Early Death and Survival of Patients With Acute Promyelocytic Leukemia in ATRA Plus Arsenic Era: A Population-Based Study

Abstract

Most randomized trials for acute promyelocytic leukemia (APL) have investigated highly selected patients under idealized conditions, and the findings need to be validated in the real world. We conducted a population-based study of all APL patients in Zhejiang Province, China, with a total population of 82 million people, to assess the generalization of all-trans retinoic acid (ATRA) and arsenic as front-line treatment. The outcomes of APL patients were also analyzed. Between January 2015 and December 2019, 1,233 eligible patients were included in the final analysis. The rate of ATRA and arsenic as front-line treatment increased steadily from 66.2% in 2015 to 83.3% in 2019, with no difference among the size of the center (≥5 or <5 patients per year, p = 0.12) or age (≥60 or <60 years, p = 0.35). The early death (ED) rate, defined as death within 30 days after diagnosis, was 8.2%, and the 3-year overall survival (OS) was 87.9% in the whole patient population. Age (≥60 years) and white blood cell count (>10 × 10⁹/L) were independent risk factors for ED and OS in the multivariate analysis. This population-based study showed that ATRA and arsenic as front-line treatment are widely used under real-world conditions and yield a low ED rate and a high survival rate, which mimic the results from clinical trials, thereby supporting the wider application of APL guidelines in the future.

Keywords: ATRA; acute promyelocytic leukemia; arsenic; early death; survival.

Figure 1

The flow and treatment protocol recommended by guideline 2014. (A) Shown is the flow of screening, exclusion, and retention. A total of 99 patients transferred to at least two medical centers. Moreover, 103 patients did not have a definitive diagnosis [11 patients did not perform bone marrow puncture examination, including four early deaths; four patients had a typical acute promyelocytic leukemia (APL) morphology, but the karyotype and molecular biology was negative; 88 patients had a typical APL morphology without karyotype and molecular biology results, including 15 early deaths]. The treatment information of 26 patients was missing. (B) Induction therapy lasts for at least 4 weeks until complete remission is achieved. The chemotherapy drugs included anthracycline, cytarabine, and homoharringtonine. One single agent was usually used as induction chemotherapy regimen.

Figure 2

The rate of all-trans retinoic acid (ATRA)/arsenic as first-line treatment for acute promyelocytic leukemia and outcomes. Shown is the rate of ATRA/arsenic as first-line treatment which changed with the alteration of year (A), center size (B), and age (C). The early death rate (D) and estimated survival (E, F) were compared between ATRA/arsenic group and ATRA/anthracycline group.

Figure 3

The survival between different risk groups and ages. The early death rate (A) and estimated survival (B, C) were compared between high-risk group (WBC>10×10E9/L) and non-high-risk group (WBC≤10×10E9/L). The early death rate (D) and estimated survival (E, F) were also compared between patients ≥60 years and <60 years.