Predictors of early death and clinical features in newly diagnosed patients with low-intermediate risk acute promyelocytic leukemia

Abstract

BackgroundAlthough most acute promyelocytic leukemia(APL) with low-intermediate risk could survive the induction treatment, early death still a big problem to have effects on overall survival in real world.This study aimed to analyze the clinical characteristics and possible predictors of early death in newly diagnosed patients with low-intermediate-risk acute promyelocytic leukemia.MethodsSixty patients with newly diagnosed low/intermediate-risk APL admitted to Mianyang Central Hospital from January 2013 to December 2021 were retrospectively analyzed.ResultsSixty patients with a median age of 46 years (range, 17-75 years) were included. Fourteen patients (23.3%) were in low-risk group, and 46 patients (76.7%) were in intermediate-risk group. Fourteen patients (23.3%) died during induction treatment. Five patients died of hemorrhage, 5 of severe infection and 4 of differentiation syndrome. Multivariate analysis showed that HGB <65g/L at diagnosis (OR=38.474, 95%CI: 2.648~558.923, P=0.008) during induction treatment was an independent risk factors for early death in low- intermediate risk APL patients. In survival group, all patients achieved complete remission, the time to achieve remission was 25.87 ± 5.02 days, the average ATO dosage was 0.16 ± 0.03 mg/kg/day. In univariate analysis, there was no statistically significant difference in time span for remission when ATO dosage was in the 0.11~0.16mg/kg/day range. Compared with patients with low-risk APL, those with intermediate-risk APL had higher white blood cell counts (at diagnosis, day 3, day 5 and peak), higher level of lactate dehydrogenase, higher percentage of bone marrow promyelocytes, more platelet transfusions during treatment, and more early deaths (P<0.05). The overall survival of intermediate-risk APL patients seemed worse than those with low-risk APL (χ=5.033, P =0.025).ConclusionsIn patients with low-intermediate risk APL, HGB <65g/L at diagnosis was an independent risk factors for early death. Remission could still be achieved at low-dose ATO without affecting the required time for low-intermediate risk APL patients. Differences in clinical characteristics were found between low-risk and intermediate-risk APL. The intermediate-risk group had higher early mortality risk than the low-risk group.

Risk stratification for early mortality in newly diagnosed acute promyelocytic leukemia: a multicenter, non-selected, retrospective cohort study

“…In this multicenter retrospective analysis of 313 consecutive patients, the majority of whom received early ATRA administration before the diagnostic confirmation of suspected APL, we observed an EM rate of 13.1%, which was comparable with previous real-world reports (11)(12)(13)(14)(15)(16)(17). The main causes of EM and its major occurrence period were also similar to those in previous reports (11)(12)(13)(14)(15)(16)(17)20), with ICH occurring within the first seven days of APL presentation being the most common cause of death. We identified clinical variables related to an increased risk of EM: age ≥65 years, initial WBC ≥8.0 x 10 9 /L, and delayed ATRA administration >24 hours after disease presentation.…”

“…The introduction of all-trans retinoic acid (ATRA) and more recently, arsenic trioxide (ATO) in the management of APL has improved treatment outcomes, accounting for cure rates of at least 80% (3-10). However, treatment failure occurs in a substantial number of patients, particularly within the first 30 days of disease presentation (11)(12)(13)(14)(15)(16)(17). This early mortality (EM) in APL might be associated with thrombo-hemorrhagic complications such as intracranial hemorrhage (ICH) secondary to a complex coagulopathy at initial presentation (11)(12)(13)(14)(15)(16)(17).…”

“…However, treatment failure occurs in a substantial number of patients, particularly within the first 30 days of disease presentation (11)(12)(13)(14)(15)(16)(17). This early mortality (EM) in APL might be associated with thrombo-hemorrhagic complications such as intracranial hemorrhage (ICH) secondary to a complex coagulopathy at initial presentation (11)(12)(13)(14)(15)(16)(17).…”

Venetoclax as a cytoreduction therapy for acute promyelocytic leukaemia: A single‐centre experience

“…1,2 However, the early death within 30 days of induction therapy continues to present a significant challenge in achieving successful outcomes for all patients with APL. 3 As such, the rational utilization of cytoreduction therapy plays a crucial role in reducing early mortality rates of APL. 4 Since traditional cytoreduction agents can lead to severe disseminated intravascular coagulation (DIC) and even death, the development of novel cytoreduction agents to minimize early mortality is urgently needed.…”