A Long-Term Retrospective Analysis of Arsenic-Containing Triple-Agents Treatment for Acute Promyelocytic Leukemia (APL) in a Cohort from a Single Hospital
Authors: Zhang Xian , Yang Junfang , LV Fanyong , Zhang Gailing , Su Yunchao , Lu Peihua 
Published: October 2019

Abstract
Objective: The long-term efficacy (June 2001 - May 2018) of newly diagnosed APL patients (pts) treated with either As4S4 or As2O3 in combination of all-trans retinoid acid (ATRA), and anthracycline-based chemotherapy in Lu Dao-Pei Hospital is analyzed.
Methods: Firstly, 8 years from June 2001 to December 2009, a total of 88 newly diagnosed with APL patients were divided into two groups, who were treated with a protocol of either oral(po) As4S4 (n=42) or intravenous (IV) arsenic trioxide (ATO) (n=46) combined with ATRA and anthracycline-based chemotherapy. Secondly, 17 years from June 2001 till June 2018, 63 cases of newly diagnosed with APL patients were all treated with the protocol of oral As4S4 based triple-agents treatment.
The oral As4S4 and IV ATO treatment protocols were as follows. In the first month of induction, either As4S4 60mg/kg/day po or ATO 0.15mg / kg IV × 30 days in combination with ATRA 45mg / m2/day po × 30 days and NVT1.5-3mg / kg IV × 5-7 days were given. This was followed by consolidation chemotherapy 3 to 5 cycles after CR, consistence with : ① IDA12mg/m2 IV×3d; ② Aar-C 75mg/m2 IV×7d + ACLA 14mg/m2×7d; ③ NVT 6mg/kg×3d; ④ Ara-C 75mg/m2×7d + HHT 1.4mg/m2×7d; ⑤MD-Ara-C (the fifth was only given to pts with WBC>10×109/L before treatment). After which, maintenance treatment was given either with As4S4 60mg/kg po or ATO 0.15mg / kg IV ×15d every 30 days. Both groups were also given ATRA 45mg/m2 po×15d every 30 days. The interval was increased by more than 15 days every half year. The total treatment duration lasted 3-4 years.
Results:(1) All of the two groups who were treated with a protocol of either oral As4S4 (n=42) or IV arsenic trioxide (ATO) (n=46) from 2001 to 2009 reached 100% of molecular complete remission (MCR). The 8-year estimated disease-free survival (DFS) rate was 100% in oral As4S4 group with a median follow-up of 66 (15-109) months(mos). In ATO group, the DFS rate was 87.1% with a median follow-up of 42 (14-102) mos. The difference of the DFS rate between both groups was statistically significant (p=0.028, Log-Rank test).
(2) In view of the outstanding DFS result in oral As4S4 group, after 2009, another 21 APL patients were treated with the protocol of oral As4S4. So in total 63 patients treated with the protocol of oral As4S4, there were 9 children and 54 adults, 24 cases with high WBC>10×109/L before treatment, 11 cases of additional chromosomal abnormalities other than t(15;17), 9 cases of central nervous system leukemia(CNSL), and 2 cases of FLT3-ITD positive in the 22 cases with FLT3 results. All the patients attained hematological complete remission (HCR) after induction therapy without treatment-related death and achieved MCR. The median duration of MCR time was 2 (1-7) mos. The long-term overall survival (OS) rate was 98.4%(Fig1) (one died from endometrial carcinoma), and DFS rate was 100%(Fig2) (With 2 cases relapsed, respectively because of hematological and CNS, of which the current DFS time were 40mos and 30mos after CR again). The median follow-up time was 124 (21-198) mos.
Conclusions: APL patients treated with either oral As4S4 or IV As2O3 combined with ATRA and anthracycline-based chemotherapy can obtain 100% MCR and high long-term DFS. Compared with IV ATO, patients in oral As4S4 group achieved significantly better efficacy, with a 17-year DFS of 100%. Moreover, oral As4S4 is easy to give.

Disclosures
No relevant conflicts of interest to declare.