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Myelodysplastic syndromes are a group of diseases in which the bone marrow does not make enough healthy blood cells. It is also called preleukemia or smoldering leukemia. Learn about myelodysplastic syndromes and find information on how we support and care for people with myelodysplastic syndromes before, during, and after treatment.
The Hematologic Oncology Center provides specialized care for all types of cancers of the blood, including leukemia, lymphoma, multiple myeloma and Waldenström’s macroglobulinemia.
The center also includes the hematopoietic stem cell transplantation program, which is one of the largest and most experienced in the world.
To make sure your care is as seamless as possible, a dedicated team of clinicians, who are highly specialized experts in your type of blood cancer, will care for you throughout the treatment process, from diagnosis though long-term follow-up.
Your care team will include oncologists, surgeons, hematologists, physician assistants, nurses, and clinical social workers who are committed to delivering safe, high-quality patient care.
We develop personalized, comprehensive treatment plans for all our patients, offering the latest therapies and supportive resources and taking your individual needs into account.
In addition to conventional treatment approaches, you may have the opportunity to participate in clinical trials that offer access to new, innovative treatments for your type of cancer.
A variety of services and programs also support your care, including nutrition services, emotional support and counseling, pain management, donor services for stem cell transplantation, and support for cancer survivors.
Learn more about treatment and care in the Hematologic Oncology Center
New patients: See Center page for phone numbers by treatment program
All other inquiries: 617-632-6140
In a healthy person, the bone marrow makes bloodstem cells (immature cells) that become mature blood cells over time.
A blood stem cell may become a lymphoid stem cell or a myeloid stem cell. A lymphoid stem cell becomes a white blood cell. A myeloid stem cell becomes one of three types of mature blood cells:
In a patient with a myelodysplastic syndrome, the blood stem cells (immature cells) do not become healthy red blood cells, white blood cells, or platelets. These immature blood cells, called blasts, do not work the way they should and either die in the bone marrow or soon after they go into the blood. This leaves less room for healthy white blood cells, red blood cells, and platelets to form in the bone marrow. When there are fewer healthy blood cells, infection, anemia, or easy bleeding may occur.
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. Talk with your doctor if you think you may be at risk. Risk factors for myelodysplastic syndromes include the following:
The cause of myelodysplastic syndromes in most patients is not known.
Myelodysplastic syndromes often do not cause early signs or symptoms. They may be found during a routine blood test. Signs and symptoms may be caused by myelodysplastic syndromes or by other conditions. Check with your doctor if you have any of the following:
The following tests and procedures may be used:
The following tests may be done on the sample of tissue that is removed:
The prognosis (chance of recovery) and treatment options depend on the following:
Different types of treatment 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 cancer. 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.
Patients with a myelodysplastic syndrome who have symptoms caused by low blood counts are given supportive care to relieve symptoms and improve quality of life. Drug therapy may be used to slow progression of the disease. Certain patients can be cured with aggressive treatment with chemotherapy followed by stem cell transplant using stem cells from a donor.
Supportive care is given to lessen the problems caused by the disease or its treatment. Supportive care may include the following:
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. A red blood cell transfusion is given when the red blood cell count is low and signs or symptoms of anemia, such as shortness of breath or feeling very tired, occur. A platelet transfusion is usually given when the patient is bleeding, is having a procedure that may cause bleeding, or when the platelet count is very low.
Patients who receive many blood cell transfusions may have tissue and organ damage caused by the buildup of extra iron. These patients may be treated with iron chelation therapy to remove the extra iron from the blood.
Erythropoiesis-stimulating agents (ESAs) may be given to increase the number of mature red blood cells made by the body and to lessen the effects of anemia. Sometimes granulocyte colony-stimulating factor (G-CSF) is given with ESAs to help the treatment work better.
Antibiotics may be given to fight infection.
Patients with myelodysplastic syndrome associated with an isolated del(5q) chromosomeabnormality who need frequent red blood cell transfusions may be treated with lenalidomide. Lenalidomide is used to lessen the need for red blood cell transfusions.
Antithymocyte globulin (ATG) works to suppress or weaken the immune system. It is used to lessen the need for red blood cell transfusions.
Azacitidine and decitabine are used to treat myelodysplastic syndromes by killing cells that are dividing rapidly. They also help genes that are involved in cell growth to work the way they should. Treatment with azacitidine and decitabine may slow the progression of myelodysplastic syndromes to acute myeloid leukemia.
