Can a bone marrow transplant cure Acute Myeloid Leukemia (AML)?

Bone Marrow Transplantation Can Cure AML in Specific Patient Populations

Allogeneic stem cell transplantation is a potentially curative treatment for acute myeloid leukemia (AML), particularly for intermediate and high-risk patients in first complete remission. 1

Risk Stratification for Transplant Decisions

Risk assessment is crucial for determining which AML patients should receive bone marrow transplantation:

Good Risk Patients

• Patients with favorable cytogenetics (t(8;21), t(16;16), inv(16)) or molecular markers (mutations in C/EBPa or nucleophosmin genes) 2
• These patients have a relapse risk ≤35% and should receive high-dose cytarabine consolidation chemotherapy without transplant 1, 2
• Transplantation is not justified in first remission for these patients as the risk of transplant-related mortality exceeds the benefit 2

Intermediate and Poor Risk Patients

• Patients with intermediate-risk cytogenetics who have an HLA-identical sibling are candidates for allogeneic stem cell transplantation in first remission 2, 1
• Patients with poor-risk features (complex karyotype, FLT3 alterations) should be considered for allogeneic transplantation, even with an unrelated matched donor if no sibling donor is available 2
• Cure rates of up to 60% can be achieved in properly selected patients 3

Transplantation Timing and Patient Selection

The timing of transplantation significantly impacts outcomes:

• Early identification of transplant candidates during induction therapy is essential 2
• Age is an important consideration:
  • Patients <60 years generally have better outcomes 2
  • Older patients (≥60-65 years) are more susceptible to treatment complications 2
• Pre-existing medical conditions (diabetes, coronary heart disease, COPD) must be evaluated 2
• For relapsed/refractory AML:
  • Primary refractory AML has better outcomes following allogeneic transplantation than refractory relapse 4
  • Up to 30% of patients with refractory or relapsed AML can achieve durable remissions after allogeneic transplantation 4

Transplantation Procedure and Outcomes

Conditioning Regimens

• Standard conditioning includes busulfan/cyclophosphamide or cyclophosphamide/total body irradiation 5
• Reduced-intensity conditioning regimens are increasingly used, especially for patients >40-45 years 2

Donor Selection

• HLA-identical sibling donors are preferred 1
• Matched unrelated donors should be considered for high-risk disease with no sibling donor 1
• In cases of KIR mismatch, haploidentical transplants may be considered 2

Outcomes

• Long-term survival is achievable in approximately 32% of patients at 10 years post-autologous transplantation for relapsed AML in second remission 6
• Relapse remains the major reason for transplant failure, affecting 40-50% of patients 7
• The 10-year actuarial overall survival rate can reach 32%, with progression-free survival of 28% 6

Post-Transplant Monitoring and Care

• Patients should be followed clinically with hematological examinations to detect early relapse 2
• Minimal residual disease monitoring and prompt application of pre-emptive strategies are imperative 7
• Novel agents and targeted therapies have enriched the therapeutic landscape for post-transplant relapse 7

Common Pitfalls and Caveats

• Delaying donor search in high-risk disease can limit treatment options
• Failure to identify transplant candidates early during induction
• Underutilization of transplantation in eligible patients with refractory/relapsed disease
• Overlooking the importance of post-transplant monitoring for early relapse detection
• Not considering reduced-intensity conditioning for older patients who might benefit from transplantation

In conclusion, bone marrow transplantation offers a curative option for many AML patients, particularly those with intermediate or high-risk disease. The decision to proceed with transplantation must be based on careful risk assessment, donor availability, and patient factors.