Clinical study of children with acute promyelocytic leukemia treated with arsenic trioxide with positive PML-RARa fusion gene

Abstract

Objective To evaluate the efficacy of different treatment regimens for children with acute promyelocytic leukemia (APL) with positive PML-RARa fusion gene. Methods Thirty-two newly diagnosed APL patients were included in this study, treated either with all-trans-retinoic acid (ATRA) and chemotherapy (CT) (group A) or with ATRA and arsenic trioxide (ATO) (group B). Clinical situation and clinical efficacy were analyzed in patients in different groups.They were also separated into low risk group, intermediate risk group and high risk group according to different risk criteria.Clinical characteristics, complete remission, long-time survival and urine arsenic concentration were analyzed and compared. Results (1) Fourteen of 15 patients (93.3%) in group A achieved hematological complete remission (HCR) with a median time of 38 days (28-63 days). Sixteen of 17 patients (94.1%) in group B achieved HCR with a median time of 29 days (10-42 days), which was significantly shorter than group A, and there was a significant difference between 2 groups(t=3.53, P=0.002). (2) The 5-year event-free survival (EFS) of group A and group B was (60.0±12.6)% and (81.9±9.5)%, respectively; the 5-year EFS of group B was almost 20% higher than group A; while there was no significant difference between the 2 groups(χ2=1.15, P=0.28). The 5-year overall survival (OS) of group A and group B was (72.2±11.9)% and (94.1±5.7)%, respectively, the 5-year OS of group B was almost 20% higher than group A; while there was no significant difference between the 2 groups(χ2=2.88, P=0.16). (3)The 5-year EFS of low plus intermediate group and high risk group patients was (74.0±10.1)% and (64.8±14.3)%, the 5-year EFS of low plus intermediate group was almost 10% higher than high risk group, but there was no significant difference between the 2 groups(χ2=0.14, P=0.71). The 5-year OS of low plus intermediate group and high risk group patients was (84.7±8.1)% and (71.3±14.1)%, the 5-year OS of low plus intermediate group was almost 10% higher than high risk group, while there was no significant difference between the 2 groups(χ2=0.36, P=0.55). (4)ATO related side effects were mild, including abnormal liver tests and electrocardiogram, but were invertible after supportive therapy.At the end of each chemotherapy course, the urine arsenic concentration remained low and no chronic arsenic toxicity or second malignancies were found during the follow-up period. Conclusions The ATRA plus ATO regimen is a promising and better treatment for childhood APL with positive PML-RARa fusion gene compared with conventional chemotherapy.It was necessary to take risk stratification in APL patients. Key words: Acute promyelocytic leukemia; PML-RARa fusion gene; All-trans-retinoic acid; Arsenic trioxide; Child