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Background: Strategies using oral arsenic trioxide (As 2 O 3 ) are efficacious in relapsed acute promyelocytic leukemia (APL), but they have not been examined in newly diagnosed cases., Methods: Sixty-two consecutive patients (24 men and 38 women) with a median age of 52 years (range, 22-85 years), 36% of whom had high-risk features, underwent induction with all-trans retinoic acid at 45 mg/m 2 /d, oral As 2 O 3 at 10 mg/d, and ascorbic acid at 1 g/d (the all-trans retinoic acid-arsenic trioxide-ascorbic acid [AAA] regimen) for 6 weeks (with patients younger than 70 years additionally receiving daunorubicin at 50 mg/m 2 /d × 3); they then underwent consolidation with 2 monthly cycles of daunorubicin (50 mg/m 2 /d × 2) and cytarabine (100 mg/m 2 /d × 5) and received AAA maintenance (2 weeks every 8 weeks) for 2 years. A contemporaneous cohort of 37 newly diagnosed patients (15 men and 22 women) with a median age of 51 years (range, 23-78 years), not consenting to oral As 2 O 3 induction but receiving similar induction, consolidation, and AAA maintenance, served as a comparator group; 46% of these patients had high-risk features., Results: The oral As 2 O 3 induction cohort showed a complete remission (CR) rate of 100%. After a median of 37 months (range, 13-82 months), there were no relapses, so conventional risks (age, leukocyte and platelet counts, and Fms-like tyrosine kinase 3 [FLT3] mutations) were not relevant. The leukemia-free survival (LFS) and overall survival (OS) rates were 100% at 3 years and 94.1% at 5 years. The non-As 2 O 3 induction cohort showed a CR rate of 100%. After a median of 52 months (range, 14-77 months), there were 3 relapses (8%). Comparable patients in the oral As 2 O 3 induction and non-As 2 O 3 induction cohorts showed similar OS, but LFS was significantly superior in the oral As 2 O 3 induction cohort., Conclusions: The incorporation of oral As 2 O 3 into induction for newly diagnosed APL was safe and decreased relapses., (© 2019 American Cancer Society.)

Background: For patients who have acute promyelocytic leukemia (APL) in second complete remission (CR2), optimal postremission strategies remain undefined., Methods: The role of an oral arsenic trioxide (As 2 O 3 )-based regimen in the management of patients who had APL in CR2 was examined., Results: Seventy-three patients with APL in first relapse (R1) were studied. Oral As 2 O 3 -based reinduction resulted uniformly in CR2, irrespective of previous As 2 O 3 exposure. All patients received oral As 2 O 3 -based maintenance in CR2. At a median follow-up of 94 months (range, 9-205 months), 43 patients (58.9%) were still in CR2, and 49 (67.1%) had finished the planned 2-year CR2 maintenance with all-trans retinoic acid, oral As 2 O 3 , and ascorbic acid. Reinduction and maintenance treatments were well tolerated. Grade 1 and 2 headache occurred in 20 patients (27.4%). Hepatotoxicity, all in the form of transaminitis, occurred in 35 patients (47.9%; grade 1 and 2, n = 26; grade 3 and 4, n = 9). Three patients had self-limiting QTc prolongation. The 10-year leukemia-free survival rate was 56.8%. Thirty patients developed R2. Oral As 2 O 3 -based reinduction led to CR3 in 27 patients (90%). Post-CR3 strategies included autologous hematopoietic stem cell transplantation and oral As 2 O 3 maintenance. At a post-CR3 follow-up of 30 months (range, 3-166 months), 11 patients were still in CR3. The 5-year and 10-year overall survival rates in the R1 cohort were 79.5% and 67.3%, respectively. Prior receipt of oral As 2 O 3 maintenance in CR1 was the only risk factor for inferior leukemia-free survival. Central nervous system involvement occurred in 15 patients, including 5 who remained alive. Relapse during oral As 2 O 3 therapy was the only significant risk factor for central nervous system involvement., Conclusions: For patients with relapsed APL, As 2 O 3 remained effective despite repeated As 2 O 3 exposures. Oral As 2 O 3 maintenance was an effective postremission strategy for CR2. Cancer 2018;124:2316-26. © 2018 American Cancer Society., (© 2018 American Cancer Society.)