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Background: The epidemiology and treatment of acute promyelocytic leukaemia (APL) are changing. We have incorporated oral arsenic trioxide (oral-ATO) into induction/maintenance. Methods: Newly-diagnosed APL from 1991 to 2021 divided into three 10-year periods were studied to define its epidemiology and how oral-ATO impacted on its outcome. Primary endpoints included APL incidence, early deaths (ED, first 30 days), and overall survival (OS). Secondary endpoints included post-30-day OS, relapse-free survival (RFS), and incidence of second cancers. Results: APL occurred in 374 males and 387 females at a median age of 44 (1–97) years. Annual incidences increased progressively, averaging 0.32 per 100,000 people. All-trans retinoic acid (ATRA)-based and oral-ATO-based regimens were used in 469 and 282 patients. There were 144 EDs, occurring almost exclusively in ATRA-based inductions (N = 139), being more with males, age > 50 years, leucocyte > 10 × 109/L, diagnosis during 1991–2009 and fewer with oral-ATO-based regimens. After a median of 75 (interquartile range: 14–161) months, 5-year and 10-year OS were 68.1% and 63.3%, inferior with males, age > 50 years, leucocyte > 10 × 109/L, high-risk Sanz score and superior with oral-ATO-based regimens. Factoring out EDs, 5-year and 10-year post-30-day OS were 84.0% and 78.1%, inferior with males and superior with oral-ATO-based regimens. In 607 CR1 patients, the 5-year RFS was 83.8%, superior with diagnosis in 2010–2021 and oral-ATO-based regimens. Second cancers developed in 21 patients, unrelated to oral-ATO-based regimens. Conclusions: There was an increasing incidence of APL, and all survivals were superior with the use of oral-ATO-based regimens. This study formed part of the Acute Promyelocytic Leukaemia Asian Consortium Project (ClinicalTrials.gov identifier: NCT04251754). [ABSTRACT FROM AUTHOR]

Appreciation of the properties of arsenic trioxide (ATO) has redefined the treatment landscape for acute promyelocytic leukaemia (APL) and offers promise as a treatment for numerous other diseases. The benefits of ATO in patients with APL is related to its ability to counteract the effects of PML::RARA, an oncoprotein that is invariably detected in the blood or bone marrow of affected individuals. The PML::RARA oncoprotein is degraded specifically by binding to ATO. Thus ATO, in combination with all-trans retinoic acid, has become the curative treatment for ATO. The multiple mechanisms of action of ATO has also paved the way for application in various condition encompassing autoimmune or inflammatory disorders, solid organ tumours, lymphomas and other subtypes of AML. The development of oral formulation of ATO (oral ATO) has reduced costs of treatment and improved treatment convenience allowing widespread applicability. In this review, we discuss the mechanisms of action of ATO, the development of oral ATO, and the applications of oral ATO in APL and other diseases. [ABSTRACT FROM AUTHOR]

Acute promyelocytic leukemia, chemotherapy-free, arsenic trioxide, tetraarsenic tetrasulfide, oral arsenic trioxide With regard to the therapeutic application of intravenous arsenic trioxide, Russell and Dillon summarize the United Kingdom's NCRI AML17 experience using the attenuated arsenic trioxide regimen in newly diagnosed APL. Keywords: acute promyelocytic leukemia; arsenic trioxide; chemotherapy-free; tetraarsenic tetrasulfide; oral arsenic trioxide EN acute promyelocytic leukemia arsenic trioxide chemotherapy-free tetraarsenic tetrasulfide oral arsenic trioxide 1 3 3 01/24/22 20220120 NES 220120 Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML) characterized by t(15;17)(q24;21) and the fusion gene I PML-RARA i . [Extracted from the article]

Various forms of arsenic were used in China and elsewhere for over 5,000 years. Following the initial success of intravenous arsenic trioxide (i.v. As2O3), we revived an oral formulation of pure As2O3 in 1998 for the treatment of acute promyelocytic leukemia (APL). We were the first to produce a 1 mg/ml oral-As2O3 solution and showed that it had comparable bioavailability to i.v. As2O3. Moreover, we also reported that intracellular arsenic concentrations were considerably higher than the corresponding plasma values. Our oral-As2O3 was patented internationally and registered in Hong Kong for the treatment of APL. Safety, tolerability and clinical efficacy was confirmed in long-term follow-up studies. We have extended the use of oral-As2O3 to frontline induction of newly diagnosed APL. With these findings, we are moving toward an era of completely oral and chemotherapy-free management of APL. [ABSTRACT FROM AUTHOR]