Patients with a myelodysplastic syndrome and a high number of blasts in their bone marrow have a high risk of acute leukemia. They may be treated with the same chemotherapy regimen used in patients with acute myeloid leukemia.
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.
This treatment may not work as well in patients whose myelodysplastic syndrome was caused by past treatment for cancer.
Stem Cell Transplant
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.
Information about clinical trials is available from the NCI Web site.
For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.
Many of today's standard treatments for cancer 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 cancer 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.
Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer 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 listing of clinical trials.
Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer 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. This is sometimes called re-staging.
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 cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.
Standard Treatment Options for Myelodysplastic Syndromes
Standard treatment options for myelodysplastic syndromes include:
Treatment of Therapy-Related Myeloid Neoplasms
Patients who were treated in the past with chemotherapy or radiation therapy may develop myeloidneoplasms related to that therapy. Treatment options are the same as for other myelodysplastic syndromes.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with adult myelodysplastic syndromes. 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. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.
There is no standard treatment for refractory or relapsedmyelodysplastic syndromes. Patients whose cancer does not respond to treatment or has come back after treatment may want to take part in a clinical trial.
For more information from the National Cancer Institute about myelodysplastic syndromes, see the following:
For general cancer information and other resources from the National Cancer Institute, see the following:
This information is provided by the National Cancer Institute.
This information was last updated on June 11, 2014.
The myelodysplastic syndromes (MDS) are a collection of myeloid malignancies characterized by one
or more peripheral blood cytopenias. MDS are diagnosed in slightly more than 10,000 people in the United States yearly, for an annual age-adjusted incidence rate of approximately 4.4 to 4.6 cases per 100,000 people. They 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 cancers or, rarely, after environmental exposures.
Prognosis is directly
related to the number of bone marrow blast cells, to certain cytogenetic abnormalities, and to the amount of
peripheral blood cytopenias. By convention, MDS are reclassified as acute myeloid leukemia (AML) with myelodysplastic features when blood or bone marrow blasts reach or exceed 20%. Many patients succumb to complications of cytopenias before progression to this stage. (Refer to the Pathologic and Prognostic Systems for Myelodysplastic Syndromes section of this summary for more
information.) The acute leukemic phase is less responsive to
chemotherapy than is de novo AML.
MDS are characterized by abnormal bone marrow and blood cell morphology.
Megaloblastoid erythroid hyperplasia with macrocytic anemia, associated with
normal vitamin B12 and folate levels, is frequently observed. Circulating granulocytes
are often hypogranular or hypergranular, and may display the
acquired pseudo-Pelger-Huët abnormality. Early, abnormal myeloid progenitors
are identified in the marrow in varying percentages. Abnormally small megakaryocytes
(micromegakaryocytes) may be seen in the marrow and hypogranular or giant
platelets may appear in the blood.
MDS occur predominantly in older patients (usually those older than 60 years),
with a median age at diagnosis of approximately 70 years, although patients as young as 2 years have been reported. Anemia, bleeding,
easy bruising, and fatigue are common initial findings. (Refer to the PDQ summary on Fatigue for more information.) Splenomegaly or
hepatosplenomegaly may indicate an overlapping myeloproliferative neoplasm. Approximately 50% of patients have a detectable cytogenetic abnormality, most commonly a deletion of all
or part of chromosome 5 or 7, or trisomy 8. Single-nucleotide polymorphism array technology may increase the detection of genetic abnormalities to 80%. Although the bone marrow is
usually hypercellular at diagnosis, 10% of patients present with a
hypoplastic bone marrow. Hypoplastic myelodysplastic patients tend to have
profound cytopenias and may respond more frequently to immunosuppressive therapy.
Approximately 90% of MDS cases occur de novo with no identifiable cause. Potential environmental risk factors for developing MDS include exposure to the following:
A PDQ summary containing information about myelodysplastic syndromes in children is:
Ma X, Does M, Raza A, et al.: Myelodysplastic syndromes: incidence and survival in the United States. Cancer 109 (8): 1536-42, 2007.
Sekeres MA, Schoonen WM, Kantarjian H, et al.: Characteristics of US patients with myelodysplastic syndromes: results of six cross-sectional physician surveys. J Natl Cancer Inst 100 (21): 1542-51, 2008.
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.
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.
Tiu RV, Gondek LP, O'Keefe CL, et al.: Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies. Blood 117 (17): 4552-60, 2011.
