Myelodysplastic Syndromes Treatment (PDQ®): Treatment - Health Professional Information [NCI]

General Information About Myelodysplastic Syndromes (MDS)

Incidence and Mortality

The 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.[1] They are more common in men and White individuals. 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

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. For more information, see the Pathological and Prognostic Systems for MDS section. The acute leukemic phase is less responsive to chemotherapy than is de novo AML.

Pathology

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.

Clinical Features

MDS occur predominantly in older patients (usually older than 60 years), with a median age at diagnosis of approximately 70 years,[2] although patients as young as 2 years have been reported.[3] Anemia, bleeding, easy bruising, and fatigue are common initial findings. For more information, see Fatigue. 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%.[4,5] Although the bone marrow is usually hypercellular at diagnosis, 10% of patients present with a hypoplastic bone marrow.[6] Hypoplastic myelodysplastic patients tend to have profound cytopenias and may respond more frequently to immunosuppressive therapy.

Risk Factors

Approximately 90% of MDS cases occur de novo with no identifiable cause. Potential environmental risk factors for developing MDS include exposure to the following:[7,8]

• Tobacco smoke.
• Ionizing radiation.
• Organic chemicals (e.g., benzene, toluene, xylene, and chloramphenicol).
• Heavy metals.
• Herbicides.
• Pesticides.
• Fertilizers.
• Stone and cereal dusts.
• Exhaust gases.
• Nitro-organic explosives.
• Petroleum and diesel derivatives.

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. 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.
3. 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.
4. 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.
5. 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.
6. Nand S, Godwin JE: Hypoplastic myelodysplastic syndrome. Cancer 62 (5): 958-64, 1988.
7. 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.
8. Strom SS, Gu Y, Gruschkus SK, et al.: Risk factors of myelodysplastic syndromes: a case-control study. Leukemia 19 (11): 1912-8, 2005.

Pathological and Prognostic Systems for MDS

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.[1] The clinical classification of the MDS depends on whether there is an identifiable etiology and whether the MDS has been treated previously.

Pathological Systems

The World Health Organization (WHO) classification [2] has supplanted the historic French-American-British (FAB) classification,[1] as shown in Table 1.

MDS cellular types and subtypes in either cellular classification scheme have different degrees of disordered hematopoiesis, frequencies of transformation to acute leukemia, and prognoses.

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 ring 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 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).

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 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.

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 × 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.

Refractory cytopenia with unilineage dysplasia (RCUD)

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.

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 AML.

Therapy-related myeloid neoplasms

The latest version of the WHO pathological 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 analogues.

Chronic myelomonocytic leukemia (CMML)

Although previously classified with the myelodysplastic syndromes, CMML is now assigned to a group of overlap myelodysplastic/myeloproliferative neoplasms. For more information, see Myelodysplastic/ Myeloproliferative Neoplasms Treatment.

Prognostic Scoring Systems

A variety of pathological 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;[3] the WHO Prognostic Scoring System (WPSS); and the MD Anderson Cancer Center Prognostic Scoring Systems.[4,5] 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.

IPSS

The IPSS incorporates bone marrow blast percentage, number of peripheral blood cytopenias, and cytogenetic risk group.

IPSS-R

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.[3]

WPSS

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.

MD Anderson

The MD Anderson Cancer Center has published two prognostic scoring systems, one of which is focused on lower-risk patients.[4,5]

References:

1. Bennett JM, Catovsky D, Daniel MT, et al.: Proposals for the classification of the myelodysplastic syndromes. Br J Haematol 51 (2): 189-99, 1982.
2. 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.
3. Greenberg PL, Tuechler H, Schanz J, et al.: Revised international prognostic scoring system for myelodysplastic syndromes. Blood 120 (12): 2454-65, 2012.
4. 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.
5. 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.

Treatment of MDS

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.

