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Long‐term outcome of relapsed acute promyelocytic leukemia treated with oral arsenic trioxide‐based reinduction and maintenance regimens: A 15‐year prospective study
Author(s) -
Gill Harinder,
Yim Rita,
Lee Harold K. K.,
Mak Vivien,
Lin ShekYing,
Kho Bonnie,
Yip SzeFai,
Lau June S. M.,
Li Wah,
Ip HoWan,
Hwang YuYan,
Chan Thomas S. Y.,
Tse Eric,
Au WingYan,
Kumana Cyrus R.,
Kwong YokLam
Publication year - 2018
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.31327
Subject(s) - medicine , arsenic trioxide , acute promyelocytic leukemia , gastroenterology , regimen , maintenance therapy , hematopoietic stem cell transplantation , surgery , transplantation , chemotherapy , retinoic acid , arsenic , chemistry , biochemistry , gene , materials science , metallurgy
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 .