Nand S, Godwin JE: Hypoplastic myelodysplastic syndrome. Cancer 62 (5): 958-64, 1988.
Du Y, Fryzek J, Sekeres MA, et al.: Smoking and alcohol intake as risk factors for myelodysplastic syndromes (MDS). Leuk Res 34 (1): 1-5, 2010.
Strom SS, Gu Y, Gruschkus SK, et al.: Risk factors of myelodysplastic syndromes: a case-control study. Leukemia 19 (11): 1912-8, 2005.
Myelodysplastic syndromes (MDS) are classified according to features of cellular morphology, etiology, and clinical presentation. The morphological classification of 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 ring sideroblasts. The clinical classification of the MDS depends upon whether there is an identifiable etiology and whether the MDS has been treated previously.
The World Health Organization (WHO) classification  has supplanted the historic French-American-British (FAB) classification, as shown in Table 1.
Refractory cytopenia with multilineage dysplasia. Refractory cytopenia with unilineage dysplasia.
Refractory anemia with ring sideroblasts.
Refractory anemia with excess blasts.
Refractory anemia with excess blasts -1 and -2.
Myelodysplastic syndrome, unclassifiable.
Myelodysplastic syndrome associated with del(5q).
Reclassified from MDS to:
Refractory anemia with excess blasts in transformation.
Acute myeloid leukemia identified as AML with multilineage dysplasia following a myelodysplastic syndrome.
Chronic myelomonocytic leukemia.
Myelodysplastic and myeloproliferative diseases.
AML = acute myeloid leukemia; FAB = French-American-British classification scheme; MDS = myelodysplastic syndromes; WHO = World Health Organization.
MDS cellular types and subtypes in either cellular classification scheme have different degrees of disordered hematopoiesis, frequencies of transformation to acute leukemia, and prognoses.
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.
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 ring 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 acute myeloid leukemia (AML).
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 composed of two categories: RAEB-1 and 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.
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 × 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 ring sideroblasts (RCMD-RS) represents another category of RCMD. In RCMD-RS, features of RCMD are present, and more than 15% of erythroid precursors in the bone marrow are ring sideroblasts. RCMD-RS accounts for approximately 15% of cases of MDS. Survival in RCMD-RS is similar to that in primary RCMD.
In patients with RCUD, a single cytopenia is present, involving either erythrocytes, neutrophils, or platelets. 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 × 109.
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.
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 AML.
The latest version of the WHO pathologic classification system identifies patients with therapy-related MDS or AML and places them in the same category as “therapy-related myeloid neoplasms.” This group of disorders evolves in patients who were previously treated with chemotherapy or radiation therapy for other cancers and in whom there is a clinical suspicion that the prior therapy caused the myeloid neoplasm. Classic chemotherapy agents associated with these disorders include alkylating agents, topoisomerase inhibitors, and purine nucleoside analogs.
Although previously classified with the myelodysplastic syndromes, CMML is now assigned to a group of overlap myelodysplastic/myeloproliferative
neoplasms. (Refer to the PDQ summary on Myelodysplastic/ Myeloproliferative Neoplasms
for more information.)
A variety of pathologic and risk classification systems have been developed to predict the overall survival of patients with MDS and the evolution from MDS to AML. Major prognostic classification systems include the International Prognostic Scoring System (IPSS), revised as the IPSS-R; the WHO Prognostic Scoring System (WPSS); and the MD Anderson Cancer Center Prognostic Scoring Systems. Clinical variables in these systems have included bone marrow and blood myeloblast percentage, specific cytopenias, transfusion requirements, age, performance status, and bone marrow cytogenetic abnormalities.
The IPSS incorporates bone marrow blast percentage, number of peripheral blood cytopenias, and cytogenetic risk group.
Compared with the IPSS, the IPSS-R updates and gives greater weight to cytogenetic abnormalities and severity of cytopenias, while reassigning the weighting for blast percentages.
In contrast to the IPSS and IPSS-R, which should be applied only at the time of diagnosis, the WPSS is dynamic, meaning that patients can be reassigned categories as their disease progresses.
The MD Anderson Cancer Center has published two prognostic scoring systems, one of which is focused on lower-risk patients.
Bennett JM, Catovsky D, Daniel MT, et al.: Proposals for the classification of the myelodysplastic syndromes. Br J Haematol 51 (2): 189-99, 1982.
Vardiman JW, Thiele J, Arber DA, et al.: The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 114 (5): 937-51, 2009.
