Última actualización:
01/18/2024
Años publicados: 2004, 2005, 2006, 2012, 2017, 2020
NORD gratefully acknowledges the MDS Foundation, Inc. and Peter L. Greenberg, MD, Professor of Medicine/Hematology, Stanford University School of Medicine, for assistance in the preparation of this report.
Summary
Myelodysplastic syndromes (MDS) are a rare group of blood disorders that occur as a result of disordered development of blood cells within the bone marrow. The three main types of blood elements (i.e., red blood cells, white blood cells and platelets) are affected. Red blood cells deliver oxygen to the body, white blood cells help fight infections, and platelets assist in clotting to stop blood loss. In MDS, dysfunctional blood cells fail to develop normally and enter the bloodstream. As a result, individuals with MDS generally have abnormally low blood cell levels (low blood counts). General symptoms associated with MDS include fatigue, dizziness, weakness, bruising and bleeding, frequent infections, and headaches. In some affected individuals, MDS may progress to life-threatening failure of the bone marrow or develop into acute leukemia. The exact cause of MDS is unknown but genetics and certain chemotherapeutic drugs or toxic exposures in the environment may play a part.
Introduction
Myelodysplastic syndromes were first noted in the medical literature in 1950s where they were described as pre-leukemic conditions. Myelodysplastic syndromes were not regarded as separate, distinct disorders until 1982. In the past, these disorders have also been known by a variety of names including refractory anemia, oligoblastic anemia, myelodysplastic anemia, pre-leukemia, and smoldering leukemia.
The symptoms of MDS occur because the bone marrow fails to produce enough functioning blood cells. The specific symptoms and progression of the disorder vary greatly from person to person. Some individuals may have mild symptoms that remain stable for many years; others may rapidly develop serious symptoms that can progress to life-threatening complications.
The bone marrow, occupies the spongy center of large bones of the body. Blood cells, produced in the red marrow, are released into the bloodstream to travel throughout the body performing their specific functions. In individuals with MDS, the bone marrow develops immature or defective versions of red cells white cells and platelets, some of which are destroyed within the bone marrow. In the process, healthy marrow cells are progressively eliminated. The consequence is a lack of healthy blood cells in the bloodstream and a reduced supply of MDS blood cells, causing symptoms associated with MDS.
The most common symptom in individuals with MDS is fatigue due to low levels of circulating red blood cells. Anemia causes tiredness, increased need for sleep, weakness, lightheadedness, dizziness, irritability, palpitations, headaches, and pale skin color. Low levels of white blood cells (neutropenia) increase the risk of contracting bacterial and fungal infections. Low levels of platelets (thrombocytopenia) makes the individual more susceptible to excessive bruising following minimal injury and spontaneous bleeding from the gums and nose. Women may develop increased menstrual blood loss. Bleeding may also occur in the digestive tube causing blood loss in the stools. Sometimes the bleeding occurs as a scattered red rash chiefly on the limbs–so-called petechial hemorrhages.
MDS has a tendency to get worse with time as the normal bone marrow function dwindles. The pace of progression varies. In some individuals the condition worsens within a few months of diagnosis, while others have relatively little problem for several decades. In about 50 percent of cases, MDS deteriorates into a form of cancer known as acute myeloid leukemia (AML). The transition to leukemia is accompanied by worsening marrow function and the accumulation, first in the marrow and subsequently in the blood, of undeveloped immature cells called blasts which have no useful function and suppress any remaining marrow cell production. As a consequence, the complications from anemia, bleeding, and infection become life-threatening. Because some cases of MDS may progress into leukemia, myelodysplastic syndromes have also been known as pre-leukemia and smoldering leukemia. Patients who do not progress to leukemia may experience a gradual fall-off in marrow function leading to worsening anemia bleeding and infection which despite transfusions of red cells and platelets and antibiotics to treat infection can ultimately be fatal.
MDS is sub-classified according to the type and number of blasts in the bone marrow. A group of French, American and British hematologists created the so-called FAB classification. This classification describes five MDS subtypes: refractory anemia; refractory anemia with sideroblasts; refractory anemia with excess blasts; refractory anemia with excess blasts in transformation; and chronic myelomonocytic leukemia. The first two types are the most common forms of myelodysplastic syndromes and are also the most stable.
The World Health Organization (WHO) released its own classification system for MDS that modifies the FAB classification system, using different terms for the MDS subtypes. The new system has been universally accepted. For more information on the WHO system, contact the World Health Organization listed in the Resources section below.
When the cause of MDS is unknown it is called idiopathic MDS. A so-called secondary MDS can develop after chemotherapy and radiation treatment for cancer or autoimmune diseases. It is possible that some chemicals (pesticides and benzene), cigarette smoking, and possibly viral infections can predispose to MDS. However, these links are circumstantial and in the majority of individuals developing MDS no obvious connection with environmental hazards can be found. MDS sometimes runs in families, suggesting a genetic link with the disease, particularly in younger patients with this disease.
