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Role of arsenic trioxide in APL
performed using SAS 9.1 (SAS Inc, Cary, NC, USA) and R software packages.
Here we present the results based on all patients included in the trial and data collected before June, 2017.
Results
Eight-hundred and seven patients were included in the trial. The diagnosis of APL could be confirmed in 795 of the patients who had t(15;17) and/or a PML-RAR rearrange- ment. The remaining 12 patients were excluded as diagnos- tic errors. The further analyses only dealt with the 795 patients with a confirmed diagnosis of APL who gave their consent to participation in the study and comprised 581 patients with standard-risk APL and 214 with high-risk APL.
Standard-risk acute promyelocytic leukemia
Of the 581 patients with standard-risk APL; 570 (98.1%) achieved a complete remission; the others died early. Forty- three patients were not randomized for consolidation treat- ment, including the 11 patients who did not achieve a com- plete remission, 15 due to adverse events, 12 due to the patients’ decision and five for other reasons (Figure 1).
Five-hundred and thirty-eight patients were randomized to different consolidation treatment (178, 180 and 180 in the AraC, ATO and ATRA arms, respectively). Pre-treat- ment characteristics were well-balanced between the three consolidation groups (Table 1).
A
Overall, 8, 0, and 14 patients relapsed (P=0.001) and 11, 5, and 11 patients (P=0.28) died in complete remission in the AraC, ATO and ATRA consolidation groups, respectively. Causes of death in complete remission were sepsis (n=2), hemorrhage (n=16), AML/myelodysplastic syndrome (MDS) (n=2), other (n=7). Overall, five patients developed AML/MDS including two, one and two patients treated in the AraC, ATO and ATRA arms, respectively.
Five-year event-free survival rates from randomization were 88.7%, 95.7% and 85.4% in the AraC, ATO and ATRA consolidation groups, respectively (P=0.0067). The 5-year cumulative incidences of relapse were 5.5%, 0% and 8.2% (P=0.001) and the 5-year overall survival rates were 93.6%, 95.7% and 91.9% (P=0.349) in the AraC, ATO and ATRA consolidation groups, respectively (Figure 2).
The median times to an absolute neutrophil count >1x109/L after the first consolidation course were 23.5, 22.8 and 18 days in the AraC, ATO and ATRA groups, respec- tively (P<0.0001). Similarly, the times to an absolute neu- trophil count >1x109/L after the second consolidation course were 23.3, 18.2 and 13.8 days (P<0.0001). The medi- an durations of hospitalization after the first and the second consolidation courses were 31.5, 32.2, and 19.5 days (P<0.0001) and 28.2, 29.9, and 16.5 days in the AraC, ATO and ATRA group, respectively (P<0.0001).
High-risk acute promyelocytic leukemia
Of the 214 patients with high-risk APL, 205 (95.7%) achieved a complete remission, seven (3.2%) died early (1 from bleeding, 3 from thrombosis, 1 from sepsis and 2 from
B
Figure 1. Consort diagrams. (A) Patients with a white blood cell count <109/L; (B) Patients with a white blood cell count >109/L. APL: acute promyelocytic leukemia; ARAC: cytarabine; ATO: arsenic trioxide; ATRA: all-trans retinoic acid.
haematologica | 2018; 103(12)
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