A white blood cell count above 10,000/ml at diagnosis defines the high-risk category of acute promyelocytic leukemia (APL). Clinicians today stratify APL into two principal groups — high-risk (WBC >10,000/ml) and low/intermediate-risk — because the elevated leukocyte burden carries a meaningfully higher risk of early complications and relapse.
Induction for high-risk APL centres on a combination of all-trans retinoic acid (ATRA) with arsenic trioxide and an anthracycline. An alternative agent is available for patients ineligible for anthracycline therapy due to cardiac or other comorbidities. The protocol additionally addresses CNS prophylaxis relevant to the high leukocyte burden, as well as structured management of coagulopathy and a known early treatment complication.
DOI: 10.3389/fonc.2022.1062524
In the era of ATRA, APL has been stratified into three categories of risk with regards to relapse-free survival (RFS): WBC >10,000/ml (high-risk), WBC ≤10,000 ml with platelet count ≤40,000/ml (intermediate-risk), and WBC ≤10,000/ml with platelet count >40,000/ml (low-risk).
Today, most clinicians will categorize APL within two categories, high risk (>10,000/ml) and low/intermediate risk.
The APML4 study in 2015 studied an induction strategy utilizing ATRA, ATO, and idarubicin, with an improved 5-year disease-free survival of 83% and OS of 87% in high-risk patients, further establishing ATRA/ATO/chemotherapy as the standard of care in high-risk disease.
Although ATRA with ATO and an anthracycline is the preferred induction regimen for patients with high-risk APL at most centers, GO remains an alternative to anthracycline, especially for patients ineligible for anthracycline therapy due to cardiac and other comorbidities; this is reflected in the current NCCN guidelines.
Although patients may achieve hematologic normalization and molecular clearance of PML-RARA by the end of induction, consolidation therapy remains essential to prevent relapse.
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