Myelodysplastic syndromes affect males slightly more often than females. The disorder occurs in any age group, but is far more common in older adults, occurring most often in individuals over 60 years of age. According to one estimate, 22 to 45 per 100,000 people over the age of 70 years have MDS. Approximately 20,000 new patients are diagnosed each year in the United States. The number of new cases diagnosed each year is increasing, possibly due to better recognition of the disorder combined with an increasing proportion of elderly adults in the general population. Determining the exact frequency of MDS in the general population is difficult because of lack of reporting of patients with mild cytopenias.
A diagnosis of myelodysplastic syndrome is made based upon a thorough clinical evaluation, a detailed patient history, and a variety of specialized tests including complete blood counts, examination of the blood smear and bone marrow aspiration and biopsy. A complete blood count measures the number of red and white blood cells and platelets in the body. The blood smear and the small sample of bone marrow removed via a needle (the aspirate) is examined under a microscope to evaluate for the characteristic features of MDS. Chromosome analysis is helpful for diagnostic and prognostic purposes as is a blood test determining the presence of certain mutations (changes) within the blood cells.
Treatment
Treatment varies, depending upon the individual’s age, general health, prognostic risk status, specific cytopenia (low blood count) and subtype of MDS. The first aim of treatment is supportive care – giving red cell transfusions to correct anemia, platelet transfusions to treat or prevent serious bleeding, and antibiotics to treat or prevent infections.
A consequence of multiple red cell transfusions of red cells is the accumulation of iron derived from red cell hemoglobin being broken down in the body. Too much build-up of iron can lead to complications which can be avoided by treatment with drugs that bind the iron and eliminate it from the body. In 2005, the drug Exjade (desferasirox) given in tablet form was approved by the U.S. Food and Drug Administration (FDA) for marketing for the treatment of some MDS individuals who have been transfused for many years and have dangerous build-up of iron in the body.
Further treatment aims, where possible, to correct the bone marrow failure. The marrow failure in some patients responds to immunosuppressive treatment with an agent called antithymocyte globulin (ATG). This can sometimes restore the blood count to normal indefinitely and can be repeated if relapses occur. The same treatment is used with success to treat aplastic anemia. Younger patients with the refractory anemia MDS subtype respond best to ATG.
Growth factors are substances normally found in the body that control production of blood cells. They include Neupogen (filgrastim granulocyte-colony stimulating factor [G-CFS]) and Procrit or Epogen (erythropoietin). These growth factors stimulate the production of red white cells and red cells (but not platelets) in MDS. Given by daily to weekly injection, according to blood count severity, these marrow stimulators can be very helpful in some patients.
Replacement of the MDS bone marrow with that of a healthy donor is the only curative treatment for MDS. Patients who are relatively fit even into their 70s may be suitable for a bone marrow stem cell transplant (SCT) from a healthy related donor or an unrelated volunteer. Although SCT can cure MDS this success is offset by the mortality from the transplant. SCT is therefore only performed in selected patients and in specialized centers. Many centers throughout the United States perform marrow stem cell transplants for MDS. For more information, contact the International Bone Marrow Transplant Registry (IBMTR) in Milwaukee (see Resources section).
In the bone marrow, immature cells known as stem cells and myeloblasts develop through cell divisions into the mature healthy cells that populate the bloodstream, a process known as differentiation. In MDS the marrow cells fail to differentiate normally. Certain drugs including Vidaza (5-azacytidine) and Dacogen (decitabine) may correct the problem and improve blood cell production in MDS. Clinical studies have demonstrated the effectiveness of these agents. These drugs were approved in 2004 by the FDA for treatment of MDS. These drugs can delay progression of MDS and prolong survival, but may cause a temporary drop in blood counts during the treatment period requiring dose adjustments.
In 2005, the FDA approved the drug Revlimid (lenalidomide) for the treatment of patients with a subtype of myelodysplastic syndrome. The subtype is MDS patients with deletion 5q cytogenetic abnormality. Revlimid is structurally similar to thalidomide, a drug known to cause severe birth defects. Additional studies are ongoing in animals to address whether there is a risk that Revlimid will also cause birth defects when taken during pregnancy. While these studies are underway, Revlimid is being marketed under a risk management plan called RevAssist, designed to prevent fetal exposure. Under RevAssist, only pharmacists and prescribers registered with the program will prescribe and dispense Revlimid.
In 2020, the FDA approved Inqovi (decitabine and cedazuridine) to treat adult patients with MDS. Inqovi is the first therapy for MDS patients that does not require them to go into a treatment facility to receive intravenous (IV) treatment.
In 2023, the FDA approved ivosidenib (Tibsovo) for adults with MDS who have a IDH1 gene variant and disease that has recurred or has not responded to treatment.
Many studies are currently being conducted to develop better treatments for MDS. Information on current clinical trials is posted on the Internet at www.clinicaltrials.org. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.
For information about clinical trials being conducted at the National Institutes of Health (NIH) Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
E-mail: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltiralsregister.eu/
Please note that some of these organizations may provide information concerning certain conditions potentially associated with this disorder.
TEXTBOOKS
Fauci AS, et al., eds. Harrison’s Principles of Internal Medicine, 14th Ed. New York, NY: McGraw-Hill, Inc; 1998:676-9.
