What is the recommended treatment approach for myelodysplastic syndrome, including first‑line and subsequent therapies based on risk category?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: February 7, 2026 • View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

Treatment of Myelodysplastic Syndrome

Risk Stratification Determines All Treatment Decisions

Treatment of MDS must be stratified by IPSS-R risk category, which divides patients into lower-risk (very low, low, intermediate) and higher-risk (intermediate, high, very high) groups with fundamentally different therapeutic goals and approaches. 1

The IPSS-R incorporates peripheral blood cytopenias, bone marrow blast percentage, and cytogenetic abnormalities to predict overall survival and AML transformation risk. 1 Patients in the IPSS-R intermediate category may be managed as either risk group depending on age, performance status, serum ferritin, LDH levels, and response to initial therapy. 1

Lower-Risk MDS Treatment Algorithm

Primary Goal: Improve Cytopenias and Quality of Life

For lower-risk MDS, the primary objective is treating symptomatic cytopenias (especially anemia), improving quality of life, and reducing transfusion burden—not necessarily altering disease natural history. 1, 2

First-Line Treatment for Anemia

Erythropoiesis-stimulating agents (ESAs) such as recombinant erythropoietin or darbepoetin (150-300 mcg subcutaneously weekly) ± G-CSF are first-line for symptomatic anemia. 1, 2

  • ESAs achieve 40-60% erythroid response rates when baseline serum EPO is <200-500 U/L and transfusion requirements are low (<2 units/month). 1, 2
  • Predictors of ESA response include low serum EPO, low marrow blasts, and minimal prior transfusions. 1
  • Median response duration is 8-23 months. 3

Second-Line for Lower-Risk MDS with del(5q)

Lenalidomide is highly effective for transfusion-dependent anemia in patients with isolated del(5q) cytogenetic abnormality. 2, 4

  • Check for TP53 mutations before lenalidomide, as these predict diminished response or early relapse. 1

Immunosuppressive Therapy

Antithymocyte globulin (ATG) is most effective in younger patients (<65 years) with low-risk MDS, transfusion history <2 years, normal karyotype or trisomy 8, no excess blasts, and thrombocytopenia in addition to anemia. 2

Supportive Care for All Lower-Risk Patients

  • Red blood cell transfusions for symptomatic anemia (maintain hemoglobin >8-10 g/dL based on symptoms). 1
  • Iron chelation therapy when serum ferritin >1000 mcg/L in transfusion-dependent patients, as iron overload increases infection-related mortality. 2
  • Platelet transfusions for bleeding or severe thrombocytopenia. 1
  • G-CSF for recurrent infections with neutropenia. 1

Higher-Risk MDS Treatment Algorithm

Primary Goal: Alter Disease Natural History and Prolong Survival

For higher-risk MDS, treatment aims to delay AML progression, achieve complete or partial remission, and prolong overall survival—not just improve cytopenias. 1, 2

First-Line Treatment: Hypomethylating Agents

Azacitidine 75 mg/m² subcutaneously for 7 consecutive days every 28 days is the first-line reference treatment for higher-risk MDS patients not immediately eligible for allogeneic stem cell transplantation. 1, 5, 3

  • Administer at least 6 cycles before assessing response, as most patients only respond after several courses. 1, 2
  • Azacitidine extends survival by up to 74% compared to conventional care despite modest complete response rates (15-20%). 1, 2
  • Alternative "5-2-2" regimens (5 days on, 2 days off, 2 days on) are acceptable for logistical reasons. 1
  • Decitabine or oral decitabine/cedazuridine are alternative hypomethylating agents with similar efficacy. 6, 3, 7

Allogeneic Stem Cell Transplantation: The Only Curative Option

Allogeneic stem cell transplantation is the only potentially curative treatment and should be evaluated at diagnosis for all higher-risk patients aged ≤65-70 years (or fit patients >70 years) with an HLA-identical sibling or matched unrelated donor. 1, 2

  • Patients aged <55 years without comorbidities should receive myeloablative conditioning; older or less fit patients receive reduced-intensity conditioning. 1
  • Hypomethylating agents for 2-6 cycles before transplant can reduce blast burden or allow time to identify a donor. 1

