Efficacy and prognosis of arsenic trioxide in treatment of patients with acute promyelocytic leukemia

Abstract

Objective To analyze the long-term survival and prognostic factors of patients with acute promyelocytic leukemia (APL) who were treated with arsenic trioxide (ATO). Methods From January 2007 to December 2017, a total of 154 newly diagnosed APL patients who were treated with ATO were included in the study from Tangdu Hospital, Air Force Military Medical University. According to the time of diagnosis and the treatment regimen, the subjects were divided into all trans-retinoic acid (ATRA) + chemotherapy-induced group (n= 87, diagnosed before 2012) and ATRA + ATO double-induced group (n= 67, diagnosed after 2012). The retrospective investigation method was used to collect early mortality, complete remission (CR) rate, conversion rate of PML/RARΑ fusion gene, recurrence rate, peripheral blood granulocyte ratio, bone marrow granulocyte ratio, PML/RARα fusion gene phenotype, risk stratification, CD2 and CD34 expression in ATRA+ chemotherapy-induced group and ATRA+ ATO double-induced group. And the efficacy and prognosis were compared between two groups. The follow-up time of this study was up to June 30, 2018, with a median follow-up of 58 months (6-134 months). The Chi-square test or Fisher′s exact test were used to compare the early mortalities, CR rates, and PML/PARα fusion gene conversion rates between the ATRA + chemotherapy-induced group and the ATRA + ATO double-induced group. The Kaplan-Meier method was used to map the survival curves of the patients in both groups. The life table method was used to compare the overall survival (OS) rate and recurrence-free survival (RFS) rates of patients in both groups. Univariate analysis was used to determine the influencing factors affecting the prognosis of patients with APL. The procedure followed in this study was in line with the requirements of Helsinki Declaration of the Word Medical Association revised in 2013. All individuals were routinely signed with informed consent for chemotherapy and toxic drugs before treatment. Results ① The CR rate of all patients in this study was 92.8% (143/154). The CR rate in ATRA + chemotherapy-induced group was 89.6% (60/67), and that of the ATRA + ATO double-induced group was 95.4 % (83/87), the difference was not statistically significant (χ2 = 1.953, P=0.162). There was significant difference in conversion rate of PML/RARα fusion gene between ATRA + chemotherapy-induced group and ATRA + ATO double-induced group(98.9% vs 89.5%; χ2=4.891, P=0.027). The early mortality during induction therapy was 7.1% (11/154). ② In the 154 APL patients, eleven patients had recurrence during consolidation and maintenance treatment. The recurrence rates of ATRA + chemotherapy-induced group and ATRA + ATO double induction group were 13.4% (9/67) and 2.3%(2/87), respectively, and the difference was statistically significant(χ2=5.495, P=0.019). ③ The 5-year OS rate and RFS rate in ATRA+ chemotherapy-induced group were 83.6% and 85.0%, respectively, which of ATO + ATRA double-induced group were 95.4% and 96.5%, respectively. The differences between two groups were statistically significant(χ2=6.838, P=0.029; χ2=3.297, P=0.040), respectively. ④ Results of univariate analysis showed that the 5-year OS rate of patients with duration of ATO usage≥84 d and 0.05). Conclusions Early death is still the main factor affecting the survival of APL, and ATO can improve the increase the CR rate and the molecular biology conversion rate during induction therapy. The cumulative treatment with ATO for more than 84 d is an important prognostic factor, but it cannot change the adverse effect of myeloblast in peripheral blood. Key words: Leukemia, promyelocytic, acute; Arsenicals; Antineoplastic combined chemotherapy protocols; Prognosis; Survival