Greenberg PL, Tuechler H, Schanz J, et al.: Revised international prognostic scoring system for myelodysplastic syndromes. Blood 120 (12): 2454-65, 2012.
Garcia-Manero G, Shan J, Faderl S, et al.: A prognostic score for patients with lower risk myelodysplastic syndrome. Leukemia 22 (3): 538-43, 2008.
Kantarjian H, O'Brien S, Ravandi F, et al.: Proposal for a new risk model in myelodysplastic syndrome that accounts for events not considered in the original International Prognostic Scoring System. Cancer 113 (6): 1351-61, 2008.
Therapies for myelodysplastic syndromes (MDS) are initiated in patients with a shorter predicted survival or in patients with clinically significant cytopenias. The impact of most MDS therapies on survival remains unproven.
Standard treatment options:
The mainstay of treatment for MDS has traditionally been supportive
care, particularly for those patients with symptomatic cytopenias or who are at high risk of infection or bleeding. Transfusions are reserved for the treatment of active bleeding; many centers offer prophylactic platelet transfusions for patients with platelet counts lower than 10,000/mm3. Anemia should be treated with red-cell transfusions to avoid symptoms. (Refer to the PDQ summary on Fatigue for more information on anemia.)
No prospective trials have demonstrated the benefit of prophylactic use of myeloid growth factors in asymptomatic neutropenic MDS patients. Similarly, the use of prophylactic antibiotics in such patients is of uncertain benefit. While appropriate use of antibiotics in febrile patients is standard clinical practice, the benefit of myeloid growth factors in such settings is unknown.
The use of erythropoiesis-stimulating agents (ESAs) may
improve anemia. The likelihood of response to exogenous erythropoietin
administration is dependent on the pretreatment serum erythropoietin
level and on baseline transfusion needs.
In a meta-analysis summarizing the data on erythropoietin in 205
patients with MDS from 17 studies, responses were most likely in patients
who were anemic but who did not yet require a transfusion, patients who did not
have ring sideroblasts, and patients who had a serum erythropoietin level lower than 200 u/L. Effective treatment requires substantially
higher doses of erythropoietin than are used for other indications; the minimum effective dose studied is 60,000 IU per week. The use of high-dose darbepoetin (300 µg/dose weekly or 500 µg/dose every 2–3 weeks) has been reported to produce a major erythroid response rate of almost 50% in patients whose endogenous erythropoietin level was lower than 500 µ/mL. Most studies discontinued ESAs in patients who failed to show hematologic improvement after 3 to 4 months of therapy. Average response duration is approximately 2 years.
One decision model found that the likelihood of responding to growth factors was higher in patients with a low serum erythropoietin level (defined as a level <500/µL) and low transfusion needs (defined as <2 units of packed red blood cells every month), but growth factors were rarely effective in patients with a high erythropoietin level and high transfusion needs. Some patients with poor response to
erythropoietin alone may have improved response with the addition of low doses
of granulocyte colony-stimulating factor (G-CSF) (0.5–1.0 µg/kg/day). Rates of response to the combination treatment vary with classification, with responses more likely in patients with refractory anemia and ring
sideroblasts (RARS) and less likely in patients with excess blasts. Patients with RARS are unlikely to respond to erythropoietin
The availability of the oral iron-chelating agent deferasirox has led to its widespread use in MDS patients. While some consensus panels advocate prophylactic iron chelation in patients with ongoing transfusion needs and substantial transfusion history, the impact of iron chelation on survival and disease progression is unknown.
Lower-risk patients (conventionally defined as International Prognostic Scoring System (IPSS) low-risk and intermediate-1–risk groups) who have failed to respond or have ceased responding to ESAs may be treated with one of several disease-modifying agents. The impact of this practice on survival in lower-risk patients is unknown. Whether these drugs should be used following an ESA failure or as up-front therapy has never been determined. In contrast, in higher-risk patients, azacitidine has been shown to improve survival. (Refer to the DNA methyltransferase inhibitors section of this summary for more information.)
Lenalidomide is FDA-approved for the treatment of lower-risk, transfusion-dependent MDS patients who harbor a del(5q) cytogenic abnormality. In a phase II registration study of 148 transfusion-dependent low-risk and intermediate-1–risk patients with del(5q) chromosomal abnormalities (alone, or associated with other abnormalities), lenalidomide induced transfusion independence in 67%, with a median time to response of 4 to 5 weeks. The median duration of transfusion independence had not been reached after a median of 104 weeks of follow-up. Of 62 evaluable patients, 38 patients developed complete cytogenetic remission.
