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Oral arsenic trioxide, all‐ trans retinoic acid, and ascorbic acid maintenance after first complete remission in acute promyelocytic leukemia: Long‐term results and unique prognostic indicators
Author(s) -
Gill Harinder S.,
Yim Rita,
Kumana Cyrus R.,
Tse Eric,
Kwong YokLam
Publication year - 2020
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.32937
Subject(s) - medicine , acute promyelocytic leukemia , gastroenterology , daunorubicin , arsenic trioxide , cytarabine , concomitant , surgery , ascorbic acid , asymptomatic , leukemia , retinoic acid , apoptosis , biochemistry , chemistry , food science , gene
Background The role of arsenic trioxide (As 2 O 3 ) 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/m 2 /day), oral As 2 O 3 (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 As 2 O 3 ‐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.