Myelodysplastic Syndromes Treatment Protocols 

Updated: Jan 18, 2016
  • Author: Matthew C Foster, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Treatment Protocols

Treatment recommendations for myelodysplastic syndromes (MDS) are based on a patient’s  Revised International Prognostic Scoring System score in addition to evaluation of a patient’s performance status. Currently, only a few FDA-approved therapies for MDS are available, including hypomethylating agents such as azacitidine and decitabine, iron chelators such as deferasirox, and lenalidomide. [1] Special considerations and supportive care are also described below. [2]

See Myelodysplastic Syndromes: Classification, Features, Diagnosis, and Treatment Options, a Critical Images slideshow, to help identify, classify, work up, and treat these disorders.

R-IPSS very-low-, low-, or intermediate-risk patients

These patients should receive supportive care. Selected patients who have not required transfusion and have modest, asymptomatic cytopenias may be observed initially.

Patients with symptomatic anemia; <2 units (U) of red blood cell (RBC) transfusion required per month; and 5q31 deletion, with or without other cytogenetic abnormalities:

  • Lenalidomide 10 mg PO daily, either continuous dosing or on days 1-21 every 28 d
  • If no response or intolerance, treat as for patients without del5q

low (≤500 mU/mL) serum erythropoietin levels:

Patients with symptomatic anemia; <2 units (U) of red blood cell (RBC) transfusion required per month; no del5q; ring sideroblasts <15%; and low (≤500 mU/mL) serum erythropoietin levels:

Patients with symptomatic anemia; <2 units (U) of red blood cell (RBC) transfusion required per month; no del5q; ring sideroblasts ≥15%; and low (≤500 mU/mL) serum erythropoietin levels:

  • Epoetin alfa 40,000-60,000 U SC 1-3 times weekly, or
  • Darbepoetin alfa 150-300 µg SC weekly [3, 4]   plus
  • Filgrastim 300 µg SC 3 times weekly, doses adjusted to hemoglobin (Hb) level of 11-13 g/dL, and total white blood cell (WBC) count ≤10 × 10 9/L [5]

Patients with symptomatic anemia; <2 units (U) of red blood cell (RBC) transfusion required per month; no del5q, and serum erythropoietin levels >500 mU/mL:

  • Evaluate likelihood of response to immunosuppressive therapy
  • Patients who are < 60y and have ≤5% marrow blasts or those with hypocellular marrows, are human leukocyte antigen (HLA)–DR15 positive, paroxysmal nocturnal hemoglobinuria (PNH) clone positive, or have  STAT-3 mutant cytotoxic T cell clonesare likely to respond to  equine antithymocyte globulin (ATG) 40 mg/kg/day IV over 4-6h for 4d plus  cyclosporine starting at 5-12 mg/kg/day IV beginning on day 14, dosed to maintain therapeutic levels of 200-400 ng/mL [6]
  • Patients without those characteristics are unlikely to respond to immunosuppressive therapy and should be considered for  azacitidine/decitabine or lenalidomide [6]
  • Recommended azacitidine dose is 75 mg/m 2 SC or IV on days 1-7; every 28 d [7, 8, 9] or
  • Alternative azacitidine schedule, associated with similar response rates: 75 mg/m 2 SC or IV on days 1-5, 8, and 9; every 28 d [10] or
  • Decitabine on FDA-approved schedule: 15 mg/m 2 IV over 3 h every 8 h (or 45 mg/m 2/day) for 3 d; every 6 wk [11] or
  • Decitabine on outpatient schedule, now widely adopted: 20 mg/m 2 IV over 1 h daily on days 1-5; every 28 d [11, 12, 13] or
  • Lenalidomide , 10 mg PO daily, either continuous dosing or on days 1-21 every 28 d

R-IPSS high-risk or very-high-risk patients

R-IPSS high-risk or very-high-risk patients regardless of transfusion frequency or intermediate-risk patients with high transfusion needs (>2 U RBC per month):

  • Evaluate patients for candidacy for high-intensity therapy
  • Good candidates for high-intensity therapy include young patients with few or no comorbidities, good performance status, and adequate psychosocial support

