In a patient with myelodysplastic syndrome (MDS) and bone marrow blast percentage below 8%, is allogeneic hematopoietic stem cell transplantation (HSCT) indicated, and what conditioning regimen should be used?

Allogeneic HSCT for MDS with <8% Blasts

For patients with MDS and bone marrow blasts below 8%, allogeneic HSCT is indicated if they have higher-risk disease (IPSS-R intermediate or above) and are fit candidates aged ≤70 years with an available donor, and they should proceed directly to transplant without cytoreductive therapy. 1

Risk Stratification Determines Transplant Indication

The decision for HSCT in MDS with <8% blasts hinges entirely on risk category, not blast percentage alone:

• Higher-risk MDS (IPSS-R intermediate, high, or very high): HSCT is the only potentially curative treatment and should be offered to all patients ≤70 years without major comorbidities who have a donor 1
• Lower-risk MDS: HSCT is generally not indicated unless specific poor prognostic features emerge (certain high-risk mutations, treatment failure, or progression) 1

The ESMO guidelines explicitly state that allo-SCT should be proposed to all higher-risk MDS patients <70 years old without major comorbidities and with a donor [I, A recommendation] 1. The NCCN 2025 guidelines similarly recommend early referral for transplant evaluation in higher-risk disease 2.

No Cytoreductive Therapy Needed for <10% Blasts

Patients with <10% bone marrow blasts should proceed directly to transplant without cytoreductive therapy. 1, 3

The evidence is clear on this point:

• Cytoreductive treatment (chemotherapy or hypomethylating agents) is generally considered only when marrow blasts are ≥10%, especially for non-myeloablative conditioning 1
• The 2017 international expert panel recommended upfront HSCT in higher-risk patients with <10% BM blasts 3
• Recent 2026 data suggests pretransplant hypomethylating agents may actually worsen outcomes in lower-blast MDS, showing significantly worse relapse-free survival and overall survival compared to proceeding directly to transplant 4

Conditioning Regimen Selection

For patients aged <55 years without comorbidities, use myeloablative conditioning; for older patients or those with comorbidities, use reduced-intensity conditioning. 1

The conditioning choice depends on age and fitness:

• Myeloablative HSCT: Recommended for patients aged <55 years without comorbidities, as relapse risk is higher with reduced-intensity conditioning 1
• Reduced-intensity conditioning (RIC): Appropriate for older patients or those with comorbidities, though it carries higher relapse risk but lower non-relapse mortality 5

The 2021 ESMO guidelines state that patients aged <55 years without comorbidities should probably be offered myeloablative HSCT [II, B recommendation] 1.

Donor Selection

HLA-identical or single antigen mismatched siblings or matched unrelated donors are preferred; haploidentical donors and cord blood are acceptable alternatives with comparable outcomes. 1

The donor hierarchy has evolved:

• HLA-matched siblings or matched unrelated individuals remain the standard [I, A recommendation] 1
• Haploidentical donors and cord blood are now widely used as alternative donors with comparable outcomes [II, B recommendation] 1
• Recent data suggests younger unrelated donors may be preferable over HLA-matched relatives in the post-transplant cyclophosphamide setting 5

Critical Pre-Transplant Consideration: Iron Chelation

All transplant candidates should receive iron chelation therapy if they have transfusion-related iron overload. 1

This is strongly emphasized across guidelines:

• Iron overload contributes to negative outcomes after allo-HSCT, with elevated labile plasma iron predicting increased infection-related non-relapse mortality 1
• Iron chelation is strongly recommended in candidates for allo-SCT [III, B recommendation] 1
• Chelation should continue at least until the onset of conditioning treatment 1

Timing Considerations

Early transplant (<6 months from diagnosis) may optimize outcomes in higher-risk MDS. 6

Recent 2025 data showed:

• Significantly higher 3-year overall survival with early HSCT (70% vs 50%, p=0.05) 6
• Lower transplant-related mortality with early approach (22.7% vs 46.5%, p=0.02) 6
• Early HSCT was the only significant factor influencing both OS and TRM 6

Common Pitfalls to Avoid

1. Don't delay transplant for cytoreduction in patients with <10% blasts - this may worsen outcomes 4
2. Don't use blast percentage alone to determine transplant eligibility - risk stratification by IPSS-R is essential 1
3. Don't overlook iron chelation - even moderate iron overload increases transplant-related mortality 1
4. Don't assume all lower-risk MDS patients should avoid transplant - some with poor prognostic features may benefit 1