Lenalidomide administration is limited by dose-limiting neutropenia and thrombocytopenia.[Level of evidence: 3iiiDiv] Treatment-related thrombocytopenia also correlated with cytogenetic responses, emphasizing the importance of successful suppression of the del(5q) clone with lenalidomide to achieve meaningful responses.
A subsequent phase III study randomly assigned lower-risk del(5q) MDS patients to receive placebo and lenalidomide at either 5 mg daily for 28 days or 10 mg daily for 21 days of a 28-day cycle. Transfusion independence responses lasting longer than 6 months occurred in 43% to 52% of subjects treated on the lenalidomide arms, compared with 6% of controls. The cytogenetic response rate was 25% to 50% on the active treatment arms, and the 3-year risk of AML transformation was 25%.
Lenalidomide has limited activity in lower-risk, red blood cell transfusion–dependent MDS patients who do not harbor the del(5q) lesion. In a phase II study similar in design to the registration study, 56 of 215 patients (26%) achieved transfusion independence. Median duration of response was 41 weeks (range, 8–136 weeks). Grade 3 or 4 myelosuppression occurred in only 20% to 25% of patients, and unlike for del(5q) patients, was not associated with subsequent attainment of a transfusion independence response to therapy.
Antithymocyte globulin (ATG) has shown activity in MDS patients in several small series. The National Heart, Lung, and Blood Institute conducted a phase II trial including 25 MDS patients with less than 20% blasts. Of all the patients studied, 11 (or 44%) responded and became transfusion-independent after ATG (three complete responses, six partial responses, and two minimal responses). Multivariate analysis identified HLA-DR-15 (phenotype) expression, briefer period of red cell transfusion dependence, and younger age as predictors of response to ATG. One study used alemtuzumab to treat a heavily preselected population of lower-risk MDS patients, in whom the response rate was 80%.
The nucleoside 5-azacitidine and decitabine are inhibitors of DNA methyltransferase. Both drugs require prolonged administration before benefits are seen. The median number of cycles required to see first hematologic response to 5-azacitidine was 3; 90% of responders showed response by 6 cycles; and the median number of cycles of decitabine required to see first response was 2.2. Azacitidine received FDA approval based on the results of a randomized trial that was not designed to study survival.
A phase III randomized controlled trial (AZA PH GL 2003 CL 001 [NCT00071799]) of azacitidine versus other regimens, including low-dose cytarabine, AML-type remission induction chemotherapy, or best supportive care, was limited to patients with higher-risk MDS subtypes (IPSS intermediate-2 risk and high risk). The median and 2-year overall survival (OS) favored the azacitidine arm, at 24 months versus 16 months (P = .0001) and 51% versus 26% (P < .0001), respectively.[Level of evidence: 1iiA] The FDA-approved azacitidine dose schedule used in this study (75 mg/m2 per day for 7 consecutive days) has proven inconvenient to some practitioners. A community-based study has suggested that alternate dosing schedules may provide similar hematologic benefits; however, the impact of such dosing schedules on survival is not known.
While the azacitidine congener decitabine demonstrated similar activity in phase II trials, two randomized trials of decitabine versus supportive care failed to show a survival benefit. Both decitabine studies used the FDA-approved dose schedule (15 mg/m2 every 8 hours for nine doses). In the European phase III study in higher-risk patients, median OS and a combined OS and delay in AML transformation endpoint were similar for patients in both the decitabine and best supportive care arms, at 10.1 months versus 8.5 months, respectively, for OS (P = .38) and 8.8 months versus 6.1 months, respectively, for the combined endpoint (P = .24).[Level of evidence: 1iiA]
Decitabine can be given as daily intravenous or subcutaneous infusions at doses that differ from the original labeled schedule, with hematologic response rates that appear comparable to the phase III study.
Both of these drugs have been approved for refractory anemia, RARS (if accompanied by neutropenia, or thrombocytopenia, or requiring transfusions), refractory anemia with excess blasts, and refractory anemia with excess blasts in transformation, though the highest response rates and levels of evidence have been generated in trials in which patients with higher-risk MDS (IPSS risk groups of intermediate-2 or high) have been treated. In lower-risk patients, response rates appear similar to those in higher-risk patients, although the survival benefit is unknown. The use of these drugs in low-risk patients may preclude their subsequent use upon disease progression.
