What is the success rate of Hematopoietic Stem Cell Transplantation (HSCT) in treating Myelodysplastic Syndromes (MDS)?

Success Rate of Hematopoietic Stem Cell Transplantation in Myelodysplastic Syndromes

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment option for myelodysplastic syndromes (MDS), with long-term survival rates ranging from 30% to 70% depending on disease risk factors and patient characteristics.

Disease Risk Stratification and Transplant Outcomes

The success of HSCT in MDS is highly dependent on disease risk stratification, which should be performed using the Revised International Prognostic Scoring System (IPSS-R):

• Lower-risk MDS patients (IPSS-R very low, low, or some intermediate):

  • 3-year survival rates of 65-70% with HLA-identical related or unrelated donors 1
  • Disease recurrence probability <5% 2
  • Median survival without transplant: 3-10 years 3

• Higher-risk MDS patients (IPSS-R high, very high, or some intermediate):

  • Relapse probability ranges from 10-40% 2
  • Lower relapse-free survival compared to lower-risk patients
  • Median survival without transplant: <3 years 3

Key Factors Affecting HSCT Success

Patient-Related Factors

• Age: While chronological age influences outcomes, the introduction of reduced-intensity conditioning (RIC) regimens has extended HSCT to older patients (70-75 years) 1
• Performance status: Karnofsky status ≥80% is associated with better survival 1
• Comorbidities: Lower comorbidity index correlates with better outcomes 1

Disease-Related Factors

• Bone marrow blast percentage: <10% at time of transplantation significantly improves outcomes 1
• Cytogenetics: Very poor-risk and monosomal karyotypes have inferior outcomes 1
• Molecular mutations: TP53, EZH2, and ETV6 mutations are associated with poor prognosis 1
• Disease status: Response to pre-transplant therapy affects outcomes

Timing of Transplantation

The optimal timing for HSCT must balance disease risk with transplant-related mortality:

• Higher-risk MDS patients: Should receive HSCT as first-line treatment 1
• Lower-risk MDS patients: Should follow surveillance with transplantation only upon disease progression 1

Pre-Transplant Strategies

For patients with >10% bone marrow blasts, cytoreductive therapy before transplantation is recommended:

• Hypomethylating agents (HMAs): Azacitidine is recommended for higher-risk MDS patients not immediately eligible for HSCT 1

  • At least six cycles are recommended
  • Patients with stable disease after 6+ courses of HMA therapy are candidates for HSCT 1
  • Median survival after HMA failure is only 6 months without HSCT 1

• Intensive chemotherapy (ICT):

  • Can be considered for younger patients with highly proliferative disease without adverse cytogenetics or TP53 mutations 1
  • Complete remission rates around 50%, but duration is commonly short 1
  • Patients who achieve CR should proceed directly to HSCT without consolidation courses 1

Donor Selection

Donor selection significantly impacts HSCT success:

• Standard donors: HLA-identical siblings, syngeneic donors, and 8/8 matched unrelated donors provide optimal outcomes 1
• Alternative donors: Should be considered for higher-risk patients when no matched donor is available within a reasonable timeframe 1
• Donor characteristics: Age, sex, and CMV status should be considered during selection 1

Pitfalls and Caveats

1. Treatment-related mortality: Remains a major obstacle, especially in older and frail patients 4
2. Graft-versus-host disease (GVHD): A significant complication that affects quality of life and survival 2
3. Disease relapse: Remains a major challenge, particularly in higher-risk disease 1
4. Patient selection: Not all MDS patients are candidates for HSCT due to age, comorbidities, or disease characteristics
5. Pre-transplant therapy response: Failure to respond to pre-transplant therapy, especially in patients with TP53 mutations, predicts poor outcomes 1

Conclusion

While HSCT offers the only potential cure for MDS, careful patient selection and timing are crucial for optimizing outcomes. Disease risk stratification using IPSS-R, along with consideration of patient-related factors, should guide the decision-making process. For appropriate candidates, HSCT can provide long-term disease-free survival in a significant proportion of patients.