Severe Peripheral Neuropathy From Treatment With Arsenic Trioxide in a Patient Suffering From Acute Promyelocytic Leukemia

Helsø, Søren Niemi; Roug, Anne Stidsholt; Mørk, Morten; Maksten, Eva Futtrup; Severinsen, Marianne Tang

doi:10.14740/jh617

Cited by 5 publications

(3 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Despite its remarkable success in APL, arsenic is a known poison and carcinogen, and its use is limited by its toxicity [ 8 ]. Arsenic has known hepatotoxicity and cardiotoxicity and can less frequently cause dermatologic, neurologic, and gastrointestinal side effects [ 9 , 10 ].…”

Section: Discussionmentioning

confidence: 99%

Poison With a Purpose: A Case Report on Arsenic Cardiotoxicity and Obesity

Nachtigal¹,

Doan²

2022

Cureus

View full text Add to dashboard Cite

Acute promyelocytic leukemia (APL) is a form of leukemia in which there is an arrest of the maturation of the myeloid lineage at the promyelocyte stage. Although there is high early mortality due to coagulopathy, APL is now a curable disease with the use of arsenic trioxide (ATO) and all-trans-retinoic acid (ATRA). Arsenic is weight-based for the treatment of APL, and many toxicities are dose-dependent, although there are no guidelines regarding dosing adjustments for obese patients. We present a case of a 34-year-old male with obesity and APL who developed arsenic-induced QTc prolongation and symptomatic sinus tachycardia while receiving treatment. Further research is needed to guide appropriate dosing for obese patients to determine if ideal body weight dosing is able to provide similar cure rates with fewer adverse events.

show abstract

Section: Discussionmentioning

confidence: 99%

Poison With a Purpose: A Case Report on Arsenic Cardiotoxicity and Obesity

Nachtigal¹,

Doan²

2022

Cureus

View full text Add to dashboard Cite

show abstract

“…In earlier phase II trials of arsenic (0.15 mg/kg), all grade neurotoxicity was reported in 29–43% of patients 5,6 . While most cases are self‐limiting and mild, there are rare patients who develop severe, debilitating symptoms 7 . Despite being well described, there is a paucity of data regarding risk factors.…”

Section: Introductionmentioning

confidence: 99%

“…5,6 While most cases are selflimiting and mild, there are rare patients who develop severe, debilitating symptoms. 7 Despite being well described, there is a paucity of data regarding risk factors.…”

mentioning

confidence: 99%

Arsenic‐induced neurotoxicity in patients with acute promyelocytic leukaemia

Loh,

Ashby,

Van Veldhuizen

et al. 2024

Br J Haematol

View full text Add to dashboard Cite

SummaryArsenic 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.

show abstract