Combinations of azacitidine with lenalidomide  and vorinostat  are currently being compared with single-agent azacitidine in a national randomized phase II trial (S1117 [NCT01522976]).
Induction chemotherapy typically used to treat AML may be used to treat patients with higher-risk MDS with excess blasts. Low-dose cytarabine has benefitted some patients; however,
this treatment was associated with a higher infection rate when compared with
observation in a randomized trial. No difference in time to
progression or OS was observed for patients treated with low-dose cytarabine
or supportive care.
Allogeneic HSCT is the only potentially curative treatment for MDS. Retrospective data suggest cure rates in selected patients ranging from 30% to 60%; outcomes varied with IPSS score at time of transplant, with inferior survival in patients with higher IPSS scores.[Level of evidence: 3iiiDiv] The role of cytoreductive therapy in reducing the blast percentage before HSCT remains uncertain. Outcomes
may not be as good for patients with treatment-related MDS (5-year disease-free survival of 8% to 30%).
Although HSCT represents the only treatment modality with curative potential, the relatively high morbidity and mortality of this approach limits its use. A decision analysis predating approval of azacitidine, in patients with a median age younger than 50 years, suggested optimal survival when transplant was delayed until disease progression for lower-risk patients but implemented at diagnosis for higher-risk patients.
Allogeneic stem cell transplantation with reduced-intensity conditioning (RIC) has extended transplantation as a possible modality for treatment of older patients. In a retrospective analysis of 1,333 patients aged 50 years or older (median, 56 years) who underwent allogeneic transplants for MDS using HLA-matched sibling and unrelated donors, 62% of the patients received RIC HSCT, and the others received standard-dose HSCT. On multivariate analysis, use of RIC and advanced disease stage at transplantation were associated with increased relapse (hazard ratio [HR] of 1.44 and 1.51, respectively).[Level of evidence: 3iiiDiv] The predictors of non-relapse mortality included advanced disease stage (HR, 1.43), use of an unrelated donor, and standard dose HSCT (HR, 1.27). The 4-year OS was similar in both groups (30% after myeloablative conditioning vs. 32% in RIC.
In the absence of prospective data, therapy-related myeloid neoplasms are treated similarly to de novo MDS.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with adult myelodysplastic syndromes. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
Tricot GJ, Lauer RC, Appelbaum FR, et al.: Management of the myelodysplastic syndromes. Semin Oncol 14 (4): 444-53, 1987.
Boogaerts MA: Progress in the therapy of myelodysplastic syndromes. Blut 58 (6): 265-70, 1989.
Hellström-Lindberg E: Efficacy of erythropoietin in the myelodysplastic syndromes: a meta-analysis of 205 patients from 17 studies. Br J Haematol 89 (1): 67-71, 1995.
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Greenberg PL, Rigsby CK, Stone RM, et al.: NCCN Task Force: Transfusion and iron overload in patients with myelodysplastic syndromes. J Natl Compr Canc Netw 7 (Suppl 9): S1-16, 2009.
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Sekeres MA, Maciejewski JP, Giagounidis AA, et al.: Relationship of treatment-related cytopenias and response to lenalidomide in patients with lower-risk myelodysplastic syndromes. J Clin Oncol 26 (36): 5943-9, 2008.
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Lack of response or progression after the use of erythropoiesis-stimulating agents is not considered relapsed or refractory myelodysplastic syndromes (MDS).
With the exception of the use of lenalidomide for low-risk patients with abnormalities of chromosome 5, there are no clinical trials informing the appropriate selection of current therapies for patients with specific subtypes of MDS. Patients who have ceased to respond or did not respond to one therapy are frequently offered another from the therapies described in the previous sections. Retrospective data suggest that patients who do not respond or have ceased responding to DNA methyltransferase inhibitors have a median survival of only 4 to 6 months. Relapsed patients should be considered for enrollment in clinical trials.
Prébet T, Gore SD, Esterni B, et al.: Outcome of high-risk myelodysplastic syndrome after azacitidine treatment failure. J Clin Oncol 29 (24): 3322-7, 2011.
Jabbour E, Garcia-Manero G, Batty N, et al.: Outcome of patients with myelodysplastic syndrome after failure of decitabine therapy. Cancer 116 (16): 3830-4, 2010.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with myelodysplastic syndromes. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
This information was last updated on December 3, 2012.
