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. 2024 Nov 19:15:20406207241299699.
doi: 10.1177/20406207241299699. eCollection 2024.

Standard dose anthracycline plus all-trans retinoic acid and arsenic trioxide as induction chemotherapy significantly reduces early death and relapse for high-risk acute promyelocytic leukemia: a single-center real-world analysis

Kai Shen  1 , Jie Huang  1 , Chenlu Yang  1 , Xiao Shuai  1 , Yong Guo  1 , Liping Xie  1 , Jianjun Li  1 , Yongqian Jia  1 , Yuping Gong  1 , Ting Niu  1 , Hongbing Ma  2
Affiliations

Standard dose anthracycline plus all-trans retinoic acid and arsenic trioxide as induction chemotherapy significantly reduces early death and relapse for high-risk acute promyelocytic leukemia: a single-center real-world analysis

Kai Shen et al. Ther Adv Hematol. .

Abstract

Background: All-trans retinoic acid (ATRA) and arsenic trioxide (ATO) have revolutionized the treatment of acute promyelocytic leukemia (APL). However, the management of high-risk APL has not been conclusively established. The optimal dosage of anthracycline in the induction has long been debated when ATO is added.

Objectives: To explore the management of high-risk APL regarding the optimal dosage of anthracycline in the induction and the predicators of prognosis.

Design: This was a retrospective study in the real-world setting.

Methods: High-risk APL patients defined as white blood cell (WBC) greater than 10 × 109/L who received ATO-based induction regimens were included. Data on clinical characteristics, treatment regimens, and prognosis including early death (ED) and overall survival (OS) were collected from medical records. Risk factors of ED and OS were analyzed.

Results: This research included a total of 130 participants. Fifty (38.5%) patients received ATO+ATRA dual induction plus standard-dose anthracycline (ATO + ATRA + stDNR). Fifty-nine (45.4%) patients received ATO + ATRA with consecutive low-dose anthracycline (ATO + ATRA + ldDNR). Twenty-one (16.2%) patients were treated with ATO and various chemotherapies (ATO + others). Compared with the other two groups, the ATO + ATRA + stDNR group had the lowest ED rate of 4.0% (10.2% and 52.4%, respectively; p < 0.001). Multivariate analysis revealed that age ⩾60 years (odds ratio (OR) = 8.888, 95% confidence interval (CI): 1.126-70.129), prothrombin time (PT) ⩾18 s (OR = 4.749, 95% CI: 1.252-18.007) and WBC ⩾100 × 109/L (OR = 10.591, 95% CI: 1.995-56.232) were independent risk factors for ED. The 5-year OS rates of the three induction groups were 96%, 80%, and 31%, respectively. None of the 48 patients who underwent ATO + ATRA + stDNR induction relapsed, whereas 9.4% (5/53) patients in ATO + ATRA + ldDNR group relapsed, and the relapse rate was 30.0% (3/10) in ATO + others group (p = 0.003). The survival advantage of ATO + ATRA + stDNR was demonstrated by a Cox regression (hazard ratio (HR) = 5.079, 95% CI: 1.071-24.079). WBC ⩾100 × 109/L was correlated with an inferior OS (HR = 3.402, 95% CI: 1.359-8.518).

Conclusion: Compared with low-dose anthracycline, standard-dose anthracycline combined with ATO and ATRA dual induction resulted in excellent outcome for high-risk APL patients.

Keywords: acute promyelocytic leukemia; anthracycline; arsenic trioxide; leukocytosis.

Plain language summary

Standard dose anthracycline plus all-trans retinoic acid and arsenic trioxide as induction chemotherapy brought in excellent outcome for high-risk APL patients All-trans retinoic acid (ATRA) and arsenic trioxide (ATO) have revolutionized the treatment of acute promyelocytic leukaemia (APL). However, optimal management of high-risk APL patients have not been conclusively established especially for the role of cytoreductive anthracycline chemotherapy in the dual induction era. This study reviewed 130 high-risk APL patients treated with an ATO-based induction regimen in a single center in China. Rather than reducing anthracyclien doses and giving it in a prolonged course, using standard dose anthracycline in the dual induction brought in excellent outcome for high-risk APL patients which had lower early mortality and relapse rate. Thus, standard dose anthracycline is still indisposable for high-risk APL even though the voice of chemofree induction regimen with ATRA and ATO is getting louder in many centers.

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Conflict of interest statement

The authors declare that there is no conflict of interest.

Figures

Figure 1.
Figure 1.
The Kaplan–Meier curve of the total high-risk APL patients. APL, acute promyelocytic leukemia.
Figure 2.
Figure 2.
The Kaplan–Meier curves of the OS of high-risk APL patients stratified by (a) induction regimens (ATO + ATRA + stDNR vs ATO + ATRA + ldDNR vs ATO + others), (b)WBC count(WBC ⩾100 × 109/L vs WBC 50–100 × 109/L vs WBC < 50 × 109/L), (c) induction regimens (ATO + ATRA + stDNR vs ATO + ATRA + ldDNR vs ATO + others) with WBC < 100 × 109/L, (d) induction regimens (ATO + ATRA + stDNR vs ATO + ATRA + ldDNR vs ATO + others) with WBC ⩾100 × 109/L, (e) PT < 18 s vs PT⩾18 s, and (f) era before 2017 vs era after 2017. APL, acute promyelocytic leukemia; ATO, arsenic trioxide; ATO+ATRA+ldDNR, ATO+ATRA with consecutive low-dose anthracycline; ATO+ATRA+stDNR, ATO+ATRA dual induction plus standard-dose anthracycline; PT, prothrombin time; WBC, white blood cell.
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