DeVita Jr VT, et al., eds. Cancer Principles and Practice of Oncology. 5th Ed. New York, NY: J.B. Lippincott Company; 1997:2388-96.
Bennett JC, Plum F, eds. Cecil Textbook of Medicine. 20th ed. Philadelphia, PA: W.B. Saunders Co; 1996:836-7.
Greenberg PL, The Myelodysplastic Syndromes, in Hoffman R, et al., eds. Hematology Basic Principles and Practice, 2nd ed. New York, NY: Churchill-Livingstone, Inc; 1994:1098-1121.
JOURNAL ARTICLES
Sekeres MA, List A. Lenalidomide (Revlimid, CC-5013) in myelodysplastic syndromes: is it any good? Curr Hematol Rep. 2005;4:182-5.
Komrokji R, Bennett JM. The myelodysplastic syndromes: classification and prognosis. Curr Hematol Rep. 2003;2:179-85.
Vergilio JA, Bagg A. Myelodysplastic syndromes. Contemporary biologic concepts and emerging diagnostic approaches. Am J Clin Pathol. 2003;119:S58-77.
Benesch M, Deeg HJ. Hemopoietic cell transplantation for myelodysplastic syndromes. Curr Hematol Rep. 2003;2:209-16.
Wayne AS, Barrett AJ. Allogeneic hematopoietic stem cell transplantation for myeloproliferative disorders and myelodysplastic syndromes. Hematol Oncol Clin North Am. 2003;17:1243-60.
Mufti G, et al. Myelodysplastic Syndromes. Hematology (Am Soc Hematol Educ Program). 2003;176-99.
Valent P, et al. Pathogenesis, classification, and treatment of myelodysplastic syndromes (MDS). Wien Klin Wochenschr. 2003;115:515-36.
Greenberg PL, et al. Myelodysplastic Syndromes. Hematology (Am Soc Hematol Educ Program). 2002;136-61.
Raza A, et al. Thalidomide produces transfusion independence in long-standing refractory anemia of patients with myelodysplastic syndromes. Blood. 2001;98:958-65.
Zorat F, et al. The clinical and biological effects of thalidomide in patients with myelodysplastic syndromes. Br J Haematol. 2001;115:881-94.
Cheson BD, Bennett JM, Kantarjian H, , et al. Report of an international working group to standardize response criteria for myelodysplastic syndromes. Blood. 2000;96(12):3671-4.
Cheson BD. Standard and low-dose chemotherapy for the treatment of myelodysplastic syndromes. Leuk Res. 1998;22:S17-21.
Ferrero D, et al. Combined differentiating therapy for myelodysplastic syndromes: a phase II study. Leuk Res. 1996;20:867-76.
Negrin RS, et al. Maintenance treatment of the anemia of myelodysplastic syndromes with recombinant human granulocyte colony-stimulating factor and erythropoietin: evidence for in vivo surgery. Blood. 1996;87:4076-81.
Anderson JE, et al. Allogeneic bone marrow transplantation for 93 patients with myelodysplastic syndrome. Blood. 1993;82:677-81.
Aul C, et al. Age-related incidence and other epidemiological aspects of myelodysplastic syndromes. Br J Haematol. 1992;82:358-67.
Hellstrom-Lindberg E, Tobiasson M, Greenberg PL. Centenary Review: Myelodysplastic Syndromes: Moving towards personalized management. Haematologica 105:1765-1769, 2020.
INTERNET
Besa EC, Woermann UJ. Myelodysplastic Syndrome. Medscape. Last Update Apr 10, 2020. https://emedicine.medscape.com/article/207347-overview Accessed July 7, 2020.
National Cancer Institute. Myelodysplastic Syndromes Treatment. Last Update October 30, 2019. https://www.cancer.gov/cancertopics/pdq/treatment/myelodysplastic/Patient. Accessed July 7, 2020.
Aplastic Anemia & MDS International Foundation. Myelodysplastic Syndromes Basic Explanations. Last Update 04/05/2016. https://www.aamds.org/about/MDS. Accessed July 7, 2020.
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Aprende más https://rarediseases.org/patient-assistance-programs/caregiver-respite/The information provided on this page is for informational purposes only. The National Organization for Rare Disorders (NORD) does not endorse the information presented. The content has been gathered in partnership with the MONDO Disease Ontology. Please consult with a healthcare professional for medical advice and treatment.
The Genetic and Rare Diseases Information Center (GARD) has information and resources for patients, caregivers, and families that may be helpful before and after diagnosis of this condition. GARD is a program of the National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health (NIH).
View reportOrphanet has a summary about this condition that may include information on the diagnosis, care, and treatment as well as other resources. Some of the information and resources are available in languages other than English. The summary may include medical terms, so we encourage you to share and discuss this information with your doctor. Orphanet is the French National Institute for Health and Medical Research and the Health Programme of the European Union.
View reportOnline Mendelian Inheritance In Man (OMIM) has a summary of published research about this condition and includes references from the medical literature. The summary contains medical and scientific terms, so we encourage you to share and discuss this information with your doctor. OMIM is authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine.
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