Patients who are not good candidates for high-intensity therapy:

  • Azacitidine has been associated with improvements in transfusion dependence, quality of life (QOL), and overall survival (OS) in phase III trials
  • Azacitidine 75 mg/m 2 SC or IV on days 1-7; every 28 d; this regimen has been associated with improvements in transfusion dependence, QOS, and OS in phase III trials [7, 8, 9] or
  • Alternative schedule of azacitidine, associated with similar response rates: 75 mg/m 2 SC or IV on days 1-5, 8, and 9; every 28 d [10] or
  • Decitabine on FDA-approved schedule: 15 mg/m 2 IV over 3 h every 8h (or 45 mg/m 2/day) for 3 d; every 6 wk [11] or
  • Decitabine on outpatient schedule, now widely adopted: 20 mg/m 2 IV over 1 h daily on days 1-5; every 28 d [11, 12, 13]

Patients who are good candidates for high-intensity therapy:

  • Acute myelogenous leukemia (AML)–type induction therapy, such as 7+3 ( idarubicin 12 mg/m 2 IV push on days 1-3 plus  cytarabine 100-200 mg/m 2/day continuous IV infusion on days 1-7) [14] or azacitidine or decitabine, as outlined above
  • Allogeneic stem cell transplantation consultation should also be recommended
  • Allogeneic stem cell transplantation may be performed as initial therapy or following cytoreduction with any of the other therapies for MDS

Special considerations

See the list below:

  • Allogeneic stem cell transplantation is the only potentially curative therapy for MDS
  • Appropriate patients should be referred early for consultation with a transplant specialist, before extensive transfusion support, infectious complications, or transformation to AML
  • Generally, early transplantation is advocated for young patients who are IPSS INT-2–risk and high-risk patients [15]
  • Consider referral for clinical trial participation at any stage of therapy
  • The regimens above have been tested in the frontline setting, and there is no standard of care at the inevitable time of frontline therapeutic failure
  • Clinical trial participation in this situation is highly recommended
  • When considering the choice of a particular therapeutic regimen, it is important to consider the time to best response; the duration of time to response is also critical in evaluating the success of therapies
  • Therapeutic regimens should generally not be changed in the absence of progression or toxicity unless an adequate trial of the current regimen has been undertaken

The median time to response for the therapies listed above is as follows:

  • ESAs with or without granulocyte-colony stimulating factor (G-CSF): 8-12wk [16, 12]
  • Lenalidomide: 4.6wk [17]
  • ATG + cyclosporine: 4mo [18]
  • Azacitidine or decitabine: 1.7 mo [13] to 3 mo [19]
  • 7+3 induction therapy: 4-6wk

Supportive care

Infection prophylaxis

  • Indicated for patients with prolonged, severe neutropenia (< 0.5 × 10 9/L ≥ 7 d) due to either disease or therapy, who are at risk for opportunistic infections and febrile neutropenia
  • Infection prophylaxis during periods of neutropenia should be considered with a fluoroquinolone, [20] a second-generation azole antifungal, [21] and an antiherpetic agent [22]

Transfusion support

  • RBC transfusions (leuko-reduced) for patients who have symptomatic anemia
  • Platelet transfusions for thrombocytopenia-related bleeding
  • Irradiated packed RBCs are suggested for transplant candidates

Management of transfusion iron overload

  • For patients who survive long enough to receive over 20-30 U of packed RBCs, transfusion iron overload is probable
  • End-organ iron deposition may cause cardiac, hepatic, or endocrine dysfunction
  • Iron-chelating agents ( deferoxamine, deferasirox) are available, but they have not been shown to decrease complications in MDS patients in prospective randomized trials. For this reason, many experts limit the use of these agents to patients likely to survive several years with transfusion dependence (eg, R-IPSS very-low-risk and low-risk patients).
  • Each iron-chelating agent has the following drawbacks: Deferoxamine is associated with inconvenient subcutaneous infusions, infusion-site reactions, and cataracts; deferasirox is an oral agent, but it is costly, requires monitoring of vision and renal and hepatic function, and is contraindicated in severe thrombocytopenia