What is the management approach for Acute Myeloid Leukemia (AML) with CD36 expression?

Management of AML with CD36 Expression

The management of AML with CD36 expression follows standard AML treatment protocols, with intensive induction chemotherapy using a "7+3" regimen (7 days of cytarabine and 3 days of an anthracycline) as the cornerstone of treatment for eligible patients, followed by risk-stratified consolidation therapy.

Initial Diagnosis and Risk Assessment

• Complete diagnostic workup should include peripheral blood and bone marrow examination with morphology, cytochemistry, immunophenotyping, cytogenetic and molecular analysis 1
• Risk stratification must consider both patient factors (age, performance status, comorbidities) and disease characteristics (leukocyte count, karyotype, molecular markers) 1
• Pre-treatment evaluation should include:
  • Cardiac assessment with echocardiography for patients with cardiac risk factors 1
  • Coagulation screening prior to central venous line insertion 1
  • HLA typing for potential transplant candidates and their family members 1

Induction Therapy

• Standard induction therapy comprises:
  • 7 days of cytarabine (100-200 mg/m² continuously or twice daily intravenously)
  • 3 days of an anthracycline (daunorubicin ≥60 mg/m², idarubicin 10-12 mg/m², or mitoxantrone 10-12 mg/m²) 2
• This "7+3" regimen achieves complete remission in >85% of younger patients 2
• For patients with hyperleukocytosis (WBC >100×10⁹/L) and signs of leukostasis:
  • Cytoreduction with hydroxycarbamide (50-60 mg/kg/day), IV/subcutaneous cytarabine, or IV daunorubicin 2
  • Leukapheresis is not generally recommended as it does not reduce early mortality 2
• For CNS involvement:
  • Intrathecal cytarabine twice weekly until CSF clearance plus two additional injections 2

Response Assessment

• Bone marrow evaluation should be performed:
  • After hematological recovery from induction or between days 28-35 if recovery is lacking 2
  • Before each consolidation cycle 2
  • Before allogeneic stem cell transplantation 2
• Complete remission (CR) is defined as:
  • Normal bone marrow cellularity with <5% blasts
  • Recovery of normal hematopoiesis 1
• Measurable residual disease (MRD) assessment is recommended:
  • At diagnosis to establish the aberrant marker profile
  • After 2 cycles of chemotherapy
  • After the end of treatment 2

Consolidation Therapy

• Consolidation strategy depends on risk stratification:
  • Favorable risk: High-dose cytarabine-based chemotherapy consolidation 1
  • Intermediate/adverse risk: Consider allogeneic stem cell transplantation 1
• Patients who achieve CR after first induction have significantly better outcomes:
  • 5-year overall survival of 83% for early remission vs. 35% for delayed remission 3
  • 5-year disease-free survival of 81% for early remission vs. 28% for delayed remission 3
• Patients not achieving CR after first induction have poor outcomes even if CR is achieved with additional chemotherapy 4

Allogeneic Stem Cell Transplantation

• Recommended for:
  • Intermediate or high-risk cytogenetics in first CR 1
  • Patients who achieved CR only after second course of therapy 1
• Reduced-intensity conditioning should be considered for:
  • Older patients (≥60 years) in first CR with minimal comorbidities 1
  • Patients with medical contraindications to standard conditioning 5
• Sequential approach of intensive chemotherapy followed by reduced-intensity conditioning transplantation shows promise for high-risk AML 5

Treatment of Refractory or Relapsed Disease

• Options include:
  • Clinical trials (preferred) 1
  • Intensive re-induction (better success with longer first remission duration) 2
  • Allogeneic stem cell transplantation for patients in second remission 2
  • Best supportive care for patients unsuited for intensive approaches 2

Follow-up After Treatment

• After completion of intensive treatment:
  • Bone marrow morphology every 3 months for 24 months 2
  • Differential blood counts every 3 months for 5 years 2
• Molecular MRD assessment:
  • Every 3 months from bone marrow or every 4-6 weeks from peripheral blood for 24 months in patients with a molecular marker 2

Special Considerations for CD36 Expression

• CD36 expression should be considered alongside other markers when determining eligibility for targeted therapies
• For CD33-positive AML, gemtuzumab ozogamicin may be added to standard induction (7+3+GO) 2
• Treatment should be conducted in centers with multidisciplinary expertise and adequate infrastructure 2
• Clinical trials should be considered whenever possible 2

Pitfalls and Caveats

• Anthracycline cumulative dose should be monitored due to cardiotoxicity risk:
  • Cumulative doses >300 mg/m² have been associated with significant cardiac toxicity 2
• Early mortality in AML is often due to complications rather than disease progression:
  • Supportive care is essential and should include prophylaxis and management of tumor lysis syndrome, infection, bleeding, and thrombosis 2
• Time to CR is a critical prognostic factor:
  • Patients achieving CR only after prolonged time (>29 days) have higher relapse rates and should be considered for allogeneic transplantation 3