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Objective: We aimed to compare the kinetics of white blood cell (WBC) and explore predictive factors of leukocytosis in non-high-risk acute promyelocytic leukemia (APL), with oral arsenic plus all-trans retinoic acid (ATRA) or intravenous arsenic trioxide (ATO) plus ATRA as a first-line treatment., Methods: The absolute count, doubling time and peak time of WBC were analyzed in 64 newly diagnosed non-high-risk APL patients who were treated with different induction regimens containing either oral Realgar-indigo naturalis formula (RIF) (n=35) or ATO (n=29). The end points were the dynamic changes of the WBC counts during induction. The time points started at day 1 and were selected over 3-day intervals for 28days., Results: Among the 64 included patients, the median initial and peak WBC counts were 1.78×10 9 /L (range 0.31-9.89) and 12.16×10 9 /L (range 1.56-80.01), respectively. The incidence of differentiation syndrome was 9.38%. The dynamic changes in leukocytosis showed a single peak wave in all the patients, and the median time to peak was 10 (range 2-26) days. A higher WBC count was observed in the RIF group than in the ATO group after 10days of treatment (9.22×10 9 /L vs. 4.10×10 9 /L, p=0.015). Patients with the peak WBC count >10×10 9 /L had a shorter WBC doubling time compared to patients with a lower peak WBC (RIF group 4days vs. 7days, p=0.001; ATO group 4.5days vs. 23days, p=0.002). Univariate and multivariable analyses showed that the doubling time of WBC is an independent factor for the peak WBC count., Conclusion: Different kinetics of WBC proliferation were observed during induction with oral arsenic plus ATRA and ATO plus ATRA. The doubling time of WBC is an important independent factor for predicting the peak WBC count., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

To improve the recovery rate of high-risk patients with acute promyelocytic leukemia (APL), we used all-trans retinoic acid (ATRA)/arsenic trioxide (ATO)/daunorubicin combination in remission induction, daunorubicin and cytarabine in consolidation, and ATRA/ATO/methotrexate ± 6-mercaptopurine in maintenance treatment of APL patients with various risks for relapse. Our results showed a high complete remission rate of 95.3%. Excluding the cases of early-death, no significant differences in event-free survival were observed between the intermediate-risk and high-risk group (p = 0.393) and the low-risk and high-risk group (p = 0.162). In addition, there were no significant differences between the groups in cumulative incidence of central nervous system relapse. In conclusion, our results suggest that APL patients benefit from combination ATO/ATRA/chemotherapy, and that this regimen is especially beneficial for patients with high-risk prognostic factors., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Twenty-two patients with myelodysplastic syndromes (MDS) were treated with thalidomide plus arsenic trioxide (ATO). Twenty-two MDS patients receiving supportive care were used as controls. The remission was achieved in 4 patients (18.2%) receiving thalidomide/ATO, and none in the control group (p<0.05). Fifteen of 22 patients in the treatment group achieved hematologic improvement (68.2% vs. 27.3% in the control, p<0.05). The progression-free survival was longer in the treatment group than that in the control (26 vs. 10 months, p<0.05). The overall survival was also longer in the treatment group than that in the control (36 vs. 16 months, p<0.05). No severe adverse reactions were observed. These preliminary findings suggest that thalidomide/ATO combination treatment is effective and safe for MDS., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Arsenic trioxide (ATO) and all-trans-retinoic acid (ATRA) could induce apoptosis and differentiation in acute promyelocytic leukemia (APL) cells, respectively, thus the possibility of synergism between them was raised. This meta-analysis assessed the effectiveness and safety of ATO combined with ATRA in the treatment of APL. Compared with ATO alone, induction therapy with ATO/ATRA significantly increased the complete remission (CR) rate (RR: 1.08, 95% CI: 1.00-1.17, P=0.04), shortened the time to achieve CR (WMD: -6.51, 95% CI: -11.32 to -1.70, P=0.008), and improved the molecular remission rate after consolidation therapy (RR: 1.74, 95% CI: 1.14-2.66, P=0.01) and the 1-year disease-free survival rate (RR: 1.22, 95% CI: 1.00-1.50, P=0.05). There were no statistically significant differences between two treatments in terms of early death and main adverse events. These results suggested that ATO/ATRA could synergistically improve the overall outcome of newly diagnosed and relapsed APL patients, supporting the use of ATO/ATRA as an effective treatment for all APL patients previously untreated with ATO., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Advanced myelodysplastic syndrome (MDS) carries a poor prognosis. In this phase I/II study, arsenic trioxide was combined with low-dose cytarabine in 49 previously untreated patients with intermediate-2 and high-risk MDS. Complete remission was achieved in 8 (17%) patients, including 3/14 (21%) with treatment-related disease, 4/31 (13%) with unfavorable cytogenetics and 2/36 (6%) with baseline poor performance status. Mortality within the first 4 weeks was 8%. The regimen was active and had a tolerable extramedullary toxicity profile, but it was cumbersome and intensive compared to other currently available treatments., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Objective: To evaluate the clinical efficacy and safety of arsenic trioxide, retinoic acid and thalidomide combination therapy in higher risk MDS., Methods: Twenty-one patients diagnosed with higher risk MDS were administered 10mg/day arsenic trioxide intravenously for 10 days, 40mg/day retinoic acid orally for 2 weeks and 100mg/day thalidomide orally for 4 weeks per cycle., Results: After at least two treatment cycles, 10 patients showed hematologic responses. One achieved CR, one achieved PR, three patients achieved major hematological improvements. The efficacy rate was 24% (5/21), and the response rate was 48% (10/21). The schedule was tolerated well by all patients and toxicities were moderate and reversible., Conclusion: The combination of arsenic trioxide, retinoic acid and thalidomide could have therapeutic benefit in higher risk MDS with safety.

Arsenic trioxide (As(2)O(3)) is highly efficacious for acute promyelocytic leukemia (APL). Environmental arsenic exposure predisposes to malignancies, but the risk for therapeutic arsenic is undefined. Three APL patients (de novo, 2; therapy-related, 1) in a cohort of 59 cases given oral-As(2)O(3) for induction and maintenance treatment developed secondary cancers (nasopharyngeal carcinoma, 2; colonic adenocarcinoma, 1) at 16, 36 and 55 months post-As(2)O(3) therapy. Retrospective analysis of biomarkers (Epstein Barr virus serology and quantification, carcinoembryonic antigen) showed the potential presence of cancers before or shortly after As(2)O(3) therapy, suggesting that As(2)O(3) had not initiated these malignancies. Compared against matched background population, there was an increased risk of second cancer (p=0.012, standard incidence ratio=6.5; 95% confidence interval=1.4-19.0).