AML-Like Intensive Chemotherapy: Limited Role

Intensive AML-like chemotherapy (cytarabine + idarubicin or fludarabine) has limited indication and should only be considered for fit patients <70 years with favorable cytogenetics (especially normal karyotype), >10% marrow blasts, and as a bridge to allogeneic transplant. 1

  • Patients with unfavorable karyotype show few complete responses and shorter remission duration. 1
  • A randomized trial suggested azacitidine may provide superior survival compared to intensive chemotherapy, though the study was underpowered. 1

Low-Dose Cytarabine: Inferior Option

Low-dose cytarabine (20 mg/m²/day for 14-21 days every 4 weeks) is significantly inferior to azacitidine and should only be used when hypomethylating agents are unavailable (including for economic reasons) in patients with normal karyotype. 1

Treatment After Hypomethylating Agent Failure

Patients with higher-risk MDS who fail or are refractory to hypomethylating agents have extremely poor survival (median <6 months) and should be enrolled in clinical trials or proceed directly to allogeneic transplant if eligible. 1

  • Retreatment with intensive chemotherapy or low-dose cytarabine yields dismal results. 1
  • No approved second-line therapies exist for HMA-refractory disease. 6, 7

Special Populations and Considerations

Very Frail Patients

Very frail patients with higher-risk MDS should receive supportive care only (transfusions, antibiotics, growth factors) rather than disease-modifying therapy. 1

Therapy-Related MDS

Therapy-related MDS patients have poorer prognoses with a high proportion of poor-risk cytogenetics and should generally be managed as higher-risk disease regardless of IPSS-R score. 1

Monitoring and Response Assessment

  • Use IWG 2006 response criteria to assess treatment effectiveness (complete remission, partial remission, hematologic improvement). 1, 2
  • Monitor complete blood counts frequently during treatment with hypomethylating agents or intensive chemotherapy. 5
  • Assess for tumor lysis syndrome risk, particularly when initiating hypomethylating agents in patients with high blast counts. 5

Critical Pitfalls to Avoid

  • Do not substitute oral azacitidine for subcutaneous/intravenous azacitidine—they have different indications and dosing regimens. 5
  • Do not discontinue azacitidine before 6 cycles unless clear disease progression, as responses are often delayed. 1, 2
  • Do not use intensive chemotherapy in patients with unfavorable cytogenetics outside of clinical trials—outcomes are poor. 1
  • Do not delay allogeneic transplant evaluation in eligible higher-risk patients—it should occur at diagnosis. 1, 2
  • Do not overlook iron chelation in chronically transfused patients—iron overload significantly increases mortality. 2

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

2
Guideline

Myelodysplastic Syndrome (MDS) Treatment Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Related Questions

What is Myelodysplastic Syndrome (MDS)?
What are the risk factors for Myelodysplastic Syndromes (MDS)?
What are the causes of Myelodysplastic Syndromes (MDS)?
What are the treatment options for a patient diagnosed with myelodysplastic syndrome (MDS)?
What are the clinical characteristics and diagnosis of myelodysplastic syndrome (MDS)?
What is the most appropriate next step for a 42-year-old man with a normal digital rectal examination and a father diagnosed with prostate cancer at age 76?
Is the current regimen of ceftriaxone, pantoprazole, ondansetron, furosemide (Dytor), spironolactone (Aldactone) and propranolol (Inderol) with the given dosing frequencies appropriate for an 80‑year‑old female with a urinary‑tract infection, metabolic‑associated fatty liver disease with esophageal varices, hypertension, diabetes, presenting with hematuria and vomiting, and labs showing severe anemia, thrombocytopenia, mild renal impairment, hyponatremia, hyperglycemia, elevated bilirubin, hypoalbuminemia and coagulopathy?
When is red‑cell transfusion not indicated for an awake, hemodynamically stable adult with a hemoglobin concentration of 3 mmol/L and no active bleeding or high‑risk cardiac/cerebrovascular disease?
How do I calculate systemic vascular resistance (SVR)?
What percentage of older patients with diabetes, peripheral arterial disease, or chronic venous insufficiency undergoing below‑knee amputation develop reduced venous return?
A patient presenting with hypothyroidism symptoms was diagnosed with hypothyroidism without considering autoimmune thyroiditis; which clinical step was missed?

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.

Ask Question