Preinduction phase

1. Once a diagnosis of APL is suspected upon morphologic examination, the disease should be managed as a medical emergency.

2. Genetic confirmation of diagnosis is mandatory.

3. Supportive measures should be rapidly instituted to reverse the coagulopathy and the associated risk of life-threatening hemorrhages. Liberally transfuse with fresh frozen plasma, fibrinogen, or both, as well as provide platelet support to maintain the fibrinogen level and the platelet counts above 1.5 g/L (150 mg/dL) and 30 to 50 × 10⁹/L until disappearance of all clinical or laboratory signs of coagulopathy.

4. The benefit of heparin, tranexamic acid, or other anticoagulant or antifibrinolytic therapy remains undetermined.

5. Treatment with ATRA should be started immediately when diagnosis of APL is suspected.

6. In addition to conventional karyotyping, FISH, and RT-PCR, immunoassay with anti-PML can be used for rapid diagnosis of APL.

Induction phase

1. Induction therapy should consist of simultaneous administration of ATRA and anthracycline-based chemotherapy.

2. Standard induction therapy should not be “reinforced” based on the presence of secondary chromosomal abnormalities or other leukemia cell characteristics evoking an association with poor response.

3. Preemptive therapy with dexamethasone should be started when the diagnosis of RAS is suspected in the presence of any symptom or sign that characterizes the syndrome.

4. Treatment with ATRA should be continued until terminal differentiation of blasts and achievement of CR, which invariably occurs in all patients. Temporary discontinuation of ATRA is only indicated in case of severe RAS.

5. Morphologic features in bone marrow during differentiation therapy with ATRA can lead to erroneously labeling some patients as resistant by inexperienced pathologists. These misleading cytomorphologic features, which are occasionally detectable several weeks after the start of treatment (up to 40-50 days), should not lead to therapeutic changes.

6. Early morphologic evaluation in bone marrow, as well as molecular and cytogenetic evaluation at the end of induction, has little or no value in APL. Clinicians should refrain from making therapeutic decisions on the basis of these results.

Consolidation phase

1. Two or 3 courses of anthracycline-based chemotherapy are considered the standard approach for consolidation therapy. Simultaneous administration of ATRA seems to provide a clinical benefit.

2. Molecular remission should be assessed at completion of consolidation by low-sensitivity RT-PCR methods.

3. The small fraction of patients with confirmed molecular persistence (as assessed in 2 successive bone marrow samples) should be considered for allogeneic stem cell transplantation. Alternatively, ATO or gentuzumab ozogamicin may be considered in these patients.

Maintenance phase

1. The combination of ATRA with or without low-dose chemotherapy has been adopted as the standard maintenance therapy by most groups.

2. Molecular monitoring in this phase seems cost-effective only for patients with WBC count at presentation greater than 10 × 10⁹/L, while its utility is questionable for patients with low risk of relapse (ie, patients with WBC count at presentation ≤ 10 × 10⁹/L).

Special situations

1. Elderly patients in good clinical condition should be managed with a treatment approach similar to that used in younger patients.

2. Elderly and younger patients with severe comorbidities are candidates to receive arsenic trioxide.

3. Both ATRA and anthracycline-based chemotherapy appear reasonably safe for patients with APL diagnosed in the second or third trimester of pregnancy. By contrast, the use of ATRA therapy in the first trimester of pregnancy is not recommended because retinoids are known teratogenics.