What is the recommended management approach for patients with 10-19% blasts in bone marrow?

Management of Patients with 10-19% Bone Marrow Blasts

Patients with 10-19% bone marrow blasts should be treated with intensive therapy aimed at reducing blast percentage, with allogeneic hematopoietic stem cell transplantation (allo-HCT) as the preferred definitive treatment whenever possible. 1

Disease Classification and Risk Assessment

• Patients with 10-19% bone marrow blasts fall into a critical diagnostic category that represents higher-risk myelodysplastic syndrome (MDS) or early transformation to acute myeloid leukemia (AML) 1
• These patients should be risk-stratified using the International Prognostic Scoring System (IPSS), which incorporates bone marrow cytogenetics, blast percentage, and number of cytopenias 1
• Patients with 10-19% blasts typically fall into the Intermediate-2 or High risk IPSS categories, which are associated with poorer outcomes and require more aggressive management 1
• Cytogenetic analysis is essential for these patients, as the presence of poor-risk cytogenetics further worsens prognosis and may influence treatment decisions 1

Treatment Approach

First-Line Therapy

• For transplant-eligible patients, upfront allo-HCT without prior disease-modifying treatment is the preferred approach to maximize chances of long-term survival 1
• For patients who cannot proceed immediately to transplant, hypomethylating agents (HMAs) such as azacitidine (75 mg/m² daily for 7 days every 4 weeks) or decitabine (15 mg/m² every 8 hours for 3 consecutive days, repeated every 6 weeks) are recommended 2, 3, 4
• Clinical trials show that azacitidine treatment resulted in a response rate (complete + partial response) of 15.7% compared to 0% with supportive care alone in higher-risk MDS patients 3
• Decitabine has demonstrated similar efficacy with an overall response rate of 17% in higher-risk MDS patients 4

Transplant Considerations

• All transplant-eligible patients with 10-19% blasts should be considered for allo-HCT as the only potentially curative option 1, 2
• For patients with aggressive disease showing rapid progression, bridging therapy with hypomethylating agents (possibly in combination with venetoclax, though this is off-label) may be considered before proceeding to transplant 1
• Iron chelation therapy should be considered for transplant candidates with serum ferritin levels exceeding 1000 μg/L to reduce transplant-related complications 1, 5

Management of Non-Transplant Candidates

• For patients ineligible for transplant, continuous therapy with hypomethylating agents is recommended to control disease progression 2, 3
• Older patients (≥70 years) with 10-19% blasts may benefit more from epigenetic therapy (HMAs) than from intensive chemotherapy, with at least equivalent outcomes and less toxicity 6
• Response assessment should follow the International Working Group (IWG) criteria, with complete remission defined as <5% myeloblasts with normal maturation of all cell lines 1

Monitoring and Response Assessment

• Regular bone marrow evaluations should be performed to assess treatment response, with complete remission defined as <5% blasts with normal maturation of all cell lines 1
• Peripheral blood counts should be monitored for improvement in cytopenias, with hematologic improvement defined as lasting at least 2 months 1
• Disease progression is defined as a 50% or more increase in blasts to >20% blasts for patients with 10-20% blasts at baseline 1
• Transformation to AML is defined as progression to ≥30% blasts 1, 7

Prognostic Considerations

• Patients with 10-19% blasts have worse outcomes compared to those with <10% blasts but better outcomes than those with ≥30% blasts, with median overall survival of approximately 16 months compared to 13.5 months for those with ≥30% blasts 6
• The presence of additional poor prognostic factors such as advanced age, poor-risk cytogenetics, and elevated white blood cell count significantly worsens survival 6
• Younger patients (≤60 years) with 10-19% blasts benefit from intensive AML-type therapy regardless of blast percentage 6

Supportive Care

• Red blood cell transfusions should be provided for symptomatic anemia, generally at hemoglobin thresholds of at least 8 g/dL 2
• Platelet transfusions should be considered for severe thrombocytopenia or bleeding 2
• Iron chelation therapy should be considered for patients receiving multiple transfusions, especially if serum ferritin rises above 1000-2500 U/L 2, 5

By following this management approach, clinicians can optimize outcomes for patients with 10-19% bone marrow blasts, potentially improving survival and quality of life in this high-risk patient population.