Acute promyelocytic leukaemia: population-based study of epidemiology and outcome with ATRA and oral-ATO from 1991 to 2021

Abstract

Background The epidemiology and treatment of acute promyelocytic leukaemia (APL) are changing. We have incorporated oral arsenic trioxide (oral-ATO) into induction/maintenance. Methods Newly-diagnosed APL from 1991 to 2021 divided into three 10-year periods were studied to define its epidemiology and how oral-ATO impacted on its outcome. Primary endpoints included APL incidence, early deaths (ED, first 30 days), and overall survival (OS). Secondary endpoints included post-30-day OS, relapse-free survival (RFS), and incidence of second cancers. Results APL occurred in 374 males and 387 females at a median age of 44 (1–97) years. Annual incidences increased progressively, averaging 0.32 per 100,000 people. All-trans retinoic acid (ATRA)-based and oral-ATO-based regimens were used in 469 and 282 patients. There were 144 EDs, occurring almost exclusively in ATRA-based inductions (N = 139), being more with males, age > 50 years, leucocyte > 10 × 109/L, diagnosis during 1991–2009 and fewer with oral-ATO-based regimens. After a median of 75 (interquartile range: 14–161) months, 5-year and 10-year OS were 68.1% and 63.3%, inferior with males, age > 50 years, leucocyte > 10 × 109/L, high-risk Sanz score and superior with oral-ATO-based regimens. Factoring out EDs, 5-year and 10-year post-30-day OS were 84.0% and 78.1%, inferior with males and superior with oral-ATO-based regimens. In 607 CR1 patients, the 5-year RFS was 83.8%, superior with diagnosis in 2010–2021 and oral-ATO-based regimens. Second cancers developed in 21 patients, unrelated to oral-ATO-based regimens. Conclusions There was an increasing incidence of APL, and all survivals were superior with the use of oral-ATO-based regimens. This study formed part of the Acute Promyelocytic Leukaemia Asian Consortium Project (ClinicalTrials.gov identifier: NCT04251754).

Management of Acute Promyelocytic Leukemia at Extremes of Age

“…However, recent data utilizing the US National Inpatient Sample database from 2016 to 2019 suggest an increasing incidence with age, with a peak incidence of 0.62 (per 100,000 inhabitants) in patients aged 75-79 years as compared to APL's annual age-adjusted incidence rate of 0.28 (per 100,000 inhabitants) [16]. These results were recently confirmed by a retrospective cohort analysis from the Acute Promyelocytic Leukaemia Asian Consortium Project, which included 761 newly diagnosed APL patients between 1991 and 2021 [17]. The authors observed an increasing incidence of APL in elderly (60-79 years) patients, rising from 0.22 in 1991-1999 to 0.53 in 2010-2021.…”

Distinctive Features Associated with Differentiation Syndrome in Acute Promyelocytic Leukemia in Patients treated by All-Trans Retinoic Acid and Arsenic Trioxide

“…In a recent study analyzing data from 2000 to 2021, there was lower mortality attributed to APL-DS and intracranial hemorrhage in academic centers. Conversely, mortality rates in non-academic centers persisted at elevated levels, highlighting the importance of centralizing care and the early recognition of subtle symptoms by trained personnel (25).…”

Thrombosis in Acute Promyelocytic Leukemia: The Current Understanding

“…4,5 Moreover, novel data have shown that intracranial hemorrhage has been the most significant contributor of early treatment failure and has led to ED in 42%. 6 Although hemorrhagic complications have always received the most attention in APL, the rate of thrombotic complication, at the opposite end of the spectrum, has been overlooked. It is thought that the incidence of thrombosis in APL is higher than in all other types of AML, but there are still little data on this complication.…”