Skip to content
GERICLINICS

GeriQBank · Paper III · Q5

Myelodysplasia

Very High YieldAsked ×315-mark essay + 7-mark note
Topic
Haematology, Oncology & Screening
Chapter
Haematology
Years asked
Not recorded in the source
Frequency
Set 3× in Paper III (2009–2025)

As set in the university paper

  • Myelodysplastic syndrome — classification, etiology, clinical features, differential diagnosis, investigations and treatment in the elderly.

    Paper III · Haematology & Oncology · asked ×3 · 15-mark essay + 7-mark note · see in paper list

Answer framework

  1. Definition and epidemiology
  2. Aetiology — primary, therapy-related, inherited
  3. Pathophysiology — ineffective haematopoiesis, methylation, key mutations
  4. Clinical features — anaemia, infection, bleeding; easily overlooked
  5. Diagnosis — blood and film, marrow, cytogenetics, excluding reactive causes; IWG/NCCN criteria
  6. WHO 2016 classification
  7. Prognostic scoring — IPSS, IPSS-R, comorbidity indices
  8. Management — lower-risk, higher-risk, transplant, frail patients
  9. Recent updates — WHO 2022 and ICC, IPSS-M, luspatercept, imetelstat, VERONA

An exam answer plan drawn from the detailed answer below. Use it to attempt the question first.

Detailed answer

Pro · free in beta
Attempt it firstOutline your answer as a 15-mark essay + 7-mark note before revealing it — definition, causes, evaluation, management and the geriatric angle.Reveal answer

Short revision answer

  • MDS are clonal stem-cell disorders with ineffective haematopoiesis — cytopenias despite a hypercellular marrow — and a variable risk of AML. They are the commonest haematological neoplasm in older people: median age at diagnosis 75–76, with 86% aged 60 or over.
  • Therapy-related MDS (10–20%) follows alkylating agents, radiation or benzene after 5–10 years, often with loss of chromosome 5 or 7.
  • Hypermethylation silences tumour suppressor genes (the basis for hypomethylating drugs); SF3B1 mutation gives ring sideroblasts and a favourable prognosis; TP53 marks higher-risk disease.
  • Presentation: macrocytic anaemia (90%), infections from dysfunctional neutrophils, and bleeding even with a normal platelet count; splenomegaly suggests CMML. It is easily dismissed as chronic anaemia.
  • Diagnosis: film (pseudo-Pelger–Huët cells); marrow with dysplasia in >10% of a lineage and Perls' stain; cytogenetics (60% normal; a complex karyotype is poor); exclude B12 or folate deficiency, hypothyroidism, viral infection, alcohol and drugs.
  • IWG/NCCN: stable cytopenia for ≥6 months (≥2 with a specific karyotype or bilineage dysplasia) with other causes excluded, plus dysplasia ≥10%, blasts 5–19% or an MDS-associated karyotype.
  • Prognosis: IPSS-R; CGA and comorbidity indices add value in older people.
  • Lower risk: watchful waiting, ESAs, transfusion with chelation, lenalidomide for del(5q), luspatercept. Higher risk: azacitidine 75 mg/m² for 7 days every 28 days, for at least 4–6 cycles. Allogeneic transplant is the only cure (reduced intensity up to 70–75); best supportive care in the very frail.
  • Updates: WHO 2022 "myelodysplastic neoplasms" with genetic and morphological groups; IPSS-M (31 genes); luspatercept first-line (COMMANDS); imetelstat (2024); VERONA — venetoclax adds nothing to azacitidine.

Condensed by GeriClinics from the detailed answer below, with no new facts added.

Well covered: Pathy's Ch. 26 ("Myelodysplasia") and Ch. 27 ("Management of MDS and AML in the Elderly") cover this topic in genuine depth — this answer is largely textbook-derived.

High-Yield Points

A. Definition & Epidemiology

1.

Heterogeneous clonal haematopoietic stem cell disorders — cytopenia from dysplastic, ineffective production, with variable risk of AML transformation.

2.

Most common haematological neoplasm in the elderly — median diagnosis age 75–76; 86% occur ≥60 years. Incidence 75/1,00,000 over 65; 70/1,00,000/yr over 85.

3.

Age is the primary risk factor — accumulating stem cell DNA mutations.

B. Aetiology

4.

Secondary (therapy-related) MDS: 10–20%, 5–10 years after alkylating agents/radiation/benzene. Alkylator exposure → loss of chromosome 5/7.

5.

Inherited predisposition: Down syndrome, Fanconi anaemia, Bloom syndrome, ataxia-telangiectasia, NF1.

C. Pathophysiology

6.

Clonal myeloid precursor abnormality → excess intramedullary apoptosis → peripheral cytopenias despite a hypercellular marrow (the hallmark paradox).

7.

Aberrant hypermethylation silences tumour suppressor genes (TET2, DNMT3A, EZH2, ASXL1 mutations) — basis for hypomethylating agent therapy.

8.

SF3B1 mutation → ring sideroblasts, favourable prognosis. TP53 (5–20%) → higher-risk, therapy-related disease.

