Treatment of Myelodysplastic Syndrome
Treatment of MDS is fundamentally determined by risk stratification using IPSS or IPSS-R, which divides patients into lower-risk and higher-risk categories, each requiring distinct therapeutic approaches prioritized by survival benefit. 1
Risk Stratification Framework
Risk assessment must incorporate bone marrow blast percentage, cytogenetic abnormalities, degree of cytopenias, and molecular mutations to categorize patients appropriately. 2 Patient age, performance status, comorbidities, and transfusion requirements further guide treatment selection. 1, 2
Higher-Risk MDS Treatment Algorithm
First-Line Therapy
Azacitidine at 75 mg/m² daily for 7 days every 4 weeks is the recommended first-line treatment for higher-risk MDS patients without major comorbidities who are not immediately eligible for allogeneic stem cell transplantation (allo-SCT). 1, 2 This hypomethylating agent (HMA) has demonstrated survival improvement in this population. 1
Decitabine represents an alternative HMA option, FDA-approved for all MDS subtypes including intermediate-1, intermediate-2, and high-risk IPSS groups, administered either as 15 mg/m² IV over 3 hours every 8 hours for 3 days (repeated every 6 weeks) or 20 mg/m² IV over 1 hour daily for 5 days (repeated every 4 weeks). 3
Allogeneic Stem Cell Transplantation
Allo-SCT should be offered to all higher-risk MDS patients under 70 years old without major comorbidities who have an available donor, as this remains the only potentially curative therapy. 1
For fit patients generally under 70 years with favorable cytogenetics and marrow blasts ≥10%, AML-like chemotherapy is recommended, preferably as a bridge to allo-SCT. 1 When marrow blasts are ≥10%, reducing blast count before allo-SCT with either AML-like chemotherapy or HMAs should be considered, particularly for non-myeloablative conditioning regimens. 1
Lower-Risk MDS Treatment Algorithm
Anemia Management
For anemia in lower-risk MDS without del(5q), erythropoiesis-stimulating agents (ESAs), particularly EPO alpha at weekly doses of 30,000-80,000 units, are first-line therapy. 1, 2
For transfusion-dependent anemia in lower-risk MDS with del(5q), lenalidomide is the most effective treatment, achieving 60-65% response rates with median transfusion independence of 2-2.5 years. 1, 2
Second-Line Options After ESA Failure
After ESA failure in RBC transfusion-dependent MDS with ring sideroblasts (MDS-RS), luspatercept is recommended. 1 This represents a significant advance for this specific subgroup.
For younger patient cohorts with lower-risk MDS after ESA failure, antithymocyte globulin (ATG) with cyclosporine demonstrates efficacy. 1 Other second-line options include lenalidomide plus ESA or HMAs, though these are not approved in Europe for this indication. 1
Thrombocytopenia Management
Thrombopoietin receptor agonists (romiplostim, eltrombopag) show efficacy in severe thrombocytopenia but are not approved for MDS and should only be used in patients with marrow blasts <5% due to concerns about transient blast increases. 1, 2 These agents should be restricted to clinical trials or registries. 1
Neutropenia Management
G-CSF can improve neutropenia in 60-75% of cases and may be added to anti-infective drugs during severe infections, but prolonged prophylactic use has not demonstrated survival impact. 1 Rapid initiation of broad-spectrum antibiotics is mandatory for fever or infection symptoms. 1
Supportive Care Essentials
Transfusion Strategy
RBC transfusions should be administered at hemoglobin thresholds of at least 8 g/dL, with higher thresholds (9-10 g/dL) for patients with comorbidities, poor functional tolerance, or active elderly individuals. 1, 2 Transfuse sufficient RBC concentrates over 2-3 days to increase hemoglobin above 10 g/dL, limiting chronic anemia effects on quality of life. 1
Iron Chelation Therapy
Iron chelation is strongly recommended for all allo-SCT candidates with transfusion iron overload, as even moderate iron overload before transplantation increases transplant-related mortality. 1 Early chelation in transplant candidates is critical. 1
For non-transplant candidates with lower-risk MDS, iron chelation is strongly recommended when major iron overload is present (e.g., significantly reduced cardiac T2* on MRI imaging). 1 Chelation should generally be initiated in patients with relatively favorable prognosis who have received 20-60 RBC concentrates or when serum ferritin rises above 1000-2500 U/L. 1, 2
Deferasirox is the preferred oral iron chelator, though it cannot be used in renal failure. 1 Deferiprone is not approved for MDS in most countries due to potential neutropenia. 1
Critical Treatment Pitfalls
The ESMO guidelines emphasize that treatment decisions must account for patient age, performance status, comorbidities, frailty, and patient preferences after adequate information provision. 1 Prophylactic platelet transfusions and prophylactic antibiotics/G-CSF are not routinely recommended outside of myelosuppressive therapy contexts. 1 For higher-risk patients, azacitidine should be administered for at least 6 cycles before assessing failure. 1