Table 2.

Management during induction, consolidation therapy, and beyond

Recommendation	Level of evidence–grade of recommendation	Changes compared with the 2009 recommendations
2.1. Eligible patients should be offered entry into a clinical trial	IV–C	Unchanged
Induction therapy
2.2. For patients with a WBC count ≤10 × 109/L, induction therapy should consist of ATRA and ATO without chemotherapy; ATRA and anthracycline–based chemotherapy is a second option when ATO is contraindicated or unaffordable	Ib–A	New recommendation
2.3. For patients with a WBC count >10 × 109/L, there are 2 valid options, either ATRA + ATO with a certain amount of chemotherapy or conventional ATRA + anthracycline–based chemotherapy	Ib–A	New recommendation
2.4. Induction therapy should not be modified based on the presence of leukemia cell characteristics that have variably been considered to predict a poorer prognosis (eg, secondary chromosomal abnormalities, FLT3 mutations, CD56 expression, and BCR3 PML-RARA isoform)	IIa–B	Unchanged
2.5. Treatment with ATRA should be continued until terminal differentiation of blasts and achievement of CR, which occurs in virtually all patients following conventional ATRA + anthracycline or ATRA + ATO induction treatment	IIa–B	Updated
2.6. Clinicians should refrain from making therapeutic modifications on the basis of incomplete blast maturation (differentiation) detected up to 50 d or more after the start of treatment by morphology or cytogenetic or molecular assessment	IV–C	Unchanged
Consolidation therapy
2.7. For patients treated with chemotherapy-free approaches, 4 consolidation courses of ATO (0.15 mg/kg/d 5 days/wk, 4 wk on 4 wk off) and 7 courses of ATRA (45 mg/m2/d for adults; 25 mg/m2/d for children, 2 wk on 2 wk off) are recommended	Ib–A	New recommendation
2.8. For patients treated with the conventional ATRA + chemotherapy approach:		Slightly modified
• 2-3 courses of anthracycline-based chemotherapy should be given for consolidation therapy	Ib–A
• The addition of ATRA to chemotherapy in consolidation seems to provide a clinical benefit	IIb–B
• Consolidation for high-risk patients younger than 60 years of age with WBC counts higher than 10 × 109/L should include at least 1 cycle of intermediate- or high-dose cytarabine	IIb–B
2.9. Molecular remission in the BM should be assessed at completion of consolidation by RT-PCR or RQ-PCR assay affording a sensitivity of at least 1 in 104	IIa–B	Slightly modified
Management after consolidation
2.10. For patients treated with chemotherapy-free approaches (WBC count ≤10 × 109/L), no maintenance is needed	Ib–A	New recommendation
2.11. For patients treated with conventional ATRA + chemotherapy approaches: maintenance therapy should be used for patients who have received an induction and consolidation treatment regimen wherein maintenance has shown a clinical benefit	Ib–A	Unchanged
2.12. Because early treatment intervention in patients with evidence of MRD affords a better outcome than treatment in hematologic relapse, MRD monitoring of BM every 3 mo should be offered to high-risk patients (WBC count >10 × 109/L) for up to 3 y after completion of consolidation therapy; given the very low probability of relapse for non–high-risk patients (WBC count ≤10 × 109/L), prolonged MRD monitoring could be avoided in this setting or carried out using PB	IIb–B	Slightly modified
2.13. BM generally affords greater sensitivity for detection of MRD than blood and therefore is the sample type of choice for MRD monitoring to guide therapy	IIa–B	Unchanged
2.14. For patients testing PCR+ at any stage following completion of consolidation, it is recommended that a BM is repeated for MRD assessment within 2 wk and that samples are sent to the local laboratory, as well as to a reference laboratory for independent confirmation	IV–C	Unchanged
2.15. CNS prophylaxis can be considered only for patients with hyperleukocytosis	IV–C	Unchanged