Navigating Ethical Dilemmas in Blast Crisis Management

Show Notes

Topic Overview

• Blast crisis is an oncologic emergency, most commonly seen in chronic myeloid leukemia (CML).
• Defined by:
  • >20% blasts in peripheral blood or bone marrow.
  • May include extramedullary blast proliferation.
• Without treatment, median survival is only 3–6 months.

Pathophysiology & Associated Conditions

• Usually occurs in CML, but also in:
  • Myeloproliferative neoplasms (MPNs)
  • Myelodysplastic syndromes (MDS)
• Transition from chronic to blast phase often reflects disease progression or treatment resistance.

Risk Factors

• 10% of CML patients progress to blast crisis.
• Risk increased in:
  • Patients refractory to tyrosine kinase inhibitors (e.g., imatinib).
  • Those with Philadelphia chromosome abnormalities.
  • WBC >100,000, which increases risk for leukostasis.

Clinical Presentation

• Symptoms often stem from pancytopenia and leukostasis:
  • Anemia: fatigue, malaise.
  • Functional neutropenia: high WBC count, but increased infection/sepsis risk.
  • Thrombocytopenia: bleeding, bruising.
• Leukostasis/hyperviscosity effects by system:
  • Neurologic: confusion, visual changes, stroke-like symptoms.
  • Cardiopulmonary: ARDS, myocardial injury.
  • Others: priapism, limb ischemia, bowel infarction.
• Rapid deterioration is common — early recognition is critical.

Diagnostic Workup

• CBC with differential: assess blast % and cytopenias.
• Peripheral smear and manual diff: confirm immature blasts.
• CMP: screen for tumor lysis syndrome:
  • Elevated potassium, phosphate, uric acid.
  • Low calcium.
• LDH & uric acid: markers of high cell turnover.
• Coagulation studies (PT, PTT): assess for DIC.
• Definitive tests (done inpatient): bone marrow biopsy, flow cytometry.

Emergency Department Management

• Resuscitation & ABCs: oxygen, IV fluids, vitals monitoring.
• Avoid aggressive transfusions:
  • Risk of hyperviscosity with PRBCs and platelets.
• Initiate broad-spectrum antibiotics early:
  • High suspicion for sepsis in functionally neutropenic patients.
• Consider antifungals for prolonged febrile neutropenia.
• Cytoreduction strategies:
  • Hydroxyurea to lower WBCs quickly.
  • Tyrosine kinase inhibitors (TKIs).
  • High-dose chemotherapy.
• Early consultation with hematology/oncology is essential.
• Mutation testing may guide targeted therapy.

Prognosis

• Without treatment: median survival ~3 months.
• With treatment:
  • Potential survival >1 year.
  • Best outcomes in patients who enter a second chronic phase and undergo allogeneic stem cell transplant.

Ethical & Logistical Considerations

• Treatment may involve aggressive interventions with serious side effects.
• Important to assess:
  • Patient goals of care.
  • Capacity for informed consent.
• Resource limitations:
  • Not all hospitals have oncology services.
  • Patients may require transfer over long distances.
• Emphasize early, transparent discussions with patients and families.

Top 3 Take-Home Points

• Recognize early: Look for cytopenias, leukostasis, and rapid clinical decline.
• Resuscitate appropriately: Start antibiotics; be cautious with transfusions.
• Call for help: Early hematology/oncology involvement is essential for definitive care.