Treatment options:

• Supportive care.
• Disease-modifying agents.
  • Lenalidomide.
  • Immunosuppressive therapy.
  • DNA methyltransferase inhibitors.
  • Acute myeloid leukemia (AML) induction-type chemotherapy.
• Allogeneic hematopoietic stem cell transplantation (HSCT).

Supportive Care

The mainstay of treatment for MDS has traditionally been supportive care, particularly for patients with symptomatic cytopenias or who are at high risk of infection or bleeding.[1,2] 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. For more information, see Fatigue.

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 depends on the pretreatment serum erythropoietin level and baseline transfusion needs.

A meta-analysis summarized 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 IU/L.[3] 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.[4] 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 mIU/mL.[5,6] 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.[7]

One decision model found that the likelihood of responding to growth factors was higher in patients with a low serum erythropoietin level (<500 IU/L) and low transfusion needs (<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.[8] 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).[9,10,11] 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.[7] Patients with RARS are unlikely to respond to erythropoietin alone.[3]

The availability of the oral iron-chelating agent deferasirox has led to its widespread use in patients with MDS. 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.[12]

Disease-Modifying Agents

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. For more information, see the DNA methyltransferase inhibitors section.

Lenalidomide

The U.S. Food and Drug Administration (FDA) approved lenalidomide for the treatment of lower-risk, transfusion-dependent patients with MDS 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.[13] 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.[14][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.[15]

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.[16] 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 patients in MDS 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.[17] 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.

Immunosuppressive 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).[18] Multivariate analysis identified HLA-DR-15 (phenotype) expression, briefer period of red cell transfusion dependence, and younger age as predictors of response to ATG.[19] One study used alemtuzumab to treat a heavily preselected population of lower-risk MDS patients, in whom the response rate was 80%.[20]

DNA methyltransferase inhibitors

The nucleoside analogues 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 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.[21] Azacitidine received FDA approval based on the results of a randomized trial that was not designed to study survival.[22]

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).[17] 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.[17][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.[23]

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.[21,24] 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 was similar for patients in both the decitabine and best supportive care arms, at 10.1 months versus 8.5 months, respectively (P = .38). A combined OS and delay in AML transformation end point was 8.8 months versus 6.1 months, respectively (P = .24).[25][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.[26,27]

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. However, 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) were treated.[28] 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 [29] and vorinostat [30] were compared with single-agent azacitidine in a national randomized phase II trial (S1117 [NCT01522976]).

AML induction-type chemotherapy

Induction chemotherapy typically used to treat AML may be used to treat patients with higher-risk MDS with excess blasts.[31] 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 Hematopoietic Stem Cell Transplantation (HSCT)

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.[32][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 rate of 8% to 30%).[33]

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.[34]

Allogeneic stem cell transplantation with reduced-intensity conditioning (RIC) has extended transplantation as a possible modality for treatment of older patients.[35] 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).[35][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 rate was similar in both groups (30% after myeloablative conditioning vs. 32% in RIC.[35]

Therapy-Related Myeloid Neoplasms

In the absence of prospective data, therapy-related myeloid neoplasms are treated similarly to de novo MDS.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

References:

