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 |