6  APL treatment

6.1 APL treatment Algorithm

6.2 ATRA+ATO

6.2.1 Original Papers

From China Shen et al. (2004); Hu et al. (2009)

6.2.2 Lo-Cocoo regimen

  • The ATRA-ATO combination is continued until CR, which takes approximately 4 weeks, following which a BM with MRD assessment by PCR for PML::RARα is done.
  • Consolidation is with ATRA, 2 weeks on, 2 weeks off, for 8 months and arsenic trioxide 5 days per week for 4 weeks (20 doses) every other month for 4 courses (approximately 110 doses in induction + consolidation)

6.2.3 APOLLO trial: AIDA vs ATRA+ATO in High-risk APL

  • A RANDOMIZED PHASE III STUDY
  • Superior 2 year EFS (89% vs 72%) with ATRA-ATO (Two doses of IDA administered in induction) compared to AIDA for high-risk APL.

6.3 GO in APL

  • Ravandi et al (Jen et al. 2024; Abaza et al. 2017)showed that the addition of GO (9 mg/m² as a single infusion on day 1) to ATO and ATRA combination therapy in patients with baseline high-risk APL (WBC ≥ 10 x10⁹/L), or those who developed leukocytosis during treatment, was feasible and could potentially eliminate the need for anthracycline in these patients.

6.3.1 SWOG 0535 study Lancet et al. (2020)

6.4 Venetoclax for ATO-resistant APL

  • APL cells are sensitive to BCL2 inhibition and venetoclax based therapy could be attempted, even in ATO resistant patients, though the level of clinical evidence remains poor
  • Some evidence Wang et al. (2022) Dutta et al. (2023) shows its use

6.5 When to do BM biopsy in APL patient?

  • I always do bone marrow after induction chemotherapy (after finishing day 30 of treatment and recovery of blood counts, barring any complications) to document morphologic remission.
  • I will repeat it at the end of the consolidation to document complete molecular remission.
  • I looked back at Marty’s “how I treat”, and he basically says (to paraphrase), you don’t have to do molecular studies at the end of induction, but if you happen to do so and they are negative, then you don’t need to repeat a marrow at the end of consolidation and can just do PB PML-RARA monitoring. Again, the new ELN guidelines suggest getting rid of the post-induction marrow completely and then just doing after consolidation with molecular studies.