1. Tricot GJ, Lauer RC, Appelbaum FR, et al.: Management of the myelodysplastic syndromes. Semin Oncol 14 (4): 444-53, 1987.
2. Boogaerts MA: Progress in the therapy of myelodysplastic syndromes. Blut 58 (6): 265-70, 1989.
3. 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.
4. Park S, Grabar S, Kelaidi C, et al.: Predictive factors of response and survival in myelodysplastic syndrome treated with erythropoietin and G-CSF: the GFM experience. Blood 111 (2): 574-82, 2008.
5. Mannone L, Gardin C, Quarre MC, et al.: High-dose darbepoetin alpha in the treatment of anaemia of lower risk myelodysplastic syndrome results of a phase II study. Br J Haematol 133 (5): 513-9, 2006.
6. Gabrilove J, Paquette R, Lyons RM, et al.: Phase 2, single-arm trial to evaluate the effectiveness of darbepoetin alfa for correcting anaemia in patients with myelodysplastic syndromes. Br J Haematol 142 (3): 379-93, 2008.
7. Jädersten M, Montgomery SM, Dybedal I, et al.: Long-term outcome of treatment of anemia in MDS with erythropoietin and G-CSF. Blood 106 (3): 803-11, 2005.
8. Hellström-Lindberg E, Gulbrandsen N, Lindberg G, et al.: A validated decision model for treating the anaemia of myelodysplastic syndromes with erythropoietin + granulocyte colony-stimulating factor: significant effects on quality of life. Br J Haematol 120 (6): 1037-46, 2003.
9. Hellström-Lindberg E, Ahlgren T, Beguin Y, et al.: Treatment of anemia in myelodysplastic syndromes with granulocyte colony-stimulating factor plus erythropoietin: results from a randomized phase II study and long-term follow-up of 71 patients. Blood 92 (1): 68-75, 1998.
10. Hellström-Lindberg E, Kanter-Lewensohn L, Ost A: Morphological changes and apoptosis in bone marrow from patients with myelodysplastic syndromes treated with granulocyte-CSF and erythropoietin. Leuk Res 21 (5): 415-25, 1997.
11. Negrin RS, Stein R, Doherty K, et al.: Maintenance treatment of the anemia of myelodysplastic syndromes with recombinant human granulocyte colony-stimulating factor and erythropoietin: evidence for in vivo synergy. Blood 87 (10): 4076-81, 1996.
12. 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.
13. List A, Dewald G, Bennett J, et al.: Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med 355 (14): 1456-65, 2006.
14. List A, Kurtin S, Roe DJ, et al.: Efficacy of lenalidomide in myelodysplastic syndromes. N Engl J Med 352 (6): 549-57, 2005.
15. 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.
16. Fenaux P, Giagounidis A, Selleslag D, et al.: RBC transfusion independence and safety profile of lenalidomide 5 or 10 mg in pts with low- or int-1-risk MDS with Del5q: results from a randomized phase III trial (MDS-004). [Abstract] Blood 114 (22): A-944, 2009.
17. Fenaux P, Mufti GJ, Hellstrom-Lindberg E, et al.: Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol 10 (3): 223-32, 2009.
18. Molldrem JJ, Caples M, Mavroudis D, et al.: Antithymocyte globulin for patients with myelodysplastic syndrome. Br J Haematol 99 (3): 699-705, 1997.
19. Saunthararajah Y, Nakamura R, Nam JM, et al.: HLA-DR15 (DR2) is overrepresented in myelodysplastic syndrome and aplastic anemia and predicts a response to immunosuppression in myelodysplastic syndrome. Blood 100 (5): 1570-4, 2002.
20. Sloand EM, Olnes MJ, Shenoy A, et al.: Alemtuzumab treatment of intermediate-1 myelodysplasia patients is associated with sustained improvement in blood counts and cytogenetic remissions. J Clin Oncol 28 (35): 5166-73, 2010.
21. Kantarjian H, Issa JP, Rosenfeld CS, et al.: Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer 106 (8): 1794-803, 2006.
22. Silverman LR, Demakos EP, Peterson BL, et al.: Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol 20 (10): 2429-40, 2002.
23. Lyons RM, Cosgriff TM, Modi SS, et al.: Hematologic response to three alternative dosing schedules of azacitidine in patients with myelodysplastic syndromes. J Clin Oncol 27 (11): 1850-6, 2009.
24. Wijermans P, Lübbert M, Verhoef G, et al.: Low-dose 5-aza-2'-deoxycytidine, a DNA hypomethylating agent, for the treatment of high-risk myelodysplastic syndrome: a multicenter phase II study in elderly patients. J Clin Oncol 18 (5): 956-62, 2000.
25. Lübbert M, Suciu S, Baila L, et al.: Low-dose decitabine versus best supportive care in elderly patients with intermediate- or high-risk myelodysplastic syndrome (MDS) ineligible for intensive chemotherapy: final results of the randomized phase III study of the European Organisation for Research and Treatment of Cancer Leukemia Group and the German MDS Study Group. J Clin Oncol 29 (15): 1987-96, 2011.
