by Dr. Ingrid Aronson, BScHons, MBChB, MMed (Path)(Haem) (UCT)
PATHCHAT Edition No. 8
Please contact your local Ampath pathologist for more information.
Overview of Myelodysplastic Syndromes (MDS)
Myelodysplastic syndromes (MDS) are a group of clonal haematopoietic disorders characterized by:
- Progressive bone marrow failure due to ineffective haematopoiesis.
- Cytopenias affecting one or more myeloid cell lines.
- Variable risk of progression to acute myeloid leukaemia (AML).
Epidemiology of MDS
- MDS can occur at any age, including childhood, but is most common in the elderly.
- Median age at diagnosis: 7th decade of life.
- Incidence increases significantly with age:
- 0.7 per 100,000 in the fourth decade of life.
- 20.8 – 36.3 per 100,000 in individuals aged >70 years.
- More common in males at all ages.
- 13,000 new cases annually (1999 data), making it more common than chronic lymphocytic leukaemia (CLL) in the Western Hemisphere.
- Global prevalence is similar across populations.
Causes & Risk Factors (Aetiology)
MDS results from haematopoietic stem cell injury, but the cause is unknown in most cases.
🔹 Known risk factors include:
- Previous exposure to alkylating agents or ionizing radiation (latency period: 5–10 years).
- Topoisomerase II inhibitors (latency period: 1–5 years, sometimes with a preceding myelodysplastic phase).
- Environmental exposures:
- Tobacco smoke
- Pesticides
- Industrial chemicals (e.g., benzene)
- Heavy metals (lead, mercury)
Clinical Features of MDS
🔹 Common Presentations:
- Many patients are asymptomatic, and MDS is diagnosed incidentally on a routine blood count.
- Anaemia (often macrocytic, unresponsive to folate or B12 treatment).
- Neutropenia and/or thrombocytopenia may be present initially or develop later.
- Organomegaly is usually absent.
Laboratory Findings in MDS
🔹 Full Blood Count (FBC):
- Macrocytic anaemia or pancytopenia, usually mild to moderate at presentation.
🔹 Peripheral Blood Smear:
- Macrocytes
- Dysplastic neutrophils (hyposegmentation, hypogranularity)
- Large, abnormal platelets
🔹 Bone Marrow Findings:
- Hypercellular marrow with dysplasia affecting one or more cell lineages.
- Erythroid dysplasia (abnormal nuclear shape, ring sideroblasts on iron staining).
- Granulocytic dysplasia (hypolobulated or hypersegmented neutrophils).
- Megakaryocytic dysplasia (micromegakaryocytes, nuclear hypolobulation).
- Blast count in bone marrow & peripheral blood is essential for classification & prognosis.
WHO Classification of MDS
🔹 Refractory Cytopenia with Unilineage Dysplasia (RCUD):
- Peripheral blood: Unicytopenia or bicytopenia, <1% blasts
- Bone marrow: Dysplasia in a single lineage, <5% blasts, <15% ring sideroblasts
🔹 Refractory Anaemia with Ring Sideroblasts (RARS):
- Peripheral blood: Anaemia, No blasts
- Bone marrow: ≥15% ring sideroblasts, Erythroid dysplasia, <5% blasts
🔹 Refractory Cytopenia with Multilineage Dysplasia (RCMD):
- Peripheral blood: Cytopenias, <1% blasts, no Auer rods
- Bone marrow: Dysplasia in ≥2 lineages, <5% blasts, ±15% ring sideroblasts
🔹 Refractory Anaemia with Excess Blasts-1 (RAEB-1):
- Peripheral blood: Cytopenias, <5% blasts, no Auer rods
- Bone marrow: Unilineage or multilineage dysplasia, 5–9% blasts, no Auer rods
🔹 Refractory Anaemia with Excess Blasts-2 (RAEB-2):
- Peripheral blood: Cytopenias, 5–19% blasts, ± Auer rods
- Bone marrow: 10–19% blasts, ± Auer rods
🔹 MDS with Isolated del(5q):
- Peripheral blood: Anaemia, Normal or increased platelets, <1% blasts
- Bone marrow: Hypolobated megakaryocytes, <5% blasts, del(5q) cytogenetic abnormality
📌 Adapted from WHO Classification of Tumours of Haematopoietic & Lymphoid Tissues (4th edition, 2008).
Prognosis & Risk Stratification: IPSS Scoring System
IPSS Risk Score Components:
- Bone marrow blast percentage
- Cytogenetics
- Number & severity of cytopenias
🔹 Risk Scores:
- Low-risk: Score 0 → Bone marrow blasts <5%, good cytogenetics, 0–1 cytopenia
- Intermediate-1: Score 0.5–1 → Blasts 5–10%, intermediate cytogenetics, 2–3 cytopenias
- Intermediate-2: Score 1.5–2 → Blasts 11–19%, poor cytogenetics, 2–3 cytopenias
- High-risk: Score >2.5 → Blasts ≥20% (WHO defines this as AML), poor cytogenetics, 2–3 cytopenias
🔹 Median Survival by Risk Group:
- Low risk: 5.7 years
- Intermediate-1: 3.5 years
- Intermediate-2: 1.2 years
- High risk: 0.4 years
📌 Adapted from Greenberg et al., Blood, 1997.
Treatment Approaches
🔹 Low-Risk MDS:
- Supportive care (transfusions, erythropoietin, G-CSF).
- Lenalidomide (especially in del(5q) MDS).
🔹 High-Risk MDS:
- Haematopoietic Stem Cell Transplantation (HSCT) (best chance for cure).
- Hypomethylating agents (azacitidine, decitabine).
- Low-dose chemotherapy (cytarabine).
Conclusion
- MDS is a common cause of unexplained macrocytic anaemia & cytopenias in elderly patients.
- Diagnosis requires FBC, bone marrow studies, and cytogenetic analysis.
- Risk stratification (IPSS) guides prognosis & treatment decisions.
- Treatment ranges from supportive care to aggressive therapies for high-risk cases.