What is the role of bone marrow transplant in the treatment of Chronic Myeloid Leukemia (CML) and Acute Myeloid Leukemia (AML)?

Role of Bone Marrow Transplantation in CML and AML Treatment

Chronic Myeloid Leukemia (CML)

Bone marrow transplantation is no longer recommended as first-line therapy for chronic phase CML but remains an important option for patients who fail tyrosine kinase inhibitor (TKI) therapy or have advanced disease. 1

Treatment Algorithm for CML:

1. First-line treatment: TKI therapy (imatinib, dasatinib, bosutinib, nilotinib, or asciminib)

   • TKI therapy has dramatically improved CML-related mortality from 10-20% per year to 1-2% per year
   • Patients on TKIs now have survival rates similar to age-matched general population

2. Consider allogeneic BMT only for:

   • Patients who fail to respond to second-generation TKIs
   • Those with intolerance to multiple TKIs
   • Patients with accelerated-phase CML or blast phase CML

3. Risk stratification for transplant decisions:

   • Use CPSS-Mol score to identify transplant candidates 2
   • High and Intermediate-2 risk patients should be considered for earlier transplantation
   • Low and Intermediate-1 risk patients should receive non-transplant approaches initially

4. Post-transplant relapse management:

   • TKI therapy is active in the post-transplant setting and may be preferred over donor lymphocyte infusions (DLI) 3

Acute Myeloid Leukemia (AML)

For AML, allogeneic stem cell transplantation remains a critical consolidation therapy option for intermediate and high-risk patients in first complete remission. 2

Treatment Algorithm for AML:

1. Induction therapy:

   • Standard induction: anthracycline + cytarabine 2
   • For APL: anthracycline + all-trans retinoic acid (ATRA) 2

2. Post-remission (consolidation) therapy:

   • Good-risk cytogenetics (t(8;21), t(16;16), inv(16)):

     • High-dose cytarabine chemotherapy without transplant 2

   • Intermediate-risk cytogenetics with HLA-identical sibling:

     • Allogeneic stem cell transplantation in first remission 2

   • Poor-risk cytogenetics or failed first induction:

     • Allogeneic transplant (including consideration of matched unrelated donor) 2

3. For relapsed/refractory AML:

   • Allogeneic transplantation with unrelated donor is recommended 2
   • For APL specifically: arsenic trioxide for ATRA-refractory disease 2

Transplant Considerations:

• Age: Patients <60 years are generally better candidates
• Performance status and comorbidities must be evaluated
• Donor availability: HLA-matched sibling preferred; matched unrelated donor for high-risk disease
• Timing: Earlier transplant associated with better outcomes in high-risk disease

Key Differences Between CML and AML Transplant Approaches

1. Role in initial therapy:

   • CML: Reserved for TKI failures or advanced disease
   • AML: Standard consolidation for intermediate/high-risk patients in first remission

2. Timing:

   • CML: Delayed until TKI failure
   • AML: Early consolidation after achieving first remission

3. Outcomes:

   • CML: Cure rates 20-60% depending on disease stage at transplant 1
   • AML: Outcomes heavily dependent on cytogenetic/molecular risk factors and disease status

Complications and Monitoring

• Common complications include graft-versus-host disease, venoocclusive disease, interstitial pneumonitis, and infections 4, 5
• Post-transplant monitoring includes clinical examination, serial peripheral blood counts, and bone marrow evaluations as needed 2
• Molecular monitoring is increasingly important, particularly in CML and certain AML subtypes

Practical Considerations

• Treatment should be performed at centers with multidisciplinary expertise and adequate infrastructure 2
• Clinical trial participation should be encouraged whenever possible 2
• Dynamic reassessment of disease status is essential, particularly for CML patients 2

The treatment landscape continues to evolve, particularly for CML where TKIs have revolutionized management. For AML, allogeneic transplantation remains a cornerstone of therapy for intermediate and high-risk disease.