Background: The role of arsenic trioxide (As2 O3 ) in the maintenance of first complete remission (CR1) in acute promyelocytic leukemia (APL) is unclear.Methods: A total of 129 consecutive adult patients with APL of all risk categories who achieved CR1 with conventional induction (all-trans retinoic acid [ATRA]/daunorubicin) and consolidation (daunorubicin/cytarabine [induction daunorubicin and consolidation omitted for age ≥70 years]) underwent maintenance comprising ATRA (45 mg/m2 /day), oral As2 O3 (10 mg/day), and ascorbic acid (1 g/day) (AAA) for 2 weeks every 2 months for 2 years.Results: Over a 17-year period from August 1, 2002, to July 31, 2019, 63 men and 66 women (median age, 46 years [range, 18-82 years]) received AAA maintenance, which was already completed in 117 patients. At a median follow-up of 100 months (range, 8-215 months), 17 patients (13%) developed first relapse (R1) (hematologic, n = 14; molecular, n = 3) after a median of 19 months (range, 7-96 months) from CR1. Two R1 patients had concomitant central nervous system (CNS) involvement. All patients achieved CR2 with oral As2 O3 -based salvage. Five patients had a subsequent relapse and died. Eight patients died of unrelated causes while still in CR1. The 5-year and 10-year rates of relapse-free survival (RFS) were 89% and 85%, respectively. The 5-year and 10-year rates of overall survival (OS) were 94% and 87%, respectively. Multivariate analysis showed that inferior RFS was associated with FLT3-ITD (P = .005) and CNS involvement on presentation (P = .004), and inferior OS was associated with therapy-related APL (P = .03), FLT3-ITD (P = .03), and relapse (P = .03). The safety profile was favorable, with no grade 3/4 organ toxicities.Conclusion: CR1 maintenance with AAA is safe and results in favorable long-term survival in patients with APL. [ABSTRACT FROM AUTHOR]

Background: Strategies using oral arsenic trioxide (As2O3) 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/m2/d, oral As2O3 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/m2/d × 3); they then underwent consolidation with 2 monthly cycles of daunorubicin (50 mg/m2/d × 2) and cytarabine (100 mg/m2/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 As2O3 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 As2O3 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–As2O3 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 As2O3 induction and non–As2O3 induction cohorts showed similar OS, but LFS was significantly superior in the oral As2O3 induction cohort. Conclusions: The incorporation of oral As2O3 into induction for newly diagnosed APL was safe and decreased relapses. In the current study, 62 patients with newly diagnosed acute promyelocytic leukemia are treated with oral arsenic trioxide, all‐trans retinoic acid, and ascorbic acid as part of their induction regimen, with all achieving complete remission, and this is followed by consolidation with daunorubicin and cytarabine and maintenance with oral arsenic trioxide, all‐trans retinoic acid, and ascorbic acid. In comparison with a contemporaneous cohort of 37 patients with newly diagnosed acute promyelocytic leukemia who are treated similarly but without oral arsenic trioxide during induction, the oral arsenic trioxide cohort appears to have significantly superior leukemia‐free survival. [ABSTRACT FROM AUTHOR]

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 (As2 O3 )-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 As2 O3 -based reinduction resulted uniformly in CR2, irrespective of previous As2 O3 exposure. All patients received oral As2 O3 -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 As2 O3 , 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 As2 O3 -based reinduction led to CR3 in 27 patients (90%). Post-CR3 strategies included autologous hematopoietic stem cell transplantation and oral As2 O3 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 As2 O3 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 As2 O3 therapy was the only significant risk factor for central nervous system involvement.Conclusions: For patients with relapsed APL, As2 O3 remained effective despite repeated As2 O3 exposures. Oral As2 O3 maintenance was an effective postremission strategy for CR2. Cancer 2018;124:2316-26. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 55-year-old man who was diagnosed with acute promyelocytic leukemia (APL). His Karyotyping and molecular analysis showed PML-RARA of the BCR3 isoform while his induction treatment with all-trans retinoic acid (ATRA) and idarubicin resulted in first complete remission.