Management during induction, consolidation therapy, and beyond
| Recommendation . | Level of evidence . | Grade of recommendation . |
|---|---|---|
| 2.1. Eligible patients should be offered entry into a clinical trial. | IV | C |
| Induction therapy | ||
| 2.2. Induction therapy should consist of the administration of concomitant ATRA and anthracycline-based chemotherapy. | Ib | A |
| 2.3. Standard 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 |
| 2.4. ATO should be used as standard therapy in countries where pharmaceutical quality locally produced arsenic compounds provide a more affordable treatment approach than ATRA plus chemotherapy. | III | B |
| 2.5. Treatment with ATRA should be continued until terminal differentiation of blasts and achievement of CR, which occurs in virtually all patients after conventional ATRA + anthracycline induction schedules. | IIa | B |
| 2.6. Clinicians should refrain from making therapeutic modifications on the basis of incomplete blast maturation (differentiation) detected up to 50 days or more after the start of treatment by morphology, cytogenetics, or molecular assessment. | IV | C |
| Consolidation therapy | ||
| 2.7. Two or 3 courses of anthracycline-based chemotherapy are considered the standard approach for consolidation therapy. | Ib | A |
| 2.8. The addition of ATRA to chemotherapy in consolidation seems to provide a clinical benefit. | IIb | B |
| 2.9. Consolidation for high-risk patients younger than 60 years with WBC counts higher than 10 × 109/L should include at least one cycle of intermediate- or high-dose cytarabine. | IIb | B |
| 2.10. ATO in consolidation should at present be restricted to investigation within clinical trials or those patients considered unfit for conventional chemotherapy. | IV | C |
| 2.11. Molecular remission in the bone marrow should be assessed at completion of consolidation by RT-PCR assay affording a sensitivity of at least 1 in 104. | IIa | B |
| 2.12. Patients with confirmed molecular persistence should be considered for allogeneic HSCT. | IV | C |
| 2.13. For patients with molecular persistence who are not candidates for allogeneic HSCT, ATO or gemtuzumab ozogamicin may be considered. | IIa | B |
| Management after consolidation | ||
| 2.14. 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 |
| 2.15. Because early treatment intervention in patients with evidence of MRD affords a better outcome than treatment in full-blown relapse, every 3 months MRD monitoring of bone marrow should be offered to all patients for up to 3 years after completion of consolidation therapy. | IIb | B |
| 2.16. Bone marrow 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 |
| 2.17. For patients testing PCR-positive at any stage after completion of consolidation, it is recommended that a bone marrow is repeated for MRD assessment within 2 weeks and that samples are sent to the local laboratory, as well as to a reference laboratory for independent confirmation. | IV | C |
| 2.18. CNS prophylaxis can be considered only for patients with hyperleukocytosis. | IV | C |
| Recommendation . | Level of evidence . | Grade of recommendation . |
|---|---|---|
| 2.1. Eligible patients should be offered entry into a clinical trial. | IV | C |
| Induction therapy | ||
| 2.2. Induction therapy should consist of the administration of concomitant ATRA and anthracycline-based chemotherapy. | Ib | A |
| 2.3. Standard 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 |
| 2.4. ATO should be used as standard therapy in countries where pharmaceutical quality locally produced arsenic compounds provide a more affordable treatment approach than ATRA plus chemotherapy. | III | B |
| 2.5. Treatment with ATRA should be continued until terminal differentiation of blasts and achievement of CR, which occurs in virtually all patients after conventional ATRA + anthracycline induction schedules. | IIa | B |
| 2.6. Clinicians should refrain from making therapeutic modifications on the basis of incomplete blast maturation (differentiation) detected up to 50 days or more after the start of treatment by morphology, cytogenetics, or molecular assessment. | IV | C |
| Consolidation therapy | ||
| 2.7. Two or 3 courses of anthracycline-based chemotherapy are considered the standard approach for consolidation therapy. | Ib | A |
| 2.8. The addition of ATRA to chemotherapy in consolidation seems to provide a clinical benefit. | IIb | B |
| 2.9. Consolidation for high-risk patients younger than 60 years with WBC counts higher than 10 × 109/L should include at least one cycle of intermediate- or high-dose cytarabine. | IIb | B |
| 2.10. ATO in consolidation should at present be restricted to investigation within clinical trials or those patients considered unfit for conventional chemotherapy. | IV | C |
| 2.11. Molecular remission in the bone marrow should be assessed at completion of consolidation by RT-PCR assay affording a sensitivity of at least 1 in 104. | IIa | B |
| 2.12. Patients with confirmed molecular persistence should be considered for allogeneic HSCT. | IV | C |
| 2.13. For patients with molecular persistence who are not candidates for allogeneic HSCT, ATO or gemtuzumab ozogamicin may be considered. | IIa | B |
| Management after consolidation | ||
| 2.14. 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 |
| 2.15. Because early treatment intervention in patients with evidence of MRD affords a better outcome than treatment in full-blown relapse, every 3 months MRD monitoring of bone marrow should be offered to all patients for up to 3 years after completion of consolidation therapy. | IIb | B |
| 2.16. Bone marrow 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 |
| 2.17. For patients testing PCR-positive at any stage after completion of consolidation, it is recommended that a bone marrow is repeated for MRD assessment within 2 weeks and that samples are sent to the local laboratory, as well as to a reference laboratory for independent confirmation. | IV | C |
| 2.18. CNS prophylaxis can be considered only for patients with hyperleukocytosis. | IV | C |