Insights into the All-trans-Retinoic Acid and Arsenic Trioxide Combination Treatment for Acute Promyelocytic Leukemia: A Meta-Analysis.
BACKGROUND
This study aimed to compare the curative effects of the combination therapy of all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO, As₂O₃) with ATRA monotherapy on newly diagnosed acute promyelocytic leukemia (APL).


METHODS
The studies were retrieved from PubMed, EMBASE, Cochrane Library, ChinaInfo and China National Knowledge Infrastructure (CNKI) databases from the inception to June 20, 2014. Thereafter, the eligible studies were selected based on the predefined criteria, and the literature quality was assessed. The meta-analysis was conducted using Review Manager 5.2 software. The pooled effect size was relative risk (RR) and its 95% confidence interval (CI).


RESULTS
A total of 8 studies containing 480 cases were included, among which 264 were assigned to the ATRA + ATO group and the other 216 to the ATRA group. The meta-analysis showed that ATRA + ATO combination therapy significantly improved the complete remission (CR) rate (RR = 1.09, 95% CI = 1.03-1.16, p = 0.004), decreased the early mortality rate (RR = 0.42, 95% CI = 0.20-0.9, p = 0.03) and relapse rate (RR = 0.17, 95% CI = 0.07-0.42, p < 0.0001), but increased the high risk of liver dysfunction (RR = 2.43, 95% CI = 1.72-3.41, p < 0.00001), comparing with ATRA monotherapy.


CONCLUSIONS
The ATRA + ATO combination therapy may be more effective for newly diagnosed APL with a higher CR rate but lower early mortality rate and relapse rate. However, the risks of liver damage should be of concern.
Hematology Department, West China Hospital, Sichuan University, Chengdu, China.
Hongbing
H
Ma
Jing
J
Yang
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology; D018849:Controlled Clinical Trials as Topic; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D010087:Oxides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012074:Remission Induction; D012306:Risk; D014212:Tretinoin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D014212:Tretinoin; D000077237:Arsenic Trioxide