Table 4

Management of relapse

RecommendationLevel of evidenceGrade of recommendation
4.1. For patients with confirmed molecular relapse (defined as 2 successive PCR-positive 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.IIaB
4.2. Although ATRA in combination with chemotherapy can be used as salvage therapy, ATO-based regimens are presently regarded the first option for treatment of relapsed APL.IVC
4.3. Patients achieving second CR should receive intensification with SCT or chemotherapy, if possible.IVC
4.4. Allogeneic HSCT is recommended for patients failing to achieve a second molecular remission.IVC
4.5. Autologous HSCT is a valid option for patients without detectable MRD in the marrow and with an adequate PCR negative harvest.IIaB
4.6. For patients in whom HSCT is not feasible, the available options include repeated cycles of ATO with or without ATRA with or without chemotherapy.IVC
4.7. For patients with CNS relapse, induction treatment consists of weekly triple intrathecal therapy (ITT) with methotrexate, hydrocortisone, and cytarabine until complete clearance of blasts in the cerebrospinal fluid, followed by 6 to 10 more spaced out ITT treatments as consolidation. Systemic treatment should also be given.IVC