Consolidation therapy has typically included ATRA given with an anthracycline with or without cytarabine. The role of cytarabine in consolidation therapy regimens is controversial. While a randomized study addressing the contribution of cytarabine to a daunorubicin plus ATRA regimen in adults with low-risk APL showed a benefit for the addition of cytarabine, regimens using high-dose anthracycline appear to produce as good or better results for low-risk patients. For high-risk patients (WBC ≥10 × 109 /L), a historical comparison of the LPA2005 trial to the preceding PETHEMA LPA99 trial suggested that the addition of cytarabine to anthracycline-ATRA combinations can lower the relapse rate. The results of the AIDA-2000 trial confirmed that the cumulative incidence of relapse for adult patients with high-risk disease can be reduced to approximately 10% with consolidation regimens containing ATRA, anthracyclines, and cytarabine.
Maintenance therapy includes ATRA plus 6-mercaptopurine and methotrexate; this combination showed an advantage over ATRA alone in randomized trials in adults with APL.[31,40] A randomized study in adults has reported that maintenance therapy does not improve event-free survival (EFS) for patients with APL who achieve a complete molecular remission at the end of consolidation. However, the utility of maintenance therapy in APL may be dependent on multiple factors (e.g., risk group, the anthracycline used during induction, the intensity of induction and consolidation therapy, etc.), and at this time maintenance therapy remains standard for children with APL. Because of the favorable outcomes observed with chemotherapy plus ATRA (EFS rates of 70%-80%), hematopoietic stem cell transplantation is not recommended in first CR.
Central nervous system (CNS) relapse is uncommon for patients with APL, particularly for those with WBC count less than 10 × 109 /L.[42,43] In two clinical trials enrolling over 1,400 adults with APL in which CNS prophylaxis was not administered, the cumulative incidence of CNS relapse was less than 1% for patients with WBC less than 10 × 109 /L, while it was approximately 5% for those with WBC of 10 × 109 /L or greater.[42,43] In addition to high WBC at diagnosis, CNS hemorrhage during induction is also a risk factor for CNS relapse. A review of published cases of pediatric APL also observed low rates of CNS relapse. Because of the low incidence of CNS relapse among children with APL presenting with WBC less than 10 × 109 /L, CNS surveillance and prophylactic CNS therapy may not be needed for this group of patients, although there is no consensus on this topic.