Clinical Outcomes of Different Regimens in Patients Newly Diagnosed with Acute Promyelocytic Leukemia

Objective: This study aims to evaluate the efficacy and safety of all-trans retinoic acid (ATRA) combined with arsenic trioxide (ATO) compared with those of ATRA combined with chemotherapy for induction and maintenance therapy for acute promyelocytic leukemia (APL).

Method: From March 2009 to March 2016, 134 patients newly diagnosed with APL were enrolled and divided into different groups. In the experimental group (Exp.G) (n= 37), the patients received ATRA combined with ATO for induction treatment, followed by three courses of anthracycline-based chemotherapy for consolidation therapy and 6-9 courses of ATRA combined with ATO for maintenance treatment. In the control group 1 (Ctrl 1, n= 57), the patients received ATRA combined with ATO for induction therapy, followed by three courses of anthracycline-based chemotherapy for consolidation therapy and six courses of ATRA combined with ATO plus MTX for 2 years (6-MP) for maintenance therapy. In the control group 2 (Ctrl 2, n= 40), the patients received induction therapy of ATRA combined with chemotherapy and three courses of anthracycline-based chemotherapy, followed by six courses of ATRA combined with MTX for 2 years (6-MP) for maintenance therapy. The 4-year RFS, OS, and DFS probabilities were investigated. The side effects of the regimens were also evaluated.

Result: The median follow-up times were 56, 47, and 50 months for patients in Exp. G, Ctrl 1, and Ctrl 2, respectively, and the complete remission rates were 100%, 94.7%, and 90%, respectively (Exp vs.Ctrl 1, P=0.156; Exp vs.Ctrl 2, P=0.048; and Ctrl 1 vs. Ctrl 2, P=0.375). The remission rate of patients in Exp.G was higher than that in Ctrl 2, and the difference was statistically significant (P=0.048). Prior to the maintenance therapy, the molecular biological remission rates ofthe PML / RARα fusion gene in the three groups were 91.2% (34/37), 89.5% (51/57), and 85% (34/40), respectively (P=0.036). The negative rate ofthe PML / RARα fusion gene was significantly higher in Exp.G than that in Ctrl 2 (P<0.05). The median times to induce remission were 43, 44, and 48 days in the three groups (Ex.G vs.Ctrl 1, P=0.733; Exp.G vs.Ctrl 2, P=0.026; and Ctrl 1 vs. Ctrl 2, P=0.035). The median times in Exp.G and Ctrl 1 were significantly shorter than that in Ctrl 2 (P <0.05). Furthermore, the 4-year RFS values were 94.6%, 91.2%, and 65% (Exp.G vs.Ctrl 1, P=0.544; Exp.G vs.Ctrl 2, P<0.001; and Ctrl 1 vs. Ctrl 2, P=0.001). The 4-year RFS values in Exp.G and Ctrl 1 were significantly higher than that in Ctrl 2 (P<0.05). The four-year OS values were 100%, 96.5%, and 90% (Ex.G vs.Ctrl 1, P=0.249; Exp.G vs.Ctrl 2, P=0.048; and Ctrl 1 vs. Ctrl 2, P=0.191). The 4-year OS in Exp.G was significantly higher than that in Ctrl 2 (P = 0.048). The 4-year DFS values were 94.6%, 87.7%, and 60% (Exp.G vs.Ctrl 1, P=0.268; Exp.G vs.Ctrl 2, P=0.010; and Ctrl 1 vs. Ctrl 2, P=0.020). The 4-year DFS values in Exp.G and Ctrl 1 was significantly higher than that in Ctrl 2 (P<0.05). During the entire course of treatment, no death, recurrence of CNS, and formation of second tumor were observed in Exp.G. In Ctrl 1, two patients died. One case died of severe infection after recurrence of the second tumor. Five patients displayed relapsed; among which, two cases were of CNS leukemia recurrence. Five patients are still alive. In Ctrl 2, four patients died, and 14 patients relapsed; among which, two cases were of CNS leukemia recurrence. Twelve patients are still alive. The incidences of induced differentiation syndrome in Exp.G, Ctrl 1, and Ctrl 2 were 45.9%, 28%, and 40%, respectively.

Conclusion: Patients newly diagnosed with APL and treated with ATRA and ATO double-induced and maintenance therapy showed a high induced remission rate, a short induction time, and high values for 4-year RFS, EFS, and OS. Patients in the observation group received a simple treatment regimen, and no CNS recurrence and second tumor formation were observed in this group. The rates of adverse events in patients given with ATRA combined with the ATO regimen were similar to those in patients treated with ATRA combined with chemotherapy regimen.