26. Issa JP, Garcia-Manero G, Giles FJ, et al.: Phase 1 study of low-dose prolonged exposure schedules of the hypomethylating agent 5-aza-2'-deoxycytidine (decitabine) in hematopoietic malignancies. Blood 103 (5): 1635-40, 2004.
27. Kantarjian H, Oki Y, Garcia-Manero G, et al.: Results of a randomized study of 3 schedules of low-dose decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia. Blood 109 (1): 52-7, 2007.
28. Kaminskas E, Farrell A, Abraham S, et al.: Approval summary: azacitidine for treatment of myelodysplastic syndrome subtypes. Clin Cancer Res 11 (10): 3604-8, 2005.
29. Sekeres MA, List AF, Cuthbertson D, et al.: Phase I combination trial of lenalidomide and azacitidine in patients with higher-risk myelodysplastic syndromes. J Clin Oncol 28 (13): 2253-8, 2010.
30. Garcia-Manero G, Estey EH, Jabbour E, et al.: Final report of a phase II study of 5-azacitidine and vorinostat in patients with newly diagnosed myelodysplastic syndrome or acute myelogenous leukemia not eligible for clinical trials because poor performance and presence of other comorbidities. [Abstract] Blood 118 (21): A-608, 2011.
31. de Witte T, Suciu S, Verhoef G, et al.: Intensive chemotherapy followed by allogeneic or autologous stem cell transplantation for patients with myelodysplastic syndromes (MDSs) and acute myeloid leukemia following MDS. Blood 98 (8): 2326-31, 2001.
32. Deeg HJ, Storer B, Slattery JT, et al.: Conditioning with targeted busulfan and cyclophosphamide for hemopoietic stem cell transplantation from related and unrelated donors in patients with myelodysplastic syndrome. Blood 100 (4): 1201-7, 2002.
33. Witherspoon RP, Deeg HJ, Storer B, et al.: Hematopoietic stem-cell transplantation for treatment-related leukemia or myelodysplasia. J Clin Oncol 19 (8): 2134-41, 2001.
34. Cutler CS, Lee SJ, Greenberg P, et al.: A decision analysis of allogeneic bone marrow transplantation for the myelodysplastic syndromes: delayed transplantation for low-risk myelodysplasia is associated with improved outcome. Blood 104 (2): 579-85, 2004.
35. Schetelig J, van Biezen A, Brand R, et al.: Allogeneic hematopoietic stem-cell transplantation for chronic lymphocytic leukemia with 17p deletion: a retrospective European Group for Blood and Marrow Transplantation analysis. J Clin Oncol 26 (31): 5094-100, 2008.

Treatment of Relapsed or Refractory MDS

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 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.[1,2] Patients with relapses should be considered for enrollment in clinical trials.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

References:

1. 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.
2. 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.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

Changes to This Summary (09 / 30 / 2022)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Editorial changes were made to this summary.

This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of myelodysplastic syndromes. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Board members review recently published articles each month to determine whether an article should:

• be discussed at a meeting,
• be cited with text, or
• replace or update an existing article that is already cited.

Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

The lead reviewer for Myelodysplastic Syndromes Treatment is:

• Aaron Gerds, MD

Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

Permission to Use This Summary

PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as "NCI's PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary]."

The preferred citation for this PDQ summary is:

PDQ® Adult Treatment Editorial Board. PDQ Myelodysplastic Syndromes Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/myeloproliferative/hp/myelodysplastic-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389450]

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Disclaimer

Based on the strength of the available evidence, treatment options may be described as either "standard" or "under clinical evaluation." These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page.

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Last Revised: 2022-09-30