Arsenic trioxide is required in the treatment of newly diagnosed acute promyelocytic leukemia. Analysis of a randomized trial (APL 2006) by the French Belgian Swiss APL group.

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License: CC BY-NC 4.0
Serval ID
serval:BIB_A8F861CC78B6
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Arsenic trioxide is required in the treatment of newly diagnosed acute promyelocytic leukemia. Analysis of a randomized trial (APL 2006) by the French Belgian Swiss APL group.
Journal
Haematologica
Author(s)
Adès L., Thomas X., Bresler A.G., Raffoux E., Spertini O., Vey N., Marchand T., Récher C., Pigneux A., Girault S., Deconinck E., Gardin C., Tournilhac O., Lambert J.F., Chevallier P., de Botton S., Lejeune J., Dombret H., Chevret S., Fenaux P.
ISSN
1592-8721 (Electronic)
ISSN-L
0390-6078
Publication state
Published
Issued date
12/2018
Peer-reviewed
Oui
Volume
103
Number
12
Pages
2033-2039
Language
english
Notes
Publication types: Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
In standard-risk acute promyelocytic leukemia, recent results have shown that all-trans retinoic acid plus arsenic trioxide combinations are at least as effective as classical all-trans retinoic acid plus anthracycline-based chemotherapy while being less myelosuppressive. However, the role of frontline arsenic trioxide is less clear in higher-risk acute promyelocytic leukemia, and access to arsenic remains limited for front-line treatment of standard-risk acute promyelocytic leukemia in many countries. In this randomized trial, we compared arsenic, all-trans retinoic acid and the "classical" cytarabine for consolidation treatment (after all-trans retinoic acid and chemotherapy induction treatment) in standard-risk acute promyelocytic leukemia, and evaluated the addition of arsenic during consolidation in higher-risk disease. Patients with newly diagnosed acute promyelocytic leukemia with a white blood cell count <10x10 <sup>9</sup> /L, after an induction treatment consisting of all-trans retinoic acid plus idarubicin and cytarabine, received consolidation chemotherapy with idarubicin and cytarabine, arsenic or all-trans retinoic acid. Patients with a white blood cell count >10x10 <sup>9</sup> /L received consolidation chemotherapy with or without arsenic. Overall, 795 patients with acute promyelocytic leukemia were enrolled in this trial. Among those with standard-risk acute promyelocytic leukemia (n=581), the 5-year event-free survival rates from randomization were 88.7%, 95.7% and 85.4% in the cytarabine, arsenic and all-trans retinoic acid consolidation groups, respectively (P=0.0067), and the 5-year cumulative incidences of relapse were was 5.5%, 0% and 8.2%. (P=0.001). Among those with higher-risk acute promyelocytic leukemia (n=214), the 5-year event-free survival rates were 85.5% and 92.1% (P=0.38) in the chemotherapy and chemotherapy plus arsenic groups, respectively, and the corresponding 5-year cumulative incidences of relapse were 4.6% and 3.5% (P=0.99). Given the prolonged myelosuppression that occurred in the chemotherapy plus arsenic arm, a protocol amendment excluded cytarabine during consolidation cycles in the chemotherapy plus arsenic group, resulting in no increase in relapse. Our results therefore advocate systematic introduction of arsenic in the first-line treatment of acute promyelocytic leukemia, but probably not concomitantly with intensive chemotherapy, a situation in which we found myelosuppression to be significant. (ClinicalTrials.gov Identifier: NCT00378365).
Keywords
Adult, Anthracyclines/administration & dosage, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Arsenic Trioxide/administration & dosage, Belgium, Disease-Free Survival, Female, France, Humans, Leukemia, Promyelocytic, Acute/diagnosis, Leukemia, Promyelocytic, Acute/drug therapy, Male, Middle Aged, Switzerland, Treatment Outcome, Tretinoin/administration & dosage
Pubmed
Web of science
Open Access
Yes
Create date
31/07/2018 12:46
Last modification date
26/10/2019 6:09
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