D. Clinical Features

9.

Non-specific; macrocytic anaemia predominates — dyspnoea, fatigue, angina.

10.

Infection is a primary cause of death — neutrophil dysfunction (impaired chemotaxis/killing), T-cell function intact so viral/mycobacterial infection uncommon.

11.

Bleeding may occur despite normal platelet count (dysfunctional platelets). Splenomegaly unusual — suggests CMML.

12.

"MDS may easily be overlooked in the elderly" — presents simply as chronic macrocytic anaemia; tendency to "leave well enough alone".

E. Diagnosis

13.

Blood: macrocytic anaemia (90%), thrombocytopenia (10%), neutropenia (20–30%). Film: hypogranular/hypolobated neutrophils, pseudo-Pelger-Huët cells ("pince-nez").

14.

Marrow: dysplastic lineage = >10% of cells abnormal. Perls' stain for ring sideroblasts (≥5 iron granules around ≥1/3 nucleus in >15% erythroblasts).

15.

Cytogenetics essential — 60% normal karyotype; trisomy 8, del(5q/7q/11q/13q/20q); complex karyotype (≥3) = poor prognosis.

16.

Exclude reactive causes: B12/folate deficiency, hypothyroidism, EBV/HIV, alcohol, chemotherapy, benzene.

IWG/NCCN Diagnostic Criteria

Two prerequisites: (1) stable cytopenia ≥6 months (or ≥2 months with specific karyotype/bilineage dysplasia); (2) exclusion of other causes.

Plus ≥1 of three: dysplasia ≥10% of a lineage; blast count 5–19%; MDS-associated karyotype (del5q, del20q, +8, −7/del7q).

WHO 2016 Classification (Pathy's)

Subtype Key features

MDS-SLD 1 dysplastic lineage, 1–2 cytopenias, RS <15%, blasts <5% MD Geriatrics – Haematology Compendium Page 11 of 34 MDS-RS RS ≥15% (or ≥5% if SF3B1+)

MDS-MLD 2–3 dysplastic lineages

MDS-EB-1 / EB-2 Blasts 5–9% / 10–19% or Auer rods MDS with isolated del(5q) Normal/high platelets, hypolobated megakaryocytes MDS-U 1% PB blasts on ≥2 occasions, or defined by cytogenetics alone Prognostic Scoring IPSS: Low/Int-1/Int-2/High by blast%, cytopenias, cytogenetics. IPSS-R uses 5 cytogenetic groups + blasts/Hb/platelets/neutrophils. CGA and comorbidity indices (MDS-CI, ACE-27, Charlson) add prognostic value in the elderly.

Management

Risk Approach

Lower- Watchful waiting; ESAs first-line (epoetin alfa preferred); G-CSF synergy; transfusion + iron chelation (start after 20–50 units risk or ferritin >1000–2500 ng/mL); lenalidomide for del(5q); luspatercept post-ESA failure Higher- Azacitidine 75 mg/m² SC × 7 days/28-day cycle, ≥4–6 cycles before failure; continue indefinitely if responding risk Curative Allogeneic HSCT — the only cure; RIC feasible to 70–75; CGA crucial for selection Very Best supportive care frail Latest Updates (2023–Present)

WHO 2022/ICC 2022 renamed "myelodysplastic neoplasms" — split into genetically defined (MDS-5q, MDS-SF3B1 [RS ≥15% criterion removed], MDS-biTP53 [new]) and morphologically defined (MDS-LB, MDS-h [hypoplastic, new formal entity], MDS-IB1/IB2, MDS-f). ICC creates separate "MDS/AML" for 10–19% blasts. IPSS-M (31-gene molecular score, 6 categories) supersedes IPSS-R. COMMANDS (Lancet Haematol 2024): luspatercept superior to epoetin alfa as first-line in ESA-naïve lower-risk MDS — FDA-approved first-line, though benefit limited in RS-negative patients. Imetelstat (telomerase inhibitor, FDA June 2024) — 8-week transfusion independence ~40% vs 15% placebo after ESA failure. VERONA trial (2025): azacitidine + venetoclax showed NO survival benefit in higher-risk MDS — single-agent azacitidine remains standard.

Current Practice Update

Domain Pathy's (WHO 2016) WHO-HAEM5 (2022)

Nomenclature Myelodysplastic syndromes Myelodysplastic neoplasms Ring sideroblasts ≥15% RS defines MDS-RS SF3B1 mutation alone defines the entity TP53 Poor-prognosis mutation, no category MDS-biTP53 — distinct entity Prognostic score IPSS/IPSS-R IPSS-M is the new reference standard Post-ESA anaemia Lenalidomide (del5q), luspatercept (RS/SF3B1) Luspatercept now first-line; imetelstat added (2024) Higher-risk MDS Single-agent azacitidine Unchanged — VERONA confirms venetoclax adds no benefit MD Geriatrics – Haematology Compendium Page 12 of 34

How was your recall?

Rating marks the question complete. “Need another pass” also adds it to your bookmarks.

References

Spotted an error or something out of date?Report a problem with this page