Our licensed social workers are here to help adult patients and their loved ones face the many new concerns and anxieties following a cancer diagnosis, offering emotional support and assistance with obtaining needed resources.
If you are dealing with the death of a loved one, grief can be a lonely and isolating experience. The Bereavement Program provides support to bereaved family members and friends following the death of a patient.
Concierge Services is your one-stop place to learn about Dana-Farber programs, services and resources, as well as information on getting around Boston, finding lodging or restaurants, and activities in the area.
The Expressive Arts Therapy program, sponsored by the Leonard P. Zakim Center for Integrative Therapies, provides adult patients, family members, and caregivers with a variety of options to support well-being during cancer treatment. From live music meditation to painting technique workshops, the program offers a range of creative outlets to suit every interest.
Dana-Farber and Brigham and Women's Hospital, including parking facilities, are fully accessible to people with disabilities. There are wheelchairs at the main entrance, and security staff can provide personal assistance. We also have many educational materials available in large print and audiotape formats.
The Ethics Consultation Service is available for patients and families who may be facing difficult decisions and choices regarding care. Our goal is to bring together patients, families and health care providers to talk about ethical concerns and help everyone involved arrive at a resolution that is right for all.
This comprehensive resource offers guidance, information and resources to support the entire family, including how to talk to children about cancer, advice for the well partner, and creating a support network.
Find practical tips and suggestions for individuals caring for a family member or friend with cancer, including creating a caregiving plan, finding community resources, and looking after your own well-being.
Friends' Place provides personal consultations to help cancer patients of all ages cope with changes in physical appearance that result from cancer treatment. Our experienced, compassionate team provides fittings for compression garments or breast prostheses, helps with wigs and other head coverings, and offers make-up and skincare advice.
The Friends' Corner Gift Shop, located on the first floor of the Yawkey Center for Cancer Care, offers a wide selection of unique gifts and everyday items for patients, families and staff.
Dana-Farber offers several services to help you and your family manage the financial side of cancer treatment. From creating bill payment schedules and estate planning advice to debt management and resource assistance for patients in need, our team is here for you.
Every year, thousands of patients with cancer from around the world come to Dana-Farber for their care. We provide a wide array of logistical and other services for individuals who live outside the United States.
Dana-Farber provides interpreting services for patients whose first language is not English. Interpreters may be requested for any activity, including registration, booking appointments, attending treatments and exams, support groups, and meetings with doctors and other members of your health care team.
Our nutritionists are registered dietitians who can assist you in planning an optimal diet during any stage of your cancer journey, cope with any side effects you may experience, and answer your questions about the latest findings on cancer and nutrition.
One-to-One connects adult patients, family members and caregivers with individuals who have gone through cancer themselves, providing an experienced and reassuring perspective for those facing a cancer diagnosis, treatment and recovery.
The Eleanor and Maxwell Blum Patient and Family Resource Center and its satellite resource rooms are staffed by health care professionals and provide computer stations, books, brochures, videos, and CDs to help you find information and support on a variety of issues about cancer treatment and care.
Patients websites help friends and family members stay up-to-date on their loved ones' condition and write messages of support and encouragement.
The Dana-Farber pharmacy fills prescriptions for all pediatric and adult patients. Our pharmacists are an extension of the patient care team and work closely with your physicians to provide seamless, convenient, safe care.
More than 1,200 Dana-Farber patients and their families have enjoyed free trips to baseball games, theater shows, museums, and other attractions this year through the Recreational Resources program.
The Sexual Health Program provides education, consultation and personalized rehabilitation for patients and their partners who have experienced changes in sexual health during and after cancer treatment.
Through all stages of cancer treatment and survivorship, our Spiritual Care staff is available 24 hours a day to provide emotional and spiritual support for adults and pediatric patients and family members.
Young adults with cancer face very different challenges than patients who were diagnosed earlier in childhood or later in adulthood. The Young Adult Program can help you to find the resources and expertise available at Dana-Farber to help support your cancer experience.
Integrative therapies, also known as complementary therapies, range from acupuncture and massage to nutritional guidance and music therapy. Patients treated at the Zakim Center credit its services with easing nausea, improving circulation, and reducing pain, stress, and anxiety associated with cancer treatment.
In this video, Dr. Daniel DeAngelo talks about his work with stem cell transplant patients in the Hematologic Oncology Treatment Center at Dana-Farber/Brigham and Women's Cancer Center.