Which of the following statements about myelodysplastic syndromes is correct: they usually affect individuals over 60, cause macrocytosis, have allogeneic stem‑cell transplantation as the only curative therapy, and are characterized by fewer than 20% blasts in bone marrow?

All of the Above Statements Are Correct

All five statements (A through E) about myelodysplastic syndromes are accurate, making E the correct answer.

Age Distribution (Statement A)

MDS predominantly affects elderly individuals, with a median age at diagnosis of approximately 70 years 1. The incidence dramatically increases with age, reaching 40-50 cases per 100,000 in patients aged ≥70 years, compared to only 4 per 100,000 in the general population 1. While more than 10% of patients are younger than 50 years, the disease clearly clusters in those over 60 1, 2.

Macrocytosis (Statement B)

MDS is indeed a cause of macrocytosis. The anemia in MDS is typically normo- or macrocytic and non-regenerative 3. The morphologic examination reveals megaloblastoid erythropoiesis with nucleocytoplasmic asynchrony in early erythroid precursors 2. Peripheral blood examination shows anisocytosis, poikilocytosis, and megalocytes 4. This macrocytic presentation is a key diagnostic feature that should prompt bone marrow evaluation.

Allogeneic Transplantation as Only Curative Treatment (Statement C)

Allogeneic stem cell transplantation (alloSCT) remains the only definitive curative treatment for MDS 1. This is consistently stated across all major guidelines. While other therapies (hypomethylating agents, lenalidomide, luspatercept) can improve disease control and quality of life, they do not cure the disease 5, 6, 7. The 2017 expert panel recommendations specifically emphasize that despite improved understanding of molecular pathogenesis, currently available therapeutic agents lead to prolongation of life but no cure, making alloSCT the only curative option 8.

Important caveat: The typical MDS patient (median age 70 years) often cannot tolerate intensive transplant conditioning, which is why reduced-intensity conditioning (RIC) regimens have expanded eligibility 8, 5. However, advanced age and comorbidities remain significant barriers to this curative approach.

Blast Percentage <20% (Statement D)

MDS is characterized by fewer than 20% blasts in bone marrow. The WHO classification established that ≥20% blasts defines acute myeloid leukemia (AML), not MDS 9. This represents a decrease from the previous FAB threshold of 30% blasts. The distinction is critical:

• MDS subtypes by blast percentage:
  • Refractory anemia (RA): <5% blasts
  • RA with excess blasts (RAEB): 5-20% blasts
  • ≥20% blasts = AML diagnosis 9, 2

This threshold is not arbitrary—it reflects fundamental differences in disease biology, pace of progression, and response to therapy 9.

Clinical Application Algorithm

When evaluating a patient with suspected MDS:

1. Confirm age >60 years (increases pre-test probability significantly)
2. Document macrocytosis on CBC (typical finding)
3. Perform bone marrow biopsy showing:
   • Dysplasia in ≥2 cell lines
   • Blasts <20% (if ≥20%, diagnose as AML)
   • Cytogenetic analysis for risk stratification
4. Risk-stratify using IPSS-R or IPSS-M to guide treatment
5. Assess transplant candidacy early:
   • Age, performance status, comorbidities (HCT-CI score)
   • Donor availability
   • Patient preference

Common pitfall: Delaying transplant evaluation until disease progression. For eligible patients with higher-risk MDS, early referral to transplant centers is essential, as alloSCT offers the only chance for cure 8, 5.

The evidence consistently supports all five statements, making E (All of the above) the definitive answer.