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This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.
The Bottom Line
- Group of clonal haematopoietic stem cell disorders characterised by cytopenias, dysplastic morphology, and risk of AML transformation (30% overall)
- Predominantly affects elderly (median age 70). Often presents with unexplained macrocytic anaemia refractory to B12/folate/iron replacement
- Bone marrow biopsy is essential for diagnosis — shows dysplastic features ± ring sideroblasts ± increased blasts
- Prognostic scoring: IPSS-R (Revised International Prognostic Scoring System) — determines risk category and guides treatment
- Treatment: low-risk = supportive (transfusions, EPO, lenalidomide for del(5q)). High-risk = azacitidine ± allogeneic stem cell transplant (only curative option)
Overview
Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal bone marrow disorders characterised by ineffective haematopoiesis, peripheral cytopenias, and morphological dysplasia in one or more cell lines. The marrow is typically hypercellular (unlike aplastic anaemia) but produces dysfunctional cells. MDS carries a significant risk of transformation to AML — the risk varies from <5% in low-risk MDS to >40% in high-risk subtypes. MDS may arise de novo (primary) or secondary to prior chemotherapy, radiotherapy, or toxin exposure.
Epidemiology
MDS predominantly affects the elderly, with a median age at diagnosis of approximately 70 years. The incidence is approximately 4-5 per 100,000 per year, rising to >30 per 100,000 in those over 70. Males are more commonly affected (1.5:1). Therapy-related MDS (t-MDS) occurs after exposure to alkylating agents (5-7 years later) or topoisomerase II inhibitors (1-3 years later). Environmental exposures (benzene, radiation) are also risk factors.
Clinical Features
Symptoms
Fatigue and breathlessness — from anaemia (the most common presenting feature)
Recurrent or severe infections — from neutropenia
Easy bruising and bleeding — from thrombocytopenia
Insidious onset over months — often initially attributed to "old age"
Signs
Pallor
Petechiae, purpura
Signs of infection
Usually NO lymphadenopathy or significant organomegaly (unlike leukaemia)
Splenomegaly may develop in CMML subtype
Investigations
First-line
FBCOne or more cytopenias: anaemia (most common, often macrocytic MCV >100 fL), neutropenia, thrombocytopenia. Pancytopenia in advanced cases
Blood filmDysplastic features: oval macrocytes, hypogranular neutrophils, pseudo-Pelger-Huet cells (bilobed neutrophils), abnormal platelet morphology
Reticulocyte countLow or inappropriately normal (ineffective erythropoiesis — marrow is active but output is defective)
Second-line
Bone marrow aspirate and trephineESSENTIAL for diagnosis. Shows dysplasia in ≥1 lineage, ring sideroblasts (iron-laden mitochondria encircling the nucleus — Prussian blue stain), and blast percentage (<20%, otherwise AML)
Cytogenetics/FISHImportant for prognosis and classification: del(5q) = good prognosis (responds to lenalidomide), complex karyotype = poor prognosis
Serum EPOGuides ESA treatment decisions — EPO <200 IU/L predicts better response to erythropoiesis-stimulating agents
Specialist
IPSS-R scoringRevised International Prognostic Scoring System: based on cytogenetics, blast %, Hb, platelets, ANC. Divides into very low → very high risk
Molecular genetics panelSF3B1 (ring sideroblasts, good prognosis), TP53 (very poor prognosis), TET2, ASXL1, RUNX1 — increasingly guide treatment
Iron studies, B12, folateExclude deficiency causes of macrocytic anaemia before attributing to MDS
1
Lower-risk MDS (IPSS-R very low to intermediate)
- Supportive care: red cell transfusions, platelet transfusions as needed
- Erythropoiesis-stimulating agents (ESA): epoetin or darbepoetin — effective in ~40-60% if EPO <200 IU/L
- Iron chelation if transfusion-dependent (ferritin >1000 µg/L) — deferasirox
- Lenalidomide: specifically effective for MDS with isolated del(5q) — can achieve transfusion independence in ~67%
- Luspatercept: for ring sideroblast MDS (SF3B1 mutation) with anaemia failing ESA
2
Higher-risk MDS (IPSS-R high or very high)
- Azacitidine (hypomethylating agent): standard of care — prolongs overall survival and delays AML transformation
- 75 mg/m² SC for 7 days every 28-day cycle, continue until progression
- Allogeneic stem cell transplant: the ONLY curative option. Consider in fit patients <70 with matched donor
- Intensive chemotherapy (AML-type): rarely used unless good-risk cytogenetics and fit for transplant
3
Supportive care for all
- Infection prevention: prompt antibiotics for fever, annual vaccinations
- Transfusion support with leucodepleted, irradiated blood products if transplant candidate
- Quality of life assessment — many elderly patients appropriately managed supportively
Complications
- AML transformation: The major disease-related complication — overall ~30% but varies by risk group (5% in low-risk to >40% in high-risk)
- Iron overload: From chronic transfusion dependence — cardiac and hepatic siderosis
- Infection: Neutropenia and qualitative neutrophil dysfunction
- Bleeding: From thrombocytopenia — can be severe and life-threatening
UKMLA Exam Tips
- 1Elderly patient + unexplained macrocytic anaemia + normal B12/folate = think MDS (bone marrow biopsy needed)
- 2Ring sideroblasts on marrow iron stain = MDS with ring sideroblasts (typically SF3B1-mutated)
- 3Pseudo-Pelger-Huet cells (bilobed neutrophils) on blood film = MDS — classic exam morphology
- 4Del(5q) MDS = responds to lenalidomide. This is a high-yield pharmacology point
- 5MDS vs aplastic anaemia: MDS = hypercellular dysplastic marrow. AA = hypocellular empty marrow
- 6Azacitidine for high-risk MDS — the key treatment to know. Only SCT is curative
practicetest your knowledge on myelodysplastic syndromeApply what you've learnt with UKMLA-style questions from the iatroX Q-Bank — haematology and beyond.
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