Management of molecular persistence, molecular relapse, and hematologic relapse
| Recommendation . | Level of evidence–grade of recommendation . | Changes compared with the 2009 recommendations . |
|---|---|---|
| 5.1. For patients with confirmed molecular relapse (defined as 2 successive PCR+ assays, with stable or rising PML-RARA transcript levels detected in independent samples analyzed in 2 laboratories), preemptive therapy has to be started promptly to prevent frank relapse | IIa–B | Unchanged |
| 5.2. Salvage therapy for molecular persistence after consolidation, molecular relapse, or hematologic relapse should be chosen considering the previously used first-line treatment and duration of first relapse: | IV–C | New recommendation |
| • Patients relapsing after ATRA + chemotherapy should be managed with ATRA + ATO–based approaches | ||
| • Patients relapsing after ATRA + ATO should be managed with ATRA + chemotherapy | ||
| • A potential exception for crossing over to a different treatment of relapsed patients may be considered for those with late relapse (eg, CR1 >2 y) | ||
| 5.3. Patients achieving second CR should receive intensification with HSCT or chemotherapy, if possible | IV–C | Unchanged |
| 5.4. Allogeneic HSCT is recommended for patients failing to achieve a second molecular remission | IV–C | Unchanged |
| 5.5. Autologous HSCT is the first option for patients without detectable MRD in the marrow and with an adequate PCR− harvest | IIa–B | Slightly modified |
| 5.6. For patients in whom HSCT is not feasible, the available options include repeated cycles of ATO with or without ATRA with or without chemotherapy | IV–C | Unchanged |
| 5.7. For patients with CNS relapse, induction treatment consists of weekly triple ITT with methotrexate, hydrocortisone, and cytarabine until complete clearance of blasts in the cerebrospinal fluid, followed by 6-10 more spaced out ITT treatments as consolidation; systemic treatment should also be given following recommendations 5.1 to 5.6 | IV–C | Unchanged |
| Recommendation . | Level of evidence–grade of recommendation . | Changes compared with the 2009 recommendations . |
|---|---|---|
| 5.1. For patients with confirmed molecular relapse (defined as 2 successive PCR+ assays, with stable or rising PML-RARA transcript levels detected in independent samples analyzed in 2 laboratories), preemptive therapy has to be started promptly to prevent frank relapse | IIa–B | Unchanged |
| 5.2. Salvage therapy for molecular persistence after consolidation, molecular relapse, or hematologic relapse should be chosen considering the previously used first-line treatment and duration of first relapse: | IV–C | New recommendation |
| • Patients relapsing after ATRA + chemotherapy should be managed with ATRA + ATO–based approaches | ||
| • Patients relapsing after ATRA + ATO should be managed with ATRA + chemotherapy | ||
| • A potential exception for crossing over to a different treatment of relapsed patients may be considered for those with late relapse (eg, CR1 >2 y) | ||
| 5.3. Patients achieving second CR should receive intensification with HSCT or chemotherapy, if possible | IV–C | Unchanged |
| 5.4. Allogeneic HSCT is recommended for patients failing to achieve a second molecular remission | IV–C | Unchanged |
| 5.5. Autologous HSCT is the first option for patients without detectable MRD in the marrow and with an adequate PCR− harvest | IIa–B | Slightly modified |
| 5.6. For patients in whom HSCT is not feasible, the available options include repeated cycles of ATO with or without ATRA with or without chemotherapy | IV–C | Unchanged |
| 5.7. For patients with CNS relapse, induction treatment consists of weekly triple ITT with methotrexate, hydrocortisone, and cytarabine until complete clearance of blasts in the cerebrospinal fluid, followed by 6-10 more spaced out ITT treatments as consolidation; systemic treatment should also be given following recommendations 5.1 to 5.6 | IV–C | Unchanged |
CR1, first CR; ITT, intrathecal therapy.