When is a bone marrow transplant recommended for Myelodysplastic Syndrome (MDS)?

Bone Marrow Transplantation for Myelodysplastic Syndrome

Allogeneic hematopoietic stem cell transplantation (HSCT) is strongly recommended for higher-risk MDS patients (<70 years without major comorbidities) and should be considered at diagnosis, as it represents the only potentially curative treatment option. 1, 2

Risk Stratification to Determine Transplant Eligibility

The decision for bone marrow transplantation in MDS should be based primarily on disease risk stratification using the Revised International Prognostic Scoring System (IPSS-R):

Higher-Risk MDS (IPSS-R High/Very High)

• Primary recommendation: Proceed to allogeneic HSCT if patient is:
  • Under 70 years of age
  • Without significant comorbidities
  • Has an available donor 1
• Median survival without transplant: <3 years 2
• Consider hypomethylating agents (azacitidine or decitabine) as a bridge to transplantation 1
• Cytoreductive therapy recommended prior to transplant if bone marrow blasts ≥10% 1

Lower-Risk MDS (IPSS-R Very Low, Low, Some Intermediate)

• Consider HSCT only after failure of conventional therapies or disease progression 3
• Transplant may be considered for selected patients with severe cytopenias despite appropriate non-transplant therapies 1
• 3-year survival rates with HSCT: 65-70% with HLA-identical related or unrelated donors 3

Donor Selection

1. Standard donors (in order of preference) 1:

   • HLA-identical siblings
   • Syngeneic donors
   • 8/8 or 10/10 matched unrelated donors (MUDs)

2. Alternative donors should be considered for higher-risk patients when no matched donor is available within a reasonable timeframe 1

3. Consider donor characteristics including age, sex, and cytomegalovirus (CMV) status during selection 1

Pre-Transplant Considerations

Cytoreduction Before Transplant

• For patients with ≥10% bone marrow blasts, cytoreduction is recommended before starting conditioning 1
• Options include:
  • Hypomethylating agents (HMAs): azacitidine or decitabine
  • Intensive chemotherapy (for younger patients with favorable cytogenetics) 3

Timing of Transplant

• For higher-risk MDS: proceed to transplant as soon as a donor is identified 1, 2
• After failure of hypomethylating agents: proceed directly to HSCT as median survival after HMA failure is <6 months 1
• After failure of intensive chemotherapy: if relapse occurs within 1 year of CR1, proceed directly to HSCT; if relapse occurs after prolonged CR1 (>1 year), consider remission induction with ICT to achieve CR2 before HSCT 1

Conditioning Regimens

• Standard myeloablative conditioning: Preferred for younger, fit patients
• Reduced-intensity conditioning: Consider for older patients (60-70 years) or those with comorbidities 3, 4

Post-Transplant Challenges

• Disease relapse remains a major challenge (10-40% probability) 3
• Graft-versus-host disease (both acute and chronic) requires careful management 4

Common Pitfalls to Avoid

1. Delayed referral: Patients with higher-risk MDS should be referred for transplant evaluation at diagnosis
2. Excessive cytoreduction attempts: Multiple failed cycles of chemotherapy can increase comorbidities and reduce transplant success
3. Overlooking iron overload: Patients with significant transfusion burden should receive iron chelation before transplant 1
4. Ignoring molecular markers: TP53, EZH2, and ETV6 mutations are associated with poor prognosis and may influence transplant timing 3

Allogeneic HSCT remains the only potentially curative option for MDS, with the decision to transplant requiring careful consideration of disease risk, patient factors, and donor availability.