML with multilineage dysplasia following a myelodysplastic syndrome.[6]
The elimination of RAEB-t from the WHO cellular classification scheme met some resistance. Some have argued that the biology of RAEB-t is distinct from AML and should be retained as a diagnostic category of MDS.[7,8] Others have emphasized the similar prognoses and responses to treatment for RAEB-t and AML with trilineage dysplasia.[9,10] The diagnosis of AML, which is based upon a threshold of 20% bone marrow or peripheral blood myeloblasts, does not represent a therapeutic mandate. The decision to treat must include other factors, such as patient age, prior history of MDS, clinical findings, disease progression, and most importantly, patient preference, in addition to the blast count. The same factors influence treatment options for patients with 30% or more myeloblasts in the blood or marrow.
The addition of refractory cytopenia with multilineage dysplasia (RCMD), myelodysplastic syndrome, unclassifiable (MDS-u), and the myelodysplastic syndrome associated with an isolated del(5q) chromosome abnormality completes the WHO cellular classification scheme for MDS. Finally, the WHO classification of MDS removed CMML from MDS and placed it in a new category, myelodysplastic syndromes and myeloproliferative diseases (MDS and MPD).[11]
MDS cellular types and subtypes in either cellular classification scheme have different degrees of disordered hematopoiesis, frequencies of transformation to acute leukemia, and prognoses. All WHO cellular types and subtypes and the FAB cellular type, RAEB-t, are described in detail below.
Refractory anemia (RA)
In patients with RA, the myeloid and megakaryocytic series in the bone marrow appear normal, but megaloblastoid erythroid hyperplasia is present. Dysplasia is usually minimal. Marrow blasts are less than 5%, and no peripheral blasts are present. Macrocytic anemia with reticulocytopenia is present in the blood. Transformation to acute leukemia is rare, and median survival varies from 2 years to 5 years in most series. RA accounts for 20% to 30% of all patients with MDS.
Refractory anemia with ringed sideroblasts (RARS)
In patients with RARS, the blood and marrow are identical to those in patients with RA, except that at least 15% of marrow red cell precursors are ringed sideroblasts. Approximately 10% to 12% of patients present with this type, and prognosis is identical to that of RA. Approximately 1% to 2% of RARS evolve to AML.
Refractory anemia with excess blasts (RAEB)
In patients with RAEB, there is significant evidence of disordered myelopoiesis and megakaryocytopoiesis in addition to abnormal erythropoiesis. Because of differences in prognosis related to progression to a frank AML, this cellular classification is comprised of two categories, refractory anemia with excess blasts-1 (RAEB-1) and refractory anemia with excess blasts-2 (RAEB-2). Combined, the two categories account for approximately 40% of all patients with MDS. RAEB-1 is characterized by 5% to 9% blasts in the bone marrow and less than 5% blasts in the blood. Approximately 25% of cases of RAEB-1 progress to AML. Median survival is approximately 18 months. RAEB-2 is characterized by 10% to 19% blasts in the bone marrow. Approximately 33% of cases of RAEB-2 progress to AML. Median survival for RAEB-2 is approximately 10 months.
Refractory anemia with excess blasts in transformation (RAEB-t)
In the FAB classification, RAEB-t represents a panmyelosis in which 20% to 30% of marrow cells are blasts, and more than 5% blasts are seen in the blood. Auer rods may be seen. Sixty percent to 75% of patients develop overt acute leukemia, and median survival is 6 months or less. Approximately 25% of patients present with RAEB-t. In the WHO classification, RAEB-t is not a distinct clinical entity; rather, it is included within the broader category, AML with multilineage dysplasia, and identified as AML with multilineage dysplasia following a myelodysplastic syndrome.[6]
Refractory cytopenia with multilineage dysplasia (RCMD)
In patients with RCMD, bicytopenia or pancytopenia is present. In addition, dysplastic changes are present in 10% or more of the cells in two or more myeloid cell lines. There are less than 1% blasts in the blood and less than 5% blasts in the bone marrow. Auer rods are not present. Monocytes in the blood are less than 1 x 109. RCMD accounts for approximately 24% of cases of MDS. The frequency of evolution to acute leukemia is 11%. The overall median survival is 33 months. Refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS) represents another category of RMDS. In RCMD-RS, features of RCMD are present, and more than 15% of erythroid precursors in the bone marrow are ringed sideroblasts. RCMD-RS accounts for approximately 15% of cases of MDS. Survival in RCMD-RS is similar to that in primary RCMD.
Unclassifiable myelodysplastic syndrome (MDS-U)
The cellular subtype, MDS-U, lacks findings appropriate for classification as RA, RARS, RCMD or RAEB. Blasts in the blood and bone marrow are not increased.
Myelodysplastic syndrome associated with an isolated del(5q) chromosome abnormality
This MDS cellular subtype, the 5q- syndrome, is associated with an isolated del(5q) cytogenetic abnormality. Blasts in both blood and bone marrow are less than 5%. This subtype is associated with a long survival. Karyotypic evolution is uncommon. Additional cytogenetic abnormalities may be associated with a more aggressive MDS cellular subtype or may evolve to acute myeloid leukemia.
Clinical Classification
The clinical classification of MDS is used to determine disease prognosis and treatment strategy, and to define entry requirements for many MDS clinical trials.
De novo myelodysplastic syndrome
Most MDS cases occur de novo with no known cause. Secondary myelodysplastic syndrome
The risk of developing MDS may be increased by exposure to a variety of agents including:[12-14]