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Myelodysplastic Syndromes Treatment (PDQ®)

Treatment for 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.

Standard treatment options:

Supportive Care

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.[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. (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.[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 µ/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 (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.[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).[9-11] 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 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.[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. (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.[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 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.[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 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.[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 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).[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, 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.[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 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 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

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.


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  • Updated: April 2, 2015