Arsenic-induced neurotoxicity in patients with acute promyelocytic leukaemia

Loh, Z; Ashby, M; Van Veldhuizen, E; Li, W; Chee, A; Aung, W; Lavrukhina, Y; Mason, G; Pelly, T; Nedumannil, R; Kosciejew, S; Mokoonlall, M; Lim, J; Calov, G; Butler, L; Hillebrand, P; Beekman, A; Rathnasekara, GK; Raj, S; Zhang, C; Yao, Y; Iland, H; Grigg, A

Author(s): Loh, Z; Ashby, M; Van Veldhuizen, E; Li, W; Chee, A; Aung, W; Lavrukhina, Y; Mason, G; Pelly, T; Nedumannil, R; Kosciejew, S; Mokoonlall, M; Lim, J; Calov, G; Butler, L; Hillebrand, P; Beekman, A; Rathnasekara, GK; Raj, S; Zhang, C; Yao, Y; Iland, H; Grigg, A;
Details: Publication Year 2024-05,Volume 204,Issue #5,Page 1732-1739
Journal Title: British Journal of Haematology
Publication Type: Research article
Abstract: Arsenic trioxide is an essential component of therapy for acute promyelocytic leukaemia (APL) and is currently dosed on actual body weight with no upper limit. Arsenic-induced neurotoxicity is a well-recognised complication; however, there is uncertainty about its relationship to arsenic dose and obesity. We conducted a large multicentre retrospective study of 487 patients with APL treated with arsenic-based therapy across 23 sites in Australia from 2008 to 2023. The primary outcome was incidence of neurotoxicity, and secondary outcomes included relationship of neurotoxicity to obesity and cumulative arsenic dose. Any-grade neurotoxicity occurred in 113 (23%) patients, predominantly peripheral neuropathy (91%). Most events were grade 1-2 severity (85%), with grade 3 events in 12% and grade 4-5 in 3%. The incidence of neurotoxicity increased with BMI (non-obese: 16%, obesity class I: 25%, obesity class II-III: 41%; p < 0.001). On univariable analysis, obesity class I (OR 1.81, p = 0.036), obesity class II-III (OR 3.93, p < 0.001), weight >100 kg (OR 2.72, p < 0.001), daily arsenic trioxide dose >15 mg (OR 5.05, p < 0.001) and cumulative induction dose >500 mg (OR 3.95, p < 0.001) were all significantly associated with neurotoxicity. Obesity class II-III and induction dose >500 mg remained significant on multivariable analysis. Our study highlights the strong association between BMI, arsenic trioxide dose and neurotoxicity. Pre-emptive dose reductions should be considered for obese patients receiving high doses of arsenic.
Publisher: Wiley
Keywords: Humans; *Leukemia, Promyelocytic, Acute/drug therapy; Male; Female; Middle Aged; Adult; Retrospective Studies; *Arsenic Trioxide/adverse effects/administration & dosage/therapeutic use; Aged; *Neurotoxicity Syndromes/etiology/epidemiology; Obesity/complications; Australia/epidemiology; Arsenic/adverse effects/toxicity; Young Adult; Adolescent; Aged, 80 and over; acute promyelocytic leukaemia; leukaemia therapy; pharmacology
Department(s): Clinical Haematology
Publisher's Version: https://doi.org/10.1111/bjh.19297
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-07-11 07:07:12

Last Modified: 2024-07-11 07:07:39