In a patient with acute leukemia undergoing chemotherapy, on what day should blasts in the peripheral blood be expected to start decreasing?

Blast Clearance Timeline During AML Induction Chemotherapy

Peripheral blood blasts should begin decreasing within the first 6 days after starting induction chemotherapy, with complete clearance by day 6 being the optimal prognostic indicator for achieving complete remission. 1

Expected Timeline for Blast Clearance

Peripheral Blood Blast Clearance

• Blasts should start decreasing immediately after chemotherapy initiation, with optimal clearance occurring by day 6 1, 2
• Patients achieving blast clearance within 6 days (early blast clearance) have significantly better outcomes compared to those requiring more than 6 days (delayed blast clearance) 1
• The blast decrease rate during the first week, measured by flow cytometry, serves as an independent prognostic factor for complete remission achievement 2
• A blast decrease slope of less than -25% per day during the first week strongly predicts complete remission (P<0.0001) 2

Bone Marrow Assessment Timeline

• Bone marrow aspirate/biopsy should be performed 7-10 days after completion of cytarabine-based chemotherapy to document hypoplasia 3
• For standard-dose cytarabine induction, bone marrow assessment should occur 14-21 days after start of therapy 3
• At day 14, approximately 80% of patients who will achieve complete remission have less than 5% blasts in the bone marrow 4
• Patients with less than 5% blasts at day 14 have a 96.7% likelihood of achieving complete remission 4

Clinical Monitoring Protocol

Daily Monitoring During Induction

• CBC with differential should be performed daily during chemotherapy 3
• Differential counts should continue daily during active chemotherapy and every other day after WBC recovery above 500/mcL 3
• Chemistry profile including electrolytes, BUN, creatinine, uric acid, and phosphate should be checked at least daily during active treatment 3

Interpretation of Day 14 Bone Marrow Results

If hypoplasia is documented (cellularity <20% with residual blasts <5%):

• Repeat bone marrow at time of hematologic recovery to document remission 3
• No additional induction chemotherapy is needed 3

If significant residual disease without hypoplasia (>5% blasts):

• Consider additional therapy with standard-dose cytarabine and anthracycline or escalation to high-dose cytarabine 3
• However, the benefit of immediate re-induction versus observation until count recovery remains unclear, as no significant difference in complete remission rates has been demonstrated between these approaches (58.3% vs 45.5%, P=0.684) 4

If hypoplasia is indeterminate:

• Repeat biopsy in 7-14 days to clarify persistence of leukemia 3

Important Clinical Pitfalls

Distinguishing Regeneration from Relapse

• When bone marrow contains 5-20% blasts in the setting of recent treatment with no circulating blasts, repeat bone marrow at least one week later is necessary to distinguish relapse from bone marrow regeneration 3
• The reappearance of blasts during count recovery does not necessarily indicate treatment failure 3
• In rare cases, transient peripheral blastosis can occur during marrow regeneration (rebound phenomenon), which may resolve spontaneously without additional chemotherapy 5

Special Consideration for APL

• In acute promyelocytic leukemia (APL) treated with ATRA and chemotherapy, there is often no obligatory period of bone marrow aplasia 3
• The bone marrow aspirate performed 7-14 days after induction in APL usually reveals a hypercellular specimen with the misleading impression of resistant disease 3
• This finding is not an indicator for additional induction therapy in APL 3
• The first post-treatment bone marrow in APL need not be performed until 10-14 days after completion of ATRA therapy 3

Prognostic Implications of Delayed Clearance

• Patients with delayed peripheral blood blast clearance (>6 days) have significantly shorter relapse-free survival (202 vs 442 days, P=0.0017) and overall survival (429 vs 930 days, P<0.0001) compared to early clearance 1
• Early blast clearance independently predicts day 14 marrow blast clearance (P=0.0018), complete remission (P=0.0179), relapse-free survival (P=0.0171), and overall survival (P=0.0122) 1
• Time required to reach 90% depletion of peripheral blast load (threshold of 5 days) carries high statistical significance for disease-free survival (P<0.0001) 2