Prognosis of Myelodysplastic Syndromes (MDS)

Overall Survival and Disease Progression

• The median overall survival for MDS patients is 15-30 months across all risk categories, with a 25-35% risk of progression to acute myeloid leukemia at 5 years, according to the International Prognostic Scoring System (IPSS) 1, 2
• The American Society of Hematology recommends using the IPSS or IPSS-R for predicting outcomes and guiding treatment decisions, as the natural course of MDS demonstrates extreme heterogeneity 1, 2
• The 5-year survival rate for lower-risk MDS (IPSS Low/Intermediate-1) is approximately 68%, with a median survival of 3-10 years 3
• The risk of AML transformation is 25-35% at 5 years, with bone marrow failure being the primary cause of death, including infection and hemorrhage 1, 2, 4

Risk Stratification Systems

• The International Prognostic Scoring System (IPSS) incorporates three critical prognostic factors, including bone marrow blast percentage, cytogenetic abnormalities, and the number and severity of cytopenias, and remains the reference standard used in clinical trials and for regulatory drug approval 5
• The Revised IPSS (IPSS-R) provides enhanced prognostic precision by stratifying patients into five risk groups, with distinct outcomes, and includes refined categories for bone marrow blasts and peripheral blood cytopenias 6, 1, 2
• The WHO Classification-Based Prognostic Scoring System (WPSS) adds prognostic value beyond IPSS, particularly for lower-risk patients, and incorporates multilineage dysplasia, severe anemia or transfusion dependency, and bone marrow fibrosis 6, 7, 8

Disease-Related Prognostic Factors

• Cytogenetic abnormalities are among the most powerful prognostic indicators, with poor-risk cytogenetics associated with median survival less than 5 years, and favorable cytogenetics associated with better prognosis 1, 2
• Bone marrow blast percentage and multilineage dysplasia are adverse prognostic factors, with higher blast percentages predicting worse outcomes 1, 2
• Somatic mutations, including TET2, SF3B1, ASXL1, SRSF2, RUNX1, DNMT3a, U2AF1, TP53, and IDH1/2, influence overall survival and disease progression, although data on independent prognostic impact are still insufficient to recommend routine use in clinical practice 1, 2, 4

Patient-Related Prognostic Factors

• Increasing age is an independent adverse prognostic factor, with age-adjusted survival estimates provided in various prognostic scoring systems 6, 7
• ECOG performance status and comorbidities, especially cardiovascular disease, are relevant for establishing prognosis and treatment choice, and are independent prognostic factors that reduce overall survival 1, 2, 4

Treatment Impact on Prognosis

• Allogeneic hematopoietic stem cell transplantation is the only potentially curative treatment and should be considered for higher-risk patients at diagnosis, although it is not always feasible due to patient-related factors 2
• Hypomethylating agents, such as azacitidine and decitabine, are first-line therapy for higher-risk MDS and impact disease evolution, with prognostic factors potentially differing in patients treated with these agents compared to supportive care alone 1, 2

Prognostic Assessment and Outcomes in Myelodysplastic Syndromes

Overall Survival and Mortality

• Median overall survival for all MDS patients is 15–30 months, with a 5‑year risk of progression to acute myeloid leukemia (AML) of 25–35 %【9】.
• Bone‑marrow failure (infection and hemorrhage) is the leading cause of death, accounting for the majority of mortality before overt AML develops【9】【10】【11】.

Risk‑Stratified Survival Expectations (IPSS‑R)

• The Revised International Prognostic Scoring System (IPSS‑R) divides patients into five risk groups that show markedly different survival outcomes【10】【12】【11】.
• In lower‑risk (very low, low, intermediate) IPSS‑R categories, the 5‑year survival rate is approximately 68 %【13】.
• In higher‑risk (intermediate, high, very high) IPSS‑R categories, median survival is less than 3 years【11】.

Core Prognostic Variables (IPSS‑R Components)

• Cytogenetics – The most powerful prognostic parameter in the IPSS‑R scoring system【11】.
• Bone‑marrow blast percentage – Higher blast percentages predict worse outcomes and faster AML progression【9】【10】【11】; patients with 5–9 % blasts (RAEB‑1) have better prognosis than those with 10–19 % blasts (RAEB‑2)【9】.
• Severity of cytopenias – The number and depth of cytopenias (anemia, thrombocytopenia, neutropenia) independently predict survival【9】【10】【11】.

Additional Patient‑Related Prognostic Factors

• Age – Increasing age independently worsens prognosis beyond the IPSS‑R score【10】【12】.
• Performance status – Poor ECOG performance status is associated with reduced survival【10】【12】.
• Comorbidities – Cardiovascular disease and other comorbid conditions independently lower overall survival【10】【12】.

Additional Disease‑Related Prognostic Factors

• Transfusion dependence – Red blood cell transfusion dependence predicts poorer outcomes【10】【12】.
• Multilineage dysplasia – Presence of dysplasia in multiple lineages is linked to adverse outcomes【10】【12】.
• Laboratory markers – Elevated serum ferritin, lactate dehydrogenase, and β₂‑microglobulin are associated with shorter survival【10】【12】.
• Bone‑marrow fibrosis – Marked fibrosis is an adverse factor; 18 % of such patients progress directly to AML【10】【12】.

Molecular Mutations and Their Prognostic Impact

• Adverse mutations – ASXL1, TP53, RUNX1, EZH2, DNMT3A, and CBL are associated with poorer prognosis【14】【12】.
• TP53 – Mutations in TP53 predict particularly poor outcomes and resistance to therapy【14】【11】.
• SF3B1 – Isolated SF3B1 mutations in MDS with ring sideroblasts confer a favorable prognosis when not accompanied by other high‑risk mutations【14】【11】.

Influence of Treatment on Prognosis

• Allogeneic hematopoietic cell transplantation – The only potentially curative therapy; should be evaluated at diagnosis for all higher‑risk patients【10】【12】.

Recommendations for Prognostic Assessment

• Do not rely solely on IPSS or IPSS‑R scores; incorporate patient age, performance status, comorbidities, and transfusion dependence into the overall prognostic evaluation【10】【12】.